Body-Weight Variability and Risk of Cardiovascular Outcomes in Type 1 Diabetes: Results from the DCCT/EDIC Studies

Cardiovascular (CV) complications are a major cause of morbimortality in long-standing type 1 diabetes (T1D) . Excessive weight gain has been associated with higher rates of CV events in the DCCT/EDIC studies. Moreover, fluctuation of body weight has emerged as an independent predictor of increased mortality and risk of CV outcomes, with evidence from the general population, from patients with coronary artery disease, and from patients with type 2 diabetes. We evaluated the association between weight fluctuation and CV events in patients with T1D from the DCCT/EDIC population. Body-weight fluctuation was measured by the average successive variability (ASV: average absolute difference between successive values) over the 9-year period of the DCCT. The primary outcome was a composite of major adverse CV events (MACE: nonfatal myocardial infarctions or cerebrovascular events, CV deaths) occurring during the first 15 years of EDIC follow-up. The risk of outcomes during follow-up was analyzed using adjusted Cox models according to tertiles of ASV. For the primary outcome, 1371 out of 1441 patients fulfilled the inclusion criteria for analysis [males: 52.41%, age: (37.53±6.82) years, mean HbA1c: (8.08±1.35) %, conventional/intensive treatment: 690/681 patients]. The cumulative incidence of MACE was 4.81%, 5.02%, and 6.58% for tertiles 1, 2, and 3, respectively (T1, T2, T3) (p=0.44) during (15.40±6.24) years of follow-up. Cox analysis adjusted for baseline EDIC characteristics (age, sex, treatment group) and time-dependent variables during DCCT (average BMI, CV risk factors, nephropathy) showed a hazard ratio (HR) for MACE of 1. (95% CI 0.58-1.92; p=0.85) for T2 and 1.34 (0.74-2.41; p=0.34) for T3, both compared to T1. For every increase of 1 standard deviation of ASV, the HR for MACE was 1. (0.86-1.42; p=0.44) . Despite a trend for a positive association, body-weight fluctuation was not significantly associated with an increased risk of MACE in patients with T1D. Disclosure I.Petria: None. S.Albuquerque: None. G.Varoquaux: None. J.Vie: None. G.Velho: None. G.Perseghin: Advisory Panel; AstraZeneca, Lilly, Merck Sharp & Dohme Corp., Novo Nordisk, PIKDARE S.p.A., Sanofi. R.Roussel: None. L.Potier: Board Member; Boehringer Ingelheim International GmbH, Lilly, Novo Nordisk, Consultant; AstraZeneca, Sanofi.