Diabetes is a chronic illness that requires continuing medical care and ongoing patient
self-management education and support to prevent acute complications and to reduce
the risk of long-term complications. Diabetes care is complex and requires that many
issues, beyond glycemic control, be addressed. A large body of evidence exists that
supports a range of interventions to improve diabetes outcomes.
These standards of care are intended to provide clinicians, patients, researchers,
payors, and other interested individuals with the components of diabetes care, general
treatment goals, and tools to evaluate the quality of care. While individual preferences,
comorbidities, and other patient factors may require modification of goals, targets
that are desirable for most patients with diabetes are provided. These standards are
not intended to preclude clinical judgment or more extensive evaluation and management
of the patient by other specialists as needed. For more detailed information about
management of diabetes, refer to references 1
–3.
The recommendations included are screening, diagnostic, and therapeutic actions that
are known or believed to favorably affect health outcomes of patients with diabetes.
A grading system (Table 1), developed by the American Diabetes Association (ADA) and
modeled after existing methods, was used to clarify and codify the evidence that forms
the basis for the recommendations. The level of evidence that supports each recommendation
is listed after each recommendation using the letters A, B, C, or E.
Table 1
ADA evidence grading system for clinical practice recommendations
Level of evidence
Description
A
Clear evidence from well-conducted, generalizable, randomized controlled trials that
are adequately powered, including:
Evidence from a well-conducted multicenter trial
Evidence from a meta-analysis that incorporated quality ratings in the analysis
Compelling nonexperimental evidence, i.e., “all or none” rule developed by Center
for Evidence Based Medicine at Oxford
Supportive evidence from well-conducted randomized controlled trials that are adequately
powered, including:
Evidence from a well-conducted trial at one or more institutions
Evidence from a meta-analysis that incorporated quality ratings in the analysis
B
Supportive evidence from well-conducted cohort studies:
Evidence from a well-conducted prospective cohort study or registry
Evidence from a well-conducted meta-analysis of cohort studies
Supportive evidence from a well-conducted case-control study
C
Supportive evidence from poorly controlled or uncontrolled studies
Evidence from randomized clinical trials with one or more major or three or more minor
methodological flaws that could invalidate the results
Evidence from observational studies with high potential for bias (such as case series
with comparison to historical controls)
Evidence from case series or case reports
Conflicting evidence with the weight of evidence supporting the recommendation
E
Expert consensus or clinical experience
These standards of care are revised annually by the ADA multidisciplinary Professional
Practice Committee, and new evidence is incorporated. Members of the Professional
Practice Committee and their disclosed conflicts of interest are listed in the Introduction.
Subsequently, as with all position statements, the standards of care are reviewed
and approved by the Executive Committee of ADA's Board of Directors.
I. CLASSIFICATION AND DIAGNOSIS
A. Classification
The classification of diabetes includes four clinical classes:
type 1 diabetes (results from β-cell destruction, usually leading to absolute insulin
deficiency)
type 2 diabetes (results from a progressive insulin secretory defect on the background
of insulin resistance)
other specific types of diabetes due to other causes, e.g., genetic defects in β-cell
function, genetic defects in insulin action, diseases of the exocrine pancreas (such
as cystic fibrosis), and drug- or chemical-induced diabetes (such as in the treatment
of AIDS or after organ transplantation)
gestational diabetes mellitus (GDM) (diabetes diagnosed during pregnancy)
Some patients cannot be clearly classified as having type 1 or type 2 diabetes. Clinical
presentation and disease progression vary considerably in both types of diabetes.
Occasionally, patients who otherwise have type 2 diabetes may present with ketoacidosis.
Similarly, patients with type 1 diabetes may have a late onset and slow (but relentless)
progression despite having features of autoimmune disease. Such difficulties in diagnosis
may occur in children, adolescents, and adults. The true diagnosis may become more
obvious over time.
B. Diagnosis of diabetes
Recommendations
For decades, the diagnosis of diabetes has been based on plasma glucose (PG) criteria,
either fasting PG (FPG) or 2-h 75-g oral glucose tolerance test (OGTT) values. In
1997, the first Expert Committee on the Diagnosis and Classification of Diabetes Mellitus
revised the diagnostic criteria using the observed association between glucose levels
and presence of retinopathy as the key factor with which to identify threshold FPG
and 2-h PG levels. The committee examined data from three cross-sectional epidemiologic
studies that assessed retinopathy with fundus photography or direct ophthalmoscopy
and measured glycemia as FPG, 2-h PG, and HbA1c (A1C). The studies demonstrated glycemic
levels below which there was little prevalent retinopathy and above which the prevalence
of retinopathy increased in an apparently linear fashion. The deciles of FPG, 2-h
PG, and A1C at which retinopathy began to increase were the same for each measure
within each population. The analyses helped to inform a then-new diagnostic cut point
of ≥126 mg/dl (7.0 mmol/l) for FPG and confirmed the long-standing diagnostic 2-h
PG value of ≥200 mg/dl (11.1 mmol/l) (4).
ADA has not previously recommended the use of A1C for diagnosing diabetes, in part
due to lack of standardization of the assay. However, A1C assays are now highly standardized,
and their results can be uniformly applied both temporally and across populations.
In a recent report (5), after an extensive review of both established and emerging
epidemiological evidence, an international expert committee recommended the use of
the A1C test to diagnose diabetes with a threshold of ≥6.5%, and ADA affirms this
decision (6). The diagnostic test should be performed using a method certified by
the National Glycohemoglobin Standardization Program (NGSP) and standardized or traceable
to the Diabetes Control and Complications Trial (DCCT) reference assay. Point-of-care
A1C assays are not sufficiently accurate at this time to use for diagnostic purposes.
Epidemiologic datasets show a relationship between A1C and the risk of retinopathy
similar to that which has been shown for corresponding FPG and 2-h PG thresholds.
The A1C has several advantages to the FPG, including greater convenience, since fasting
is not required; evidence to suggest greater preanalytical stability; and less day-to-day
perturbations during periods of stress and illness. These advantages must be balanced
by greater cost, limited availability of A1C testing in certain regions of the developing
world, and incomplete correlation between A1C and average glucose in certain individuals.
In addition, the A1C can be misleading in patients with certain forms of anemia and
hemoglobinopathies. For patients with a hemoglobinopathy but normal red cell turnover,
such as sickle cell trait, an A1C assay without interference from abnormal hemoglobins
should be used (an updated list of A1C assays and whether abnormal hemoglobins impact
them is available at www.ngsp.org/prog/index3.html). For conditions with abnormal
red cell turnover, such as pregnancy or anemias from hemolysis and iron deficiency,
the diagnosis of diabetes must use glucose criteria exclusively.
The established glucose criteria for the diagnosis of diabetes (FPG and 2-h PG) remain
valid. Patients with severe hyperglycemia such as those who present with severe classic
hyperglycemic symptoms or hyperglycemic crisis can continue to be diagnosed when a
random (or casual) PG of ≥200 mg/dl (11.1 mmol/l) is found. It is likely that in such
cases the health care professional would also conduct an A1C test as part of the initial
assessment of the severity of the diabetes and that it would be above the diagnostic
cut point. However, in rapidly evolving diabetes such as the development of type 1
in some children, the A1C may not be significantly elevated despite frank diabetes.
Just as there is <100% concordance between the FPG and 2-h PG tests, there is not
perfect concordance between A1C and either glucose-based test. Analyses of National
Health and Nutrition Examination Survey (NHANES) data indicate that, assuming universal
screening of the undiagnosed, the A1C cut point of ≥6.5% identifies one-third fewer
cases of undiagnosed diabetes than a fasting glucose cut point of ≥126 mg/dl (7.0
mmol/l) (E. Gregg, personal communication). However, in practice, a large portion
of the diabetic population remains unaware of their condition. Thus, the lower sensitivity
of A1C at the designated cut point may well be offset by the test's greater practicality,
and wider application of a more convenient test (A1C) may actually increase the number
of diagnoses made.
As with most diagnostic tests, a test result diagnostic of diabetes should be repeated
to rule out laboratory error, unless the diagnosis is clear on clinical grounds, such
as a patient with classic symptoms of hyperglycemia or hyperglycemic crisis. It is
preferable that the same test be repeated for confirmation, since there will be a
greater likelihood of concurrence in this case. For example, if the A1C is 7.0% and
a repeat result is 6.8%, the diagnosis of diabetes is confirmed. However, there are
scenarios in which results of two different tests (e.g., FPG and A1C) are available
for the same patient. In this situation, if the two different tests are both above
the diagnostic threshold, the diagnosis of diabetes is confirmed.
On the other hand, if two different tests are available in an individual and the results
are discordant, the test whose result is above the diagnostic cut point should be
repeated, and the diagnosis is made on the basis of the confirmed test. That is, if
a patient meets the diabetes criterion of the A1C (two results ≥6.5%) but not the
FPG (<126 mg/dl or 7.0 mmol/l), or vice versa, that person should be considered to
have diabetes. Admittedly, in most circumstance the “nondiabetic” test is likely to
be in a range very close to the threshold that defines diabetes.
Since there is preanalytic and analytic variability of all the tests, it is also possible
that when a test whose result was above the diagnostic threshold is repeated, the
second value will be below the diagnostic cut point. This is least likely for A1C,
somewhat more likely for FPG, and most likely for the 2-h PG. Barring a laboratory
error, such patients are likely to have test results near the margins of the threshold
for a diagnosis. The healthcare professional might opt to follow the patient closely
and repeat the testing in 3–6 months.
The current diagnostic criteria for diabetes are summarized in Table 2.
Table 2
Criteria for the diagnosis of diabetes
1.
A1C ≥6.5%. The test should be performed in a laboratory using a method that is NGSP
certified and standardized to the DCCT assay.*
OR
2.
FPG ≥126 mg/dl (7.0 mmol/l). Fasting is defined as no caloric intake for at least
8 h.*
OR
3.
Two-hour plasma glucose ≥200 mg/dl (11.1 mmol/l) during an OGTT. The test should be
performed as described by the World Health Organization, using a glucose load containing
the equivalent of 75 g anhydrous glucose dissolved in water.*
OR
4.
In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random
plasma glucose ≥200 mg/dl (11.1 mmol/l).
*In the absence of unequivocal hyperglycemia, criteria 1–3 should be confirmed by
repeat testing.
C. Categories of increased risk for diabetes
In 1997 and 2003, The Expert Committee on the Diagnosis and Classification of Diabetes
Mellitus (4,7) recognized an intermediate group of individuals whose glucose levels,
although not meeting criteria for diabetes, are nevertheless too high to be considered
normal. This group was defined as having impaired fasting glucose (IFG) (FPG levels
of 100 mg/dl [5.6 mmol/l] to 125 mg/dl [6.9 mmol/l]) or impaired glucose tolerance
(IGT) (2-h OGTT values of 140 mg/dl [7.8 mmol/l] to 199 mg/dl [11.0 mmol/l]).
Individuals with IFG and/or IGT have been referred to as having pre-diabetes, indicating
the relatively high risk for the future development of diabetes. IFG and IGT should
not be viewed as clinical entities in their own right but rather risk factors for
diabetes as well as cardiovascular disease (CVD). IFG and IGT are associated with
obesity (especially abdominal or visceral obesity), dyslipidemia with high triglycerides
and/or low HDL cholesterol, and hypertension. Structured lifestyle intervention, aimed
at increasing physical activity and producing 5–10% loss of body weight, and certain
pharmacological agents have been demonstrated to prevent or delay the development
of diabetes in people with IGT (see Table 7). It should be noted that the 2003 ADA
Expert Committee report reduced the lower FPG cut point to define IFG from 110 mg/dl
(6.1 mmol/l) to 100 mg/dl (5.6 mmol/l), in part to make the prevalence of IFG more
similar to that of IGT. However, the World Health Organization (WHO) and many other
diabetes organizations did not adopt this change.
As the A1C becomes increasingly used to diagnose diabetes in individuals with risk
factors, it will also identify those at high risk for developing diabetes in the future.
As was the case with the glucose measures, defining a lower limit of an intermediate
category of A1C is somewhat arbitrary, since risk of diabetes with any measure or
surrogate of glycemia is a continuum extending well into the normal ranges. To maximize
equity and efficiency of preventive interventions, such an A1C cut point, should balance
the costs of false negatives (failing to identify those who are going to develop diabetes)
against the costs of false positives (falsely identifying and then spending intervention
resources on those who were not going to develop diabetes anyway).
Linear regression analyses of nationally representative U.S. data (NHANES 2005–2006)
indicate that among the nondiabetic adult population, an FPG of 110 mg/dl corresponds
to an A1C of 5.6%, while an FPG of 100 mg/dl corresponds to an A1C of 5.4%. Receiver
operating curve analyses of these data indicate that an A1C value of 5.7%, compared
with other cut points, has the best combination of sensitivity (39%) and specificity
(91%) to identify cases of IFG (FPG ≥100 mg/dl [5.6 mmol/l]) (R.T. Ackerman, Personal
Communication). Other analyses suggest that an A1C of 5.7% is associated with diabetes
risk similar to that of the high-risk participants in the Diabetes Prevention Program
(DPP) (R.T. Ackerman, personal communication). Hence, it is reasonable to consider
an A1C range of 5.7–6.4% as identifying individuals with high risk for future diabetes
and to whom the term pre-diabetes may be applied (6).
As is the case for individuals found to have IFG and IGT, individuals with an A1C
of 5.7–6.4% should be informed of their increased risk for diabetes as well as CVD
and counseled about effective strategies to lower their risks (see IV. PREVENTION/DELAY
OF TYPE 2 DIABETES). As with glucose measurements, the continuum of risk is curvilinear,
so that as A1C rises, the risk of diabetes rises disproportionately. Accordingly,
interventions should be most intensive and follow-up should be particularly vigilant
for those with an A1C >6.0%, who should be considered to be at very high risk. However,
just as an individual with a fasting glucose of 98 mg/dl (5.4 mmol/l) may not be at
negligible risk for diabetes, individuals with an A1C <5.7% may still be at risk,
depending on the level of A1C and presence of other risk factors, such as obesity
and family history.
Table 3 summarizes the categories of increased risk for diabetes.
Table 3
Categories of increased risk for diabetes*
FPG 100–125 mg/dl (5.6–6.9 mmol/l) [IFG]
2-h PG on the 75-g OGTT 140–199 mg/dl (7.8–11.0 mmol/l) [IGT]
A1C 5.7–6.4%
*For all three tests, risk is continuous, extending below the lower limit of the range
and becoming disproportionately greater at higher ends of the range.
II. TESTING FOR DIABETES IN ASYMPTOMATIC PATIENTS
Recommendations
Testing to detect type 2 diabetes and assess risk for future diabetes in asymptomatic
people should be considered in adults of any age who are overweight or obese (BMI
≥25 kg/m2) and who have one or more additional risk factors for diabetes (Table 4).
In those without these risk factors, testing should begin at age 45 years. (B)
If tests are normal, repeat testing should be carried out at least at 3-year intervals.
(E)
To test for diabetes or to assess risk of future diabetes, either A1C, FPG, or 2-h
75-g OGTT are appropriate. (B)
In those identified with increased risk for future diabetes, identify and, if appropriate,
treat other CVD risk factors. (B)
Table 4
Criteria for testing for diabetes in asymptomatic adult individuals
1.
Testing should be considered in all adults who are overweight (BMI ≥25 kg/m2
*) and have additional risk factors:
physical inactivity
first-degree relative with diabetes
members of a high-risk ethnic population (e.g., African American, Latino, Native American,
Asian American, Pacific Islander)
women who delivered a baby weighing >9 lb or were diagnosed with GDM
hypertension (≥140/90 mmHg or on therapy for hypertension)
HDL cholesterol level <35 mg/dl (0.90 mmol/l) and/or a triglyceride level >250 mg/dl
(2.82 mmol/l)
women with polycystic ovary syndrome
A1C ≥5.7%, IGT, or IFG on previous testing
other clinical conditions associated with insulin resistance (e.g., severe obesity,
acanthosis nigricans)
history of CVD
2.
In the absence of the above criteria, testing diabetes should begin at age 45 years
3.
If results are normal, testing should be repeated at least at 3-year intervals, with
consideration of more frequent testing depending on initial results and risk status.
*At-risk BMI may be lower in some ethnic groups.
For many illnesses there is a major distinction between screening and diagnostic testing.
However, for diabetes the same tests would be used for “screening” as for diagnosis.
Type 2 diabetes has a long asymptomatic phase and significant clinical risk markers.
Diabetes may be identified anywhere along a spectrum of clinical scenarios ranging
from a seemingly low-risk individual who happens to have glucose testing, to a higher-risk
individual who the provider tests because of high suspicion of diabetes, to the symptomatic
patient. The discussion herein is primarily framed as testing for diabetes in individuals
without symptoms. Testing for diabetes will also detect individuals at increased future
risk for diabetes, herein referred to as pre-diabetic.
A. Testing for type 2 diabetes and risk of future diabetes in adults
Type 2 diabetes is frequently not diagnosed until complications appear, and approximately
one-fourth of all people with diabetes in the U.S. may be undiagnosed. Although the
effectiveness of early identification of pre-diabetes and diabetes through mass testing
of asymptomatic individuals has not been proven definitively (and rigorous trials
to provide such proof are unlikely to occur), pre-diabetes and diabetes meet established
criteria for conditions in which early detection is appropriate. Both conditions are
common, are increasing in prevalence, and impose significant public health burdens.
There is a long presymptomatic phase before the diagnosis of type 2 diabetes is usually
made. Relatively simple tests are available to detect preclinical disease (9). Additionally,
the duration of glycemic burden is a strong predictor of adverse outcomes, and effective
interventions exist to prevent progression of pre-diabetes to diabetes (see IV. PREVENTION/DELAY
OF TYPE 2 DIABETES) and to reduce risk of complications of diabetes (see VI. PREVENTION
AND MANAGEMENT OF DIABETES COMPLICATIONS).
Recommendations for testing for diabetes in asymptomatic undiagnosed adults are listed
in Table 4. Testing should be considered in adults of any age with BMI ≥25 kg/m2 and
one or more risk factors for diabetes. Because age is a major risk factor for diabetes,
testing of those without other risk factors should begin no later than at age 45 years.
Either A1C, FPG, or 2-h OGTT is appropriate for testing. The 2-h OGTT identifies people
with either IFG or IGT and thus more people at increased risk for the development
of diabetes and CVD. It should be noted that the two tests do not necessarily detect
the same individuals (10). The efficacy of interventions for primary prevention of
type 2 diabetes (11
–17) has primarily been demonstrated among individuals with IGT, but not for individuals
with IFG (who do not also have IGT) or those with specific A1C levels.
The appropriate interval between tests is not known (18). The rationale for the 3-year
interval is that false negatives will be repeated before substantial time elapses,
and there is little likelihood that an individual will develop significant complications
of diabetes within 3 years of a negative test result.
Because of the need for follow-up and discussion of abnormal results, testing should
be carried out within the health care setting. Community screening outside a health
care setting is not recommended because people with positive tests may not seek, or
have access to, appropriate follow-up testing and care. Conversely, there may be failure
to ensure appropriate repeat testing for individuals who test negative. Community
screening may also be poorly targeted, i.e., it may fail to reach the groups most
at risk and inappropriately test those at low risk (the worried well) or even those
already diagnosed (19,20).
B. Testing for type 2 diabetes in children
The incidence of type 2 diabetes in adolescents has increased dramatically in the
last decade, especially in minority populations (21), although the disease remains
rare in the general pediatric population (22). Consistent with recommendations for
adults, children and youth at increased risk for the presence or the development of
type 2 diabetes should be tested within the health care setting (23). The recommendations
of the ADA consensus statement on type 2 diabetes in children and youth, with some
modifications, are summarized in Table 5.
Table 5
Testing for type 2 diabetes in asymptomatic children
Criteria:
Overweight (BMI >85th percentile for age and sex, weight for height >85th percentile,
or weight >120% of ideal for height)
Plus any two of the following risk factors:
Family history of type 2 diabetes in first- or second-degree relative
Race/ethnicity (Native American, African American, Latino, Asian American, Pacific
Islander)
Signs of insulin resistance or conditions associated with insulin resistance (acanthosis
nigricans, hypertension, dyslipidemia, polycystic ovary syndrome, or small for gestational
age birthweight)
Maternal history of diabetes or GDM during the child's gestation
Age of initiation:
Age 10 years or at onset of puberty, if puberty occurs at a younger age
Frequency:
Every 3 years
C. Screening for type 1 diabetes
Generally, people with type 1 diabetes present with acute symptoms of diabetes and
markedly elevated blood glucose levels, and most cases are diagnosed soon after the
onset of hyperglycemia. However, evidence from type 1 diabetes prevention studies
suggests that measurement of islet autoantibodies identifies individuals who are at
risk for developing type 1 diabetes. Such testing may be appropriate in high-risk
individuals, such as those with prior transient hyperglycemia or those who have relatives
with type 1 diabetes, in the context of clinical research studies (see, for example,
http://www2.diabetestrialnet.org). Widespread clinical testing of asymptomatic low-risk
individuals cannot currently be recommended, as it would identify very few individuals
in the general population who are at risk. Individuals who screen positive should
be counseled about their risk of developing diabetes. Clinical studies are being conducted
to test various methods of preventing type 1 diabetes or reversing early type 1 diabetes
in those with evidence of autoimmunity.
III. DETECTION AND DIAGNOSIS OF GDM
Recommendations
Screen for GDM using risk factor analysis and, if appropriate, an OGTT. (C)
Women with GDM should be screened for diabetes 6–12 weeks postpartum and should be
followed up with subsequent screening for the development of diabetes or pre-diabetes.
(E)
For many years, GDM has been defined as any degree of glucose intolerance with onset
or first recognition during pregnancy (4). Although most cases resolve with delivery,
the definition applied whether the condition persisted after pregnancy and did not
exclude the possibility that unrecognized glucose intolerance may have antedated or
begun concomitantly with the pregnancy. This definition facilitated a uniform strategy
for detection and classification of GDM, but its limitations were recognized for many
years. As the ongoing epidemic of obesity and diabetes has led to more type 2 diabetes
in women of childbearing age, the number of pregnant women with undiagnosed type 2
diabetes has increased (24). After deliberations in 2008–2009, the International Association
of Diabetes and Pregnancy Study Groups (IADPSG), an international consensus group
with representatives from multiple obstetrical and diabetes organizations, including
ADA, recommended that high-risk women found to have diabetes at their initial prenatal
visit using standard criteria (Table 2) receive a diagnosis of overt, not gestational,
diabetes.
Approximately 7% of all pregnancies (ranging from 1 to 14% depending on the population
studied and the diagnostic tests used) are complicated by GDM, resulting in more than
200,000 cases annually.
Because of the risks of GDM to the mother and neonate, screening and diagnosis are
warranted. Current screening and diagnostic strategies, based on the 2004 ADA position
statement on GDM (25), are outlined in Table 6.
Table 6
Screening for and diagnosis of GDM
Carry out diabetes risk assessment at the first prenatal visit.
Women at very high risk should be screened for diabetes as soon as possible after
the confirmation of pregnancy. Criteria for very high risk are:
Severe obesity
Prior history of GDM or delivery of large-for-gestational-age infant
Presence of glycosuria
Diagnosis of PCOS
Strong family history of type 2 diabetes
Screening/diagnosis at this stage of pregnancy should use standard diagnostic testing
(Table 2).
All women of greater than low risk of GDM, including those above not found to have
diabetes early in pregnancy, should undergo GDM testing at 24–28 weeks of gestation.
Low-risk status, which does not require GDM screening, is defined as women with ALL
of the following characteristics:
Age <25 years
Weight normal before pregnancy
Member of an ethnic group with a low prevalence of diabetes
No known diabetes in first-degree relatives
No history of abnormal glucose tolerance
No history of poor obstetrical outcome
Two approaches may be followed for GDM screening at 24–28 weeks:
Two-step approach:
Perform initial screening by measuring plasma or serum glucose 1 h after a 50-g load
of ≥140 mg/dl identifies ∼80% of women with GDM, while the sensitivity is further
increased to ∼90% by a threshold of ≥130 mg/dl.
Perform a diagnostic 100-g OGTT on a separate day in women who exceed the chosen threshold
on 50-g screening.
One-step approach (may be preferred in clinics with high prevalence of GDM): Perform
a diagnostic 100-g OGTT in all women to be tested at 24–28 weeks.
The 100-g OGTT should be performed in the morning after an overnight fast of at least
8 h.
To make a diagnosis of GDM, at least two of the following plasma glucose values must
be found:
Fasting ≥95 mg/dl
1-h ≥180 mg/dl
2-h ≥155 mg/dl
3-h ≥140 mg/dl
Results of the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study (26), a large-scale
(∼25,000 pregnant women) multinational epidemiologic study, demonstrated that risk
of adverse maternal, fetal, and neonatal outcomes continuously increased as a function
of maternal glycemia at 24–28 weeks, even within ranges previously considered normal
for pregnancy. For most complications there was no threshold for risk. These results
have led to careful reconsideration of the diagnostic criteria for GDM. The IADPSG
recommended that all women not known to have prior diabetes undergo a 75-g OGTT at
24–28 weeks of gestation. The group developed diagnostic cut points for the fasting,
1-h, and 2-h PG measurements that conveyed an odds ratio for adverse outcomes of at
least 1.75 compared with women with the mean glucose levels in the HAPO study.
