The effect of excess weight gain with intensive diabetes mellitus treatment on cardiovascular disease risk factors and atherosclerosis in type 1 diabetes mellitus: results from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study (DCCT/EDIC) study

Abstract

Background: Intensive diabetes mellitus therapy of type 1 diabetes mellitus reduces diabetes mellitus complications but can be associated with excess weight gain, central obesity, and dyslipidemia. The purpose of this study was to determine whether excessive weight gain with diabetes mellitus therapy of type 1 diabetes mellitus is prospectively associated with atherosclerotic disease.

Methods and results: Subjects with type 1 diabetes mellitus (97% white, 45% female, mean age 35 years) randomly assigned to intensive or conventional diabetes mellitus treatment during the Diabetes Control and Complications Trial (DCCT) underwent intima-media thickness (n = 1015) and coronary artery calcium score (n = 925) measurements during follow-up in the Epidemiology of Diabetes Interventions and Complications (EDIC) Study. Intensive treatment subjects were classified by quartile of body mass index change during the DCCT. Excess gainers (4th quartile, including conventional treatment subjects meeting this threshold) maintained greater body mass index and waist circumference, needed more insulin, had greater intima-media thickness (+5%, P < 0.001 EDIC year 1, P = 0.003 EDIC year 6), and trended toward greater coronary artery calcium scores (odds ratio, 1.55; confidence interval, 0.97 to 2.49; P = 0.07) than minimal gainers. DCCT subjects meeting metabolic syndrome criteria for waist circumference and blood pressure had greater intima-media thickness in both EDIC years (P = 0.02 to < 0.001); those meeting high-density lipoprotein criteria had greater coronary artery calcium scores (odds ratio, 1.6; confidence interval, 1.1 to 2.4; P = 0.01) during follow-up. Increasing frequency of a family history of diabetes mellitus, hypertension, and hyperlipidemia was associated with greater intima-media thickness with intensive but not conventional treatment.

Conclusions: Excess weight gain in DCCT is associated with sustained increases in central obesity, insulin resistance, dyslipidemia and blood pressure, as well as more extensive atherosclerosis during EDIC.

Clinical trial registration: URL for DCCT: https://ichgcp.net/clinical-trials-registry/NCT00360815" title="See in ClinicalTrials.gov">NCT00360815. URL for EDIC: https://ichgcp.net/clinical-trials-registry/NCT00360893" title="See in ClinicalTrials.gov">NCT00360893.

Figures

Figure 1

Body mass index (left graph) and waist circumference (right graph) of subjects treated intensively in the DCCT/EDIC cohort during the DCCT and study years 1 and 6 of EDIC. P

Figure 2

Intima media thickness (IMT) of the common carotid of conventionally (n=499) and intensively in the DCCT subjects, measured at EDIC study years 1 and 6. *P<0.001 vs. minimal gainers with intensive therapy (n=394) in years 1 and 6. †P<0.001 vs. excess gainers with intensive therapy (n=122) EDIC year 1. ‡P=0.003 and §P=0.03 vs. excess gainers in year 1 and 6, respectively. Analysis by Mann-Whitney Rank Sum Test (for fully adjusted significance values see Tables 2 and 3). Box plots show 5th, 10th, 25th, median, 75th, 90th, and 95th percentiles lines, bottom to top.

Figure 3

Distribution of coronary artery calcification (CAC) scores of subjects treated intensively in the DCCT/EDIC cohort, excess gainers versus minimal gainers during DCCT. See table 4 for significance.