Objective: Intensive treatment (INT) of type 1 diabetes reduces the incidence of cardiovascular disease (CVD) events compared with conventional treatment (CONV), but it also results in more weight gain. Our objective was to examine whether excessive weight gain from INT of type 1 diabetes is independently associated with subsequent CVD events. Research Design and Methods: Quartiles (Q) of weight gain in 1,213 participants aged 18 years and older at enrollment in the Diabetes Control and Complications Trial (DCCT) were determined within randomized treatment groups (INT vs. CONV) using change in BMI from baseline to the closeout DCCT visits. Effects of this weight gain on CVD risk factors and outcomes during an additional 20 years of observational follow-up were then determined. Results: The Q4 INT group experienced greater proportional weight gain (median change in BMI, 6.08 kg/m2), increases in CVD risk factors, and need for medications for hypertension and lipids compared with the Q1-3 INT and comparable CONV groups. Over a mean of 26 years of follow-up, the numbers of major and total CVD events were not statistically different in Q4 compared with Q1-3 of either the INT or CONV group. By year 14, however, the incident CVD event curve became significantly higher in the Q4 INT group than in the Q1-3 INT groups (P = 0.024) and was similar to that for the CONV group. Conclusions: For the first 13 years after DCCT, INT for type 1 diabetes reduced macrovascular events compared with CONV, even when excessive weight gain occurred. After this, total CVD events significantly increased in the Q4 INT group, becoming equivalent to those in the CONV group. Longer follow-up is needed to determine whether this trend continues and results in more major CVD events.
Bibliographical noteFunding Information:
the memory of John D. Brunzell, MD (1937– 2015), who inspired and guided us both personally and professionally. Funding.The DCCT/EDIC hasbeensupportedby cooperative agreement grants (1982–1993, 2012–2017) and contracts (1982–2012) with the Division of Diabetes, Endocrinology, & Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Diseases (grants U01 DK094176 and U01 DK094157) and through support from the National Eye Institute, the National Institute of Neurological Disorders and Stroke, the General Clinical Research Centers Program (1993– 2007), and Clinical Translational Science Center Program (2006–present), Bethesda, MD. Duality of Interest. J.Q.P. serves on an advisory board for Novo Nordisk. No other potential