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Mortality Trends in Subjects With and Without Diabetes During 33 Years of Follow-up

, MD 1 , 2 , , MD, PHD 2 , 3 , , MD, PHD 2

Diabetes Care

American Diabetes Association

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      Abstract

      OBJECTIVE

      Mortality rates have declined substantially over the past decades in the general population, but the situation among diabetic subjects is less clear. The aim of this study was to analyze mortality trends in diabetic and nondiabetic subjects during 1972–2004.

      RESEARCH DESIGN AND METHODS

      Since 1972, all patients with diabetes are entered in a diabetes register at Laxå Primary Health Care Center; 776 incident cases were recorded up to 2001. The register has been supplemented with a nondiabetic population of 3,880 subjects and with data from the National Cause of Death Register during 1972 to 2004.

      RESULTS

      During the 33-year follow-up period, 233 (62.0%) diabetic women and 240 (60.0%) diabetic men and 995 (52.9%) nondiabetic women and 1,082 (54.1%) nondiabetic men died. The age-adjusted hazard ratio (HR) for all-cause mortality among diabetic and nondiabetic subjects was 1.17 ( P < 0.0021) for all, 1.22 ( P < 0.007) for women, and 1.13 ( P = 0.095) for men. The corresponding cardiovascular disease (CVD) mortality HRs were 1.33 ( P < 0.0001), 1.41 ( P < 0.0003), and 1.27 ( P < 0.0093), respectively. The CVD mortality reduction across time was significant in nondiabetic subjects ( P < 0.0001) and in men with diabetes ( P = 0.014) but not in diabetic women ( P = 0.69). The results regarding coronary heart disease (CHD) were similar ( P < 0.0001, P < 0.006, and P = 0.17, respectively). The CVD and CHD mortality rate change across time was fairly linear in all groups.

      CONCLUSIONS

      Diabetic subjects had less mortality rate reduction during follow-up than nondiabetic subjects. However the excess mortality risk for diabetic subjects was smaller than that found in other studies.

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      Most cited references 26

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      Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group.

       R Turner,  C Fox,  DR Matthews (1998)
      Improved blood-glucose control decreases the progression of diabetic microvascular disease, but the effect on macrovascular complications is unknown. There is concern that sulphonylureas may increase cardiovascular mortality in patients with type 2 diabetes and that high insulin concentrations may enhance atheroma formation. We compared the effects of intensive blood-glucose control with either sulphonylurea or insulin and conventional treatment on the risk of microvascular and macrovascular complications in patients with type 2 diabetes in a randomised controlled trial. 3867 newly diagnosed patients with type 2 diabetes, median age 54 years (IQR 48-60 years), who after 3 months' diet treatment had a mean of two fasting plasma glucose (FPG) concentrations of 6.1-15.0 mmol/L were randomly assigned intensive policy with a sulphonylurea (chlorpropamide, glibenclamide, or glipizide) or with insulin, or conventional policy with diet. The aim in the intensive group was FPG less than 6 mmol/L. In the conventional group, the aim was the best achievable FPG with diet alone; drugs were added only if there were hyperglycaemic symptoms or FPG greater than 15 mmol/L. Three aggregate endpoints were used to assess differences between conventional and intensive treatment: any diabetes-related endpoint (sudden death, death from hyperglycaemia or hypoglycaemia, fatal or non-fatal myocardial infarction, angina, heart failure, stroke, renal failure, amputation [of at least one digit], vitreous haemorrhage, retinopathy requiring photocoagulation, blindness in one eye, or cataract extraction); diabetes-related death (death from myocardial infarction, stroke, peripheral vascular disease, renal disease, hyperglycaemia or hypoglycaemia, and sudden death); all-cause mortality. Single clinical endpoints and surrogate subclinical endpoints were also assessed. All analyses were by intention to treat and frequency of hypoglycaemia was also analysed by actual therapy. Over 10 years, haemoglobin A1c (HbA1c) was 7.0% (6.2-8.2) in the intensive group compared with 7.9% (6.9-8.8) in the conventional group--an 11% reduction. There was no difference in HbA1c among agents in the intensive group. Compared with the conventional group, the risk in the intensive group was 12% lower (95% CI 1-21, p=0.029) for any diabetes-related endpoint; 10% lower (-11 to 27, p=0.34) for any diabetes-related death; and 6% lower (-10 to 20, p=0.44) for all-cause mortality. Most of the risk reduction in the any diabetes-related aggregate endpoint was due to a 25% risk reduction (7-40, p=0.0099) in microvascular endpoints, including the need for retinal photocoagulation. There was no difference for any of the three aggregate endpoints between the three intensive agents (chlorpropamide, glibenclamide, or insulin). Patients in the intensive group had more hypoglycaemic episodes than those in the conventional group on both types of analysis (both p<0.0001). The rates of major hypoglycaemic episodes per year were 0.7% with conventional treatment, 1.0% with chlorpropamide, 1.4% with glibenclamide, and 1.8% with insulin. Weight gain was significantly higher in the intensive group (mean 2.9 kg) than in the conventional group (p<0.001), and patients assigned insulin had a greater gain in weight (4.0 kg) than those assigned chlorpropamide (2.6 kg) or glibenclamide (1.7 kg). Intensive blood-glucose control by either sulphonylureas or insulin substantially decreases the risk of microvascular complications, but not macrovascular disease, in patients with type 2 diabetes.(ABSTRACT TRUNCATED)
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        Effect of a multifactorial intervention on mortality in type 2 diabetes.

