12374 A Prospective Study Of Plasma Levels Of Asprosin And Incident Type 2 Diabetes Among Postmenopausal Women In The Women’s Health Initiative

Abstract Disclosure: B. Yang: None. J. Li: None. E.S. Silva: None. L.S. Phillips: None. J.E. Manson: None. A.P. Reiner: None. A.R. Chopra: None. S. Liu: None. Background: Asprosin, a 30-kDa hormone identified from white adipose tissue, has been shown to play key roles in regulating hepatic glucose release and appetite stimulation. Despite an increasing body of experimental studies demonstrating asprosin as a promising therapeutic target, little is known about its distribution in the general population particularly concerning its association with incident type 2 diabetes (T2D). Objectives: To evaluate whether higher plasma levels of asprosin are associated with incident T2D among postmenopausal women independently of known risk factors for T2D. Methods: We conducted a case-control study nested in the Women’s Health Initiative (WHI), including 5,198 participants free of diabetes, cardiovascular diseases, and cancer at baseline (2,602 incident T2D cases and 2,596 controls). Plasma levels of asprosin were measured using a sandwich enzyme-linked immunosorbent (ELISA) assay. We used conditional logistic regression models to estimate the association between asprosin and T2D risk with adjustment for matching variables (age, race, sampling batch), education, body mass index (BMI), physical activity, tobacco smoking, alcohol drinking, family history of diabetes, age at menopause, total energy intake, the Alternate Healthy Eating Index (AHEI), and multivitamin use. Results: Approximately 43% of participants were white and the mean age at baseline was 63 years. The median plasma levels of asprosin were 38 (IQR: 30, 50) pmoL/L in the controls and 39 (IQR: 31, 50) pmoL/L among those who developed T2D during follow-up. Compared with the participants in the lowest quintile of plasma levels of asprosin at baseline, those in the highest quintile had a 26% increased risk of T2D (adjusted odds ratio: OR: 1.26 [95% CIs, 1.01, 1.57], p for trend=0.03) in the fully adjusted model. The OR estimates exhibited a large variation across race and BMI, although there was a linear dose-response relation between levels of asprosin and T2D risk (p for nonlinear=0.44). Genetic analysis revealed that women with the heterozygous allele (CG) at single nucleotide polymorphisms (SNP) rs56407701 had higher levels of asprosin compared to women with the homozygous reference allele (CC). Further, Mendelian Randomization analysis revealed that genetically predicted asprosin levels were associated with higher T2D risk. Conclusion: Among postmenopausal women, higher plasma levels of asprosin were prospectively associated with elevated T2D risk independent of known T2D risk factors. Further work is needed to confirm the potential causal role of this peptide hormone in the clinical risk stratification and potential prevention of T2D. Presentation: 6/2/2024