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Vaspin: a novel biomarker linking gluteofemoral body fat and type 2 diabetes risk

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posted on 2023-12-06, 21:20 authored by Harry Hezhou Wang, Michael Chong, Nicolas Perrot, James Feiner, Sibylle Hess, Salim Yusuf, Hertzel Gerstein, Guillaume Paré, Marie Pigeyre

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.

Funding

The ORIGIN trial and biomarker project were supported by Sanofi. The PURE study and biomarker project were supported by Bayer and CIHR. MP is supported by the Early Career Research Award from Hamilton Health Sciences. GP is supported by the Canada Research Chair in Genetic and Molecular Epidemiology and the CISCO Professorship in Integrated Health Biosystems.

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