At the time of this update to the Standards of Medical Care in Diabetes, ADA is planning
to work with U.S. obstetrical organizations to consider adoption of the IADPSG diagnostic
criteria and to discuss the implications of this change. While this change will significantly
increase the prevalence of GDM, there is mounting evidence that treating even mild
GDM reduces morbidity for both mother and baby (27).
Because women with a history of GDM have a greatly increased subsequent risk for diabetes
(28), they should be screened for diabetes 6–12 weeks postpartum, using nonpregnant
OGTT criteria, and should be followed up with subsequent screening for the development
of diabetes or pre-diabetes, as outlined in II. TESTING FOR DIABETES IN ASYMPTOMATIC
PATIENTS. Information on the National Diabetes Education Program (NDEP) campaign to
prevent type 2 diabetes in women with GDM can be found at http://ndep.nih.gov/media/NeverTooEarly_Tipsheet.pdf.
IV. PREVENTION/DELAY OF TYPE 2 DIABETES
Recommendations
Patients with IGT (A), IFG (E), or an A1C of 5.7–6.4% (E) should be referred to an
effective ongoing support program for weight loss of 5–10% of body weight and an increase
in physical activity of at least 150 min/week of moderate activity such as walking.
Follow-up counseling appears to be important for success. (B)
Based on potential cost savings of diabetes prevention, such counseling should be
covered by third-party payors. (E)
In addition to lifestyle counseling, metformin may be considered in those who are
at very high risk for developing diabetes (combined IFG and IGT plus other risk factors
such as A1C >6%, hypertension, low HDL cholesterol, elevated triglycerides, or family
history of diabetes in a first-degree relative) and who are obese and under 60 years
of age. (E)
Monitoring for the development of diabetes in those with pre-diabetes should be performed
every year. (E)
Randomized controlled trials have shown that individuals at high risk for developing
diabetes (those with IFG, IGT, or both) can be given interventions that significantly
decrease the rate of onset of diabetes (11
–17). These interventions include intensive lifestyle modification programs that have
been shown to be very effective (58% reduction after 3 years) and use of the pharmacologic
agents metformin, α-glucosidase inhibitors, orlistat, and thiazolidinediones, each
of which has been shown to decrease incident diabetes to various degrees. A summary
of major diabetes prevention trials is shown in Table 7.
Table 7
Therapies proven effective in diabetes prevention trials
Study (ref.)
n
Population
Mean age (years)
Duration (years)
Intervention (daily dose)
Incidence in control subjects (%/year)
Relative risk reduction (%) (95% CI)
3-Year number needed to treat*
Lifestyle
Finnish DPS (12)
522
IGT, BMI ≥25 kg/m2
55
3.2
I-D&E
6
58 (30–70)
8.5
DPP (11)
2,161†
IGT, BMI ≥24 kg/m2, FPG >5.3 mmol/l
51
3
I-D&E
10.4
58 (48–66)
6.9
Da Qing (13)
259†
IGT (randomized groups)
45
6
G-D&E
14.5
38 (14–56)
7.9
Toranomon Study (31)
458
IGT (men), BMI = 24 kg/m2
∼55
4
I-D&E
2.4
67 (P < 0.043)‡
20.6
Indian DPP (17)
269†
IGT
46
2.5
I-D&E
23
29 (21–37)
6.4
Medications
DPP (11)
2,155†
IGT, BMI >24 kg/m2, FPG >5.3 mmol/l
51
2.8
Metformin (1,700 mg)
10.4
31 (17–43)
13.9
Indian DPP (17)
269†
IGT
46
2.5
Metformin (500 mg)
23
26 (19–35)
6.9
STOP NIDDM (15)
1,419
IGT, FPG >5.6 mmol/l
54
3.2
Acarbose (300 mg)
12.4
25 (10–37)
9.6
XENDOS (32)
3,277
BMI >30 kg/m2
43
4
Orlistat (360 mg)
2.4
37 (14–54)
45.5
DREAM (16)
5,269
IGT or IFG
55
3.0
Rosiglitazone (8 mg)
9.1
60 (54–65)
6.9
Voglibose Ph-3 (33)
1,780
IGT
56
3.0 (1-year Rx)
Vogliobose (0.2 mg)
12.0
40 (18–57)
21 (1-year Rx)
ACT-NOW (34)
602
IGT or IFG
52
2.6
Pioglitizone (45 mg)
6.8
81 (61–91)
6.3
Modified and reprinted with permission (35). Percentage points:
*Number needed to treat to prevent 1 case of diabetes, standardized for a 3-year period
to improve comparisons across studies.
†Number of participants in the indicated comparisons, not necessarily in entire study.
‡Calculated from information in the article. ACT-NOW, ACTos Now Study for the Prevention
of Diabetes; DPP, Diabetes Prevention Program; DPS, Diabetes Prevention Study; DREAM,
Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication; STOP NIDDM,
Study to Prevent Non-Insulin Dependent Diabetes; XENDOS, Xenical in the prevention
of Diabetes in Obese Subjects. I, individual; G, group; D&E, diet and exercise.
Two studies of lifestyle intervention have shown persistent reduction in the role
of conversion to type 2 diabetes with 3 years (29) to 14 years (30) of postintervention
follow-up.
Based on the results of clinical trials and the known risks of progression of pre-diabetes
to diabetes, an ADA Consensus Development Panel (36) concluded that people with IGT
and/or IFG should be counseled on lifestyle changes with goals similar to those of
the DPP (5–10% weight loss and moderate physical activity of ∼30 min/day). Regarding
the more difficult issue of drug therapy for diabetes prevention, the consensus panel
felt that metformin should be the only drug considered for use in diabetes prevention.
For other drugs, the issues of cost, side effects, and lack of persistence of effect
in some studies led the panel to not recommend use for diabetes prevention. Metformin
use was recommended only for very-high-risk individuals (those with combined IGT and
IFG who are obese and have at least one other risk factor for diabetes) who are under
60 years of age. In addition, the panel highlighted the evidence that in the DPP,
metformin was most effective compared with lifestyle in individuals with BMI ≥35 kg/m2
and those under age 60 years.
V. DIABETES CARE
A. Initial evaluation
A complete medical evaluation should be performed to classify the diabetes, detect
the presence of diabetes complications, review previous treatment and glycemic control
in patients with established diabetes, assist in formulating a management plan, and
provide a basis for continuing care. Laboratory tests appropriate to the evaluation
of each patient's medical condition should be performed. A focus on the components
of comprehensive care (Table 8) will assist the health care team to ensure optimal
management of the patient with diabetes.
Table 8
Components of the comprehensive diabetes evaluation
Medical history
Age and characteristics of onset of diabetes (e.g., DKA, asymptomatic laboratory finding)
Eating patterns, physical activity habits, nutritional status, and weight history;
growth and development in children and adolescents
Diabetes education history
Review of previous treatment regimens and response to therapy (A1C records)
Current treatment of diabetes, including medications, meal plan, physical activity
patterns, and results of glucose monitoring and patient's use of data
DKA frequency, severity, and cause
Hypoglycemic episodes
Hypoglycemia awareness
Any severe hypoglycemia: frequency and cause
History of diabetes-related complications
Microvascular: retinopathy, nephropathy, neuropathy (sensory, including history of
foot lesions; autonomic, including sexual dysfunction and gastroparesis)
Macrovascular: CHD, cerebrovascular disease, PAD
Other: psychosocial problems*, dental disease*
Physical examination
Height, weight, BMI
Blood pressure determination, including orthostatic measurements when indicated
Fundoscopic examination*
Thyroid palpation
Skin examination (for acanthosis nigricans and insulin injection sites)
Comprehensive foot examination:
Inspection
Palpation of dorsalis pedis and posterior tibial pulses
Presence/absence of patellar and Achilles reflexes
Determination of proprioception, vibration, and monofilament sensation
Laboratory evaluation
A1C, if results not available within past 2–3 months
If not performed/available within past year:
Fasting lipid profile, including total, LDL- and HDL cholesterol and triglycerides
Liver function tests
Test for urine albumin excretion with spot urine albumin/creatinine ratio
Serum creatinine and calculated GFR
TSH in type 1 diabetes, dyslipidemia, or women over age 50 years
Referrals
Annual dilated eye exam
Family planning for women of reproductive age
Registered dietitian for MNT
DSME
Dental examination
Mental health professional, if needed
* See appropriate referrals for these categories.
B. Management
People with diabetes should receive medical care from a physician-coordinated team.
Such teams may include, but are not limited to, physicians, nurse practitioners, physician's
assistants, nurses, dietitians, pharmacists, and mental health professionals with
expertise and a special interest in diabetes. It is essential in this collaborative
and integrated team approach that individuals with diabetes assume an active role
in their care.
The management plan should be formulated as a collaborative therapeutic alliance among
the patient and family, the physician, and other members of the health care team.
A variety of strategies and techniques should be used to provide adequate education
and development of problem-solving skills in the various aspects of diabetes management.
Implementation of the management plan requires that each aspect is understood and
agreed to by the patient and the care providers and that the goals and treatment plan
are reasonable. Any plan should recognize diabetes self-management education (DSME)
and on-going diabetes support as an integral component of care. In developing the
plan, consideration should be given to the patient's age, school or work schedule
and conditions, physical activity, eating patterns, social situation and cultural
factors, and presence of complications of diabetes or other medical conditions.
C. Glycemic control
1. Assessment of glycemic control
Two primary techniques are available for health providers and patients to assess the
effectiveness of the management plan on glycemic control: patient self-monitoring
of blood glucose (SMBG) or interstitial glucose and A1C.
a. Glucose monitoring
Recommendations
SMBG should be carried out three or more times daily for patients using multiple insulin
injections or insulin pump therapy. (A)
For patients using less frequent insulin injections, noninsulin therapies, or medical
nutrition therapy (MNT) alone, SMBG may be useful as a guide to the success of therapy.
(E)
To achieve postprandial glucose targets, postprandial SMBG may be appropriate. (E)
When prescribing SMBG, ensure that patients receive initial instruction in, and routine
follow-up evaluation of, SMBG technique and using data to adjust therapy. (E)
Continuous glucose monitoring (CGM) in conjunction with intensive insulin regimens
can be a useful tool to lower A1C in selected adults (age ≥25 years) with type 1 diabetes
(A).
Although the evidence for A1C lowering is less strong in children, teens, and younger
adults, CGM may be helpful in these groups. Success correlates with adherence to ongoing
use of the device. (C)
CGM may be a supplemental tool to SMBG in those with hypoglycemia unawareness and/or
frequent hypoglycemic episodes. (E)
The ADA consensus and position statements on SMBG provide a comprehensive review of
the subject (37,38). Major clinical trials of insulin-treated patients that demonstrated
the benefits of intensive glycemic control on diabetes complications have included
SMBG as part of multifactorial interventions, suggesting that SMBG is a component
of effective therapy. SMBG allows patients to evaluate their individual response to
therapy and assess whether glycemic targets are being achieved. Results of SMBG can
be useful in preventing hypoglycemia and adjusting medications (particularly prandial
insulin doses), MNT, and physical activity.
The frequency and timing of SMBG should be dictated by the particular needs and goals
of the patient. SMBG is especially important for patients treated with insulin in
order to monitor for and prevent asymptomatic hypoglycemia and hyperglycemia. For
most patients with type 1 diabetes and pregnant women taking insulin, SMBG is recommended
three or more times daily. For these populations, significantly more frequent testing
may be required to reach A1C targets safely without hypoglycemia. The optimal frequency
and timing of SMBG for patients with type 2 diabetes on noninsulin therapy is unclear.
A meta-analysis of SMBG in non–insulin-treated patients with type 2 diabetes concluded
that some regimen of SMBG was associated with a reduction in A1C of 0.4%. However,
many of the studies in this analysis also included patient education with diet and
exercise counseling and, in some cases, pharmacologic intervention, making it difficult
to assess the contribution of SMBG alone to improved control (39). Several recent
trials have called into question the clinical utility and cost-effectiveness of routine
SMBG in non–insulin-treated patients (40
–42).
Because the accuracy of SMBG is instrument and user dependent (43), it is important
to evaluate each patient's monitoring technique, both initially and at regular intervals
thereafter. In addition, optimal use of SMBG requires proper interpretation of the
data. Patients should be taught how to use the data to adjust food intake, exercise,
or pharmacological therapy to achieve specific glycemic goals, and these skills should
be reevaluated periodically.
CGM through the measurement of interstitial glucose (which correlates well with PG)
is available. These sensors require calibration with SMBG, and the latter are still
recommended for making acute treatment decisions. CGM devices also have alarms for
hypo- and hyperglycemic excursions. Small studies in selected patients with type 1
diabetes have suggested that CGM use reduces the time spent in hypo- and hyperglycemic
ranges and may modestly improve glycemic control. A larger 26-week randomized trial
of 322 type 1 diabetic patients showed that adults age 25 years and older using intensive
insulin therapy and CGM experienced a 0.5% reduction in A1C (from ∼7.6 to 7.1%) compared
with usual intensive insulin therapy with SMBG (44). Sensor use in children, teens,
and adults to age 24 years did not result in significant A1C lowering, and there was
no significant difference in hypoglycemia in any group. Importantly, the greatest
predictor of A1C lowering in this study for all age-groups was frequency of sensor
use, which was lower in younger age-groups. In a smaller randomized controlled trial
of 129 adults and children with baseline A1C <7.0%, outcomes combining A1C and hypoglycemia
favored the group using CGM, suggesting that CGM is also beneficial for individuals
with type 1 diabetes who have already achieved excellent control with A1C <7.0% (45).
Although CGM is an evolving technology, emerging data suggest that it may offer benefit
in appropriately selected patients who are motivated to wear it most of the time.
CGM may be particularly useful in those with hypoglycemia unawareness and/or frequent
episodes of hypoglycemia, and studies in this area are ongoing.
b. A1C
Recommendations
Perform the A1C test at least two times a year in patients who are meeting treatment
goals (and who have stable glycemic control). (E)
Perform the A1C test quarterly in patients whose therapy has changed or who are not
meeting glycemic goals. (E)
Use of point-of-care testing for A1C allows for timely decisions on therapy changes,
when needed. (E)
Because A1C is thought to reflect average glycemia over several months (43) and has
strong predictive value for diabetes complications (11,46), A1C testing should be
performed routinely in all patients with diabetes, at initial assessment and then
as part of continuing care. Measurement approximately every 3 months determines whether
a patient's glycemic targets have been reached and maintained. For any individual
patient, the frequency of A1C testing should be dependent on the clinical situation,
the treatment regimen used, and the judgment of the clinician. Some patients with
stable glycemia well within target may do well with testing only twice per year, while
unstable or highly intensively managed patients (e.g., pregnant type 1 diabetic women)
may be tested more frequently than every 3 months. The availability of the A1C result
at the time that the patient is seen (point-of-care testing) has been reported to
result in increased intensification of therapy and improvement in glycemic control
(47,48).
The A1C test is subject to certain limitations. Conditions that affect erythrocyte
turnover (hemolysis, blood loss) and hemoglobin variants must be considered, particularly
when the A1C result does not correlate with the patient's clinical situation (43).
In addition, A1C does not provide a measure of glycemic variability or hypoglycemia.
For patients prone to glycemic variability (especially type 1 diabetic patients, or
type 2 diabetic patients with severe insulin deficiency), glycemic control is best
judged by the combination of results of SMBG testing and the A1C. The A1C may also
serve as a check on the accuracy of the patient's meter (or the patient's reported
SMBG results) and the adequacy of the SMBG testing schedule.
Table 9 contains the correlation between A1C levels and mean PG levels based on data
from the international A1C-Derived Average Glucose (ADAG) trial using frequent SMBG
and CGM in 507 adults (83% Caucasian) with type 1, type 2, and no diabetes (49). ADA
and the American Association of Clinical Chemists have determined that the correlation
(r = 0.92) is strong enough to justify reporting both an A1C result and an estimated
average glucose (eAG) result when a clinician orders the A1C test. In previous versions
of the Standards of Medical Care in Diabetes, the table describing the correlation
between A1C and mean glucose was derived from relatively sparse data (one seven-point
profile over 1 day per A1C reading) in the primarily Caucasian type 1 participants
in the DCCT (50). Clinicians should note that the numbers in the table are now different,
as they are based on ∼2,800 readings per A1C in the ADAG trial.
Table 9
Correlation of A1C with average glucose
A1C (%)
Mean plasma glucose
mg/dl
mmol/l
6
126
7.0
7
154
8.6
8
183
10.2
9
212
11.8
10
240
13.4
11
269
14.9
12
298
16.5
These estimates are based on ADAG data of ∼2,700 glucose measurements over 3 months
per A1C measurement in 507 adults with type 1, type 2, and no diabetes. The correlation
between A1C and average glucose was 0.92 (49). A calculator for converting A1C results
into estimated average glucose (eAG), in either mg/dl or mmol/l, is available at http://professional.diabetes.org/eAG.
In the ADAG trial, there were no significant differences among racial and ethnic groups
in the regression lines between A1C and mean glucose, although there was a trend toward
a difference between Africans/African Americans participants and Caucasians that might
have been significant had more Africans/African Americans been studied. A recent study
comparing A1C to CGM data in 48 type 1 diabetic children found a highly statistically
significant correlation between A1C and mean blood glucose, although the correlation
(r = 0.7) was significantly lower than in the ADAG trial (51). Whether there are significant
differences in how A1C relates to average glucose in children or in African American
patients is an area for further study. For the time being, the question has not led
to different recommendations about testing A1C or different interpretations of the
clinical meaning of given levels of A1C in those populations.
For patients in whom A1C/eAG and measured blood glucose appear discrepant, clinicians
should consider the possibilities of hemoglobinopathy or altered red cell turnover
and the options of more frequent and/or different timing of SMBG or use of CGM. Other
measures of chronic glycemia such as fructosamine are available, but their linkage
to average glucose and their prognostic significance are not as clear as is the case
for A1C.
2. Glycemic goals in adults
Lowering A1C to below or around 7% has been shown to reduce microvascular and neuropathic
complications of type 1 and type 2 diabetes. Therefore, for microvascular disease
prevention, the A1C goal for nonpregnant adults in general is <7%. (A)
In type 1 and type 2 diabetes, randomized controlled trials of intensive versus standard
glycemic control have not shown a significant reduction in CVD outcomes during the
randomized portion of the trials. Long-term follow-up of the DCCT and UK Prospective
Diabetes Study (UKPDS) cohorts suggests that treatment to A1C targets below or around
7% in the years soon after the diagnosis of diabetes is associated with long-term
reduction in risk of macrovascular disease. Until more evidence becomes available,
the general goal of <7% appears reasonable for many adults for macrovascular risk
reduction. (B)
Subgroup analyses of clinical trials such as the DCCT and UKPDS, and evidence for
reduced proteinuria in the Action in Diabetes and Vascular Disease: Preterax and Diamicron
Modified Release Controlled Evaluation (ADVANCE) trial suggest a small but incremental
benefit in microvascular outcomes with A1C values closer to normal. Therefore, for
selected individual patients, providers might reasonably suggest even lower A1C goals
than the general goal of <7%, if this can be achieved without significant hypoglycemia
or other adverse effects of treatment. Such patients might include those with short
duration of diabetes, long life expectancy, and no significant CVD. (B)
Conversely, less-stringent A1C goals than the general goal of <7% may be appropriate
for patients with a history of severe hypoglycemia, limited life expectancy, advanced
microvascular or macrovascular complications, and extensive comorbid conditions and
those with longstanding diabetes in whom the general goal is difficult to attain despite
diabetes self-management education, appropriate glucose monitoring, and effective
doses of multiple glucose-lowering agents including insulin. (C)
Glycemic control is fundamental to the management of diabetes. The DCCT, a prospective,
randomized, controlled trial of intensive versus standard glycemic control in patients
with relatively recently diagnosed type 1 diabetes, showed definitively that improved
glycemic control is associated with significantly decreased rates of microvascular
(retinopathy and nephropathy) as well as neuropathic complications (53). Follow-up
of the DCCT cohorts in the Epidemiology of Diabetes Interventions and Complications
(EDIC) study has shown persistence of this effect in previously intensively treated
subjects, even though their glycemic control has been equivalent to that of previous
standard arm subjects during follow-up (54,55).
In type 2 diabetes, the Kumamoto study (56) and the UKPDS (57,58) demonstrated significant
reductions in microvascular and neuropathic complications with intensive therapy.
Similar to the DCCT-EDIC findings, long-term follow-up of the UKPDS cohort has recently
demonstrated a “legacy effect” of early intensive glycemic control on long-term rates
of microvascular complications, even with loss of glycemic separation between the
intensive and standard cohorts after the end of the randomized controlled trial (59).
The more recent Veterans Affairs Diabetes Trial (VADT) in type 2 diabetes also showed
significant reductions in albuminuria with intensive (achieved median A1C 6.9%) compared
with standard glycemic control but no difference in retinopathy and neuropathy (60,61).
In each of these large randomized prospective clinical trials, treatment regimens
that reduced average A1C to 7% (1% above the upper limits of normal) were associated
with fewer markers of long-term microvascular complications; however, intensive control
was found to increase the risk of severe hypoglycemia and led to weight gain (46,60,62).
Epidemiological analyses of the DCCT and UKPDS (46,53) demonstrate a curvilinear relationship
between A1C and microvascular complications. Such analyses suggest that, on a population
level, the greatest number of complications will be averted by taking patients from
very poor control to fair or good control. These analyses also suggest that further
lowering of A1C from 7 to 6% is associated with further reduction in the risk of microvascular
complications, albeit the absolute risk reductions become much smaller. The ADVANCE
study of intensive versus standard glycemic control in type 2 diabetes found a statistically
significant reduction in albuminuria with an A1C target of <6.5% (achieved median
A1C 6.3%) compared with standard therapy achieving a median A1C of 7.0% (63). Given
the substantially increased risk of hypoglycemia (particularly in those with type
1 diabetes, but also in the recent type 2 diabetes trials described below), the concerning
mortality findings in the Action to Control Cardiovascular Risk in Diabetes (ACCORD)
trial described below and the relatively much greater effort required to achieve near-normoglycemia,
the risks of lower targets may outweigh the potential benefits on microvascular complications
on a population level. However, selected individual patients, especially those with
little comorbidity and long life expectancy (who may reap the benefits of further
lowering glycemia below 7%) may, at patient and provider judgment, adopt glycemic
targets as close to normal as possible as long as significant hypoglycemia does not
become a barrier.
Whereas many epidemiologic studies and meta-analyses (64,65) have clearly shown a
direct relationship between A1C and CVD, the potential of intensive glycemic control
to reduce CVD has been less clearly defined. In the DCCT, there was a trend toward
lower risk of CVD events with intensive control (risk reduction 41%, 95% CI 10–68%),
but the number of events was small. However, 9-year post-DCCT follow-up of the cohort
has shown that participants previously randomized to the intensive arm had a 42% reduction
(P = 0.02) in CVD outcomes and a 57% reduction (P = 0.02) in the risk of nonfatal
myocardial infarction (MI), stroke, or CVD death compared with participants previously
in the standard arm (66). The benefit of intensive glycemic control in this type 1
diabetic cohort has recently been shown to persist for up to 30 years (67).
The UKPDS trial of type 2 diabetes observed a 16% reduction in cardiovascular complications
(combined fatal or nonfatal MI and sudden death) in the intensive glycemic control
arm, although this difference was not statistically significant (P = 0.052), and there
was no suggestion of benefit on other CVD outcomes such as stroke. In an epidemiologic
analysis of the study cohort, a continuous association was observed such that for
every percentage point lower median on-study A1C (e.g., 8–7%), there was a statistically
significant 18% reduction in CVD events, again with no glycemic threshold. A recent
report of 10 years of follow-up of the UKPDS cohort described, for the participants
originally randomized to intensive glycemic control compared with those randomized
to conventional glycemic control, long-term reductions in MI (15% with sulfonylurea
or insulin as initial pharmacotherapy, 33% with metformin as initial pharmacotherapy,
both statistically significant) and in all-cause mortality (13 and 27%, respectively,
both statistically significant) (59).
Because of ongoing uncertainty regarding whether intensive glycemic control can reduce
the increased risk of CVD events in people with type 2 diabetes, several large long-term
trials were launched in the past decade to compare the effects of intensive versus
standard glycemic control on CVD outcomes in relatively high-risk participants with
established type 2 diabetes. In 2008, results of three large trials (ACCORD, ADVANCE,
and VADT) suggested no significant reduction in CVD outcomes with intensive glycemic
control in these populations. Details of these three studies are shown in Table 10,
and their results and implications are reviewed more extensively in a recent ADA position
statement (52).
