SAT-616 Associations Of Body Mass Index And Waist Circumference In Young Adulthood With Later Life Incident Diabetes

Background: Overweight and obesity are known risk factors for incident diabetes, but it remains unclear if exposures during young adulthood (age 18 to 39 years) contribute to mid and late-life (age ≥40 years, collectively labeled here as “later-life”) risk of incident diabetes independent of later-life risk factor exposures. Objective: We sought to assess the independent associations between young adult exposures to overweight and obesity, as assessed by body mass index (BMI) and waist circumference (WC), with later-life incident diabetes, accounting for later-life exposures. Methods: We pooled data from six US cohorts (ARIC, CARDIA, CHS, Framingham Offspring, Health ABC, and MESA), and imputed life-course risk factor trajectories for BMI and WC, as well as for multiple cardiometabolic risk factors, annually from age 18 years to end of follow-up for each participant. Incident diabetes was defined by observed fasting blood glucose ≥126 mg/dL, non-fasting glucose ≥200, or use of diabetes medications. We used Cox proportional hazards models to examine the independent associations between time-weighted average exposures to BMI and WC during young adulthood and incident diabetes. We also performed mediation analyses to assess whether these associations were mediated by young adult exposures to other cardiometabolic risk factors (blood pressure, lipids, insulin resistance). Results: 30,780 participants were included (mean age at first in-person visit 53.1±16.2 years; 56.1% female). Over a 9-year median follow-up, 4,323 participants had incident diabetes. Both young adult BMI and WC were associated with diabetes risk in a dose-dependent manner, independent of later-life BMI and WC. Compared to BMI 18.5–24.9 kg/m(2), hazard ratios (HR) for incident diabetes were 1.27 (95%CI: 1.14–1.41) and 1.99 (95%CI: 1.67–2.37) for BMI 25–29 kg/m(2) and ≥30 kg/m(2), respectively. Similarly, compared to normal WC (≤80 cm women; ≤94 cm men), the HRs were 1.42 (95%CI: 1.26–1.59) for WC 81-88cm (women)/95-102cm (men) and 2.13 (95%CI: 1.87–2.43) for WC >88cm (women)/>102cm (men). Young adult homeostatic model of insulin resistance (HOMA-IR) mediated 49% (95%CI: 23–76) and 44% (95%CI: 26–62) of the association between young adult BMI and WC with later-life incident diabetes, respectively. Conclusions: Elevated BMI or WC during young adulthood were independently associated with later-life incident diabetes, after accounting for later-life BMI and WC, with insulin resistance suggested as a key mediator.