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      Mortality in Type 1 Diabetes in the DCCT/EDIC Versus the General Population

      research-article
      The Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) Study Research Group *
      Diabetes Care
      American Diabetes Association

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          Abstract

          OBJECTIVE

          Historically, mortality in type 1 diabetes has exceeded that in the general population. We compared mortality in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study cohort to that of the current general U.S. population.

          RESEARCH DESIGN AND METHODS

          The DCCT (1983–1993) compared intensive versus conventional therapy, with HbA 1c levels of ∼7 vs. 9%, respectively, over an average of 6.5 years of treatment. EDIC is the observational follow-up study of the DCCT (1994 to the present). Vital status was ascertained for 97.5% of the original DCCT cohort ( n = 1,441) after a mean of 27 years follow-up. Expected mortality during DCCT/EDIC was estimated using the current age-, sex-, and race-specific risks in the general U.S. population, and the observed versus expected mortality compared using standardized mortality ratios (SMRs) and Poisson regression models.

          RESULTS

          Mortality in the DCCT intensive therapy group was nonsignificantly lower than that in the general U.S. population (SMR = 0.88 [95% CI 0.67, 1.16]), whereas mortality in the DCCT conventional therapy group was significantly greater than that in the general population (SMR = 1.31 [95% CI 1.05, 1.65]). The SMR increased with increasing mean HbA 1c, and above an HbA 1c of 9%, the rate of increase in SMR among females was greater than that among males.

          CONCLUSIONS

          Overall mortality in the combined DCCT/EDIC cohort was similar to that of the general population but was higher in the DCCT conventional therapy group. Mortality increased significantly with increasing mean HbA 1c, more so among females than males, especially for HbA 1c >9%.

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          Most cited references28

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          Modern-day clinical course of type 1 diabetes mellitus after 30 years' duration: the diabetes control and complications trial/epidemiology of diabetes interventions and complications and Pittsburgh epidemiology of diabetes complications experience (1983-2005).

          Clinical treatment goals of type 1 diabetes mellitus (T1DM) have changed since the Diabetes Control and Complications Trial (DCCT) demonstrated reduced long-term complications with intensive diabetes therapy. There have been few longitudinal studies to describe the clinical course of T1DM in the age of intensive therapy. Our objective was to describe the current-day clinical course of T1DM. An analysis of the cumulative incidence of long-term complications was performed. The DCCT (1983-1993) assigned patients to conventional or intensive therapy. Since 1993, the DCCT has been observational, and intensive therapy was recommended for all patients. The Pittsburgh Epidemiology of Diabetes Complications (EDC) study is an observational study of patients with T1DM from Allegheny County, Pennsylvania. The study population comprised the DCCT T1DM cohort (N = 1441) and a subset of the EDC cohort (n = 161) selected to match DCCT entry criteria. In the DCCT, intensive therapy aimed for a near-normal glycemic level with 3 or more daily insulin injections or an insulin pump. Conventional therapy, with 1 to 2 daily insulin injections, was not designed to achieve specific glycemic targets. Main outcome measures included the incidences of proliferative retinopathy, nephropathy (albumin excretion rate >300 mg/24 h, creatinine level >or=2 mg/dL [to convert to micromoles per liter, multiply by 88.4], or renal replacement), and cardiovascular disease. After 30 years of diabetes, the cumulative incidences of proliferative retinopathy, nephropathy, and cardiovascular disease were 50%, 25%, and 14%, respectively, in the DCCT conventional treatment group, and 47%, 17%, and 14%, respectively, in the EDC cohort. The DCCT intensive therapy group had substantially lower cumulative incidences (21%, 9%, and 9%) and fewer than 1% became blind, required kidney replacement, or had an amputation because of diabetes during that time. The frequencies of serious complications in patients with T1DM, especially when treated intensively, are lower than that reported historically.
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            The 30-year natural history of type 1 diabetes complications: the Pittsburgh Epidemiology of Diabetes Complications Study experience.

            Declining incidences in Europe of overt nephropathy, proliferative retinopathy, and mortality in type 1 diabetes have recently been reported. However, comparable data for the U.S. and trend data for neuropathy and macrovascular complications are lacking. These issues are addressed using the prospective observational Pittsburgh Epidemiology of Childhood-Onset Diabetes Complications Study. Participants were stratified into five cohorts by diagnosis year: 1950-1959, 1960-1964, 1965-1969, 1970-1974, and 1975-1980. Mortality, renal failure, and coronary artery disease (CAD) status were determined on the complete cohort (n = 906) at 20, 25, and 30 years. Overt nephropathy, proliferative retinopathy, and neuropathy were assessed at 20 and 25 years on the subset of participants with a clinical examination. There was a decreasing trend by diagnosis year for mortality, renal failure, and neuropathy across all time intervals (P < 0.05), with the 1950-1959 cohort having a fivefold higher mortality at 25 years than the 1970s' cohorts. Proliferative retinopathy and overt nephropathy showed nonsignificant declines at 20 years (P < 0.16 and P < 0.13, respectively) and no change at 25 years. CAD event rates, which were lower than the other complications, also showed no trend. Although some type 1 diabetes complications (mortality, renal failure, and neuropathy) are declining, others (CAD, overt nephropathy, and proliferative retinopathy) show less favorable changes by 30 years.
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              Deaths: Final Data for 2013.

              This report presents final 2013 data on U.S. deaths, death rates, life expectancy, infant mortality, and trends, by selected characteristics such as age, sex, Hispanic origin, race, state of residence, and cause of death.
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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
                August 2016
                12 July 2016
                : 39
                : 8
                : 1378-1383
                Author notes
                Corresponding author: John M. Lachin, jml@ 123456bsc.gwu.edu .
                Article
                2399
                10.2337/dc15-2399
                4955932
                27411699
                71bcd94f-3b84-42e0-80a6-ba2cc27438c6
                © 2016 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.
                History
                : 4 November 2015
                : 14 April 2016
                Page count
                Figures: 2, Tables: 1, Equations: 0, References: 31, Pages: 6
                Funding
                Funded by: Division of Diabetes Endocrinology and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Diseases
                Award ID: U01 DK094176
                Award ID: U01 DK094157
                Categories
                Epidemiology/Health Services Research

                Endocrinology & Diabetes
                Endocrinology & Diabetes

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