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      The Bidirectional Association Between Depression and Severe Hypoglycemic and Hyperglycemic Events in Type 1 Diabetes

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          Abstract

          OBJECTIVE

          Severe hyperglycemia and hypoglycemia (“severe dysglycemia”) are serious complications of type 1 diabetes (T1D). Depression has been associated with severe dysglycemia in type 2 diabetes but has not been thoroughly examined specifically in T1D. We evaluated bidirectional associations between depression and severe dysglycemia among older people with T1D.

          RESEARCH DESIGN AND METHODS

          We abstracted depression and severe dysglycemia requiring emergency room visit or hospitalization from medical health records in 3,742 patients with T1D during the study period (1996–2015). Cox proportional hazards models estimated the associations between depression and severe dysglycemia in both directions, adjusting for demographics, micro- and macrovascular complications, and HbA 1c.

          RESULTS

          During the study period, 41% had depression and 376 (11%) and 641 (20%) had hyperglycemia and hypoglycemia, respectively. Depression was strongly associated with a 2.5-fold increased risk of severe hyperglycemic events (hazard ratio [HR] 2.47 [95% CI 2.00, 3.05]) and 89% increased risk of severe hypoglycemic events (HR 1.89 [95% CI 1.61, 2.22]). The association was strongest within the first 6 months (HR hyperglycemia 7.14 [95% CI 5.29, 9.63]; HR hypoglycemia 5.58 [95% CI 4.46, 6.99]) to 1 year (HR hyperglycemia 5.16 [95% CI 3.88, 6.88]; HR hypoglycemia 4.05 [95% CI 3.26, 5.04]) after depression diagnosis. In models specifying severe dysglycemia as the exposure, hyperglycemic and hypoglycemic events were associated with 143% (HR 2.43 [95% CI 2.03, 2.91]) and 74% (HR 1.75 [95% CI 1.49, 2.05]) increased risk of depression, respectively.

          CONCLUSIONS

          Depression and severe dysglycemia are associated bidirectionally among patients with T1D. Depression greatly increases the risk of severe hypoglycemic and hyperglycemic events, particularly in the first 6 months to 1 year after diagnosis, and depression risk increases after severe dysglycemia episodes.

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          Depression and poor glycemic control: a meta-analytic review of the literature.

          Depression is common among patients with diabetes, but its relationship to glycemic control has not been systematically reviewed. Our objective was to determine whether depression is associated with poor glycemic control. Medline and PsycINFO databases and published reference lists were used to identify studies that measured the association of depression with glycemic control. Meta-analytic procedures were used to convert the findings to a common metric, calculate effect sizes (ESs), and statistically analyze the collective data. A total of 24 studies satisfied the inclusion and exclusion criteria for the meta-analysis. Depression was significantly associated with hyperglycemia (Z = 5.4, P < 0.0001). The standardized ES was in the small-to-moderate range (0.17) and was consistent, as the 95% CI was narrow (0.13-0.21). The ES was similar in studies of either type 1 or type 2 diabetes (ES 0.19 vs. 0.16) and larger when standardized interviews and diagnostic criteria rather than self-report questionnaires were used to assess depression (ES 0.28 vs. 0.15). Depression is associated with hyperglycemia in patients with type 1 or type 2 diabetes. Additional studies are needed to establish the directional nature of this relationship and to determine the effects of depression treatment on glycemic control and the long-term course of diabetes.
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            Ethnic disparities in diabetic complications in an insured population.

            Higher rates of microvascular complications have been reported for minorities. Disparate access to quality health care is a common explanation for ethnic disparities in diabetic complication rates in the US population. Examining an ethnically diverse population with uniform health care coverage may be useful. To assess ethnic disparities in the incidence of diabetic complications within a nonprofit prepaid health care organization. Longitudinal observational study conducted January 1, 1995, through December 31, 1998, at Kaiser Permanente Medical Care Program in northern California. A total of 62 432 diabetic patients, including Asians (12%), blacks (14%), Latinos (10%), and whites (64%). Incident myocardial infarction (MI), stroke, congestive heart failure (CHF), and nontraumatic lower extremity amputation (LEA), defined by primary hospitalization discharge diagnosis, procedures, or underlying cause of death; and end-stage renal disease (ESRD), defined as renal insufficiency requiring renal replacement therapy or transplantation for survival or by underlying cause of death. Patterns of ethnic differences were not consistent across complications and frequently persisted despite adjustment for a wide range of demographic, socioeconomic, behavioral, and clinical factors. Adjusted hazard ratios (relative to that of whites) were 0.56, 0.68, and 0.68 for blacks, Asians, and Latinos, respectively (P<.001), for MI; 0.76 and 0.72 for Asians and Latinos, respectively (P<.01), for stroke; 0.70 and 0.61 for Asians and Latinos, respectively (P<.01), for CHF; 0.40 for Asians (P<.001) for LEA; and 2.03, 1.85, and 1.46 for blacks, Asians, and Latinos, respectively (P<.01), for ESRD. There were no statistically significant black-white differences for stroke, CHF, or LEA and no Latino-white differences for LEA. This study confirms previous reports of elevated incidence of ESRD among ethnic minorities, despite uniform medical care coverage, and provides new evidence that rates of other complications are similar or lower relative to those of whites. The persistence of ethnic disparities after adjustment suggests a possible genetic origin, the contribution of unmeasured environmental factors, or a combination of these factors.
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              Increased Mortality of Patients With Diabetes Reporting Severe Hypoglycemia

