Abstract P049: Circulating Adiponectin Levels and Risk of Type 2 Diabetes, Cardiovascular Disease, and All-Cause Mortality in US Women

Introduction: Adiponectin is an anti-inflammatory peptide hormone secreted by adipocytes and has been related with decreased risk of type 2 diabetes (T2D) and cardiovascular disease (CVD), but longitudinal data are limited and inconsistent. Hypothesis: Higher circulating adiponectin levels are associated with lower risk of T2D, CVD, and all-cause mortality in healthy women. Methods: Baseline adiponectin levels, measured by an immunoassay, were available on 15,131 women from the Nurses’ Health study I and II, who were part of 11 separate nested case-control studies and free of T2D, CVD, and cancer at study baseline. Associations of adiponectin levels with incident T2D, CVD (including coronary heart disease [CHD], stroke, and CVD death), and all-cause mortality were estimated using Cox regressions adjusted for study design characters, established risk factors and confounders including menopausal status, hormone therapy, and continuous body mass index. We also analyzed associations of 26 adiponectin expression-associated variants (in adipose tissue) with T2D, CVD, and all-cause mortality in the UK Biobank study. Results: During up to 22 years (289,408 person-years) of follow-up, 2,578 T2D cases, 1,827 CVD cases (including 745 CHD, 1,108 stroke and 428 CVD deaths), and 2,741 deaths occurred. In multivariable models, hazard ratios (95% confidence intervals) comparing the highest quartile of plasma adiponectin to the lowest were 0.17 (0.14-0.21; P trend <0.001) for T2D, 0.82 (0.69-0.96; P trend =0.005) for CVD, 0.66 (0.51-0.86; P trend <0.001) for CHD, 0.91 (0.73-1.12; P trend =0.34) for stroke, 0.69 (0.48-0.98; P trend =0.10) for CVD death, and 0.77 (0.66-0.90; P trend =0.005) for all-cause mortality. Genetic alleles associated with increased adiponectin expression in adipose tissue were associated with decreased risk of CVD, but no associations were observed for T2D and all-cause mortality. Conclusions: Higher adiponectin levels are associated with decreased risk of cardiometabolic diseases and all-cause mortality.