
Faculty, Staff and Student Publications
Publication Date
4-1-2025
Journal
Life Metabolism
Abstract
Previous studies suggested that fecal short-chain fatty acids (SCFAs) and branched short-chain fatty acids (BCFAs) are associated with glucose regulation. However, the potential relationship between circulating SCFAs and BCFAs with incident diabetes risk in both men and women remains unidentified in prospective cohort studies. In this study, we examined a panel of nine serum SCFAs and BCFAs in 3414 subjects with incident diabetes, and matched normoglycemic controls from the China Cardiometabolic Disease and Cancer Cohort study. In fully adjusted conditional logistic regression models, total SCFAs, total BCFAs, and isovaleric acid were significantly associated with incident type 2 diabetes mellitus (T2DM) (P < 0.05). Interestingly, gender-specific analysis showed that per standard deviation (SD) increment of SCFAs were positively associated with incident T2DM among women, with the odds ratio (95% confidence interval) of 1.16 (1.05-1.29) for total SCFAs and 1.18 (1.07-1.31) for propionate, respectively (P < 0.05, false discovery rate (FDR) < 0.05). No significant associations were observed in men. A significant interaction was detected between men and women for propionate (P interaction < 0.001, FDR < 0.01). After further adjustment of insulin measurements, the associations of serum propionate with diabetes remained significant (P < 0.05, FDR < 0.05). Meanwhile, the associations of total BCFAs and isovaleric acid with diabetes were partially mediated by triglycerides, insulin resistance, and β-cell function in mediation analysis. These findings, for the first time in a large prospective cohort, provide evidence for an association between circulating SCFAs and BCFAs with T2DM risk, and support the potential role of circulating propionate with gender disparities in the early pathogenesis of diabetes.
Keywords
branched short-chain fatty acids, insulin resistance, short-chain fatty acids, type 2 diabetes
DOI
10.1093/lifemeta/loaf001
PMID
40078932
PMCID
PMC11897982
PubMedCentral® Posted Date
1-22-2025
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Endocrinology, Diabetes, and Metabolism Commons, Genetic Phenomena Commons, Medical Genetics Commons, Oncology Commons