Vaspin (visceral adipose tissue-derived serpinA12) is an adipokine suspected to be involved in type 2 diabetes (T2D) pathogenesis, linking obesity and T2D. We sought to assess epidemiological and genetic associations of vaspin with T2D and related variables.
We assessed the relationship of body-mass index (BMI) and waist-hip ratio (WHR) and plasma vaspin concentration, along with the relationship between plasma vaspin and adiposity-related variables and T2D in (i) a case-cohort within the Prospective Urban and Rural Epidemiology (PURE) prospective multi-country study (N=10,052) , and (ii) the Outcome Reduction with Initial Glargine Intervention (ORIGIN) Trial (N=7,840) of participants with dysglycemia. We next investigated the predictive value of vaspin for T2D risk. All models adjusted for age, sex, and ethnicity. Using two-sample Mendelian randomization (MR) , we analyzed if genetically higher vaspin is causal for T2D. The MR analysis used 34 independent genetic variants (linkage disequilibrium r2<0.1) associated with vaspin concentration in PURE (N=3,513) , estimating their effect on BMI-adjusted T2D risk in the DIAGRAM (DIAbetes Genetics Replication And Meta-analysis) consortium (N=898,130) .
In PURE, a 1 unit increase in BMI and WHR was associated with a 0.01 SD (95% CI 0.01 - 0.02; P = 2.04x10−15) and 0.45 SD (95% CI, 0.21 - 0.70; P = 2.87 × 10−4) increase in plasma vaspin respectively. A 1 SD increase in plasma vaspin was associated with higher triglycerides (0.09 mmol/L; 95% CI, 0.07 - 0.12, P = 4.08x10−13) . Directionally-consistent associations were observed in ORIGIN. A 1 SD increase in plasma vaspin was associated with a 19% increase in incident T2D risk in PURE (HR, 1.19; 95% CI, 1.12 - 1.26; P = 6.36x10−8) and a 16% increase in prevalent T2D in ORIGIN (OR, 1.16; 95% CI, 1.07 - 1.25; P = 2.17x10−4) . Sensitivity analyses showed vaspin's specificity for T2D. Genetically-higher vaspin was associated with increased BMI-adjusted T2D risk (OR, 1.02; 95% CI, 1.00 - 1.03; P = 5.46x10−3) .
Our data suggests that vaspin is a predictor for T2D risk, a modest causal factor for T2D development, and might represent a potential T2D therapeutic target.
H. Wang: None. M. Chong: None. N. Perrot: None. J. Feiner: None. S. Hess: Employee; Sanofi. S. Yusuf: None. H. C. Gerstein: Advisory Panel; Abbott, Eli Lilly and Company, Hanmi Pharm. Co., Ltd., Novo Nordisk, Pfizer Inc., Sanofi, Viatris Inc., Consultant; Kowa Company, Ltd., Other Relationship; DKSH, Eli Lilly and Company, Sanofi, Zuellig Pharma Holdings Pte. Ltd., Research Support; AstraZeneca, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk, Sanofi. G. Pare: Advisory Panel; Amgen Inc., Bayer AG, Sanofi, Research Support; Bayer AG. M. Pigeyre: n/a.
PURE biomarker study was sponsored by Bayer and CIHR. Origin (NCT00069784) and the biomarker-substudy in Origin were sponsored by Sanofi and CIHR.