The effect of intensive glycemic treatment on coronary artery calcification in type 1 diabetic participants of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study

Abstract

The Epidemiology of Diabetes Interventions and Complications (EDIC) study, an observational follow-up of the Diabetes Control and Complications Trial (DCCT) type 1 diabetes cohort, measured coronary artery calcification (CAC), an index of atherosclerosis, with computed tomography (CT) in 1,205 EDIC patients at approximately 7-9 years after the end of the DCCT. We examined the influence of the 6.5 years of prior conventional versus intensive diabetes treatment during the DCCT, as well as the effects of cardiovascular disease risk factors, on CAC. The prevalences of CAC >0 and >200 Agatston units were 31.0 and 8.5%, respectively. Compared with the conventional treatment group, the intensive group had significantly lower geometric mean CAC scores and a lower prevalence of CAC >0 in the primary retinopathy prevention cohort, but not in the secondary intervention cohort, and a lower prevalence of CAC >200 in the combined cohorts. Waist-to-hip ratio, smoking, hypertension, and hypercholesterolemia, before or at the time of CT, were significantly associated with CAC in univariate and multivariate analyses. CAC was associated with mean HbA(1c) (A1C) levels before enrollment, during the DCCT, and during the EDIC study. Prior intensive diabetes treatment during the DCCT was associated with less atherosclerosis, largely because of reduced levels of A1C during the DCCT.

FIG. 1

Distribution of CAC scores (Agatston units) by cohort and treatment group. □, CAC = 0; ▧, CAC 1–200;, ■, CAC >200. CONV, conventional treatment; INT, intensive treatment.

FIG. 2

Unadjusted prevalence of CAC >0 and CAC >200 Agatston units within each treatment group, separately stratified by sex and age at the time of the scan. A: CAC >0 intensive treatment. B: CAC >0 conventional treatment. C: CAC >200 intensive treatment. D: CAC >200 conventional treatment. The number of subjects evaluated in each age category is noted. □, female subjects; ■, male subjects.

FIG. 3

Estimated geometric mean ratio of CAC scores for conventional- versus intensive-treatment groups as a function of type 1 duration, using the Tobit model, at DCCT baseline in the secondary cohort. Dotted lines represent 95% CIs. The overall treatment group difference was significant (P = 0.003). Overall age effect was also significant (P < 0.0001). P values for durations of 1–15 years, respectively, are 0.002, 0.003, 0.004, 0.007, 0.015, 0.043, 0.154, 0.535, 0.756, 0.235, 0.061, 0.019, 0.008, 0.004, and 0.002. P values are a test that the ratio = 1 at each year of duration. IDDM, type 1 diabetes.

FIG. 4

ROC curve of CAC relative to cardiovascular events. True-positives are plotted on the y-axis and false-positives on the x-axis. The accuracy of the CAC is the area under the curve. An area of 1 represents a perfect test; an area of 0.5 represents a worthless test. An area under the curve of 0.78 implies that there is a 78% likelihood that a randomly selected affected case subject will have a higher CAC score than a randomly selected nonaffected control subject. The 95% CI (0.69–0.86) indicates that the lower end point is >0.50 and is better than random chance.