Metabolome contribution to sex differences in the link between alcohol consumption and type 2 diabetes

Light to moderate alcohol consumption has been linked to improved insulin resistance and a lower risk of type 2 diabetes (T2D), mainly in females but not in males. The mechanisms behind this sex difference remain unclear. A study assessed the associations between sex-specific alcohol-related metabolomic signatures (AMSs) and the risk of insulin resistance and T2D in Hispanic/Latino adults in the United States.
Serum metabolome data were analysed from the Hispanic Community Health Study/Study of Latinos, a prospective, multicentre, community-based study of Hispanics/Latinos aged 18 to 74, recruited from four US metropolitan areas between 2008 and 2011. Sex-specific AMSs were created to identify serum metabolites uniquely associated with alcohol consumption in 2,747 females and 1,737 males without diabetes at baseline, excluding heavy drinkers. The cross-sectional relationships of AMSs with insulin resistance, along with the prospective links to T2D risk over approximately six years, were examined, adjusting for demographic, socioeconomic, and behavioural factors.
Forty and 54 metabolites uniquely linked to light-to-moderate alcohol consumption were identified in females and males, respectively. Cross-sectionally, female-specific AMS (FAMS) was inversely related to insulin resistance and various metabolic traits related to T2D in females, while male-specific AMS showed positive associations with insulin resistance and related metabolic traits in males. Prospectively, females in the highest quartile of FAMS had around 82% (95% confidence interval: 70%, 89%) lower T2D risk compared to those in the lowest quartile. The beneficial link between alcohol consumption and T2D risk was reduced after adjusting for FAMS. In males, there was no statistically significant relationship between male-specific AMS and T2D risk.
The findings indicate distinct blood metabolomic profiles linked to alcohol consumption in females and males, which may help explain sex differences in the relationship between alcohol intake and T2D.
Source: Wang, B., Luo, K., Ma, W., Zhang, Y., Cordero, C., Pirzada, A., Daviglus, M., Perreira, K.M., et al. (2026) Metabolome contribution to sex differences in the link between alcohol consumption and type 2 diabetes: a prospective analysis in the Hispanic Community Health Study/Study of Latinos. Am J Clin Nutr, 123(3), 101203.