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

• Published in: Diabetes care Vol. 47; no. 2; pp. 259 - 266
• Main Authors: Wang, Harry Hezhou, Chong, Michael, Perrot, Nicolas, Feiner, James, Hess, Sibylle, Yusuf, Salim, Gerstein, Hertzel, Paré, Guillaume, Pigeyre, Marie
• Format: Journal Article
• Language: English
• Published: United States American Diabetes Association 01.02.2024
• Subjects: Adipose Tissue; Adiposity - genetics; Biomarkers; Body fat; Body Mass Index; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - epidemiology; Epidemiology; Genetic analysis; Genetic diversity; Genetic variance; Health risks; Humans; Insulin Glargine; Mendelian Randomization Analysis; Obesity; Prospective Studies; Regression analysis; Regression models; Research design; Risk; Triglycerides
• ISSN: 0149-5992; 1935-5548
• DOI: 10.2337/dc23-1488

To determine whether adiposity depots modulate vaspin levels and whether vaspin predicts type 2 diabetes (T2D) risk, through epidemiological and genetic analyses. 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). 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. 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.