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      Risk Factor Modeling for Cardiovascular Disease in Type 1 Diabetes in the Pittsburgh Epidemiology of Diabetes Complications (EDC) Study: A Comparison With the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study (DCCT/EDIC)

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      Diabetes
      American Diabetes Association

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          Abstract

          In a recent Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study report, mean HbA 1c was the strongest predictor of cardiovascular disease (CVD) after age. In DCCT/EDIC, mean diabetes duration was 6 years (median 4) at baseline and those with high blood pressure or cholesterol were excluded. We now replicate these analyses in the Pittsburgh Epidemiology of Diabetes Complications (EDC) prospective cohort study of childhood-onset (at <17 years of age) type 1 diabetes, with similar age (mean 27 years in both studies) but longer diabetes duration (mean 19 years and median 18 years) and no CVD risk factor exclusion at baseline. CVD incidence (CVD death, myocardial infarction (MI), stroke, revascularization, angina, or ischemic electrocardiogram) was associated with diabetes duration, most recent albumin excretion rate (AER), updated mean triglycerides, baseline hypertension, baseline LDL cholesterol, and most recent HbA 1c. Major atherosclerotic cardiovascular events (CVD death, MI, or stroke) were associated with diabetes duration, most recent AER, baseline systolic blood pressure, baseline smoking, and updated mean HbA 1c. Compared with findings in DCCT/EDIC, traditional risk factors similarly predicted CVD; however AER predominates in EDC and HbA 1c in DCCT/EDIC. Thus, the relative impact of HbA 1c and kidney disease in type 1 diabetes varies according to diabetes duration.

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          Quantitative determination of serum triglycerides by the use of enzymes.

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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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              Insulin resistance-related factors, but not glycemia, predict coronary artery disease in type 1 diabetes: 10-year follow-up data from the Pittsburgh Epidemiology of Diabetes Complications Study.

              To determine the independent risk factors for coronary artery disease (CAD) in type 1 diabetes by type of CAD at first presentation. This is a historical prospective cohort study of 603 patients with type 1 diabetes diagnosed before 18 years of age between 1950 and 1980. The mean age and duration of diabetes at baseline were 28 (range 8-47) and 19 years (7-37), respectively, and patients were followed for 10 years. Patients with prevalent CAD were excluded from the study. Electrocardiogram (ECG) ischemia was defined by Minnesota Code (MC) 1.3, 4.1-3, 5.1-3, or 7.1; angina was determined by Pittsburgh Epidemiology of Diabetes Complications (EDC) study physician diagnosis; and hard CAD was determined by angiographic stenosis > or =50%, revascularization procedure, Q waves (MC 1.1-1.2), nonfatal myocardial infarction (MI), or CAD death. A total of 108 incident CAD events occurred during the 10-year follow-up: 17 cases of ECG ischemia, 49 cases of angina, and 42 cases of hard CAD (5 CAD deaths, 25 nonfatal MI or major Q waves, and 12 revascularization or > or =50% stenosis). Blood pressure, lipid levels, inflammatory markers, renal disease, and peripheral vascular disease showed a positive gradient across the groups of no CAD, angina, and hard CAD (P < 0.01, trend analysis, all variables), although estimated glucose disposal rate (eGDR) and physical activity showed inverse associations (P < 0.01, trend analysis, both variables). In addition, depressive symptomatology predicted angina (P = 0.016), whereas HbA(1) showed no association with subsequent CAD. These data suggest that although the standard CAD risk factors are still operative in type 1 diabetes, greater glycemia does not seem to predict future CAD events. In addition, depressive symptomatology predicts angina and insulin resistance (eGDR) predicts hard CAD end points.
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                Author and article information

                Journal
                Diabetes
                Diabetes
                diabetes
                diabetes
                Diabetes
                Diabetes
                American Diabetes Association
                0012-1797
                1939-327X
                February 2019
                8 November 2018
                : 68
                : 2
                : 409-419
                Affiliations
                [1]Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA
                Author notes
                Corresponding author: Rachel G. Miller, millerr@ 123456edc.pitt.edu
                Author information
                http://orcid.org/0000-0003-1845-8477
                http://orcid.org/0000-0001-9303-3810
                Article
                0515
                10.2337/db18-0515
                6341302
                30409781
                94ae92e5-cb5b-40c8-9574-5d5f21d42ff3
                © 2018 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
                : 08 May 2018
                : 03 November 2018
                Page count
                Figures: 1, Tables: 4, Equations: 0, References: 33, Pages: 11
                Funding
                Funded by: National Institute of Diabetes and Digestive and Kidney Diseases, DOI http://dx.doi.org/10.13039/100000062;
                Award ID: R01-DK-034818
                Funded by: Rossi Memorial Fund, DOI ;
                Categories
                0102
                Complications

                Endocrinology & Diabetes
                Endocrinology & Diabetes

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