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 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 (i) the Prospective Urban and Rural Epidemiology (PURE)-biomarker sub-study (N=10,052), and (ii) 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 randomisation (MR).

Results: A 1 standard deviation (SD) increase in circulating vaspin was associated with a 16% increase in incident T2D in PURE (HR, 1.16; 95%CI, 1.09–1.23; P=4.26x10-7) and prevalent T2D in ORIGIN (OR, 1.16; 95%CI, 1.07–1.25; P=2.17x10-4). A 1 unit increase in BMI and triglycerides were associated with a 0.08 SD (95%CI 0.06–0.10; P=2.04x10-15) and 0.06 SD (95%CI 0.04-0.08; P=4.08x10-13) increase in vaspin in PURE respectively. Consistent associations were observed in ORIGIN. 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=2.86x10-2), 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=2.01x10-2). 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.