Table 10
Comparison of the three trials of intensive glycemic control and CVD outcomes
ACCORD
ADVANCE
VADT
Participant characteristics
n
10,251
11,140
1,791
Mean age (years)
62
66
60
Duration of diabetes (years)
10
8
11.5
History of CVD (%)
35
32
40
Median baseline A1C (%)
8.1
7.2
9.4
On insulin at baseline (%)
35
1.5
52
Protocol characteristics
A1C goals (%) (I vs. S)*
<6.0 vs. 7.0–7.9
≤6.5 vs. “based on local guidelines”
<6.0 (action if >6.5) vs. planned separation of 1.5
Protocol for glycemic control (I vs. S)*
Multiple drugs in both arms
Multiple drugs added to gliclizide vs. multiple drugs with no gliclizide
Multiple drugs in both arms
Management of other risk factors
Embedded blood pressure and lipid trials
Embedded blood pressure trial
Protocol for intensive treatment in both arms
On-study characteristics
Achieved median A1C (%) (I vs. S)
6.4 vs. 7.5
6.3 vs. 7.0
6.9 vs. 8.5
On insulin at study end (%) (I vs. S)*
77 vs. 55*
40 vs. 24
89 vs. 0.74
Weight changes (kg)
Intensive glycemic control arm
+3.5
−0.1
+7.8
Standard glycemic control arm
+0.4
−1.0
+3.4
Severe hypoglycemia (participants with one or more episodes during study) (%)
Intensive glycemic control arm
16.2
2.7
21.2
Standard glycemic control arm
5.1
1.5
9.9
Outcomes
Definition of primary outcome
Nonfatal MI, nonfatal stroke, CVD death
Microvascular plus macrovascular (nonfatal MI, nonfatal stroke, CVD death) outcomes
Nonfatal MI, nonfatal stroke, CVD death, hospitalization for heart failure, revascularization
HR for primary outcome (95% CI)
0.90 (0.78–1.04)
0.9 (0.82–0.98); macrovascular 0.94 (0.84–1.06)
0.88 (0.74–1.05)
HR for mortality findings (95% CI)
1.22 (1.01–1.46)
0.93 (0.83–1.06)
1.07 (0.81–1.42)
*Insulin rates for ACCORD are for any use during the study. I, intensive glycemic
control; S, standard glycemic control. Abridged from ref. 52.
The ACCORD study randomized 10,251 participants with either history of a CVD event
or significant CVD risk to a strategy of intensive glycemic control (target A1C <6.0%)
or standard glycemic control (A1C target 7.0–7.9%). Investigators used multiple glycemic
medications in both arms. From a baseline median A1C of 8.1%, the intensive arm reached
a median A1C of 6.4% within 12 months of randomization, while the standard group reached
a median A1C of 7.5%. Other risk factors were treated aggressively and equally in
both groups. The intensive glycemic control group had more use of insulin in combination
with multiple oral agents, significantly more weight gain, and more episodes of severe
hypoglycemia than the standard group.
In early 2008, the glycemic control arm of ACCORD was halted on the recommendation
of the study's data safety monitoring board due to the finding of an increased rate
of mortality in the intensive arm compared with the standard arm (1.41 vs. 1.14%/year,
hazard ratio 1.22, 95% CI 1.01–1.46), with a similar increase in cardiovascular deaths.
The primary outcome of ACCORD (MI, stroke, or cardiovascular death) was lower in the
intensive glycemic control group due to a reduction in nonfatal MI, although this
finding was not statistically significant when the study was terminated (68). Of note,
prespecified subset analyses showed that participants with no previous CVD event and
those who had a baseline A1C <8% had a statistically significant reduction in the
primary CVD outcome, although overall mortality was not reduced in these groups.
The cause of excess deaths in the intensive group of the ACCORD has been difficult
to pinpoint (and is discussed in some detail in a 2009 ADA position statement [52]).
However, exploratory analyses of the mortality findings of ACCORD (evaluating variables
including weight gain, use of any specific drug or drug combination, and hypoglycemia)
were reportedly unable to identify a clear explanation for the excess mortality in
the intensive arm. At the 69th Scientific Sessions of the American Diabetes Association,
the ACCORD investigators presented additional analyses showing no increase in mortality
in participants who achieved A1C levels <7% or in those who lowered their A1C quickly
after trial enrollment. In fact, the converse was observed: those at highest risk
for mortality were participants in the intensive arm with the highest A1C levels.
The ADVANCE study randomized participants to a strategy of intensive glycemic control
(with primary therapy being the sulfonylurea gliclizide and additional medications
as needed to achieve a target A1C of ≤6.5%) or to standard therapy (in which any medication
but gliclizide could be used and the glycemic target was according to “local guidelines”).
ADVANCE participants were slightly older than those in ACCORD and VADT and had similar
high CVD risk. However, they had an average duration of diabetes that was 2 years
shorter, lower baseline A1C (median 7.2%), and almost no use of insulin at enrollment.
The median A1C levels achieved in the intensive and standard arms were 6.3 and 7.0%,
respectively, and maximal separation between the arms took several years to achieve.
Use of other drugs that favorably impact CVD risk (aspirin, statins, and angiotensin
enzyme inhibitors) was lower in ADVANCE than in ACCORD or VADT.
The primary outcome of ADVANCE was a combination of microvascular events (nephropathy
and retinopathy) and major adverse cardiovascular events (MI, stroke, and cardiovascular
death). Intensive glycemic control significantly reduced the primary end point, although
this was due to a significant reduction in the microvascular outcome, primarily development
of macroalbuminuria, with no significant reduction in the macrovascular outcome. There
was no difference in overall or cardiovascular mortality between the intensive compared
with the standard glycemic control arms (63).
VADT randomized participants with type 2 diabetes uncontrolled on insulin or maximal
dose oral agents (median entry A1C 9.4%) to a strategy of intensive glycemic control
(goal A1C <6.0%) or standard glycemic control, with a planned A1C separation of at
least 1.5%. Medication treatment algorithms were used to achieve the specified glycemic
goals, with a goal of using similar medications in both groups. Median A1C levels
of 6.9 and 8.4% were achieved in the intensive and standard arms, respectively, within
the 1st year of the study. Other CVD risk factors were treated aggressively and equally
in both groups.
The primary outcome of VADT was a composite of CVD events. The cumulative primary
outcome was nonsignificantly lower in the intensive arm. There were more CVD deaths
in the intensive arm than in the standard arm, but the difference was not statistically
significant (60). Post hoc subgroup analyses suggested that duration of diabetes interacted
with randomization such that participants with duration of diabetes less than about
12 years appeared to have a CVD benefit of intensive glycemic control while those
with longer duration of disease prior to study entry had a neutral or even adverse
effect of intensive glycemic control. Other exploratory analyses suggested that severe
hypoglycemia within the past 90 days was a strong predictor of the primary outcome
and of CVD mortality (69).
All three of these trials were carried out in participants with established diabetes
(mean duration 8–11 years) and either known CVD or multiple risk factors suggesting
the presence of established atherosclerosis. Subset analyses of the three trials suggested
a significant benefit of intensive glycemic control on CVD in participants with shorter
duration of diabetes, lower A1C at entry, and/or absence of known CVD. The DCCT-EDIC
study and the long-term follow-up of the UKPDS cohort both suggest that intensive
glycemic control initiated soon after diagnosis of diabetes in patients with a lower
level of CVD risk may impart long-term protection from CVD events. As is the case
with microvascular complications, it may be that glycemic control plays a greater
role before macrovascular disease is well developed and minimal or no role when it
is advanced. Consistent with this concept, data from an ancillary study of VADT demonstrated
that intensive glycemic control was quite effective in reducing CVD events in individuals
with less atherosclerosis at baseline (assessed by coronary calcium) but not in people
with more extensive baseline atherosclerosis (70).
The benefits of intensive glycemic control on microvascular and neuropathic complications
are well established for both type 1 and type 2 diabetes. ADVANCE and VADT have added
to that evidence base by demonstrating a significant reduction in the risk of new
or worsening albuminuria with intensive glycemic control. The lack of significant
reduction in CVD events with intensive glycemic control in ACCORD, ADVANCE, and VADT
should not lead clinicians to abandon the general target of an A1C <7.0% and thereby
discount the benefit of good control on serious and debilitating microvascular complications.
The evidence for a cardiovascular benefit of intensive glycemic control primarily
rests on long-term follow-up of study cohorts treated early in the course of type
1 and type 2 diabetes as well as subset analyses of ACCORD, ADVANCE, and VADT. A recent
group-level meta-analysis of the three trials suggests that glucose lowering has a
modest (9%) but statistically significant reduction in major CVD outcomes, primarily
nonfatal MI, with no significant increase in mortality. A prespecified subgroup analysis
suggested that major CVD outcome reduction occurred in patients without known CVD
at baseline (HR 0.84 [95% CI 0.74–0.94]) (71). Conversely, the mortality findings
in ACCORD and subgroup analyses of VADT suggest that the potential risks of very intensive
glycemic control may outweigh its benefits in some patients, such as those with very
long duration of diabetes, known history of severe hypoglycemia, advanced atherosclerosis,
and advanced age/frailty. Certainly, providers should be vigilant in preventing severe
hypoglycemia in patients with advanced disease and should not aggressively attempt
to achieve near-normal A1C levels in patients in whom such a target cannot be reasonably
easily and safely achieved.
Recommended glycemic goals for nonpregnant adults are shown in Table 11. The recommendations
are based on those for A1C values, with listed blood glucose levels that appear to
correlate with achievement of an A1C of <7%. The issue of pre- versus postprandial
SMBG targets is complex (72). Elevated postchallenge (2-h OGTT) glucose values have
been associated with increased cardiovascular risk independent of FPG in some epidemiological
studies. In diabetic subjects, some surrogate measures of vascular pathology, such
as endothelial dysfunction, are negatively affected by postprandial hyperglycemia
(73). It is clear that postprandial hyperglycemia, like preprandial hyperglycemia,
contributes to elevated A1C levels, with its relative contribution being higher at
A1C levels that are closer to 7%. However, outcome studies have clearly shown A1C
to be the primary predictor of complications, and landmark glycemic control trials
such as the DCCT and UKPDS relied overwhelmingly on preprandial SMBG. Additionally,
a randomized controlled trial in patients with known CVD found no CVD benefit of insulin
regimens targeting postprandial glucose compared with those targeting preprandial
glucose (74). For individuals who have premeal glucose values within target but A1C
values above target, a reasonable recommendation for postprandial testing and targets
is monitoring postprandial plasma glucose (PPG) 1–2 h after the start of the meal
and treatment aimed at reducing PPG values to <180 mg/dl to help lower A1C.
Table 11
Summary of glycemic recommendations for non-pregnant adults with diabetes
A1C
<7.0%*
Preprandial capillary plasma glucose
70–130 mg/dl (3.9–7.2 mmol/l)
Peak postprandial capillary plasma glucose†
<180 mg/dl (<10.0 mmol/l)
Key concepts in setting glycemic goals:
A1C is the primary target for glycemic control
Goals should be individualized based on:
duration of diabetes
age/life expectancy
comorbid conditions
known CVD or advanced microvascular complications
hypoglycemia unawareness
individual patient considerations
More or less stringent glycemic goals may be appropriate for individual patients
Postprandial glucose may be targeted if A1C goals are not met despite reaching preprandial
glucose goals
*Referenced to a nondiabetic range of 4.0–6.0% using a DCCT-based assay.
†Postprandial glucose measurements should be made 1–2 h after the beginning of the
meal, generally peak levels in patients with diabetes.
As noted above, less stringent treatment goals may be appropriate for adults with
limited life expectancies or advanced vascular disease. Glycemic goals for children
are provided in VII.A.1.a. Glycemic control. Severe or frequent hypoglycemia is an
absolute indication for the modification of treatment regimens, including setting
higher glycemic goals.
Regarding goals for glycemic control for women with GDM, recommendations from the
Fifth International Workshop-Conference on Gestational Diabetes (75) are to target
maternal capillary glucose concentrations of:
Preprandial ≤95 mg/dl (5.3 mmol/l) and either
1-h postmeal ≤140 mg/dl (7.8 mmol/l) or
2-h postmeal ≤120 mg/dl (6.7 mmol/l)
For women with preexisting type 1 or type 2 diabetes who become pregnant, a recent
consensus statement (76) recommends the following as optimal glycemic goals, if they
can be achieved without excessive hypoglycemia:
premeal, bedtime, and overnight glucose 60–99 mg/dl (3.3–5.4 mmol/l)
peak postprandial glucose 100–129 mg/dl (5.4–7.1 mmol/l)
A1C <6.0%
3. Approach to treatment
a. Therapy for type 1 diabetes.
The DCCT clearly showed that intensive insulin therapy (three or more injections per
day of insulin or continuous subcutaneous insulin infusion [CSII] or insulin pump
therapy) was a key part of improved glycemia and better outcomes (53,66). At the time
of the study, therapy was carried out with short- and intermediate-acting human insulins.
Despite better microvascular outcomes, intensive insulin therapy was associated with
a high rate in severe hypoglycemia (62 episodes per 100 patient-years of therapy).
Since the time of the DCCT, a number of rapid-acting and long-acting insulin analogs
have been developed. These analogs are associated with less hypoglycemia with equal
A1C lowering in type 1 diabetes (77,78).
Recommended therapy for type 1 diabetes therefore consists of the following components:
1) use of multiple dose insulin injections (3–4 injections per day of basal and prandial
insulin) or CSII therapy; 2) matching of prandial insulin to carbohydrate intake,
premeal blood glucose, and anticipated activity; and 3) for many patients (especially
if hypoglycemia is a problem), use of insulin analogs. There are excellent reviews
available that guide the initiation and management of insulin therapy to achieve desired
glycemic goals (3,77,79).
Because of the increased frequency of other autoimmune diseases in type 1 diabetes,
screening for thyroid dysfunction, vitamin B12 deficiency, or celiac disease should
be considered based on signs and symptoms. Periodic screening in the absence of symptoms
has been recommended, but the effectiveness and optimal frequency are unclear.
b. Therapy for type 2 diabetes.
The ADA and the European Association for the Study of Diabetes (EASD) published a
consensus statement on the approach to management of hyperglycemia in individuals
with type 2 diabetes (80) and a subsequent update (81). Highlights of this approach
include: intervention at the time of diagnosis with metformin in combination with
lifestyle changes (MNT and exercise) and continuing timely augmentation of therapy
with additional agents (including early initiation of insulin therapy) as a means
of achieving and maintaining recommended levels of glycemic control (i.e., A1C <7%
for most patients). The overall objective is to achieve and maintain glycemic control
and to change interventions when therapeutic goals are not being met.
The algorithm took into account the evidence for A1C lowering of the individual interventions,
their additive effects, and their expense. The precise drugs used and their exact
sequence may not be as important as achieving and maintaining glycemic targets safely.
Medications not included in the consensus algorithm, owing to less glucose-lowering
effectiveness, limited clinical data, and/or relative expense, still may be appropriate
choices for individual patients to achieve glycemic goals. Initiation of insulin at
the time of diagnosis is recommended for individuals presenting with weight loss or
other severe hyperglycemic symptoms or signs.
D. Medical nutrition therapy
General recommendations
Individuals who have pre-diabetes or diabetes should receive individualized MNT as
needed to achieve treatment goals, preferably provided by a registered dietitian familiar
with the components of diabetes MNT. (A)
Because it can result in cost savings and improved outcomes (B), MNT should be covered
by insurance and other payors (E).
Energy balance, overweight, and obesity
In overweight and obese insulin-resistant individuals, modest weight loss has been
shown to reduce insulin resistance. Thus, weight loss is recommended for all overweight
or obese individuals who have or are at risk for diabetes. (A)
For weight loss, either low-carbohydrate or low-fat calorie-restricted diets may be
effective in the short-term (up to 1 year). (A)
For patients on low-carbohydrate diets, monitor lipid profiles, renal function, and
protein intake (in those with nephropathy) and adjust hypoglycemic therapy as needed.
(E)
Physical activity and behavior modification are important components of weight loss
programs and are most helpful in maintenance of weight loss. (B)
Primary prevention of diabetes
Among individuals at high risk for developing type 2 diabetes, structured programs
emphasizing lifestyle changes that include moderate weight loss (7% body weight) and
regular physical activity (150 min/week) with dietary strategies including reduced
calories and reduced intake of dietary fat can reduce the risk for developing diabetes
and are therefore recommended. (A)
Individuals at high risk for type 2 diabetes should be encouraged to achieve the U.S.
Department of Agriculture (USDA) recommendation for dietary fiber (14 g fiber/1,000
kcal) and foods containing whole grains (one-half of grain intake). (B)
Dietary fat intake in diabetes management
Saturated fat intake should be <7% of total calories. (A)
Reducing intake of trans fat lowers LDL cholesterol and increases HDL cholesterol
(A); therefore intake of trans fat should be minimized (E).
Carbohydrate intake in diabetes management
Monitoring carbohydrate intake, whether by carbohydrate counting, exchanges, or experience-based
estimation, remains a key strategy in achieving glycemic control. (A)
For individuals with diabetes, use of the glycemic index and glycemic load may provide
a modest additional benefit for glycemic control over that observed when total carbohydrate
is considered alone. (B)
Other nutrition recommendations
Sugar alcohols and nonnutritive sweeteners are safe when consumed within the acceptable
daily intake levels established by the Food and Drug Administration (FDA). (A)
If adults with diabetes choose to use alcohol, daily intake should be limited to a
moderate amount (one drink per day or less for adult women and two drinks per day
or less for adult men). (E)
Routine supplementation with antioxidants, such as vitamins E and C and carotene,
is not advised because of lack of evidence of efficacy and concern related to long-term
safety. (A)
Benefit from chromium supplementation in people with diabetes or obesity has not been
conclusively demonstrated and therefore cannot be recommended. (C)
Individualized meal planning should include optimization of food choices to meet recommended
dietary allowances (RDAs)/dietary reference intakes (DRIs) for all micronutrients.
(E)
MNT is an integral component of diabetes prevention, management, and self-management
education. In addition to its role in preventing and controlling diabetes, ADA recognizes
the importance of nutrition as an essential component of an overall healthy lifestyle.
A full review of the evidence regarding nutrition in preventing and controlling diabetes
and its complications and additional nutrition-related recommendations can be found
in the ADA position statement, Nutrition Recommendations and Interventions for Diabetes,
published in 2006 and updated for 2008 (82). Achieving nutrition-related goals requires
a coordinated team effort that includes the active involvement of the person with
pre-diabetes or diabetes. Because of the complexity of nutrition issues, it is recommended
that a registered dietitian who is knowledgeable and skilled in implementing nutrition
therapy into diabetes management and education be the team member who provides MNT.
Clinical trials/outcome studies of MNT have reported decreases in A1C at 3–6 months
ranging from 0.25 to 2.9% with higher reductions seen in type 2 diabetes of shorter
duration. Multiple studies have demonstrated sustained improvements in A1C at 12 months
and longer when a registered dietitian provided follow-up visits ranging from monthly
to three sessions per year (83
–90). Meta-analyses of studies in nondiabetic, free-living subjects report that MNT
reduces LDL cholesterol by 15–25 mg/dl (91) or by up to 16% (92), while clinical trials
support a role for lifestyle modification in treating hypertension (92,93).
Because of the effects of obesity on insulin resistance, weight loss is an important
therapeutic objective for overweight or obese individuals with pre-diabetes or diabetes
(94). Short-term studies have demonstrated that moderate weight loss (5% of body weight)
in subjects with type 2 diabetes is associated with decreased insulin resistance,
improved measures of glycemia and lipemia, and reduced blood pressure (95); longer-term
studies (≥52 weeks) showed mixed effects on A1C in adults with type 2 diabetes (96
–99), and results were confounded by pharmacologic weight loss therapy. A systematic
review of 80 weight loss studies of ≥1 year duration demonstrated that moderate weight
loss achieved through diet alone, diet and exercise, and meal replacements can be
achieved and maintained over the long term (4.8–8% weight loss at 12 months [100]).
The multifactorial intensive lifestyle intervention used in the DPP, which included
reduced intake of fat and calories, led to weight loss averaging 7% at 6 months and
maintenance of 5% weight loss at 3 years, associated with a 58% reduction in incidence
of type 2 diabetes (11). Look AHEAD (Action for Health in Diabetes) is a large clinical
trial designed to determine whether long-term weight loss will improve glycemia and
prevent cardiovascular events in subjects with type 2 diabetes. One-year results of
the intensive lifestyle intervention in this trial show an average of 8.6% weight
loss, significant reduction of A1C, and reduction in several CVD risk factors (101).
When completed, the Look AHEAD study should provide insight into the effects of long-term
weight loss on important clinical outcomes.
The optimal macronutrient distribution of weight loss diets has not been established.
Although low-fat diets have traditionally been promoted for weight loss, several randomized
controlled trials found that subjects on low-carbohydrate diets (<130 g/day of carbohydrate)
lost more weight at 6 months than subjects on low-fat diets (102,103); however, at
1 year, the difference in weight loss between the low-carbohydrate and low-fat diets
was not significant and weight loss was modest with both diets. Another study of overweight
women randomized to one of four diets showed significantly more weight loss at 12
months with the Atkins low-carbohydrate diet than with higher-carbohydrate diets (104).
Changes in serum triglyceride and HDL cholesterol were more favorable with the low-carbohydrate
diets. In one study, those subjects with type 2 diabetes demonstrated a greater decrease
in A1C with a low-carbohydrate diet than with a low-fat diet (103). A recent meta-analysis
showed that at 6 months, low-carbohydrate diets were associated with greater improvements
in triglyceride and HDL cholesterol concentrations than low-fat diets; however, LDL
cholesterol was significantly higher with the low-carbohydrate diets (105). In a 2-year
dietary intervention study, Mediterranean and low-carbohydrate diets were found to
be effective and safe alternatives to a low-fat diet for weight reduction in moderately
obese participants (99).
The RDA for digestible carbohydrate is 130 g/day and is based on providing adequate
glucose as the required fuel for the central nervous system without reliance on glucose
production from ingested protein or fat. Although brain fuel needs can be met on lower-carbohydrate
diets, long-term metabolic effects of very-low-carbohydrate diets are unclear, and
such diets eliminate many foods that are important sources of energy, fiber, vitamins,
and minerals that are important in dietary palatability (106).
Although numerous studies have attempted to identify the optimal mix of macronutrients
for meal plans of people with diabetes, it is unlikely that one such combination of
macronutrients exists. The best mix of carbohydrate, protein, and fat appears to vary
depending on individual circumstances. For those individuals seeking guidance as to
macronutrient distribution in healthy adults, DRIs may be helpful (106). It must be
clearly recognized that regardless of the macronutrient mix, the total caloric intake
must be appropriate to the weight management goal. Further, individualization of the
macronutrient composition will depend on the metabolic status of the patient (e.g.,
lipid profile and renal function) and/or food preferences. Plant-based diets (vegan
or vegetarian) that are well planned and nutritionally adequate have also been shown
to improve metabolic control (107,108).
The primary goal with respect to dietary fat in individuals with diabetes is to limit
saturated fatty acids, trans fatty acids, and cholesterol intake so as to reduce risk
for CVD. Saturated and trans fatty acids are the principal dietary determinants of
plasma LDL cholesterol. There is a lack of evidence on the effects of specific fatty
acids on people with diabetes; therefore, the recommended goals are consistent with
those for individuals with CVD (92,109).
The FDA has approved five nonnutritive sweeteners for use in the U.S.: acesulfame
potassium, aspartame, neotame, saccharin, and sucralose. Before being allowed on the
market, all underwent rigorous scrutiny and were shown to be safe when consumed by
the public, including people with diabetes and women during pregnancy. Reduced calorie
sweeteners approved by the FDA include sugar alcohols (polyols) such as erythritol,
isomalt, lactitol, maltitol, mannitol, sorbitol, xylitol, tagatose, and hydrogenated
starch hydrolysates. The use of sugar alcohols appears to be safe; however, they may
cause diarrhea, especially in children. Stevia (Rebaudioside A) has been designated
by the FDA as being generally recognized as safe (GRAS).
Reimbursement for MNT
MNT, when delivered by a registered dietitian according to nutrition practice guidelines,
is reimbursed as part of the Medicare program as overseen by the Centers for Medicare
and Medicaid Services (www.cms.hhs.gov/medicalnutritiontherapy).
E. Bariatric surgery
Recommendations
Bariatric surgery should be considered for adults with BMI >35 kg/m2 and type 2 diabetes,
especially if the diabetes or associated comorbidities are difficult to control with
lifestyle and pharmacologic therapy. (B)
Patients with type 2 diabetes who have undergone bariatric surgery need life-long
lifestyle support and medical monitoring. (E)
Although small trials have shown glycemic benefit of bariatric surgery in patients
with type 2 diabetes and BMI of 30–35 kg/m2, there is currently insufficient evidence
to generally recommend surgery in patients with BMI <35 kg/m2 outside of a research
protocol. (E)
The long-term benefits, cost-effectiveness, and risks of bariatric surgery in individuals
with type 2 diabetes should be studied in well-designed, randomized controlled trials
with optimal medical and lifestyle therapy as the comparator. (E)
Gastric reduction surgery, either gastric banding or procedures that involve bypassing
or transposing sections of the small intestine, when part of a comprehensive team
approach, can be an effective weight loss treatment for severe obesity, and national
guidelines support its consideration for people with type 2 diabetes who have BMI
>35 kg/m2. Bariatric surgery has been shown to lead to near or complete normalization
of glycemia in ∼55–95% of patients with type 2 diabetes, depending on the surgical
procedure. A meta-analysis of studies of bariatric surgery reported that 78% of individuals
with type 2 diabetes had complete “resolution” of diabetes (normalization of blood
glucose levels in the absence of medications) and that the resolution rates were sustained
in studies that had follow-up exceeding 2 years (110). Resolution rates are lower
with procedures that only constrict the stomach and higher with those that bypass
portions of the small intestine. Additionally, there is a suggestion that intestinal
bypass procedures may have glycemic effects that are independent of their effects
on weight.
