Vaspin: A Novel Biomarker Linking Gluteofemoral Body Fat and Type 2 Diabetes Risk

OBJECTIVE To determine whether adiposity depots modulate vaspin levels and whether vaspin predicts type 2 diabetes (T2D) risk, through epidemiological and genetic analyses. RESEARCH DESIGN AND METHODS We assessed the relationship of plasma vaspin concentration with incident and prevalent T2D and adiposity-related variables in 1) the Prospective Urban and Rural Epidemiology (PURE) biomarker substudy (N = 10,052) and 2) the Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial (N = 7,840), using regression models. We then assessed whether vaspin is causally associated with T2D and whether genetic variants associated with MRI-measured adiposity depots modulate vaspin levels, using two-sample Mendelian randomization (MR). RESULTS A 1-SD increase in circulating vaspin levels was associated with a 16% increase in incident T2D in the PURE cohort (hazard ratio 1.16; 95% CI 1.09–1.23; P = 4.26 × 10−7) and prevalent T2D in the ORIGIN cohort (odds ratio [OR] 1.16; 95% CI 1.07–1.25; P = 2.17 × 10−4). A 1-unit increase in BMI and triglyceride levels was associated with a 0.08-SD (95% CI 0.06–0.10; P = 2.04 × 10−15) and 0.06-SD (95% CI 0.04–0.08; P = 4.08 × 10−13) increase, respectively, in vaspin in the PURE group. Consistent associations were observed in the ORIGIN cohort. MR results reinforced the association between vaspin and BMI-adjusted T2D risk (OR 1.01 per 1-SD increase in vaspin level; 95% CI 1.00–1.02; P = 2.86 × 10−2) and showed that vaspin was increased by 0.10 SD per 1-SD decrease in genetically determined gluteofemoral adiposity (95% CI 0.02–0.18; P = 2.01 × 10−2). No relationships were found between subcutaneous or visceral adiposity and vaspin. CONCLUSIONS These findings support that higher vaspin levels are related to increased T2D risk and reduced gluteofemoral adiposity, positioning vaspin as a promising clinical predictor for T2D.