        Intensified multifactorial intervention - with tight glucose regulation and the use of renin-angiotensin system blockers, aspirin, and lipid-lowering agents - has been shown to reduce the risk of nonfatal cardiovascular disease among patients with type 2 diabetes mellitus and microalbuminuria. We evaluated whether this approach would have an effect on the rates of death from any cause and from cardiovascular causes. In the Steno-2 Study, we randomly assigned 160 patients with type 2 diabetes and persistent microalbuminuria to receive either intensive therapy or conventional therapy; the mean treatment period was 7.8 years. Patients were subsequently followed observationally for a mean of 5.5 years, until December 31, 2006. The primary end point at 13.3 years of follow-up was the time to death from any cause. Twenty-four patients in the intensive-therapy group died, as compared with 40 in the conventional-therapy group (hazard ratio, 0.54; 95% confidence interval [CI], 0.32 to 0.89; P=0.02). Intensive therapy was associated with a lower risk of death from cardiovascular causes (hazard ratio, 0.43; 95% CI, 0.19 to 0.94; P=0.04) and of cardiovascular events (hazard ratio, 0.41; 95% CI, 0.25 to 0.67; P<0.001). One patient in the intensive-therapy group had progression to end-stage renal disease, as compared with six patients in the conventional-therapy group (P=0.04). Fewer patients in the intensive-therapy group required retinal photocoagulation (relative risk, 0.45; 95% CI, 0.23 to 0.86; P=0.02). Few major side effects were reported. In at-risk patients with type 2 diabetes, intensive intervention with multiple drug combinations and behavior modification had sustained beneficial effects with respect to vascular complications and on rates of death from any cause and from cardiovascular causes. (ClinicalTrials.gov number, NCT00320008.) Copyright 2008 Massachusetts Medical Society.
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          Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. UK Prospective Diabetes Study Group.

          To determine whether tight control of blood pressure prevents macrovascular and microvascular complications in patients with type 2 diabetes. Randomised controlled trial comparing tight control of blood pressure aiming at a blood pressure of <150/85 mm Hg (with the use of an angiotensin converting enzyme inhibitor captopril or a beta blocker atenolol as main treatment) with less tight control aiming at a blood pressure of <180/105 mm Hg. 20 hospital based clinics in England, Scotland, and Northern Ireland. 1148 hypertensive patients with type 2 diabetes (mean age 56, mean blood pressure at entry 160/94 mm Hg); 758 patients were allocated to tight control of blood pressure and 390 patients to less tight control with a median follow up of 8.4 years. Predefined clinical end points, fatal and non-fatal, related to diabetes, deaths related to diabetes, and all cause mortality. Surrogate measures of microvascular disease included urinary albumin excretion and retinal photography. Mean blood pressure during follow up was significantly reduced in the group assigned tight blood pressure control (144/82 mm Hg) compared with the group assigned to less tight control (154/87 mm Hg) (P<0.0001). Reductions in risk in the group assigned to tight control compared with that assigned to less tight control were 24% in diabetes related end points (95% confidence interval 8% to 38%) (P=0.0046), 32% in deaths related to diabetes (6% to 51%) (P=0.019), 44% in strokes (11% to 65%) (P=0.013), and 37% in microvascular end points (11% to 56%) (P=0.0092), predominantly owing to a reduced risk of retinal photocoagulation. There was a non-significant reduction in all cause mortality. After nine years of follow up the group assigned to tight blood pressure control also had a 34% reduction in risk in the proportion of patients with deterioration of retinopathy by two steps (99% confidence interval 11% to 50%) (P=0.0004) and a 47% reduced risk (7% to 70%) (P=0.004) of deterioration in visual acuity by three lines of the early treatment of diabetic retinopathy study (ETDRS) chart. After nine years of follow up 29% of patients in the group assigned to tight control required three or more treatments to lower blood pressure to achieve target blood pressures. Tight blood pressure control in patients with hypertension and type 2 diabetes achieves a clinically important reduction in the risk of deaths related to diabetes, complications related to diabetes, progression of diabetic retinopathy, and deterioration in visual acuity.
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            Author and article information

            Affiliations
            1School of Health and Medical Sciences, Family Medicine Research Centre, Örebro University, Örebro, Sweden;
            2Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology Section, Uppsala University, Uppsala, Sweden;
            3Division of the Regional Supervision Authority, The National Board of Health and Welfare, Örebro, Sweden.
            Author notes
            Corresponding author: Stefan P.O. Jansson, stefan.jansson@ 123456orebroll.se .
            Journal
            Diabetes Care
            diacare
            dcare
            Diabetes Care
            Diabetes Care
            American Diabetes Association
            0149-5992
            1935-5548
            March 2010
            15 December 2009
            : 33
            : 3
            : 551-556
            2827506
            20009100
            0680
            10.2337/dc09-0680
            © 2010 by the American Diabetes Association.

            Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

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            Categories
            Original Research
            Epidemiology/Health Services Research

            Endocrinology & Diabetes

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