A recent randomized controlled trial compared adjustable gastric banding to the “best
available” medical and lifestyle therapy in subjects with type 2 diabetes diagnosed
<2 years before randomization and with BMI 30–40 kg/m2 (111). In this trial, 73% of
surgically treated patients achieved “remission” of their diabetes, compared with
13% of those treated medically. The latter group lost only 1.7% of body weight, suggesting
that their therapy was not optimal. Overall the trial had 60 subjects, and only 13
had a BMI <35 kg/m2, making it difficult to generalize these results to diabetic patients
who are less severely obese or with longer duration of diabetes.
Bariatric surgery is costly in the short term and has some risks. Rates of morbidity
and mortality directly related to the surgery have been reduced considerably in recent
years, with 30-day mortality rates now 0.28%, similar to those of laparoscopic cholecystectomy
(112). Longer-term concerns include vitamin and mineral deficiencies, osteoporosis,
and rare but often severe hypoglycemia from insulin hypersecretion. Cohort studies
attempting to match subjects suggest that the procedure may reduce longer-term mortality
rates (113), and it is reasonable to postulate that there may be recouping of costs
over the long term. However, studies of the mechanisms of glycemic improvement, long-term
benefits and risks, and cost-effectiveness of bariatric surgery in individuals with
type 2 diabetes will require well-designed, randomized clinical trials with optimal
medical and lifestyle therapy of diabetes and cardiovascular risk factors as the comparators.
F. Diabetes self-management education
Recommendations
People with diabetes should receive DSME according to national standards when their
diabetes is diagnosed and as needed thereafter. (B)
Effective self-management and quality of life are the key outcomes of DSME and should
be measured and monitored as part of care. (C)
DSME should address psychosocial issues, since emotional well-being is associated
with positive diabetes outcomes. (C)
Because DSME can result in cost-savings and improved outcomes (B), DSME should be
reimbursed by third-party payors. (E)
DSME is an essential element of diabetes care (114
–120), and national standards for DSME (121) are based on evidence for its benefits.
Education helps people with diabetes initiate effective self-management and cope with
diabetes when they are first diagnosed. Ongoing DSME and support also help people
with diabetes maintain effective self-management throughout a lifetime of diabetes
as they face new challenges and as treatment advances become available. DSME helps
patients optimize metabolic control, prevent and manage complications, and maximize
quality of life in a cost-effective manner (122).
DSME is the on-going process of facilitating the knowledge, skill, and ability necessary
for diabetes self-care (121). This process incorporates the needs, goals, and life
experiences of the person with diabetes. The overall objectives of DSME are to support
informed decision-making, self-care behaviors, problem-solving, and active collaboration
with the health care team and to improve clinical outcomes, health status, and quality
of life in a cost-effective manner (121).
Current best practice of DSME is a skills-based approach that focuses on helping those
with diabetes make informed self-management choices. DSME has changed from a didactic
approach focusing on providing information, to a more theoretically based empowerment
model that focuses on helping those with diabetes make informed self-management decisions.
Care of diabetes has shifted to an approach that is more patient centered and places
the person with diabetes at the center of the care model working in collaboration
with health care professionals. Patient-centered care is respectful of and responsive
to individual patient preferences, needs, and values and ensures that patient values
guide all decision making (123).
1. Evidence for the benefits of DSME
Multiple studies have found that DSME is associated with improved diabetes knowledge
and self-care behavior (115); improved clinical outcomes such as lower A1C (116,117,119,120,124),
lower self-reported weight (115), improved quality of life (118,125), and healthy
coping (126); and lower costs (127). Better outcomes were reported for DSME interventions
that were longer and included follow-up support (115,128
–131), that were culturally (132) and age appropriate (133,134) and tailored to individual
needs and preferences (114), and that addressed psychosocial issues (114,115, 119,135).
Both individual and group approaches have been found effective (136
–138). There is growing evidence for the role of community health workers and peer
(139) and lay leaders (140) in delivering DSME and support in addition to the core
team (141).
Diabetes education is associated with increased use of primary and preventive services
and lower use of acute, inpatient hospital services (127). Patients who participate
in diabetes education are more likely to follow best practice treatment recommendations,
particularly among the medicare population, and to have lower Medicare and commercial
claim costs (142).
2. National Standards for DSME
The National Standards for DSME are designed to define quality diabetes self-management
education and to assist diabetes educators in a variety of settings to provide evidence-based
education (121). The standards, most recently revised in 2007, are reviewed and updated
every 5 years by a task force representing key organizations involved in the field
of diabetes education and care.
3. Reimbursement for DSME
DSME, when provided by a program that meets ADA recognition standards, is reimbursed
as part of the Medicare program overseen by the Centers for Medicare and Medicaid
Services (www.cms.hhs.gov/DiabetesSelfManagement).
G. Physical activity
Recommendations
People with diabetes should be advised to perform at least 150 min/week of moderate-intensity
aerobic physical activity (50–70% of maximum heart rate). (A)
In the absence of contraindications, people with type 2 diabetes should be encouraged
to perform resistance training three times per week. (A)
ADA technical reviews on exercise in patients with diabetes, currently being updated,
have summarized the value of exercise in the diabetes management plan (143,144). Regular
exercise has been shown to improve blood glucose control, reduce cardiovascular risk
factors, contribute to weight loss, and improve well being. Furthermore, regular exercise
may prevent type 2 diabetes in high-risk individuals (11
–13). Structured exercise interventions of at least 8 weeks' duration have been shown
to lower A1C by an average of 0.66% in people with type 2 diabetes, even with no significant
change in BMI (145). Higher levels of exercise intensity are associated with greater
improvements in A1C and fitness (146).
1. Frequency and type of exercise
The U.S. Department of Health and Human Services' Physical Activity Guidelines for
Americans (147) suggest that adults over age 18 years perform 150 min/week of moderate-intensity
or 75 min/week of vigorous aerobic physical activity or an equivalent combination
of the two. In addition, the guidelines suggest that adults also do muscle-strengthening
activities that involve all major muscle groups two or more days per week. The guidelines
suggest that adults over age 65 years, or those with disabilities, follow the adult
guidelines if possible or (if this is not possible) be as physically active as they
are able. Studies included in the meta-analysis of effects of exercise interventions
on glycemic control (145) had a mean number of sessions per week of 3.4, with a mean
of 49 min/session. The DPP lifestyle intervention, which included 150 min/week of
moderate intensity exercise, had a beneficial effect on glycemia in those with pre-diabetes.
Therefore, it seems reasonable to recommend that people with diabetes try to follow
the physical activity guidelines for the general population.
Progressive resistance exercise improves insulin sensitivity in older men with type
2 diabetes to the same or even to a greater extent as aerobic exercise (148). Clinical
trials have provided strong evidence for the A1C-lowering value of resistance training
in older adults with type 2 diabetes (149,150) and for an additive benefit of combined
aerobic and resistance exercise in adults with type 2 diabetes (151).
2. Evaluation of the diabetic patient before recommending an exercise program
Prior guidelines have suggested that before recommending a program of physical activity,
the provider should assess patients with multiple cardiovascular risk factors for
coronary artery disease (CAD). As further discussed in VI.A.5. Coronary heart disease
screening and treatment, the area of screening asymptomatic diabetic patients for
CAD remains unclear, and a recent ADA consensus statement on this issue concluded
that routine screening is not recommended (152). Providers should use clinical judgment
in this area. Certainly, high-risk patients should be encouraged to start with short
periods of low-intensity exercise and to increase the intensity and duration slowly.
Providers should assess patients for conditions that might contraindicate certain
types of exercise or predispose to injury, such as uncontrolled hypertension, severe
autonomic neuropathy, severe peripheral neuropathy or history of foot lesions, and
unstable proliferative retinopathy. The patient's age and previous physical activity
level should be considered.
3. Exercise in the presence of nonoptimal glycemic control
a. Hyperglycemia.
When people with type 1 diabetes are deprived of insulin for 12–48 h and are ketotic,
exercise can worsen hyperglycemia and ketosis (153); therefore, vigorous activity
should be avoided in the presence of ketosis. However, it is not necessary to postpone
exercise simply based on hyperglycemia, provided the patient feels well and urine
and/or blood ketones are negative.
b. Hypoglycemia.
In individuals taking insulin and/or insulin secretagogues, physical activity can
cause hypoglycemia if medication dose or carbohydrate consumption is not altered.
For individuals on these therapies, added carbohydrate should be ingested if pre-exercise
glucose levels are <100 mg/dl (5.6 mmol/l) (154,155). Hypoglycemia is rare in diabetic
individuals who are not treated with insulin or insulin secretagogues, and no preventive
measures for hypoglycemia are usually advised in these cases.
4. Exercise in the presence of specific long-term complications of diabetes
a. Retinopathy.
In the presence of proliferative diabetic retinopathy (PDR) or severe non-proliferative
diabetic retinopathy (NPDR), vigorous aerobic or resistance exercise may be contraindicated
because of the risk of triggering vitreous hemorrhage or retinal detachment (156).
b. Peripheral neuropathy.
Decreased pain sensation in the extremities results in increased risk of skin breakdown
and infection and of Charcot joint destruction. Prior recommendations have advised
non–weight-bearing exercise for patients with severe peripheral neuropathy. Studies
have shown that moderate-intensity walking may not lead to increased risk of foot
ulcers or reulceration in those with peripheral neuropathy (157). All individuals
with peripheral neuropathy should wear proper footwear and examine their feet daily
for early detection of lesions. Anyone with a foot injury or open sore should be restricted
to non–weight-bearing activities.
c. Autonomic neuropathy.
Autonomic neuropathy can increase the risk of exercise-induced injury or adverse events
through decreased cardiac responsiveness to exercise, postural hypotension, impaired
thermoregulation, impaired night vision due to impaired papillary reaction, and unpredictable
carbohydrate delivery from gastroparesis predisposing to hypoglycemia (158). Autonomic
neuropathy is also strongly associated with CVD in people with diabetes (159,160).
People with diabetic autonomic neuropathy should undergo cardiac investigation before
beginning physical activity more intense than that to which they are accustomed.
d. Albuminuria and nephropathy.
Physical activity can acutely increase urinary protein excretion. However, there is
no evidence that vigorous exercise increases the rate of progression of diabetic kidney
disease and likely no need for any specific exercise restrictions for people with
diabetic kidney disease (161).
H. Psychosocial assessment and care
Recommendations
Assessment of psychological and social situation should be included as an ongoing
part of the medical management of diabetes. (E)
Psychosocial screening and follow-up should include, but is not limited to, attitudes
about the illness, expectations for medical management and outcomes, affect/mood,
general and diabetes-related quality of life, resources (financial, social, and emotional),
and psychiatric history. (E)
Screen for psychosocial problems such as depression and diabetes-related distress,
anxiety, eating disorders, and cognitive impairment when self-management is poor.
(C)
Psychological and social problems can impair the ability of the individual (162
–164) or the family to carry out diabetes care tasks and therefore compromise health
status. There are opportunities for the clinician to assess psychosocial status in
a timely and efficient manner so that referral for appropriate services can be accomplished.
Key opportunities for screening of psychosocial status occur at diagnosis, during
regularly scheduled management visits, during hospitalizations, at discovery of complications,
or when problems with glucose control, quality of life, or adherence are identified.
Patients are likely to exhibit psychological vulnerability at diagnosis and when their
medical status changes, i.e., the end of the honeymoon period, when the need for intensified
treatment is evident, and when complications are discovered (164).
Issues known to impact self-management and health outcomes include but are not limited
to: attitudes about the illness, expectations for medical management and outcomes,
affect/mood, general and diabetes-related quality of life, diabetes-related distress
(165), resources (financial, social, and emotional) (166), and psychiatric history
(167,168). Screening tools are available for a number of these areas (135). Indications
for referral to a mental health specialist familiar with diabetes management may include
gross noncompliance with medical regimen (by self or others) (168), depression with
the possibility of self-harm (169,170), debilitating anxiety (alone or with depression),
indications of an eating disorder, or cognitive functioning that significantly impairs
judgment. It is preferable to incorporate psychological assessment and treatment into
routine care rather than waiting for identification of a specific problem or deterioration
in psychological status (135). Although the clinician may not feel qualified to treat
psychological problems, using the patient-provider relationship as a foundation for
further treatment can increase the likelihood that the patient will accept referral
for other services. It is important to establish that emotional well-being is part
of diabetes management.
I. When treatment goals are not met
For a variety of reasons, some people with diabetes and their health care providers
do not achieve the desired goals of treatment (Table 11). Rethinking the treatment
regimen may require assessment of barriers including income, health literacy, diabetes
distress, depression, and competing demands, including those related to family responsibilities
and dynamics. Other strategies may include culturally appropriate and enhanced DSME,
co-management with a diabetes team, referral to a medical social worker for assistance
with insurance coverage, or change in pharmacological therapy. Initiation of or increase
in SMBG, utilization of CGM, frequent contact with the patient, or referral to a mental
health professional or physician with special expertise in diabetes may be useful.
Providing patients with an algorithm for self-titration of insulin doses based on
SMBG results may be helpful for type 2 patients who take insulin (171).
J. Intercurrent illness
The stress of illness, trauma, and/or surgery frequently aggravates glycemic control
and may precipitate diabetic ketoacidosis (DKA) or nonketotic hyperosmolar state,
life-threatening conditions that require immediate medical care to prevent complications
and death (172). Any condition leading to deterioration in glycemic control necessitates
more frequent monitoring of blood glucose and (in ketosis-prone patients) urine or
blood ketones. Marked hyperglycemia requires temporary adjustment of the treatment
program and, if accompanied by ketosis, vomiting, or alteration in level of consciousness,
immediate interaction with the diabetes care team. The patient treated with noninsulin
therapies or MNT alone may temporarily require insulin. Adequate fluid and caloric
intake must be assured. Infection or dehydration are more likely to necessitate hospitalization
of the person with diabetes than the person without diabetes.
The hospitalized patient should be treated by a physician with expertise in the management
of diabetes. For further information on management of patients with hyperglycemia
in the hospital, see VIII.A. Diabetes care in the hospital. For further information
on management of DKA or nonketotic hyperosmolar state, refer to the ADA consensus
statement on hyperglycemic crises (173).
K. Hypoglycemia
Recommendations
Glucose (15–20 g) is the preferred treatment for the conscious individual with hypoglycemia,
although any form of carbohydrate that contains glucose may be used. If SMBG 15 min
after treatment shows continued hypoglycemia, the treatment should be repeated. Once
SMBG glucose returns to normal, the individual should consume a meal or snack to prevent
recurrence of hypoglycemia. (E)
Glucagon should be prescribed for all individuals at significant risk of severe hypoglycemia,
and caregivers or family members of these individuals should be instructed in its
administration. Glucagon administration is not limited to health care professionals.
(E)
Individuals with hypoglycemia unawareness or one or more episodes of severe hypoglycemia
should be advised to raise their glycemic targets to strictly avoid further hypoglycemia
for at least several weeks to partially reverse hypoglycemia unawareness and reduce
risk of future episodes. (B)
Hypoglycemia is the leading limiting factor in the glycemic management of type 1 and
insulin-treated type 2 diabetes (174). Treatment of hypoglycemia (PG <70 mg/dl) requires
ingestion of glucose- or carbohydrate-containing foods. The acute glycemic response
correlates better with the glucose content than with the carbohydrate content of the
food. Although pure glucose is the preferred treatment, any form of carbohydrate that
contains glucose will raise blood glucose. Added fat may retard and then prolong the
acute glycemic response (175). Ongoing activity of insulin or insulin secretagogues
may lead to recurrence of hypoglycemia unless further food is ingested after recovery.
Severe hypoglycemia (where the individual requires the assistance of another person
and cannot be treated with oral carbohydrate due to confusion or unconsciousness)
should be treated using emergency glucagon kits, which require a prescription. Those
in close contact with or who have custodial care of people with hypoglycemia-prone
diabetes (family members, roommates, school personnel, child care providers, correctional
institution staff, or coworkers) should be instructed in use of such kits. An individual
does not need to be a health care professional to safely administer glucagon. Care
should be taken to ensure that unexpired glucagon kits are available.
Prevention of hypoglycemia is a critical component of diabetes management. Teaching
people with diabetes to balance insulin use, carbohydrate intake, and exercise is
a necessary but not always sufficient strategy. In type 1 diabetes and severely insulin-deficient
type 2 diabetes, the syndrome of hypoglycemia unawareness, or hypoglycemia-associated
autonomic failure, can severely compromise stringent diabetes control and quality
of life. The deficient counter-regulatory hormone release and autonomic responses
in this syndrome are both risk factors for and are caused by hypoglycemia. A corollary
to this “vicious cycle” is that several weeks of avoidance of hypoglycemia has been
demonstrated to improve counter-regulation and awareness to some extent in many patients
(174,176,177). Hence, patients with one or more episodes of severe hypoglycemia may
benefit from at least short-term relaxation of glycemic targets.
L. Immunization
Recommendations
Annually provide an influenza vaccine to all diabetic patients ≥6 months of age. (C)
Administer pneumococcal polysaccharide vaccine to all diabetic patients ≥2 years of
age. A one-time revaccination is recommended for individuals >64 years of age previously
immunized when they were <65 years of age if the vaccine was administered >5 years
ago. Other indications for repeat vaccination include nephrotic syndrome, chronic
renal disease, and other immunocompromised states, such as after transplantation.
(C)
Influenza and pneumonia are common, preventable infectious diseases associated with
high mortality and morbidity in the elderly and in people with chronic diseases. Though
there are limited studies reporting the morbidity and mortality of influenza and pneumococcal
pneumonia specifically in people with diabetes, observational studies of patients
with a variety of chronic illnesses, including diabetes, show that these conditions
are associated with an increase in hospitalizations for influenza and its complications.
People with diabetes may be at increased risk of the bacteremic form of pneumococcal
infection and have been reported to have a high risk of nosocomial bacteremia, which
has a mortality rate as high as 50% (178).
Safe and effective vaccines are available that can greatly reduce the risk of serious
complications from these diseases (179,180). In a case-control series, influenza vaccine
was shown to reduce diabetes-related hospital admission by as much as 79% during flu
epidemics (179). There is sufficient evidence to support that people with diabetes
have appropriate serologic and clinical responses to these vaccinations. The Centers
for Disease Control and Prevention's Advisory Committee on Immunization Practices
recommends influenza and pneumococcal vaccines for all individuals with diabetes (http://www.cdc.gov/vaccines/recs/).
For a complete discussion on the prevention of influenza and pneumococcal disease
in people with diabetes, consult the technical review and position statement on this
subject (178,181).
VI. PREVENTION AND MANAGEMENT OF DIABETES COMPLICATIONS
A. Cardiovascular disease
CVD is the major cause of morbidity and mortality for individuals with diabetes and
the largest contributor to the direct and indirect costs of diabetes. The common conditions
coexisting with type 2 diabetes (e.g., hypertension and dyslipidemia) are clear risk
factors for CVD, and diabetes itself confers independent risk. Numerous studies have
shown the efficacy of controlling individual cardiovascular risk factors in preventing
or slowing CVD in people with diabetes. Large benefits are seen when multiple risk
factors are addressed globally (182,183). Risk for coronary heart disease and CVD
in general can be estimated using multivariable risk factor approaches, and such a
strategy may be desirable to undertake in adult patients prior to instituting preventive
therapy.
1. Hypertension/blood pressure control
Recommendations
Screening and diagnosis
Blood pressure should be measured at every routine diabetes visit. Patients found
to have systolic blood pressure ≥130 mmHg or diastolic blood pressure ≥80 mmHg should
have blood pressure confirmed on a separate day. Repeat systolic blood pressure ≥130
mmHg or diastolic blood pressure ≥80 mmHg confirms a diagnosis of hypertension. (C)
Goals
Patients with diabetes should be treated to a systolic blood pressure <130 mmHg. (C)
Patients with diabetes should be treated to a diastolic blood pressure <80 mmHg. (B)
Treatment
Patients with a systolic blood pressure 130–139 mmHg or a diastolic blood pressure
80–89 mmHg may be given lifestyle therapy alone for a maximum of 3 months, and then
if targets are not achieved, patients should be treated with the addition of pharmacological
agents. (E)
Patients with more severe hypertension (systolic blood pressure ≥140 mmHg or diastolic
blood pressure ≥90 mmHg) at diagnosis or follow-up should receive pharmacologic therapy
in addition to lifestyle therapy. (A)
Lifestyle therapy for hypertension consists of weight loss if overweight, DASH-style
dietary pattern including reducing sodium and increasing potassium intake, moderation
of alcohol intake, and increased physical activity. (B)
Pharmacologic therapy for patients with diabetes and hypertension should be paired
with a regimen that includes either an ACE inhibitor or an angiotensin II receptor
blocker (ARB). If one class is not tolerated, the other should be substituted. If
needed to achieve blood pressure targets, a thiazide diuretic should be added to those
with an estimated glomerular filtration rate (GFR) (see below) ≥30 ml · min/1.73 m2
and a loop diuretic for those with an estimated GFR <30 ml · min/1.73 m2. (C)
Multiple drug therapy (two or more agents at maximal doses) is generally required
to achieve blood pressure targets. (B)
If ACE inhibitors, ARBs, or diuretics are used, kidney function and serum potassium
levels should be closely monitored. (E)
In pregnant patients with diabetes and chronic hypertension, blood pressure target
goals of 110–129/65–79 mmHg are suggested in the interest of long-term maternal health
and minimizing impaired fetal growth. ACE inhibitors and ARBs are contraindicated
during pregnancy. (E)
Hypertension is a common comorbidity of diabetes that affects the majority of patients,
with prevalence depending on type of diabetes, age, obesity, and ethnicity. Hypertension
is a major risk factor for both CVD and microvascular complications. In type 1 diabetes,
hypertension is often the result of underlying nephropathy, while in type 2 diabetes
it usually coexists with other cardiometabolic risk factors.
a. Screening and diagnosis.
Measurement of blood pressure in the office should be done by a trained individual
and should follow the guidelines established for nondiabetic individuals: measurement
in the seated position, with feet on the floor and arm supported at heart level, after
5 min of rest. Cuff size should be appropriate for the upper arm circumference. Elevated
values should be confirmed on a separate day. Because of the clear synergistic risks
of hypertension and diabetes, the diagnostic cutoff for a diagnosis of hypertension
is lower in people with diabetes (blood pressure ≥130/80 mmHg) than in those without
diabetes (blood pressure ≥140/90 mmHg) (184).
Home blood pressure self-monitoring and 24-h ambulatory blood pressure monitoring
may provide additional evidence of “white coat” and masked hypertension and other
discrepancies between office and “true” blood pressure, and studies in nondiabetic
populations show that home measurements may correlate better with CVD risk than office
measurements (185,186). However, the preponderance of the clear evidence of benefits
of treatment of hypertension in people with diabetes is based on office measurements.
b. Treatment goals.
Randomized clinical trials have demonstrated the benefit (reduction of coronary heart
disease [CHD] events, stroke, and nephropathy) of lowering blood pressure to <140
mmHg systolic and <80 mmHg diastolic in individuals with diabetes (184,187
–189). Epidemiologic analyses show that blood pressure >115/75 mmHg is associated
with increased cardiovascular event rates and mortality in individuals with diabetes
(184,190,191). Therefore, a target blood pressure goal of <130/80 mmHg is reasonable
if it can be achieved safely. The ongoing ACCORD trial is designed to determine whether
blood pressure lowering to systolic blood pressure <120 mmHg provides greater cardiovascular
protection than a systolic blood pressure level of <140 mmHg in patients with type
2 diabetes (192).
c. Treatment strategies.
Although there are no well-controlled studies of diet and exercise in the treatment
of hypertension in individuals with diabetes, the Dietary Approaches to Stop Hypertension
(DASH) study in nondiabetic individuals has shown antihypertensive effects similar
to those of pharmacologic monotherapy. Lifestyle therapy consists of reducing sodium
intake (to <1,500 mg/day) and excess body weight; increasing consumption of fruits,
vegetables (8–10 servings/day), and low-fat dairy products (2–3 servings/day); avoiding
excessive alcohol consumption (no more than two servings per day in men and no more
than one serving per day in women); and increasing activity levels (184,193). These
nonpharmacological strategies may also positively affect glycemia and lipid control.
Their effects on cardiovascular events have not been established. An initial trial
of nonpharmacologic therapy may be reasonable in diabetic individuals with mild hypertension
(systolic 130–139 mmHg or diastolic 80–89 mmHg). If the blood pressure is ≥140 mmHg
systolic and/or ≥90 mmHg diastolic at the time of diagnosis, pharmacologic therapy
should be initiated along with nonpharmacologic therapy (184).