              OBJECTIVE Hypoglycemia is a cause of significant morbidity among patients with diabetes and may be associated with greater risk of death. We conducted a retrospective study to determine whether patient self-report of severe hypoglycemia is associated with increased mortality. RESEARCH DESIGN AND METHODS Adult patients (N = 1,020) seen in a specialty diabetes clinic between August 2005 and July 2006 were questioned about frequency of hypoglycemia during a preencounter interview; 7 were lost to follow-up and excluded from analysis. Mild hypoglycemia was defined as symptoms managed without assistance, and severe hypoglycemia was defined as symptoms requiring external assistance. Mortality data, demographics, clinical characteristics, and Charlson comorbidity index (CCI) were obtained from the electronic medical record after 5 years. Patients were stratified by self-report of hypoglycemia at baseline, demographics were compared using the two-sample t test, and risk of death was expressed as odds ratio (95% CI). Associations were controlled for age, sex, diabetes type and duration, CCI, HbA1c, and report of severe hypoglycemia. RESULTS In total, 1,013 patients with type 1 (21.3%) and type 2 (78.7%) diabetes were questioned about hypoglycemia. Among these, 625 (61.7%) reported any hypoglycemia, and 76 (7.5%) reported severe hypoglycemia. After 5 years, patients who reported severe hypoglycemia had 3.4-fold higher mortality (95% CI 1.5–7.4; P = 0.005) compared with those who reported mild/no hypoglycemia. CONCLUSIONS Self-report of severe hypoglycemia is associated with 3.4-fold increased risk of death. Patient-reported outcomes, including patient-reported hypoglycemia, may therefore augment risk stratification and disease management of patients with diabetes.
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                Author and article information

                Journal
                Diabetes Care
                Diabetes Care
                diacare
                dcare
                Diabetes Care
                Diabetes Care
                American Diabetes Association
                0149-5992
                1935-5548
                March 2018
                18 December 2017
                : 41
                : 3
                : 446-452
                Affiliations
                [1] 1Division of Research, Kaiser Permanente, Oakland, CA
                [2] 2Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA
                [3] 3Icahn School of Medicine at Mount Sinai, New York, NY
                [4] 4The Joseph Sagol Neuroscience Center, Sheba Medical Center, Ramat Gan, Israel
                Author notes
                Corresponding author: Paola Gilsanz, paola.gilsanz@ 123456kp.org .
                Author information
                http://orcid.org/0000-0002-7635-381X
                Article
                1566
                10.2337/dc17-1566
                5829958
                29255060
                0092a7f7-3e35-41c6-877d-e9958be03e55
                © 2017 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. More information is available at http://www.diabetesjournals.org/content/license.

                History
                : 28 July 2017
                : 20 November 2017
                Page count
                Figures: 0, Tables: 3, Equations: 0, References: 43, Pages: 7
                Funding
                Funded by: National Institute on Aging, DOI http://dx.doi.org/10.13039/100000049;
                Award ID: R01 AG047500
                Funded by: National Institute on Aging, DOI http://dx.doi.org/10.13039/100000049;
                Award ID: T32 AG049663
                Funded by: National Institute of Diabetes and Digestive and Kidney Diseases, DOI http://dx.doi.org/10.13039/100000062;
                Award ID: R01 DK103721
                Award ID: R01 DK081796
                Funded by: National Institute of Diabetes and Digestive and Kidney Diseases, DOI http://dx.doi.org/10.13039/100000062;
                Award ID: P30 DK092924
                Categories
                0407
                Epidemiology/Health Services Research

                Endocrinology & Diabetes
                Endocrinology & Diabetes

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