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.

Disclosure

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.

Funding

PURE biomarker study was sponsored by Bayer and CIHR. Origin (NCT00069784) and the biomarker-substudy in Origin were sponsored by Sanofi and CIHR.

© 2022 by the American Diabetes Association
2022
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.