Lowering of blood pressure with regimens based on a variety of antihypertensive drugs,
including ACE inhibitors, ARBs, β-blockers, diuretics, and calcium channel blockers,
has been shown to be effective in reducing cardiovascular events. Several studies
suggested that ACE inhibitors may be superior to dihydropyridine calcium channel blockers
in reducing cardiovascular events (194
–196). However, a variety of other studies have shown no specific advantage to ACE
inhibitors as initial treatment of hypertension in the general hypertensive population,
but rather an advantage on cardiovascular outcomes of initial therapy with low-dose
thiazide diuretics (184,197,198).
In people with diabetes, inhibitors of the renin-angiotensin system (RAS) may have
unique advantages for initial or early therapy of hypertension. In a nonhypertension
trial of high-risk individuals including a large subset with diabetes, an ACE inhibitor
reduced CVD outcomes (199). In patients with congestive heart failure (CHF), including
diabetic subgroups, ARBs have been shown to reduce major CVD outcomes (200
–203), and in type 2 patients with significant nephropathy, ARBs were superior to
calcium channel blockers for reducing heart failure (204
–206). Though evidence for distinct advantages of RAS inhibitors on CVD outcomes in
diabetes remains conflicting (187,207), the high CVD risks associated with diabetes,
and the high prevalence of undiagnosed CVD, may still favor recommendations for their
use as first-line hypertension therapy in people with diabetes (184). Recently, the
blood pressure arm of the ADVANCE trial demonstrated that routine administration of
a fixed combination of the ACE inhibitor perindopril and the diuretic indapamide significantly
reduced combined microvascular and macrovascular outcomes, as well as CVD and total
mortality. The improved outcomes also could have been due to lower achieved blood
pressure in the perindopril-indapamide arm (208). In addition, the ACCOMPLISH (Avoiding
Cardiovascular Events in Combination Therapy in Patients Living with Systolic Hypertension)
trial showed a decrease in morbidity and mortality in those receiving benazapril and
amlodipine versus benazapril and hydrochlorothiazide. The compelling benefits of RAS
inhibitors in diabetic patients with albuminuria or renal insufficiency provide additional
rationale for use of these agents (see below, VI.B. Nephropathy screening and treatment).
An important caveat is that most patients with hypertension require multi-drug therapy
to reach treatment goals, especially diabetic patients whose targets are lower. Many
patients will require three or more drugs to reach target goals (184). If blood pressure
is refractory to optimal doses of at least three antihypertensive agents of different
classifications, one of which should be a diuretic, clinicians should consider an
evaluation for secondary forms of hypertension.
During pregnancy in diabetic women with chronic hypertension, target blood pressure
goals of 110–129 mmHg systolic and 65–79 mmHg diastolic are reasonable, as they contribute
to long-term maternal health. Lower blood pressure levels may be associated with impaired
fetal growth. During pregnancy, treatment with ACE inhibitors and ARBs is contraindicated,
since they can cause fetal damage. Antihypertensive drugs known to be effective and
safe in pregnancy include methyldopa, labetalol, diltiazem, clonidine, and prazosin.
Chronic diuretic use during pregnancy has been associated with restricted maternal
plasma volume, which might reduce uteroplacental perfusion (209).
2. Dyslipidemia/lipid management
Recommendations
Screening
In most adult patients, measure fasting lipid profile at least annually. In adults
with low-risk lipid values (LDL cholesterol <100 mg/dl, HDL cholesterol >50 mg/dl,
and triglycerides <150 mg/dl), lipid assessments may be repeated every 2 years. (E)
Treatment recommendations and goals
Lifestyle modification focusing on the reduction of saturated fat, trans fat, and
cholesterol intake; increase of n-3 fatty acids, viscous fiber, and plant stanols/sterols;
weight loss (if indicated); and increased physical activity should be recommended
to improve the lipid profile in patients with diabetes. (A)
Statin therapy should be added to lifestyle therapy, regardless of baseline lipid
levels, for diabetic patients:
with overt CVD. (A)
without CVD who are over the age of 40 years and have one or more other CVD risk factors.
(A)
For patients at lower risk than described above (e.g., without overt CVD and under
the age of 40 years), statin therapy should be considered in addition to lifestyle
therapy if LDL cholesterol remains >100 mg/dl or in those with multiple CVD risk factors.
(E)
In individuals without overt CVD, the primary goal is an LDL cholesterol <100 mg/dl
(2.6 mmol/l). (A)
In individuals with overt CVD, a lower LDL cholesterol goal of <70 mg/dl (1.8 mmol/l),
using a high dose of a statin, is an option. (B)
If drug-treated patients do not reach the above targets on maximal tolerated statin
therapy, a reduction in LDL cholesterol of ∼30–40% from baseline is an alternative
therapeutic goal. (A)
Triglycerides levels <150 mg/dl (1.7 mmol/l) and HDL cholesterol >40 mg/dl (1.0 mmol/l)
in men and >50 mg/dl (1.3 mmol/l) in women, are desirable. However, LDL cholesterol–targeted
statin therapy remains the preferred strategy. (C)
If targets are not reached on maximally tolerated doses of statins, combination therapy
using statins and other lipid-lowering agents may be considered to achieve lipid targets
but has not been evaluated in outcome studies for either CVD outcomes or safety. (E)
Statin therapy is contraindicated in pregnancy. (E)
a. Evidence for benefits of lipid-lowering therapy.
Patients with type 2 diabetes have an increased prevalence of lipid abnormalities,
contributing to their high risk of CVD. Over the past decade or more, multiple clinical
trials have demonstrated significant effects of pharmacologic (primarily statin) therapy
on CVD outcomes in subjects with CHD and for primary CVD prevention (210). Analyses
of diabetic subgroups of larger trials (211
–215) and trials specifically in subjects with diabetes (216,217) showed significant
primary and secondary prevention of CVD events with and without CHD deaths in diabetic
populations. As shown in Table 12, and similar to findings in nondiabetic subjects,
reduction in “hard” CVD outcomes (CHD death and nonfatal MI) can be more clearly seen
in diabetic subjects with high baseline CVD risk (known CVD and/or very high LDL cholesterol
levels), but overall the benefits of statin therapy in people with diabetes at moderate
or high risk for CVD are convincing.
Table 12
Reduction in 10-year risk of major CVD endpoints (CHD death/non-fatal MI) in major
statin trials, or sub-studies of major trials, in diabetic subjects (N = 16,032)
Study (ref.)
CVD prevention
Statin dose and comparator
Risk reduction
Relative risk reduction
Absolute risk reduction
LDL cholesterol reduction (%)
4S-DM (211)
2°
Simvastatin 20–40 mg vs. placebo
85.7 to 43.2%
50%
42.5%
186 to 119 mg/dl (36%)
ASPEN 2° (216)
2°
Atorvastatin 10 mg vs. placebo
39.5 to 24.5%
34%
12.7%
112 to 79 mg/dl (29%)
HPS-DM (212)
2°
Simvastatin 40 mg vs. placebo
43.8 to 36.3%
17%
7.5%
123 to 84 mg/dl (31%)
CARE-DM (213)
2°
Pravastatin 40 mg vs. placebo
40.8 to 35.4%
13%
5.4%
136 to 99 mg/dl (27%)
TNT-DM (214)
2°
Atorvastatin 80 mg vs. 10 mg
26.3 to 21.6%
18%
4.7%
99 to 77 mg/dl (22%)
HPS-DM (212)
1°
Simvastatin 40 mg vs. placebo
17.5 to 11.5%
34%
6.0%
124 to 86 mg/dl (31%)
CARDS (234)
1°
Atorvastatin 10 mg vs. placebo
11.5 to 7.5%
35%
4.0%
118 to 71 mg/dl (40%)
ASPEN 1° (216)
1°
Atorvastatin 10 mg vs. placebo
9.8 to 7.9%
19%
1.9%
114 to 80 mg/dl (30%)
ASCOT-DM (215)
1°
Atorvastatin 10 mg vs. placebo
11.1 to 10.2%
8%
0.9%
125 to 82 mg/dl (34%)
Studies were of differing lengths (3.3–5.4 years) and used somewhat different outcomes,
but all reported rates of CVD death and non-fatal MI. In this tabulation, results
of the statin on 10-year risk of major CVD endpoints (CHD death/non-fatal MI) are
listed for comparison between studies. Correlation between 10-year CVD risk of the
control group and the absolute risk reduction with statin therapy is highly significant
(P = 0.0007). Analyses provided by Craig Williams, PharmD, Oregon Health & Science
University, 2007.
Low levels of HDL cholesterol, often associated with elevated triglyceride levels,
are the most prevalent pattern of dyslipidemia in people with type 2 diabetes. However,
the evidence base for drugs that target these lipid fractions is significantly less
robust than that for statin therapy (217). Nicotinic acid has been shown to reduce
CVD outcomes (218), although the study was done in a nondiabetic cohort. Gemfibrozil
has been shown to decrease rates of CVD events in subjects without diabetes (219,220)
and in a diabetic subgroup of a larger trial (219). However, in a large trial specific
to diabetic patients, fenofibrate failed to reduce overall cardiovascular outcomes
(221).
b. Dyslipidemia treatment and target lipid levels.
For most patients with diabetes, the first priority of dyslipidemia therapy (unless
severe hypertriglyceridemia is the immediate issue) is to lower LDL cholesterol to
a target goal of <100 mg/dl (2.60 mmol/l) (222). Lifestyle intervention, including
MNT, increased physical activity, weight loss, and smoking cessation, may allow some
patients to reach lipid goals. Nutrition intervention should be tailored according
to each patient's age, type of diabetes, pharmacological treatment, lipid levels,
and other medical conditions and should focus on the reduction of saturated fat, cholesterol,
and trans unsaturated fat intake and increases in n-3 fatty acids, viscous fiber (such
as in oats, legumes, citrus), and plant stanols/sterols. Glycemic control can also
beneficially modify plasma lipid levels, particularly in patients with very high triglycerides
and poor glycemic control.
In those with clinical CVD or who are over age 40 years and have CVD risk factors,
pharmacological treatment should be added to lifestyle therapy regardless of baseline
lipid levels. Statins are the drugs of choice for lowering LDL cholesterol.
In patients other than those described above, statin treatment should be considered
if there is an inadequate LDL cholesterol response to lifestyle modifications and
improved glucose control or if the patient has increased cardiovascular risk (e.g.,
multiple cardiovascular risk factors or long duration of diabetes). Very little clinical
trial evidence exists for type 2 diabetic patients under the age of 40 years and for
type 1 diabetic patients of any age. In the Heart Protection Study (lower age limit
40 years), the subgroup of 600 patients with type 1 diabetes had a proportionately
similar reduction in risk as patients with type 2 diabetes although not statistically
significant (212). Although the data are not definitive, consideration should be given
to lipid-lowering goals for type 1 diabetic patients similar to those for type 2 diabetic
patients, particularly if other cardiovascular risk factors are present.
c. Alternative LDL cholesterol goals.
Virtually all trials of statins and CVD outcome have tested specific doses of statins
against placebo, other doses of statin, or other statins, rather than aiming for specific
LDL cholesterol goals (223). As can be seen in Table 10, placebo-controlled trials
generally achieved LDL cholesterol reductions of 30–40% from baseline. Hence, LDL
cholesterol lowering of this magnitude is an acceptable outcome for patients who cannot
reach LDL cholesterol goals due to severe baseline elevations in LDL cholesterol and/or
intolerance of maximal, or any, statin doses. Additionally, for those with baseline
LDL cholesterol minimally >100 mg/dl, prescribing statin therapy to lower LDL cholesterol
to ∼30–40% from baseline is probably more effective than prescribing just enough to
get LDL cholesterol slightly <100 mg/dl.
Recent clinical trials in high-risk patients, such as those with acute coronary syndromes
or previous cardiovascular events (224
–226), have demonstrated that more aggressive therapy with high doses of statins to
achieve an LDL cholesterol of <70 mg/dl led to a significant reduction in further
events. Therefore, a reduction in LDL cholesterol to a goal of <70 mg/dl is an option
in very-high-risk diabetic patients with overt CVD (227).
In individual patients, LDL cholesterol lowering with statins is highly variable,
and this variable response is poorly understood (228). Reduction of CVD events with
statins correlates very closely with LDL cholesterol lowering (229). When maximally
tolerated doses of statins fail to significantly lower LDL cholesterol (<30% reduction
from patients baseline), the primary aim of combination therapy should be to achieve
additional LDL cholesterol lowering. Niacin, fenofibrate, ezetimibe, and bile acid
sequestrants all offer additional LDL cholesterol lowering. The evidence that combination
therapy provides a significant increment in CVD risk reduction over statin therapy
alone is still elusive.
d. Treatment of other lipoprotein fractions or targets.
Severe hypertriglyceridemia may warrant immediate therapy of this abnormality with
lifestyle and usually pharmacologic therapy (fibric acid derivative or niacin) to
reduce the risk of acute pancreatitis. In the absence of severe hypertriglyceridemia,
therapy targeting HDL cholesterol or triglycerides has intuitive appeal but lacks
the evidence base of statin therapy (186). If the HDL cholesterol is <40 mg/dl and
the LDL cholesterol is 100–129 mg/dl, gemfibrozil or niacin might be used, especially
if a patient is intolerant to statins. Niacin is the most effective drug for raising
HDL cholesterol. It can significantly increase blood glucose at high doses, but recent
studies demonstrate that at modest doses (750–2,000 mg/day), significant improvements
in LDL cholesterol, HDL cholesterol, and triglyceride levels are accompanied by only
modest changes in glucose that are generally amenable to adjustment of diabetes therapy
(230,231).
Combination therapy with a statin and a fibrate or a statin and niacin may be efficacious
for treatment of all three lipid fractions, but this combination is associated with
an increased risk for abnormal transaminase levels, myositis, or rhabdomyolysis. The
risk of rhabdomyolysis is higher with higher doses of statins and with renal insufficiency
and seems to be lower when statins are combined with fenofibrate than gemfibrozil
(232). Several ongoing trials may provide much-needed evidence for the effects of
combination therapy on cardiovascular outcomes.
In 2008, a consensus panel convened by ADA and the American College of Cardiology
(ACC) recommended a greater focus on non-HDL cholesterol and apo lipoprotein B (apo
B) in patients who are likely to have small LDL particles, such as people with diabetes
(233). The consensus panel suggested that for statin-treated patients in whom the
LDL cholesterol goal would be <70 mg/dl (non-HDL cholesterol <100 mg/dl), apo B should
be measured and treated to <80 mg/dl. For patients on statins with an LDL cholesterol
goal of <100 mg/dl (non-HDL cholesterol <130 mg/dl), apo B should be measured and
treated to <90 mg/dl.
For a summary of recommendations for glycemic, blood pressure, and lipid control for
adults with diabetes, see Table 13.
Table 13
Summary of recommendations for glycemic, blood pressure, and lipid control for adults
with diabetes
A1C
<7.0%*
Blood pressure
<130/80 mmHg
Lipids
LDL cholesterol
<100 mg/dl (<2.6 mmol/l)†
*Referenced to a nondiabetic range of 4.0–6.0% using a DCCT-based assay.
†In individuals with overt CVD, a lower LDL cholesterol goal of <70 mg/dl (1.8 mmol/l),
using a high dose of a statin, is an option.
3. Antiplatelet agents
Recommendations
Consider aspirin therapy (75–162 mg/day) as a primary prevention strategy in those
with type 1 or type 2 diabetes at increased cardiovascular risk (10-year risk >10%).
This includes most men >50 years of age or women >60 years of age who have at least
one additional major risk factor (family history of CVD, hypertension, smoking, dyslipidemia,
or albuminuria). (C)
There is not sufficient evidence to recommend aspirin for primary prevention in lower
risk individuals, such as men <50 years of age or women <60 years of age without other
major risk factors. For patients in these age-groups with multiple other risk factors,
clinical judgment is required. (C)
Use aspirin therapy (75–162 mg/day) as a secondary prevention strategy in those with
diabetes with a history of CVD. (A)
For patients with CVD and documented aspirin allergy, clopidogrel (75 mg/day) should
be used. (B)
Combination therapy with ASA (75–162 mg/day) and clopidogrel (75 mg/day) is reasonable
for up to a year after an acute coronary syndrome. (B)
ADA and the American Heart Association (AHA) have, in the past, jointly recommended
that low-dose aspirin therapy be used as a primary prevention strategy in those with
diabetes at increased cardiovascular risk, including those who are over 40 years of
age or those with additional risk factors (family history of CVD, hypertension, smoking,
dyslipidemia, or albuminuria) (235). These recommendations were derived from several
older trials that included small numbers of patients with diabetes.
Aspirin has been shown to be effective in reducing cardiovascular morbidity and mortality
in high-risk patients with previous MI or stroke (secondary prevention). Its net benefit
in primary prevention among patients with no previous cardiovascular events is more
controversial, both for patients with and without a history of diabetes (236). The
U.S. Preventive Services Task Force recently updated its evidence base and recommendations
about aspirin use for primary prevention (237,238). The Task Force recommended encouraging
aspirin use in men 45–79 and women 55–79 years of age and not encouraging aspirin
use in younger adults and did not differentiate based on the presence or absence of
diabetes.
Two recent randomized controlled trials of aspirin specifically in patients with diabetes
failed to show a significant reduction in CVD end points, raising further questions
about the efficacy of aspirin for primary prevention in people with diabetes (239,240).
In 2009, ADA AHA, and ACC convened a group of experts to review and synthesize the
available evidence and use this information to create an updated recommendation. Their
report, including analyses in addition to those described below, will be published
in early 2010.
The ATT (Anti-Thrombotic Trialists') collaborators recently published an individual
patient-level meta-analysis of the six large trials of aspirin for primary prevention
in the general population (236). These trials collectively enrolled over 95,000 participants,
including almost 4,000 with diabetes. Overall, they found that aspirin reduced the
risk of vascular events by 12% (RR 0.88 [95% CI 0.82–0.94]). The largest reduction
was for nonfatal MI (0.77 [0.67–0.89]). Aspirin had little effect on CHD death (0.95
[0.78–1.15]) or total stroke (0.95 [0.85–1.06]). The net effect on total stroke reflected
a relative reduction in risk of ischemic stroke (−14%) and a relative increased risk
of hemorrhagic stroke (+32%). There was some evidence of a difference in aspirin effect
by sex. Aspirin reduced CHD events in men (0.77 [0.67–0.89]) but not in women (0.95
[0.77–1.17]). Conversely, aspirin had no effect on stroke in men (1.01 [0.74–1.39])
but reduced stroke in women (0.77 [0.59–0.99]). These potential differences in effect
by sex were of borderline statistical significance, were affected strongly by the
results of one trial, and cannot be considered definitive. Notably, sex differences
in aspirin's effects have not been observed in studies of secondary prevention (236).
In the six trials examined by the ATT collaborators, the effect of aspirin on major
vascular events was similar for patients with and without diabetes (0.88 [0.67–1.15]
and 0.87 [0.79–0.96], respectively). The CI was wider for those with diabetes because
of their smaller number.
Based on the currently available evidence, aspirin appears to have a modest effect
on ischemic vascular events with the absolute decrease in events depending on the
underlying CVD risk. The main adverse effects appear to be an increased risk of gastrointestinal
bleeding. The excess risk may be as high as 1–5 per 1,000 per year in real-world settings.
In adults with CVD risk greater than 1% per year, the number of CVD events prevented
will be similar to or greater than the number of episodes of bleeding induced, although
these complications do not have equal effects on long-term health (241).
Average daily dosages used in most clinical trials involving patients with diabetes
ranged from 50–650 mg but were mostly in the range of 100–325 mg/day. There is little
evidence to support any specific dose, but using the lowest possible dosage may help
reduce side effects (242). Although platelets from patients with diabetes have altered
function, it is unclear what, if any, impact that finding has on the required dose
of aspirin for cardioprotective effects in the patient with diabetes. Many alternate
pathways for platelet activation exist that are independent of thromboxane A2 and
thus not sensitive to the effects of aspirin (243). Therefore, while “aspirin resistance”
appears higher in diabetic patients when measured by a variety of ex vivo and in vitro
methods (platelet aggrenometry, measurement of thromboxane B2), these observations
alone are insufficient to empirically recommend at this time that higher doses of
aspirin be used in the diabetic patient (244
–246).
Aspirin use for secondary prevention continues to have a strong evidence base and
is recommended. Until further evidence is available, low-dose (75–162 mg/day) aspirin
use for primary prevention is reasonable for adults with diabetes and no previous
history of vascular disease who are at increased CVD risk (10-year risk of CVD events
>10%) and who are not at increased risk for bleeding. This generally includes most
men over age 50 years and women over age 60 years who also have one or more of the
following major risk factors: smoking, hypertension, dyslipidemia, family history
of premature CVD, and albuminuria.
Aspirin should not be recommended for those at low CVD risk (women under age 60 years
and men under age 50 years with no major CVD risk factors; 10-year CVD risk <5%),
as the low benefit is offset by the incidence of significant bleeding. Clinical judgment
should be used for those at intermediate risk (younger patients with one or risk factors
or older patients with no risk factors; those with 10-year CVD risk 5–10%) until further
research is available. Use of aspirin in patients under the age of 21 years is contraindicated
due to the associated risk of Reye's syndrome.
Clopidogrel has been demonstrated to reduce CVD events in diabetic individuals (247).
It is recommended as adjunctive therapy in the 1st year after an acute coronary syndrome
or as alternative therapy in aspirin-intolerant patients.
4. Smoking cessation
Recommendations
Advise all patients not to smoke. (A)
Include smoking cessation counseling and other forms of treatment as a routine component
of diabetes care. (B)
Issues of smoking and diabetes are reviewed in detail in the ADA technical review
(248) and position statement (249) on this topic. A large body of evidence from epidemiological,
case-control, and cohort studies provides convincing documentation of the causal link
between cigarette smoking and health risks. Cigarette smoking contributes to one of
every five deaths in the U.S. and is the most important modifiable cause of premature
death. Much of the prior work documenting the impact of smoking on health did not
separately discuss results on subsets of individuals with diabetes, suggesting that
the identified risks are at least equivalent to those found in the general population.
Other studies of individuals with diabetes consistently found a heightened risk of
CVD and premature death among smokers. Smoking is also related to the premature development
of microvascular complications of diabetes and may have a role in the development
of type 2 diabetes.
A number of large randomized clinical trials have demonstrated the efficacy and cost-effectiveness
of smoking cessation counseling in changing smoking behavior and reducing tobacco
use. The routine and thorough assessment of tobacco use is important as a means of
preventing smoking or encouraging cessation. Special considerations should include
assessment of level of nicotine dependence, which is associated with difficulty in
quitting and relapse (250,251).
5. Coronary heart disease screening and treatment
Recommendations
Screening
In asymptomatic patients, evaluate risk factors to stratify patients by 10-year risk,
and treat risk factors accordingly. (B)
Treatment
In patients with known CVD, ACE inhibitor (C), aspirin (A), and statin therapy (A)
(if not contraindicated) should be used to reduce the risk of cardiovascular events.
In patients with a prior MI, β-blockers should be continued for at least 2 years after
the event. (B)
Longer-term use of β-blockers in the absence of hypertension is reasonable if well
tolerated, but data are lacking. (E)
Avoid thiazolidinedione (TZD) treatment in patients with symptomatic heart failure.
(C)
Metformin may be used in patients with stable CHF if renal function is normal. It
should be avoided in unstable or hospitalized patients with CHF. (C)
Screening for CAD is reviewed in a recently updated consensus statement (93). To identify
the presence of CAD in diabetic patients without clear or suggestive symptoms, a risk
factor–based approach to the initial diagnostic evaluation and subsequent follow-up
has intuitive appeal. However, recent studies concluded that using this approach fails
to identify which patients will have silent ischemia on screening tests (159,252).
Candidates for cardiac testing include those with 1) typical or atypical cardiac symptoms
and 2) an abnormal resting electrocardiogram (ECG). The screening of asymptomatic
patients remains controversial, especially since intensive medical therapy, indicated
in diabetic patients at high risk for CVD, has an increasing evidence base for providing
equal outcomes to invasive revascularization, including in diabetic patients (253,254).
There is also recent preliminary evidence that silent myocardial ischemia may reverse
over time, adding to the controversy concerning aggressive screening strategies (255).
Finally, a recent randomized observational trial demonstrated no clinical benefit
to routine screening of asymptomatic patients with type 2 diabetes and normal ECGs
(256). Despite abnormal myocardial perfusion imaging in more than one in five patients,
cardiac outcomes were essentially equal (and very low) in screened versus unscreened
patients. Accordingly, the overall effectiveness, especially the cost-effectiveness,
of such an indiscriminate screening strategy is in question.
In all patients with diabetes, cardiovascular risk factors should be assessed at least
annually. These risk factors include dyslipidemia, hypertension, smoking, a positive
family history of premature coronary disease, and the presence of micro- or macroalbuminuria.
Abnormal risk factors should be treated as described elsewhere in these guidelines.
Patients at increased CHD risk should receive aspirin and a statin, and ACE inhibitor,
or ARB therapy if hypertensive, unless there are contraindications to a particular
drug class. While clear benefit exists for ACE inhibitor and ARB therapy in patients
with nephropathy or hypertension, the benefits in patients with CVD in the absence
of these conditions is less clear, especially when LDL cholesterol is concomitantly
controlled (257,258).
B. Nephropathy screening and treatment
Recommendations
General recommendations
To reduce the risk or slow the progression of nephropathy, optimize glucose control.
(A)
To reduce the risk or slow the progression of nephropathy, optimize blood pressure
control. (A)
Screening
Perform an annual test to assess urine albumin excretion in type 1 diabetic patients
with diabetes duration of 5 years and in all type 2 diabetic patients, starting at
diagnosis. (E)
Measure serum creatinine at least annually in all adults with diabetes regardless
of the degree of urine albumin excretion. The serum creatinine should be used to estimate
GFR and stage the level of chronic kidney disease (CKD), if present. (E)
Treatment
In the treatment of the nonpregnant patient with micro- or macroalbuminuria, either
ACE inhibitors or ARBs should be used. (A)
While there are no adequate head-to-head comparisons of ACE inhibitors and ARBs, there
is clinical trial support for each of the following statements:
In patients with type 1 diabetes, hypertension, and any degree of albuminuria, ACE
inhibitors have been shown to delay the progression of nephropathy. (A)
In patients with type 2 diabetes, hypertension, and microalbuminuria, both ACE inhibitors
and ARBs have been shown to delay the progression to macroalbuminuria. (A)
In patients with type 2 diabetes, hypertension, macroalbuminuria, and renal insufficiency
(serum creatinine >1.5 mg/dl), ARBs have been shown to delay the progression of nephropathy.
(A)
If one class is not tolerated, the other should be substituted. (E)
Reduction of protein intake to 0.8–1.0 g · kg body wt–1 · day–1 in individuals with
diabetes and the earlier stages of CKD and to 0.8 g · kg body wt–1 · day–1 in the
later stages of CKD may improve measures of renal function (urine albumin excretion
rate and GFR) and is recommended. (B)
When ACE inhibitors, ARBs, or diuretics are used, monitor serum creatinine and potassium
levels for the development of acute kidney disease and hyperkalemia. (E)
Continued monitoring of urine albumin excretion to assess both response to therapy
and progression of disease is recommended. (E)
Consider referral to a physician experienced in the care of kidney disease when there
is uncertainty about the etiology of kidney disease (active urine sediment, absence
of retinopathy, or rapid decline in GFR), difficult management issues, or advanced
kidney disease. (B)
Diabetic nephropathy occurs in 20–40% of patients with diabetes and is the single
leading cause of end-stage renal disease (ESRD). Persistent albuminuria in the range
of 30–299 mg/24 h (microalbuminuria) has been shown to be the earliest stage of diabetic
nephropathy in type 1 diabetes and a marker for development of nephropathy in type
2 diabetes. Microalbuminuria is also a well-established marker of increased CVD risk
(259,260). Patients with microalbuminuria who progress to macroalbuminuria (≥300 mg/24
h) are likely to progress to ESRD (261,262). However, a number of interventions have
been demonstrated to reduce the risk and slow the progression of renal disease.
Intensive diabetes management with the goal of achieving near-normoglycemia has been
shown in large prospective randomized studies to delay the onset of microalbuminuria
and the progression of micro- to macroalbuminuria in patients with type 1 (263,264)
and type 2 (57,58) diabetes. The UKPDS provided strong evidence that control of blood
pressure can reduce the development of nephropathy (187). In addition, large prospective
randomized studies in patients with type 1 diabetes have demonstrated that achievement
of lower levels of systolic blood pressure (<140 mmHg) resulting from treatment using
ACE inhibitors provides a selective benefit over other antihypertensive drug classes
in delaying the progression from micro- to macroalbuminuria and can slow the decline
in GFR in patients with macroalbuminuria (205,206,265). In type 2 diabetes with hypertension
and normoalbuminuria, RAS inhibition has been demonstrated to delay onset of microalbuminuria
(266).
In addition, ACE inhibitors have been shown to reduce major CVD outcomes (i.e., MI,
stroke, and death) in patients with diabetes (199), thus further supporting the use
of these agents in patients with microalbuminuria, a CVD risk factor. ARBs do not
prevent microalbuminuria in normotensive patients with type 1 or type 2 diabetes (267,268);
however, ARBs have been shown to reduce the rate of progression from micro- to macroalbuminuria
as well as ESRD in patients with type 2 diabetes (269
–271). Some evidence suggests that ARBs have a smaller magnitude of rise in potassium
compared with ACE inhibitors in people with nephropathy (272,273). It is important
to note that both ACE inhibitors and ARBs reduce loss of kidney function in people
with diabetic nephropathy, above and beyond any such effect attributable to a reduction
in systemic blood pressure. Combinations of drugs that block the rennin-angiotensin-aldosterone
system (e.g., an ACE inhibitor plus an ARB, a mineralocorticoid antagonist, or a direct
renin inhibitor) have been shown to provide additional lowering of albuminuria (274
–277). However, the long-term effects of such combinations on renal or cardiovascular
outcomes have not yet been evaluated in clinical trials.
Other drugs, such as diuretics, calcium channel blockers, and β-blockers, should be
used as additional therapy to further lower blood pressure in patients already treated
with ACE inhibitors or ARBs (204) or as alternate therapy in the rare individual unable
to tolerate ACE inhibitors or ARBs.
Studies in patients with varying stages of nephropathy have shown that protein restriction
helps slow the progression of albuminuria, GFR decline, and occurrence of ESRD (278
–281). Protein restriction should be considered particularly in patients whose nephropathy
seems to be progressing despite optimal glucose and blood pressure control and use
of ACE inhibitor and/or ARBs (281).
Assessment of albuminuria status and renal function
Screening for microalbuminuria can be performed by measurement of the albumin-to-creatinine
ratio in a random spot collection (preferred method); 24-h or timed collections are
more burdensome and add little to prediction or accuracy (282,283). Measurement of
a spot urine for albumin only, whether by immunoassay or by using a dipstick test
specific for microalbumin, without simultaneously measuring urine creatinine, is somewhat
less expensive but susceptible to false-negative and -positive determinations as a
result of variation in urine concentration due to hydration and other factors.
Abnormalities of albumin excretion are defined in Table 14. Because of variability
in urinary albumin excretion, two of three specimens collected within a 3- to 6-month
period should be abnormal before considering a patient to have crossed one of these
diagnostic thresholds. Exercise within 24 h, infection, fever, CHF, marked hyperglycemia,
and marked hypertension may elevate urinary albumin excretion over baseline values.
Table 14
Definitions of abnormalities in albumin excretion
Category
Spot collection (μg/mg creatinine)
Normal
<30
Microalbuminuria
30–299
Macroalbuminuria (clinical)
≥300
Information on presence of abnormal urine albumin excretion in addition to level of
GFR may be used to stage CKD. The National Kidney Foundation classification (Table
15) is primarily based on GFR levels and therefore differs from other systems, in
which staging is based primarily on urinary albumin excretion (284). Studies have
found decreased GFR in the absence of increased urine albumin excretion in a substantial
percentage of adults with diabetes (285,286). Epidemiologic evidence suggests that
a substantial fraction of those with CKD in the setting of diabetes have little or
no detectable albuminuria (285). Serum creatinine should therefore be measured at
least annually in all adults with diabetes, regardless of the degree of urine albumin
excretion.
Table 15
Stages of CKD
Stage
Description
GFR (ml/min per 1.73 m2 body surface area)
1
Kidney damage* with normal or increased GFR
≥90
2
Kidney damage* with mildly decreased GFR
60–89
3
Moderately decreased GFR
30–59
4
Severely decreased GFR
15–29
5
Kidney failure
<15 or dialysis
*Kidney damage defined as abnormalities on pathologic, urine, blood, or imaging tests.
Adapted from ref. 283.
Serum creatinine should be used to estimate GFR and to stage the level of CKD, if
present. Estimated GFR (eGFR) is commonly co-reported by laboratories or can be estimated
using formulae such as the Modification of Diet in Renal Disease (MDRD) study equation
(287). Recent reports have indicated that the MDRD is more accurate for the diagnosis
and stratification of CKD in patients with diabetes than the Cockcroft-Gault formula
(288). GFR calculators are available at http://www.nkdep.nih.gov.
The role of continued annual quantitative assessment of albumin excretion after diagnosis
of microalbuminuria and institution of ACE inhibitor or ARB therapy and blood pressure
control is unclear. Continued surveillance can assess both response to therapy and
progression of disease. Some suggest that reducing abnormal albuminuria (>30 mg/g)
to the normal or near-normal range may improve renal and cardiovascular prognosis,
but this approach has not been formally evaluated in prospective trials.
Complications of kidney disease correlate with level of kidney function. When the
eGFR is less than 60 ml · min/1.73 m2, screening for anemia, malnutrition, and metabolic
bone disease is indicated. Early vaccination against Hepatitis B is indicated in patients
likely to progress to end-stage kidney disease.
Consider referral to a physician experienced in the care of kidney disease when there
is uncertainty about the etiology of kidney disease (active urine sediment, absence
of retinopathy, or rapid decline in GFR), difficult management issues, or advanced
kidney disease. The threshold for referral may vary depending on the frequency with
which a provider encounters diabetic patients with significant kidney disease. Consultation
with a nephrologist when stage 4 CKD develops has been found to reduce cost, improve
quality of care, and keep people off dialysis longer (289,290). However, nonrenal
specialists should not delay educating their patients about the progressive nature
of diabetic kidney disease, the renal preservation benefits of aggressive treatment
of blood pressure, blood glucose, and hyperlipidemia, and the potential need for renal
replacement therapy.
C. Retinopathy screening and treatment
Recommendations
General recommendations
To reduce the risk or slow the progression of retinopathy, optimize glycemic control.
(A)
To reduce the risk or slow the progression of retinopathy, optimize blood pressure
control. (A)
Screening
Adults and children aged 10 years or older with type 1 diabetes should have an initial
dilated and comprehensive eye examination by an ophthalmologist or optometrist within
5 years after the onset of diabetes. (B)
Patients with type 2 diabetes should have an initial dilated and comprehensive eye
examination by an ophthalmologist or optometrist shortly after the diagnosis of diabetes.
(B)
Subsequent examinations for type 1 and type 2 diabetic patients should be repeated
annually by an ophthalmologist or optometrist. Less frequent exams (every 2–3 years)
may be considered following one or more normal eye exams. Examinations will be required
more frequently if retinopathy is progressing. (B)
High-quality fundus photographs can detect most clinically significant diabetic retinopathy.
Interpretation of the images should be performed by a trained eye care provider. While
retinal photography may serve as a screening tool for retinopathy, it is not a substitute
for a comprehensive eye exam, which should be performed at least initially and at
intervals thereafter as recommended by an eye care professional. (E)
Women with preexisting diabetes who are planning pregnancy or who have become pregnant
should have a comprehensive eye examination and be counseled on the risk of development
and/or progression of diabetic retinopathy. Eye examination should occur in the first
trimester with close follow-up throughout pregnancy and for 1 year postpartum. (B)
Treatment
Promptly refer patients with any level of macular edema, severe NPDR, or any PDR to
an ophthalmologist who is knowledgeable and experienced in the management and treatment
of diabetic retinopathy. (A)
Laser photocoagulation therapy is indicated to reduce the risk of vision loss in patients
with high-risk PDR, clinically significant macular edema, and in some cases of severe
NPDR. (A)
The presence of retinopathy is not a contraindication to aspirin therapy for cardioprotection,
as this therapy does not increase the risk of retinal hemorrhage. (A)
Diabetic retinopathy is a highly specific vascular complication of both type 1 and
type 2 diabetes, with prevalence strongly related to duration of diabetes. Diabetic
retinopathy is the most frequent cause of new cases of blindness among adults aged
20–74 years. Glaucoma, cataracts, and other disorders of the eye occur earlier and
more frequently in people with diabetes.
In addition to duration of diabetes, other factors that increase the risk of, or are
associated with, retinopathy include chronic hyperglycemia (291), the presence of
nephropathy (292), and hypertension (293). Intensive diabetes management with the
goal of achieving near normoglycemia has been shown in large prospective randomized
studies to prevent and/or delay the onset and progression of diabetic retinopathy
(53,57,58). Lowering blood pressure has been shown to decrease the progression of
retinopathy (187). Several case series and a controlled prospective study suggest
that pregnancy in type 1 diabetic patients may aggravate retinopathy (294,295); laser
photocoagulation surgery can minimize this risk (295).
One of the main motivations for screening for diabetic retinopathy is the established
efficacy of laser photocoagulation surgery in preventing vision loss. Two large trials,
the Diabetic Retinopathy Study (DRS) and the Early Treatment Diabetic Retinopathy
Study (ETDRS), provide the strongest support for the therapeutic benefits of photocoagulation
surgery.
The DRS (296) showed that panretinal photocoagulation surgery reduced the risk of
severe vision loss from PDR from 15.9% in untreated eyes to 6.4% in treated eyes.
The benefit was greatest among patients whose baseline evaluation revealed high-risk
characteristics (chiefly disc neovascularization or vitreous hemorrhage). Given the
risks of modest loss of visual acuity and contraction of the visual field from panretinal
laser surgery, such therapy is primarily recommended for eyes with PDR approaching
or having high-risk characteristics.
The ETDRS (297) established the benefit of focal laser photocoagulation surgery in
eyes with macular edema, particularly those with clinically significant macular edema,
with reduction of doubling of the visual angle (e.g., 20/50–20/100) from 20% in untreated
eyes to 8% in treated eyes. The ETDRS also verified the benefits of panretinal photocoagulation
for high-risk PDR, but not for mild or moderate NPDR. In older-onset patients with
severe NPDR or less-than-high-risk PDR, the risk of severe vision loss or vitrectomy
was reduced 50% by early laser photocoagulation surgery at these stages.
Laser photocoagulation surgery in both trials was beneficial in reducing the risk
of further vision loss, but generally not beneficial in reversing already diminished
acuity. This preventive effect and the fact that patients with PDR or macular edema
may be asymptomatic provide strong support for a screening program to detect diabetic
retinopathy.
As retinopathy is estimated to take at least 5 years to develop after the onset of
hyperglycemia (298), patients with type 1 diabetes should have an initial dilated
and comprehensive eye examination within 5 years after the onset of diabetes. Patients
with type 2 diabetes who generally have had years of undiagnosed diabetes (299) and
who have a significant risk of prevalent diabetic retinopathy at the time of diabetes
diagnosis should have an initial dilated and comprehensive eye examination soon after
diagnosis. Examinations should be performed by an ophthalmologist or optometrist who
is knowledgeable and experienced in diagnosing the presence of diabetic retinopathy
and is aware of its management. Subsequent examinations for type 1 and type 2 diabetic
patients are generally repeated annually. Less frequent exams (every 2–3 years) may
be cost effective after one or more normal eye exams (300
–302), while examinations will be required more frequently if retinopathy is progressing.
Examinations can also be done with retinal photographs (with or without dilation of
the pupil) read by experienced experts. In-person exams are still necessary when the
photos are unacceptable and for follow-up of abnormalities detected. Photos are not
a substitute for a comprehensive eye exam, which should be performed at least initially
and at intervals thereafter as recommended by an eye care professional. This technology
has great potential in areas where qualified eye care professionals are not available
and may also enhance efficiency and reduce costs when the expertise of ophthalmologists
can be used for more complex examinations and for therapy (303).
Results of eye examinations should be documented and transmitted to the referring
health care professional. For a detailed review of the evidence and further discussion
of diabetic retinopathy, see the ADA technical review and position statement on this
subject (304,305).
D. Neuropathy screening and treatment (306)
Recommendations
All patients should be screened for distal symmetric polyneuropathy (DPN) at diagnosis
and at least annually thereafter using simple clinical tests. (B)
Electrophysiological testing is rarely needed, except in situations where the clinical
features are atypical. (E)
Screening for signs and symptoms of cardiovascular autonomic neuropathy should be
instituted at diagnosis of type 2 diabetes and 5 years after the diagnosis of type
1 diabetes. Special testing is rarely needed and may not affect management or outcomes.
(E)
Medications for the relief of specific symptoms related to DPN and autonomic neuropathy
are recommended, as they improve the quality of life of the patient. (E)
The diabetic neuropathies are heterogeneous with diverse clinical manifestations.
They may be focal or diffuse. Most common among the neuropathies are chronic sensorimotor
DPN and autonomic neuropathy. Although DPN is a diagnosis of exclusion, complex investigations
to exclude other conditions are rarely needed.
The early recognition and appropriate management of neuropathy in the patient with
diabetes is important for a number of reasons: 1) nondiabetic neuropathies may be
present in patients with diabetes and may be treatable; 2) a number of treatment options
exist for symptomatic diabetic neuropathy; 3) up to 50% of DPN may be asymptomatic,
and patients are at risk of insensate injury to their feet; 4) autonomic neuropathy
may involve every system in the body; and 5) cardiovascular autonomic neuropathy causes
substantial morbidity and mortality. Specific treatment for the underlying nerve damage
is not currently available, other than improved glycemic control, which may slow progression
but not reverse neuronal loss. Effective symptomatic treatments are available for
some manifestations of DPN and autonomic neuropathy.
1. Diagnosis of neuropathy
a. Distal symmetric polyneuropathy.
Patients with diabetes should be screened annually for DPN using tests such as pinprick
sensation, vibration perception (using a 128-Hz tuning fork), 10-g monofilament pressure
sensation at the distal plantar aspect of both great toes and metatarsal joints, and
assessment of ankle reflexes. Combinations of more than one test have >87% sensitivity
in detecting DPN. Loss of 10-g monofilament perception and reduced vibration perception
predict foot ulcers (306).
b. Diabetic autonomic neuropathy (307).
The symptoms and signs of autonomic dysfunction should be elicited carefully during
the history and physical examination. Major clinical manifestations of diabetic autonomic
neuropathy include resting tachycardia, exercise intolerance, orthostatic hypotension,
constipation, gastroparesis, erectile dysfunction, sudomotor dysfunction, impaired
neurovascular function, “brittle diabetes,” and hypoglycemic autonomic failure.
Cardiovascular autonomic neuropathy, a CVD risk factor (93), is the most studied and
clinically important form of diabetic autonomic neuropathy. Cardiovascular autonomic
neuropathy may be indicated by resting tachycardia (>100 bpm), orthostasis (a fall
in systolic blood pressure >20 mmHg upon standing without an appropriate heart rate
response), or other disturbances in autonomic nervous system function involving the
skin, pupils, or gastrointestinal and genitourinary systems.
Gastrointestinal neuropathies (e.g., esophageal enteropathy, gastroparesis, constipation,
diarrhea, and fecal incontinence) are common, and any section of the gastrointestinal
tract may be affected. Gastroparesis should be suspected in individuals with erratic
glucose control or with upper gastrointestinal symptoms without other identified cause.
Evaluation of solid-phase gastric emptying using double-isotope scintigraphy may be
done if symptoms are suggestive, but test results often correlate poorly with symptoms.
Constipation is the most common lower-gastrointestinal symptom but can alternate with
episodes of diarrhea.
Diabetic autonomic neuropathy is also associated with genitourinary tract disturbances.
In men, diabetic autonomic neuropathy may cause erectile dysfunction and/or retrograde
ejaculation. Evaluation of bladder dysfunction should be performed for individuals
with diabetes who have recurrent urinary tract infections, pyelonephritis, incontinence,
or a palpable bladder.
2. Symptomatic treatments
a. Distal symmetric polyneuropathy.
The first step in management of patients with DPN should be to aim for stable and
optimal glycemic control. Although controlled trial evidence is lacking, several observational
studies suggest that neuropathic symptoms improve not only with optimization of control,
but also with the avoidance of extreme blood glucose fluctuations. Patients with painful
DPN may benefit from pharmacological treatment of their symptoms: many agents have
efficacy confirmed in published randomized controlled trials, with several FDA-approved
for the management of painful DPN. See Table 16 for examples of agents to treat DPN
pain.
Table 16
Table of drugs to treat symptomatic DPN
Class
Examples
Typical doses*
Tricyclic drugs
Amitriptyline
10–75 mg at bedtime
Nortriptyline
25–75 mg at bedtime
Imipramine
25–75 mg at bedtime
Anticonvulsants
Gabapentin
300–1,200 mg t.i.d.
Carbamazepine
200–400 mg t.i.d.
Pregabalin†
100 mg t.i.d.
5-Hydroxytryptamine and norepinephrine uptake inhibitor
Duloxetine†
60–120 mg daily fs
Substance P inhibitor
Capsaicin cream
0.025–0.075% applied t.i.d.-q.i.d.
*Dose response may vary; initial doses need to be low and titrated up.
†Has FDA indication for treatment of painful diabetic neuropathy.
b. Diabetic autonomic neuropathy.
Gastroparesis symptoms may improve with dietary changes and prokinetic agents such
as metoclopramide or erythromycin. Treatments for erectile dysfunction may include
phosphodiesterase type 5 inhibitors, intracorporeal or intraurethral prostaglandins,
vacuum devices, or penile prostheses. Interventions for other manifestations of autonomic
neuropathy are described in the ADA statement on neuropathy (306). As with DPN treatments,
these interventions do not change the underlying pathology and natural history of
the disease process but may have a positive impact on the quality of life of the patient.
E. Foot care
Recommendations
For all patients with diabetes, perform an annual comprehensive foot examination to
identify risk factors predictive of ulcers and amputations. The foot examination should
include inspection, assessment of foot pulses, and testing for loss of protective
sensation (LOPS) (10-g monofilament plus testing any one of: vibration using 128-Hz
tuning fork, pinprick sensation, ankle reflexes, or vibration perception threshold).
(B)
Provide general foot self-care education to all patients with diabetes. (B)
A multidisciplinary approach is recommended for individuals with foot ulcers and high-risk
feet, especially those with a history of prior ulcer or amputation. (B)
Refer patients who smoke, have LOPS and structural abnormalities, or have history
of prior lower-extremity complications to foot care specialists for ongoing preventive
care and life-long surveillance. (C)
Initial screening for peripheral arterial disease (PAD) should include a history for
claudication and an assessment of the pedal pulses. Consider obtaining an ankle-brachial
index (ABI), as many patients with PAD are asymptomatic. (C)
Refer patients with significant claudication or a positive ABI for further vascular
assessment and consider exercise, medications, and surgical options. (C)
Amputation and foot ulceration, consequences of diabetic neuropathy and/or PAD, are
common and major causes of morbidity and disability in people with diabetes. Early
recognition and management of risk factors can prevent or delay adverse outcomes.
The risk of ulcers or amputations is increased in people who have the following risk
factors:
previous amputation
past foot ulcer history
peripheral neuropathy
foot deformity
peripheral vascular disease
visual impairment
diabetic nephropathy (especially patients on dialysis)
poor glycemic control
cigarette smoking
Many studies have been published proposing a range of tests that might usefully identify
patients at risk of foot ulceration, creating confusion among practitioners as to
which screening tests should be adopted in clinical practice. An ADA task force was
therefore assembled in 2008 to concisely summarize recent literature in this area
and recommend what should be included in the comprehensive foot exam for adult patients
with diabetes. Their recommendations are summarized below, but clinicians should refer
to the task force report (308) for further details and practical descriptions of how
to perform components of the comprehensive foot examination.
At least annually, all adults with diabetes should undergo a comprehensive foot examination
to identify high-risk conditions. Clinicians should ask about history of previous
foot ulceration or amputation, neuropathic or peripheral vascular symptoms, impaired
vision, tobacco use, and foot care practices. A general inspection of skin integrity
and musculoskeletal deformities should be done in a well-lit room. Vascular assessment
would include inspection and assessment of pedal pulses.
The neurologic exam recommended is designed to identify LOPS rather than early neuropathy.
The clinical examination to identify LOPS is simple and requires no expensive equipment.
Five simple clinical tests (use of a 10-g monofilament, vibration testing using a
128-Hz tuning fork, tests of pinprick sensation, ankle reflex assessment, and testing
vibration perception threshold with a biothesiometer), each with evidence from well-conducted
prospective clinical cohort studies, are considered useful in the diagnosis of LOPS
in the diabetic foot. The task force agrees that any of the five tests listed could
be used by clinicians to identify LOPS, although ideally two of these should be regularly
performed during the screening exam—normally the 10-g monofilament and one other test.
One or more abnormal tests would suggest LOPS, while at least two normal tests (and
no abnormal test) would rule out LOPS. The last test listed, vibration assessment
using a biothesiometer or similar instrument, is widely used in the U.S.; however,
identification of the patient with LOPS can easily be carried out without this or
other expensive equipment.
Initial screening for PAD should include a history for claudication and an assessment
of the pedal pulses. A diagnostic ABI should be performed in any patient with symptoms
of PAD. Due to the high estimated prevalence of PAD in patients with diabetes and
the fact that many patients with PAD are asymptomatic, an ADA consensus statement
on PAD (309) suggested that a screening of ABI be performed in patients over 50 years
of age and considered in patients under 50 years of age who have other PAD risk factors
(e.g., smoking, hypertension, hyperlipidemia, or duration of diabetes >10 years).
Refer patients with significant symptoms or a positive ABI for further vascular assessment
and consider exercise, medications, and surgical options (309).
Patients with diabetes and high-risk foot conditions should be educated regarding
their risk factors and appropriate management. Patients at risk should understand
the implications of the LOPS, the importance of foot monitoring on a daily basis,
the proper care of the foot including nail and skin care, and the selection of appropriate
footwear. Patients with LOPS should be educated on ways to substitute other sensory
modalities (hand palpation, visual inspection) for surveillance of early foot problems.
Patients' understanding of these issues and their physical ability to conduct proper
foot surveillance and care should be assessed. Patients with visual difficulties,
physical constraints preventing movement, or cognitive problems that impair their
ability to assess the condition of the foot and to institute appropriate responses
will need other people, such as family members, to assist in their care.
People with neuropathy or evidence of increased plantar pressure (e.g., erythema,
warmth, callus, or measured pressure) may be adequately managed with well-fitted walking
shoes or athletic shoes that cushion the feet and redistribute pressure. Callus can
be debrided with a scalpel by a foot care specialist or other health professional
with experience and training in foot care. People with bony deformities (e.g., hammertoes,
prominent metatarsal heads, or bunions) may need extra-wide or -depth shoes. People
with extreme bony deformities (e.g., Charcot foot) who cannot be accommodated with
commercial therapeutic footwear may need custom-molded shoes.
Foot ulcers and wound care may require care by a podiatrist, orthopedic or vascular
surgeon, or rehabilitation specialist experienced in the management of individuals
with diabetes. For a complete discussion, see the ADA consensus statement on diabetic
foot wound care (310).
VII. DIABETES CARE IN SPECIFIC POPULATIONS
A. Children and adolescents
1. Type 1 diabetes
Three-quarters of all cases of type 1 diabetes are diagnosed in individuals <18 years
of age. Because children are not simply “small adults,” it is appropriate to consider
the unique aspects of care and management of children and adolescents with type 1
diabetes. Children with diabetes differ from adults in many respects, including changes
in insulin sensitivity related to sexual maturity and physical growth, ability to
provide self-care, supervision in child care and school, and unique neurologic vulnerability
to hypoglycemia and DKA. Attention to such issues as family dynamics, developmental
stages, and physiologic differences related to sexual maturity are all essential in
developing and implementing an optimal diabetes regimen. Although recommendations
for children and adolescents are less likely to be based on clinical trial evidence,
because of current and historical restraints placed on conducting research in children,
expert opinion and a review of available and relevant experimental data are summarized
in the ADA statement on care of children and adolescents with type 1 diabetes (311).
Ideally, the care of a child or adolescent with type 1 diabetes should be provided
by a multidisciplinary team of specialists trained in the care of children with pediatric
diabetes. At the very least, education of the child and family should be provided
by health care providers trained and experienced in childhood diabetes and sensitive
to the challenges posed by diabetes in this age-group. At the time of initial diagnosis,
it is essential that diabetes education be provided in a timely fashion, with the
expectation that the balance between adult supervision and self-care should be defined
by, and will evolve according to, physical, psychological, and emotional maturity.
MNT should be provided at diagnosis, and at least annually thereafter, by an individual
experienced with the nutritional needs of the growing child and the behavioral issues
that have an impact on adolescent diets, including risk for disordered eating.
a. Glycemic control
Recommendations
Consider age when setting glycemic goals in children and adolescents with type 1 diabetes,
with less stringent goals for younger children. (E)
While current standards for diabetes management reflect the need to maintain glucose
control as near to normal as safely possible, special consideration must be given
to the unique risks of hypoglycemia in young children. Glycemic goals need to be modified
to take into account the fact that most children <6 or 7 years of age have a form
of “hypoglycemic unawareness.” Their counterregulatory mechanisms are immature and
they may lack the cognitive capacity to recognize and respond to hypoglycemic symptoms,
placing them at greater risk for severe hypoglycemia and its sequelae. In addition,
and unlike the case in adults, young children under the age of 5 years are at risk
for permanent cognitive impairment after episodes of severe hypoglycemia (312
–314). Extensive evidence indicates that near normalization of blood glucose levels
is seldom attainable in children and adolescents after the honeymoon (remission) period.
The A1C level achieved in the “intensive” adolescent cohort of the DCCT group was
>1% higher than that achieved by adult DCCT subjects and above current ADA recommendations
for patients in general. However, the increased frequency of use of basal bolus regimens
(including insulin pumps) in youth from infancy through adolescence has been associated
with more children reaching ADA blood glucose targets (315,316) in those families
in which both parents and the child with diabetes are motivated to perform the required
diabetes-related tasks.
In selecting glycemic goals, the benefits on long-term health outcomes of achieving
a lower A1C must be weighed against the unique risks of hypoglycemia and the difficulties
achieving near-normoglycemia in children and youth. Age-specific glycemic and A1C
goals are presented in Table 17.
Table 17
Plasma blood glucose and A1C goals for type 1 diabetes by age-group
Values by age (years)
Plasma blood glucose goal range (mg/dl)
A1C
Rationale
Before meals
Bedtime/overnight
Toddlers and preschoolers (0–6)
100–180
110–200
<8.5% (but >7.5%)
High risk and vulnerability to hypoglycemia
School age (6–12)
90–180
100–180
<8%
Risks of hypoglycemia and relatively low risk of complications prior to puberty
Adolescents and young adults (13–19)
90–130
90–150
<7.5%
Risk of severe hypoglycemia
Developmental and psychological issues
A lower goal (<7.0%) is reasonable if it can be achieved without excessive hypoglycemia
Key concepts in setting glycemic goals:
Goals should be individualized and lower goals may be reasonable based on benefit-risk
assessment.
Blood glucose goals should be higher than those listed above in children with frequent
hypoglycemia or hypoglycemia unawareness.
Postprandial blood glucose values should be measured when there is a discrepancy between
pre-prandial blood glucose values and A1C levels and to help assess glycemia in those
on basal/bolus regimens.
b. Screening and management of chronic complications in children and adolescents with
type 1 diabetes
i. Nephropathy
Recommendations
Annual screening for microalbuminuria, with a random spot urine sample for microalbumin-to-creatinine
ratio, should be initiated once the child is 10 years of age and has had diabetes
for 5 years. (E)
Confirmed, persistently elevated microalbumin levels on two additional urine specimens
should be treated with an ACE inhibitor, titrated to normalization of microalbumin
excretion if possible. (E)
ii. Hypertension
Recommendations
Treatment of high-normal blood pressure (systolic or diastolic blood pressure consistently
above the 90th percentile for age, sex, and height) should include dietary intervention
and exercise aimed at weight control and increased physical activity, if appropriate.
If target blood pressure is not reached with 3–6 months of lifestyle intervention,
pharmacologic treatment should be initiated. (E)
Pharmacologic treatment of hypertension (systolic or diastolic blood pressure consistently
above the 95th percentile for age, sex, and height or consistently >130/80 mmHg, if
95% exceeds that value) should be initiated as soon as the diagnosis is confirmed.
(E)
ACE inhibitors should be considered for the initial treatment of hypertension. (E)
The goal of treatment is a blood pressure consistently <130/80 or below the 90th percentile
for age, sex, and height, whichever is lower. (E)
Hypertension in childhood is defined as an average systolic or diastolic blood pressure
95th percentile for age, sex, and height percentile measured on at least three separate
days. “High-normal” blood pressure is defined as an average systolic or diastolic
blood pressure ≥90th but <95th percentile for age, sex, and height percentile measured
on at least 3 separate days. Normal blood pressure levels for age, sex, and height
and appropriate methods for determinations are available online at www.nhlbi.nih.gov/health/prof/heart/hbp/hbp_ped.pdf.
iii. Dyslipidemia
Recommendations
Screening
If there is a family history of hypercholesterolemia (total cholesterol >240 mg/dl)
or a cardiovascular event before age 55 years, or if family history is unknown, then
a fasting lipid profile should be performed on children >2 years of age soon after
diagnosis (after glucose control has been established). If family history is not of
concern, then the first lipid screening should be performed at puberty (≥10 years).
All children diagnosed with diabetes at or after puberty should have a fasting lipid
profile performed soon after diagnosis (after glucose control has been established).
(E)
For both age-groups, if lipids are abnormal, annual monitoring is recommended. If
LDL cholesterol values are within the accepted risk levels (<100 mg/dl [2.6 mmol/l]),
a lipid profile should be repeated every 5 years. (E)
Treatment
Initial therapy should consist of optimization of glucose control and MNT using a
Step II AHA diet aimed at a decrease in the amount of saturated fat in the diet. (E)
After the age of 10 years, the addition of a statin is recommended in patients who,
after MNT and lifestyle changes, have LDL cholesterol >160 mg/dl (4.1 mmol/l) or LDL
cholesterol >130 mg/dl (3.4 mmol/l) and one or more CVD risk factors. (E)
The goal of therapy is an LDL cholesterol value <100 mg/dl (2.6 mmol/l). (E)
People diagnosed with type 1 diabetes in childhood have a high risk of early subclinical
(317
–319) and clinical (320) CVD. Although intervention data are lacking, the AHA categorizes
type 1 diabetic children in the highest tier for cardiovascular risk and recommends
both lifestyle and pharmacologic treatment for those with elevated LDL cholesterol
levels (321,322). Initial therapy should be with a Step II AHA diet, which restricts
saturated fat to 7% of total calories and restricts dietary cholesterol to 200 mg
per day. Data from randomized clinical trials in children as young as 7 months of
age indicate that this diet is safe and does not interfere with normal growth and
development (323,324).
For children over the age of 10 years with persistent elevation of LDL cholesterol
despite lifestyle therapy, statins should be considered. Neither long-term safety
nor cardiovascular outcome efficacy has been established for children. However, recent
studies have shown short-term safety equivalent to that seen in adults and efficacy
in lowering LDL cholesterol levels, improving endothelial function, and causing regression
of carotid intimal thickening (325
–327). No statin is approved for use under the age of 10 years, and statin treatment
should generally not be used in type 1 diabetic children prior to this age.
iv. Retinopathy
Recommendations
The first ophthalmologic examination should be obtained once the child is 10 years
of age and has had diabetes for 3–5 years. (E)
After the initial examination, annual routine follow-up is generally recommended.
Less frequent examinations may be acceptable on the advice of an eye care professional.
(E)
Although retinopathy most commonly occurs after the onset of puberty and after 5–10
years of diabetes duration, it has been reported in prepubertal children and with
diabetes duration of only 1–2 years. Referrals should be made to eye care professionals
with expertise in diabetic retinopathy, an understanding of the risk for retinopathy
in the pediatric population, and experience in counseling the pediatric patient and
family on the importance of early prevention/inter- vention.
v. Celiac disease
Recommendations
Children with type 1 diabetes should be screened for celiac disease by measuring tissue
transglutaminase or anti-endomysial antibodies, with documentation of normal serum
IgA levels, soon after the diagnosis of diabetes. (E)
Testing should be repeated if growth failure, failure to gain weight, weight loss,
or gastroenterologic symptoms occur. (E)
Consideration should be given to periodic rescreening of asymptomatic individuals.
(E)
Children with positive antibodies should be referred to a gastroenterologist for evaluation.
(E)
Children with confirmed celiac disease should have consultation with a dietitian and
be placed on a gluten-free diet. (E)
Celiac disease is an immune-mediated disorder that occurs with increased frequency
in patients with type 1 diabetes (1–16% of individuals compared with 0.3–1% in the
general population) (328,329). Symptoms of celiac disease include diarrhea, weight
loss or poor weight gain, growth failure, abdominal pain, chronic fatigue, malnutrition
due to malabsorption, other gastrointestinal problems, and unexplained hypoglycemia
or erratic blood glucose concentrations.
vi. Hypothyroidism
Recommendations
Children with type 1 diabetes should be screened for thyroid peroxidase and thyroglobulin
antibodies at diagnosis. (E)
Thyroid-stimulating hormone (TSH) concentrations should be measured after metabolic
control has been established. If normal, they should be rechecked every 1–2 years
or if the patient develops symptoms of thyroid dysfunction, thyromegaly, or an abnormal
growth rate. Free T4 should be measured if TSH is abnormal. (E)
Autoimmune thyroid disease is the most common autoimmune disorder associated with
diabetes, occurring in 17–30% of patients with type 1 diabetes (330). The presence
of thyroid auto-antibodies is predictive of thyroid dysfunction, generally hypothyroidism
and less commonly hyperthyroidism (331). Subclinical hypothyroidism may be associated
with increased risk of symptomatic hypoglycemia (332) and with reduced linear growth
(333). Hyperthyroidism alters glucose metabolism, potentially resulting in deterioration
of metabolic control.
c. Self-management.
No matter how sound the medical regimen, it can only be as good as the ability of
the family and/or individual to implement it. Family involvement in diabetes remains
an important component of optimal diabetes management throughout childhood and into
adolescence. Health care providers who care for children and adolescents therefore
must be capable of evaluating the behavioral, emotional, and psychosocial factors
that interfere with implementation and then must work with the individual and family
to resolve problems that occur and/or to modify goals as appropriate.
d. School and day care.
Since a sizable portion of a child's day is spent in school, close communication with
school or day care personnel is essential for optimal diabetes management, safety,
and maximal academic opportunities. See VIII.B. Diabetes Care in the School and Day
Care Setting, for further discussion.
2. Type 2 diabetes
The incidence of type 2 diabetes in adolescents is increasing, especially in ethnic
minority populations (21). Distinction between type 1 and type 2 diabetes in children
can be difficult, since the prevalence of overweight in children continues to rise
and since autoantigens and ketosis may be present in a substantial number of patients
with features of type 2 diabetes (including obesity and acanthosis nigricans). Such
a distinction at the time of diagnosis is critical because treatment regimens, educational
approaches, and dietary counsel will differ markedly between the two diagnoses.
Type 2 diabetes has a significant incidence of comorbidities already present at the
time of diagnosis (334). It is recommended that blood pressure measurement, a fasting
lipid profile, microalbuminuria assessment, and dilated eye examination be performed
at the time of diagnosis. Thereafter, screening guidelines and treatment recommendations
for hypertension, dyslipidemia, microalbuminuria, and retinopathy in youth with type
2 diabetes are similar to those for youth with type 1 diabetes. Additional problems
that may need to be addressed include polycystic ovary disease and the various comorbidities
associated with pediatric obesity such as sleep apnea, hepatic steatosis, orthopedic
complications, and psychosocial concerns. The ADA consensus statement on this subject
(23) provides guidance on the prevention, screening, and treatment of type 2 diabetes
and its comorbidities in young people.
B. Preconception care
Recommendations
A1C levels should be as close to normal as possible (<7%) in an individual patient
before conception is attempted. (B)
Starting at puberty, preconception counseling should be incorporated in the routine
diabetes clinic visit for all women of child-bearing potential. (C)
Women with diabetes who are contemplating pregnancy should be evaluated and, if indicated,
treated for diabetic retinopathy, nephropathy, neuropathy, and CVD. (E)
Medications used by such women should be evaluated prior to conception because drugs
commonly used to treat diabetes and its complications may be contraindicated or not
recommended in pregnancy, including statins, ACE inhibitors, ARBs, and most noninsulin
therapies. (E)
Major congenital malformations remain the leading cause of mortality and serious morbidity
in infants of mothers with type 1 or type 2 diabetes. Observational studies indicate
that the risk of malformations increases continuously with increasing maternal glycemia
during the first 6–8 weeks of gestation, as defined by first-trimester A1C concentrations.
There is no threshold for A1C values below which risk disappears entirely. However,
malformation rates above the 1–2% background rate of nondiabetic pregnancies appear
to be limited to pregnancies in which first-trimester A1C concentrations are >1% above
the normal range for a nondiabetic pregnant woman.
Preconception care of diabetes appears to reduce the risk of congenital malformations.
Five nonrandomized studies compared rates of major malformations in infants between
women who participated in preconception diabetes care programs and women who initiated
intensive diabetes management after they were already pregnant. The preconception
care programs were multidisciplinary and designed to train patients in diabetes self-management
with diet, intensified insulin therapy, and SMBG. Goals were set to achieve normal
blood glucose concentrations, and >80% of subjects achieved normal A1C concentrations
before they became pregnant (335
–339). In all five studies, the incidence of major congenital malformations in women
who participated in preconception care (range 1.0–1.7% of infants) was much lower
than the incidence in women who did not participate (range 1.4–10.9% of infants).
One limitation of these studies is that participation in preconception care was self-selected
rather than randomized. Thus, it is impossible to be certain that the lower malformation
rates resulted fully from improved diabetes care. Nonetheless, the evidence supports
the concept that malformations can be reduced or prevented by careful management of
diabetes before pregnancy.
Planned pregnancies greatly facilitate preconception diabetes care. Unfortunately,
nearly two-thirds of pregnancies in women with diabetes are unplanned, leading to
a persistent excess of malformations in infants of diabetic mothers. To minimize the
occurrence of these devastating malformations, standard care for all women with diabetes
who have child-bearing potential, beginning at the onset of puberty or at diagnosis,
should include 1) education about the risk of malformations associated with unplanned
pregnancies and poor metabolic control; and 2) use of effective contraception at all
times, unless the patient has good metabolic control and is actively trying to conceive.
Women contemplating pregnancy need to be seen frequently by a multidisciplinary team
experienced in the management of diabetes before and during pregnancy. The goals of
preconception care are to 1) involve and empower the patient in the management of
her diabetes, 2) achieve the lowest A1C test results possible without excessive hypoglycemia,
3) assure effective contraception until stable and acceptable glycemia is achieved,
and 4) identify, evaluate, and treat long-term diabetes complications such as retinopathy,
nephropathy, neuropathy, hypertension, and CHD (76).
Among the drugs commonly used in the treatment of patients with diabetes, a number
may be relatively or absolutely contraindicated during pregnancy. Statins are category
X (contraindicated for use in pregnancy) and should be discontinued before conception,
as should ACE inhibitors (340). ARBs are category C (risk cannot be ruled out) in
the first trimester but category D (positive evidence of risk) in later pregnancy
and should generally be discontinued before pregnancy. Among the oral antidiabetic
agents, metformin and acarbose are classified as category B (no evidence of risk in
humans) and all others as category C. Potential risks and benefits of oral antidiabetic
agents in the preconception period must be carefully weighed, recognizing that data
are insufficient to establish the safety of these agents in pregnancy.
For further discussion of preconception care, see the related ADA consensus statement
(76) and position statement (341) on preexisting diabetes and pregnancy.
C. Older adults
Recommendations
Older adults who are functional, are cognitively intact, and have significant life
expectancy should receive diabetes care using goals developed for younger adults.
(E)
Glycemic goals for older adults not meeting the above criteria may be relaxed using
individual criteria, but hyperglycemia leading to symptoms or risk of acute hyperglycemic
complications should be avoided in all patients. (E)
Other cardiovascular risk factors should be treated in older adults with consideration
of the time frame of benefit and the individual patient. Treatment of hypertension
is indicated in virtually all older adults, and lipid and aspirin therapy may benefit
those with life expectancy at least equal to the time frame of primary or secondary
prevention trials. (E)
Screening for diabetes complications should be individualized in older adults, but
particular attention should be paid to complications that would lead to functional
impairment. (E)
Diabetes is an important health condition for the aging population; at least 20% of
patients over the age of 65 years have diabetes, and this number can be expected to
grow rapidly in the coming decades. Older individuals with diabetes have higher rates
of premature death, functional disability, and coexisting illnesses such as hypertension,
CHD, and stroke than those without diabetes. Older adults with diabetes are also at
greater risk than other older adults for several common geriatric syndromes, such
as polypharmacy, depression, cognitive impairment, urinary incontinence, injurious
falls, and persistent pain.
The American Geriatric Society's guidelines for improving the care of the older person
with diabetes (342) have influenced the following discussion and recommendations.
The care of older adults with diabetes is complicated by their clinical and functional
heterogeneity. Some older individuals developed diabetes years earlier and may have
significant complications; others who are newly diagnosed may have had years of undiagnosed
diabetes with resultant complications or may have few complications from the disease.
Some older adults with diabetes are frail and have other underlying chronic conditions,
substantial diabetes-related comorbidity, or limited physical or cognitive functioning.
Other older individuals with diabetes have little comorbidity and are active. Life
expectancies are highly variable for this population but often longer than clinicians
realize. Providers caring for older adults with diabetes must take this heterogeneity
into consideration when setting and prioritizing treatment goals.
There are few long-term studies in older adults that demonstrate the benefits of intensive
glycemic, blood pressure, and lipid control. Patients who can be expected to live
long enough to reap the benefits of long-term intensive diabetes management and who
are active, have good cognitive function, and are willing should be provided with
the needed education and skills to do so and be treated using the goals for younger
adults with diabetes.
For patients with advanced diabetes complications, life-limiting comorbid illness,
or substantial cognitive or functional impairment, it is reasonable to set less-intensive
glycemic target goals. These patients are less likely to benefit from reducing the
risk of microvascular complications and more likely to suffer serious adverse effects
from hypoglycemia. However, patients with poorly controlled diabetes may be subject
to acute complications of diabetes, including dehydration, poor wound healing, and
hyperglycemic hyperosmolar coma. Glycemic goals at a minimum should avoid these consequences.
Although control of hyperglycemia may be important in older individuals with diabetes,
greater reductions in morbidity and mortality may result from control of other cardiovascular
risk factors rather than from tight glycemic control alone. There is strong evidence
from clinical trials of the value of treating hypertension in the elderly (343,344).
There is less evidence for lipid-lowering and aspirin therapy, although the benefits
of these interventions for primary and secondary prevention are likely to apply to
older adults whose life expectancies equal or exceed the time frames seen in clinical
trials.
Special care is required in prescribing and monitoring pharmacologic therapy in older
adults. Metformin is often contraindicated because of renal insufficiency or significant
heart failure. TZDs can cause fluid retention, which may exacerbate or lead to heart
failure. They are contraindicated in patients with CHF (New York Heart Association
class III and IV), and if used at all should be used very cautiously in those with,
or at risk for, milder degrees of CHF. Sulfonylureas, other insulin secretagogues,
and insulin can cause hypoglycemia. Insulin use requires that patients or caregivers
have good visual and motor skills and cognitive ability. Drugs should be started at
the lowest dose and titrated up gradually until targets are reached or side effects
develop.
Screening for diabetes complications in older adults also should be individualized.
Particular attention should be paid to complications that can develop over short periods
of time and/or that would significantly impair functional status, such as vision and
lower-extremity complications.
D. Cystic fibrosis–related diabetes
Cystic fibrosis-related diabetes (CFRD) is the most common comorbidity in people with
cystic fibrosis, occurring in ∼20% of adolescents and 40–50% of adults. The additional
diagnosis of diabetes in this population is associated with worse nutritional status,
more severe inflammatory lung disease, and greater mortality from respiratory failure.
For reasons that are not well understood, women with CFRD are particularly vulnerable
to excess morbidity and mortality. Insulin insufficiency related to partial fibrotic
destruction of the islet mass is the primary defect in CFRD. Genetically determined
function of the remaining β-cells and insulin resistance associated with infection
and inflammation may also play a role. Encouraging new data suggest that early detection
and aggressive insulin therapy have narrowed the gap in mortality between cystic fibrosis
patients with and without diabetes and have eliminated the sex difference in mortality.
A consensus conference on CFRD was cosponsored in 2009 by ADA, the Cystic Fibrosis
Foundation, and the Lawson Wilkins Pediatric Endocrine Society. Recommendations for
the clinical management of CFRD will be found in the consensus report to be published
in 2010.
VIII. DIABETES CARE IN SPECIFIC SETTINGS
Diabetes care in the hospital
Recommendations
All patients with diabetes admitted to the hospital should have their diabetes clearly
identified in the medical record. (E)
All patients with diabetes should have an order for blood glucose monitoring, with
results available to all members of the health care team. (E)
Goals for blood glucose levels
Critically ill patients: Insulin therapy should be initiated for treatment of persistent
hyperglycemia starting at a threshold of ≤180 mg/dl (10 mmol/l). Once insulin therapy
is started, a glucose range of 140–180 mg/dl (7.8–10 mmol/l) is recommended for the
majority of critically ill patients. (A) These patients require an intravenous insulin
protocol that has demonstrated efficacy and safety in achieving the desired glucose
range without increasing risk for severe hypoglycemia. (E)
Non–critically ill patients: There is no clear evidence for specific blood glucose
goals. If treated with insulin, the premeal blood glucose target should generally
be <140 mg/dl (7.8 mmol/l) with random blood glucose <180 mg/dl (10.0 mmol/l), provided
these targets can be safely achieved. More stringent targets may be appropriate in
stable patients with previous tight glycemic control. Less stringent targets may be
appropriate in those with severe comorbidites. (E)
Scheduled subcutaneous insulin with basal, nutritional, and correction components
is the preferred method for achieving and maintaining glucose control in noncritically
ill patients. (C) Using correction dose or “supplemental” insulin to correct premeal
hyperglycemia in addition to scheduled prandial and basal insulin is recommended.
(E)
Glucose monitoring should be initiated in any patient not known to be diabetic who
receives therapy associated with high risk for hyperglycemia, including high-dose
glucocorticoid therapy, initiation of enteral or parenteral nutrition, or other medications
such as octreotide or immunosuppressive medications. (B) If hyperglycemia is documented
and persistent, treatment is necessary. Such patients should be treated to the same
glycemic goals as patients with known diabetes. (E)
A plan for treating hypoglycemia should be established for each patient. Episodes
of hypoglycemia in the hospital should be tracked. (E)
All patients with diabetes admitted to the hospital should have an A1C obtained if
the result of testing in the previous 2–3 months is not available. (E)
Patients with hyperglycemia in the hospital who do not have a diagnosis of diabetes
should have appropriate plans for follow-up testing and care documented at discharge.
(E)
The subject of diabetes in the hospital is extensively reviewed in an ADA technical
review (345). A recent updated consensus statement by the American Association of
Clinical Endocrinologists (AACE) and the ADA (346) form the basis for the discussion
and guidelines in this section.
The literature on hospitalized patients with hyperglycemia typically describes three
categories:
Medical history of diabetes: diabetes previously diagnosed and acknowledged by the
patient's treating physician.
Unrecognized diabetes: hyperglycemia (fasting blood glucose ≥126 mg/dl or random blood
glucose ≥200 mg/dl) occurring during hospitalization and confirmed as diabetes after
hospitalization by standard diagnostic criteria but unrecognized as diabetes by the
treating physician during hospitalization.
Hospital-related hyperglycemia: hyperglycemia (fasting blood glucose ≥126 mg/dl or
random blood glucose ≥200 mg/dl) occurring during the hospitalization that reverts
to normal after hospital discharge.
The management of hyperglycemia in the hospital has logically been considered secondary
in importance to the condition that prompted admission (345). However, a body of literature
now supports targeted glucose control in the hospital setting for potential improved
clinical outcomes. Hyperglycemia in the hospital may result from stress; decompensation
of type 1, type 2, or other forms of diabetes; and/or may be iatrogenic due to withholding
of antihyperglycemic medications or administration of hyperglycemia-provoking agents
such as glucocorticoids or vasopressors.
People with diabetes are more likely to be hospitalized and to have longer lengths
of stay than those without diabetes. A recent survey estimated that 22% of all hospital
inpatient days were incurred by people with diabetes and that hospital inpatient care
accounted for one-half of the $174 billion total U.S. medical expenditures for this
disease (347). This is due, in part, to the continued expansion of the worldwide epidemic
of type 2 diabetes. In the U.S. alone, there are ∼1.6 million new cases of diabetes
each year with an overall prevalence of 23.6 million people (7.8% of the population,
with one-quarter of cases remaining undiagnosed). An additional 57 million American
adults are at high risk for type 2 diabetes (348). While the costs of illness-related
stress hyperglycemia are not known, they are likely to be significant given the poor
prognosis of such patients (349
–352).
There is substantial observational evidence linking hyperglycemia in hospitalized
patients (with or without diabetes) to poor outcomes. Cohort studies as well as a
few early randomized controlled trials (RCTs) suggested that intensive treatment of
hyperglycemia improved hospital outcomes (345,351,352). Interventions to normalize
glycemia, however, have had inconsistent results. Indeed, recent trials in critically
ill patients have failed to show a significant improvement in mortality with intensive
glycemic control (353,354) or have even shown increased mortality risk (355). Moreover,
these recent RCTs have highlighted the risk of severe hypoglycemia resulting from
such efforts (353
–358).
The largest study to date, NICE-SUGAR, a multicenter, multinational RCT, tested the
effect of tight glycemic control (target 81–108 mg/dl) on outcomes among 6,104 critically
ill participants, the majority of whom (>95%) required mechanical ventilation (355).
Ninety-day mortality was significantly higher in the intensive versus the conventional
group (target 144–180 mg/dl) (78 more deaths; 27.5 vs. 24.9%, P = 0.02) in both surgical
and medical patients. Mortality from cardiovascular causes was more common in the
intensive group (76 more deaths; 41.6 vs. 35.8%; P = 0.02). Severe hypoglycemia was
also more common in the intensively treated group (6.8 vs. 0.5%; P < 0.001). The precise
reason for the increased mortality in the tightly controlled group is unknown. The
results of this study lie in stark contrast to a famous 2001 single-center study that
reported a 42% relative reduction in intensive care unit (ICU) mortality in critically
ill surgical patients treated to a target blood glucose of 80–110 mg/dl. Importantly,
the control group in NICE-SUGAR had reasonably good blood glucose management, maintained
at a mean glucose of 144 mg/dl, only 29 mg/dl above the intensively managed patients.
Accordingly, this study's findings do not disprove the notion that glycemic control
in the ICU is important. However, they do strongly suggest that it is not necessary
to target blood glucose values <140 mg/dl and that a highly stringent target of <110
mg/dl actually may be dangerous.
In a recent meta-analysis of 26 trials (N = 13,567), which included the NICE-SUGAR
data, the pooled relative risk (RR) of death with intensive insulin therapy was 0.93
as compared with conventional therapy (95% CI 0.83–1.04) (358). Approximately half
of these trials reported hypoglycemia, with a pooled RR of intensive therapy of 6.0
(95% CI 4.5–8.0). The specific ICU setting influenced the findings, with patients
in surgical ICUs appearing to benefit from intensive insulin therapy (RR 0.63 [95%
CI 0.44–0.91]), while those in other critical care settings did not (medical ICU:
1.0 [0.78–1.28]; “mixed” ICU: 0.99 [0.86–1.12]). It was concluded that overall, intensive
insulin therapy increased the risk of hypoglycemia but provided no overall benefit
on mortality in the critically ill, although a benefit to patients admitted to the
surgical ICU was suggested.
It is very clear that the management of hyperglycemia in the hospital presents unique
challenges that stem from variations in a patient's nutritional status and level of
consciousness, the practical limitations of intermittent glycemic monitoring, and
the ultimate importance of patient safety. Accordingly, reasonable glucose targets
in the hospital setting are modestly higher than may be routinely advised in patients
with diabetes in the outpatient setting. The following recommendations represent a
synthesis of the evidence base over the past decade and are somewhat less stringent
than prior recommendations of the ADA Standards of Medical Care in Diabetes. For a
comprehensive review of these data, the reader is referred to the latest consensus
statement from AACE and ADA on inpatient management of hyperglycemia (346).
1. Glycemic targets in hospitalized patients
a. Definition of glucose abnormalities in the hospital setting.
Hyperglycemia has been defined as any blood glucose >140 mg/dl (7.8 mmol/l). Levels
that are significantly and persistently above this may require treatment in hospitalized
patients. In patients without a previous diagnosis of diabetes, elevated blood glucose
may be due to “stress hyperglycemia,” a condition that can be established by a review
of prior records or measurement of an A1C. A1C values >6.5% suggest that diabetes
preceded hospitalization (359). Hypoglycemia has been defined as any blood glucose
<70 mg/dl (3.9 mmol/l). This is the standard definition in outpatients and correlates
with the initial threshold for the release of counterregulatory hormones (177). Severe
hypoglycemia in hospitalized patients has been defined by many as <40 mg/dl (2.2 mmol/l),
although this is lower than the ∼50 mg/dl (2.8 mmol/l) level at which cognitive impairment
begins in normal individuals (177,360,361). As with hyperglycemia, hypoglycemia among
inpatients is also associated with adverse short- and long-term outcomes. Early recognition
and treatment of mild to moderate hypoglycemia (40 and 69 mg/dl [2.2 and 3.8 mmol/l])
can prevent deterioration to a more severe episode with potential adverse sequelae
(361,362).
i. Critically ill patients.
Based on the weight of the available evidence, for the majority of critically ill
patients in the ICU setting, insulin infusion should be used to control hyperglycemia,
with a starting threshold of ≤180 mg/dl (10.0 mmol/l). Once intravenous insulin is
started, the glucose level should be maintained between 140 and 180 mg/dl (7.8 and
10.0 mmol/l). Greater benefit may be realized at the lower end of this range. Although
strong evidence is lacking, somewhat lower glucose targets may be appropriate in selected
patients. However, targets <110 mg/dl (6.1 mmol/l) are not recommended. Use of insulin
infusion protocols with demonstrated safety and efficacy, resulting in low rates of
hypoglycemia, are highly recommended.
ii. Noncritically ill patients.
With no prospective, RCT data to inform specific glycemic targets in noncritically
ill patients, recommendations are based on clinical experience and judgment. For the
majority of noncritically ill patients treated with insulin, premeal glucose targets
should generally be <140 mg/dl (7.8 mmol/l) with random blood glucose <180 mg/dl (10.0
mmol/l), as long as these targets can be safely achieved. To avoid hypoglycemia, consideration
should be given to reassessing the insulin regimen if blood glucose levels fall below
100 mg/dl (5.6 mmol/l). Modification of the regimen is required when blood glucose
values are <70 mg/dl (3.9 mmol/l), unless the event is easily explained by other factors
(such as a missed meal, etc.).
Occasional patients with a prior history of successful tight glycemic control in the
outpatient setting who are clinically stable may be maintained with a glucose range
below the above cut points. Conversely, higher glucose ranges may be acceptable in
terminally ill patients or in patients with severe comorbidities, as well as in those
in patient-care settings where frequent glucose monitoring or close nursing supervision
is not feasible.
Clinical judgment, combined with ongoing assessment of the patient's clinical status,
including changes in the trajectory of glucose measures, severity of illness, nutritional
status, or concurrent use of medications that might affect glucose levels (e.g., steroids,
octreotide) must be incorporated into the day-to-day decisions regarding insulin dosing
(363).
2. Treatment options in hospitalized patients
In the hospital setting, insulin therapy is the preferred method of glycemic control
in majority of clinical situations (346). In the ICU, intravenous infusion is the
preferred route of insulin administration. Outside of critical care units, subcutaneous
insulin is used much more frequently. Oral agents have a limited role in the inpatient
setting.
a. Intravenous insulin infusions.
In the critical care setting, continuous intravenous insulin infusion has been shown
to be the most effective method for achieving specific glycemic targets (346). Because
of the very short half-life of circulating insulin, intravenous delivery allows rapid
dosing adjustments to address alterations in patients' status.
Intravenous insulin is ideally administered via validated written or computerized
protocols that allow for predefined adjustments to the insulin infusion rate according
to glycemic fluctuations and insulin dose. An extensive review of the merits and deficiencies
of published protocols is beyond the intent of this statement, and the reader is referred
to several available reports and reviews (364
–366). Continued education of staff with periodic ongoing review of patient data are
critical for successful implementation of any insulin protocol (364
–366).
Patients who receive intravenous insulin infusion will usually require transition
to subcutaneous insulin when they begin eating regular meals or are transferred to
lower intensity care. Typically, a percentage (usually 75–80%) of the total daily
intravenous infusion dose is proportionately divided into basal and prandial components
(see below). Importantly, subcutaneous insulin must be given 1–4 h prior to discontinuation
of intravenous insulin to prevent hyperglycemia (367).
b. Subcutaneous insulin.
Scheduled subcutaneous insulin is the preferred method for achieving and maintaining
glucose control in non-ICU patients with diabetes or stress hyperglycemia. The recommended
components of inpatient subcutaneous insulin regimens include a basal, nutritional,
and supplemental (correction) component (345,346,368). Each component can be met by
one of several available insulin products, depending on the particular hospital situation.
The reader is referred to several recent publications and reviews that describe currently
available insulin preparations and protocols (366
–370).
A topic that deserves particular attention is the persistent overuse of what has been
branded as sliding scale insulin (SSI) for management of hyperglycemia. The term “correction
insulin,” which refers to the use of additional short or rapid-acting insulin with
scheduled insulin doses to treat blood glucose above desired targets, is preferred
(345). Prolonged therapy with SSI as the sole regimen is ineffective in the majority
of patients (and potentially dangerous in type 1 diabetes) (370
–375).
c. Noninsulin agents.
These agents are inappropriate in the majority of hospitalized patients because they
are less titratable than insulin in the short tem and are meant to be used in patients
eating on a regular meal schedule. Continuation of these agents may be appropriate
in selected stable patients who are expected to consume meals at regular intervals.
Specific caution is required with metformin, due to the possibility that a contraindication
may develop during the hospitalization, such as renal insufficiency, unstable hemodynamic
status, or need for an imaging study that requires a radio-contrast dye (345,376).
Injectable noninsulin therapies such as exenatide and pramlintide have limitations
similar to those of oral agents in the hospital setting.
d. Specific clinical situations
i. Insulin pumps.
Patients who use CSII pump therapy in the outpatient setting can be candidates for
diabetes self-management in the hospital, provided that they have the mental and physical
capacity to do so (346,368). It is important that nursing personnel document basal
rates and bolus doses on a regular basis (at least daily). The availability of hospital
personnel with expertise in CSII therapy is essential.
ii. Enteral nutrition.
Hyperglycemia is a common side effect of inpatient enteral nutrition therapy (377).
A recent report using a combination of basal insulin with correction insulin achieved
a mean glucose value of 160 mg/dl (8.9 mmol/l). Similar results were achieved in the
group randomized to receive SSI alone; however, 48% of patients required the addition
of intermediate-acting insulin to achieve glycemic targets (373).
iii. Parenteral nutrition.
The high glucose load in standard parenteral nutrition frequently results in hyperglycemia,
which is associated with a higher incidence of complications and mortality in critically
ill ICU patients (378). Insulin therapy is highly recommended, with glucose targets
as defined previously by severity of illness.
iv. Glucocorticoid therapy.
Hyperglycemia is a common complication of corticosteroid therapy (363). Several approaches
have been proposed for treatment of this condition, but there are no published protocols
or studies that investigate the efficacy of these approaches. A reasonable approach
is to institute glucose monitoring for at least 48 h in all patients receiving high
dose glucocorticoid therapy and initiate insulin as appropriate. In patients who are
already being treated for hyperglycemia, early adjustment of insulin doses is recommended.
Importantly, during steroid tapers, insulin dosing should be proactively adjusted
to avoid hypoglycemia.
v. Hypoglycemia prevention.
Hypoglycemia, especially in insulin-treated patients, is the leading limiting factor
in the glycemic management of type 1 and type 2 diabetes (174). In the hospital, multiple
additional risk factors for hypoglycemia are present, even among patients who are
neither “brittle” nor tightly controlled. Patients with or without diabetes may experience
hypoglycemia in the hospital in association with altered nutritional state, heart
failure, renal or liver disease, malignancy, infection, or sepsis (379,379,380). Additional
triggering events leading to iatrogenic hypoglycemia include sudden reduction of corticosteroid
dose, altered ability of the patient to self-report symptoms, reduction of oral intake,
emesis, new NPO status, inappropriate timing of short- or rapid-acting insulin in
relation to meals, reduction of rate of administration of intravenous dextrose, and
unexpected interruption of enteral feedings or parenteral nutrition.
Despite the preventable nature of many inpatient episodes of hypoglycemia, institutions
are more likely to have nursing protocols for the treatment of hypoglycemia than for
its prevention. Tracking such episodes and analyzing their causes are important quality
improvement activities.
3. Diabetes care providers in the hospital
Inpatient diabetes management may be effectively provided by primary care physicians,
endocrinologists, or hospitalists. Involvement of appropriately trained specialists
or specialty teams may reduce length of stay, improve glycemic control, and improve
outcomes (381
–384). In the care of diabetes, implementation of standardized order sets for scheduled
and correction-dose insulin may reduce reliance on sliding-scale management. A team
approach is needed to establish hospital pathways. To achieve glycemic targets associated
with improved hospital outcomes, hospitals will need multidisciplinary support to
develop protocols for subcutaneous insulin therapy that effectively and safely achieve
glycemic targets (385).
4. Self-management in the hospital
Self-management of diabetes in the hospital may be appropriate for competent adult
patients who have a stable level of consciousness, have reasonably stable daily insulin
requirements, successfully conduct self-management of diabetes at home, have physical
skills needed to successfully self-administer insulin and perform SMBG, have adequate
oral intake, and are proficient in carbohydrate counting, use of multiple daily insulin
injections, or insulin pump therapy and sick-day management. The patient and physician,
in consultation with nursing staff, must agree that patient self-management is appropriate
under the conditions of hospitalization. For patients conducting self-management in
the hospital, it is imperative that basal, prandial, and correction doses of insulin
and results of bedside glucose monitoring be recorded as part of the patient's hospital
medical record. While many institutions allow patients on insulin pumps to continue
these devices in the hospital, others express concern regarding use of a device unfamiliar
to staff, particularly in patients who are not able to manage their own pump therapy.
If a patient is too ill to self-manage either multiple daily injections or CSII, then
appropriate subcutaneous doses can be calculated on the basis of their basal and bolus
insulin needs during hospitalization, with adjustments for changes in nutritional
or metabolic status.
5. DSME in the hospital
Teaching diabetes self-management to patients in hospitals is a challenging task.
Patients are ill, under increased stress related to their hospitalization and diagnosis,
and in an environment not conducive to learning. Ideally, people with diabetes should
be taught at a time and place conducive to learning—as an outpatient in a recognized
program of diabetes education.
For the hospitalized patient, diabetes “survival skills” education is generally a
feasible approach. Patients and/or family members receive sufficient information and
training to enable safe care at home. Those newly diagnosed with diabetes or who are
new to insulin and/or blood glucose monitoring need to be instructed before discharge.
Those patients hospitalized because of a crisis related to diabetes management or
poor care at home need education to prevent subsequent episodes of hospitalization.
An assessment of the need for a home health referral or referral to an outpatient
diabetes education program should be part of discharge planning for all patients.
6. MNT in the hospital
Hospital diets continue to be ordered by calorie levels based on the “ADA diet.” However,
since 1994 the ADA has not endorsed any single meal plan or specified percentages
of macronutrients, and the term “ADA diet” should no longer be used. Current nutrition
recommendations advise individualization based on treatment goals, physiologic parameters,
and medication usage. Because of the complexity of nutrition issues in the hospital,
a registered dietitian, knowledgeable and skilled in MNT, should serve as an inpatient
team member. The dietitian is responsible for integrating information about the patient's
clinical condition, eating, and lifestyle habits and for establishing treatment goals
in order to determine a realistic plan for nutrition therapy (386,387).
7. Bedside blood glucose monitoring
Bedside blood glucose monitoring using point-of-care glucose meters is performed before
meals and bedtime in the majority of inpatients who are eating usual meals. In patients
who are receiving continuous enteral or parenteral nutrition, glucose monitoring is
optimally performed every 4–6 h. In patients who are receiving cycled enteral or parenteral
nutrition, the schedule for glucose monitoring can be individualized but should be
frequent enough to detect hyperglycemia during feedings and risk of hypoglycemia when
feedings are interrupted (374,376). More frequent blood glucose testing ranging from
every 30 min to every 2 h is required for patients on intravenous insulin infusions.
Safe and rational glycemic management relies on the accuracy of blood glucose measurements
using point-of-care blood glucose meters, which have several important limitations.
Although the FDA allows a ±20% error for glucose meters, questions about the appropriateness
of this criterion have been raised (388). Glucose measures differ significantly between
plasma and whole blood, terms which are often used interchangeably and can lead to
misinterpretation. Most commercially available capillary glucose meters introduce
a correction factor of ∼1.12 to report a “plasma-adjusted” value (389).
Significant discrepancies between capillary, venous, and arterial plasma samples have
been observed in patients with low or high hemoglobin concentrations, hypoperfusion,
and the presence of interfering substances (389,390). Analytical variability has been
described with several point-of-care meters (391). Any glucose result that does not
correlate with the patient's status should be confirmed through conventional laboratory
sampling of PG.
While laboratory measurement of PG has less variability and interference, multiple
daily phlebotomies are not practical. The use of indwelling lines as the sampling
source also poses risks for infection. Studies performed using continuous interstitial
glucose monitoring systems in the critical care setting (392) currently are limited
by the lack of reliability in the hypoglycemic range as well as by cost.
8. Discharge planning
It is important to anticipate the postdischarge antihyperglycemic regimen in all patients
with diabetes or newly discovered hyperglycemia. The optimal program will need to
consider the type and severity of diabetes, the effects of the patient's illness on
blood glucose levels, and the capacities and desires of the patient. Smooth transition
to outpatient care should be ensured, especially in those new to insulin therapy or
in whom the diabetes regimen has been substantially altered during the hospitalization.
All patients in whom the diagnosis of diabetes is new should have, at minimum, “survival
skills” training prior to discharge.
It is recommended that the following areas be reviewed and addressed prior to hospital
discharge:
level of understanding related to the diagnosis of diabetes
SMBG and explanation of home blood glucose goals
definition, recognition, treatment, and prevention of hyperglycemia and hypoglycemia
identification of health care provider who will provide diabetes care after discharge
information on consistent eating patterns
when and how to take blood glucose–lowering medications including insulin administration
(if going home on insulin)
sick-day management
proper use and disposal of needles and syringes
More expanded diabetes education can be arranged in the community. An outpatient follow-up
visit with the primary care provider, endocrinologist, or diabetes educator within
1 month of discharge is advised for all patients having hyperglycemia in the hospital.
Clear communication with outpatient providers either directly or via hospital discharge
summaries facilitates safe transitions to outpatient care. Providing information regarding
the cause or the plan for determining the cause of hyperglycemia, related complications
and comorbidities, and recommended treatments can assist outpatient providers as they
assume ongoing care.
IX. STRATEGIES FOR IMPROVING DIABETES CARE
The implementation of the standards of care for diabetes has been suboptimal in most
clinical settings. A recent report (393) indicated that only 57.1% of adults with
diagnosed diabetes achieved an A1C of <7%, only 45.5% had a blood pressure <130/80
mmHg, and just 46.5% had a total cholesterol <200 mg/dl. Most distressing was that
only 12.2% of people with diabetes achieved all three treatment goals.
While numerous interventions to improve adherence to the recommended standards have
been implemented, the challenge of providing uniformly effective diabetes care has
thus far defied a simple solution. A major contributor to suboptimal care is a delivery
system that too often is fragmented, lacks clinical information capabilities, often
duplicates services, and is poorly designed for the delivery of chronic care. The
chronic care model (CCM) includes five core elements for the provision of optimal
care of patients with chronic disease: delivery system design, self-management support,
decision support, clinical information systems, and community resources and policies.
Redefinition of the roles of the clinic staff and promoting self-management on the
part of the patient are fundamental to the successful implementation of the CCM (394).
Collaborative, multidisciplinary teams are best suited to provide such care for people
with chronic conditions like diabetes and to empower patients' performance of appropriate
self-management. Alterations in reimbursement that reward the provision of quality
care, as defined by the attainment of quality measures developed by such programs
as the ADA/National Committee for Quality Assurance Diabetes Provider Recognition
Program, will also be required to achieve desired outcome goals.
In recent years, numerous health care organizations, ranging from large health care
systems such as the U.S. Veteran's Administration to small private practices, have
implemented strategies to improve diabetes care. Successful programs have published
results showing improvement in process measures such as measurement of A1C, lipids,
and blood pressure. Effects on in important intermediate outcomes, such as mean A1C
for populations, have been more difficult to demonstrate (395
–397), although examples do exist (398
–402), often taking more than 1 year to manifest (394). Features of successful programs
reported in the literature include
Delivery of DSME: increases adherence to standard of care and educating patients on
glycemic targets and improves the percentage of patients who reach goal A1C (142,403)
Adoption of practice guidelines, with participation of health care professionals in
the process of development: Guidelines should be readily accessible at the point of
service, preferably as computerized reminders at the point of care. Guidelines should
begin with a summary of their major recommendations instructing health care professionals
what to do and how to do it.
Use of checklists that mirror guidelines: successful at improving adherence to standards
of care
Systems changes: such as provision of automated reminders to health care professionals
and patients and audit and feedback of process and outcome data to providers
Quality improvement programs combining continuous quality improvement or other cycles
of analysis and intervention with provider performance data
Practice changes: such as availability of point of care testing of A1C, scheduling
planned diabetes visits, clustering of dedicated diabetes visits into specific times
within a primary care practice schedule, or group visits and/or visits with multiple
health care professionals on a single day
Tracking systems with either an electronic medical record or patient registry: helpful
at increasing adherence to standards of care by prospectively identifying those requiring
assessments and/or treatment modifications. They likely could have greater efficacy
if they suggested specific therapeutic interventions to be considered for a particular
patient at a particular point in time (404).
Availability of case or (preferably) care management services (405): Nurses, pharmacists,
and other nonphysician health care professionals using detailed algorithms working
under the supervision of physicians have demonstrated the greatest reduction in A1C
and blood pressure (406,407).
Evidence suggests that these individual initiatives work best when provided as components
of a multifactorial intervention. When practices are compared, those that address
more of the CCM elements demonstrate lower A1C levels and lower cardiovascular risk
scores (408). The most successful practices have an institutional priority for quality
of care, involve all of the staff in their initiatives, redesign their delivery system,
activate and educate their patients, and use electronic health record tools (409,410).
NDEP maintains an online resource (www.betterdiabetescare.nih.gov) to help health
care professionals design and implement more effective health care delivery systems
for those with diabetes.
It is clear that optimal diabetes management requires an organized, systematic approach
and involvement of a coordinated team of dedicated health care professionals working
in an environment where quality care is a priority.