Lipid Metabolites Show Complex Links to Type 2 Diabetes in Hispanic and Latino Adults

A large analysis of Hispanic and Latino adults in the United States has mapped how dozens of fatty acids and oxylipins—bioactive lipid inflammatory mediators—relate to type 2 diabetes, distinguishing associations tied to existing disease from those linked to future risk. Researchers used data from the Hispanic Community Health Study/Study of Latinos, examining 81 oxylipins and fatty acids across polyunsaturated, monounsaturated, and saturated classes. At the baseline visit, 15,138 participants were assessed, of whom 2,962 had prevalent type 2 diabetes.

Fifty-four fatty acids and oxylipins were associated with prevalent diabetes in this cross-sectional analysis. Four metabolites stood out: adrenic acid, dihomo-gamma-linolenic acid, tricosanoic acid, and lignoceric acid were associated not only with prevalent diabetes but also with incident diabetes—newly diagnosed cases—over follow-up to a second visit, which included 8,548 participants and 1,376 incident events. However, when the models were further adjusted for impaired glucose tolerance, the associations for adrenic and dihomo-gamma-linolenic acids were attenuated, suggesting their apparent predictive value may partly reflect early metabolic changes rather than independent risk.

To probe whether altered lipid levels are a consequence of diabetes rather than a precursor, the team compared fatty acid levels at the second visit between participants with and without diabetes at baseline, holding baseline-measured levels constant. Among 9,115 participants with 2,151 prevalent cases, 16 of 28 fatty acids differed significantly at follow-up between those with and without diabetes, indicating that the disease state itself is linked to changes in circulating fatty acid profiles over time. The researchers also applied Bayesian model averaging Mendelian randomization, a method that uses genetic variation to help prioritize metabolites that may be causally involved rather than merely correlated.

Because inflammation is a common pathological feature underlying type 2 diabetes risk and progression, characterizing fatty acids and these bioactive lipid mediators could inform preventive efforts and point to therapeutic targets. The overall pattern of results was nuanced. Far more metabolites were associated with prevalent diabetes than with incident risk, consistent with many lipid associations reflecting overt disease processes rather than risk-enhancing factors that precede diagnosis.

The Mendelian randomization analysis prioritized one diHETrE oxylipin as a likely causal risk factor for type 2 diabetes. The study is observational, so the remaining associations do not establish causation, and findings in this Hispanic and Latino population may not generalize elsewhere. By combining cross-sectional, prospective, and genetic approaches in a well-characterized cohort, the study documents how the lipid inflammatory landscape tracks with type 2 diabetes in this population.

Subject of Research: Associations of oxylipin metabolites and fatty acids with prevalent and incident type 2 diabetes in the Hispanic Community Health Study/Study of Latinos

Article Title: Evaluating associations of oxylipin metabolites and fatty acids with incident and prevalent type 2 diabetes in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

Article References: Downie, C. G., Highland, H. M., Howard, A. G., Alotaibi, M., Elfassy, T., Cordero, C., Below, J. E., Carnethon, M., Cheng, S., Daviglus, M., Garcia-Bedoya, O., Kaplan, R., Khambaty, T., Li, Y., Lilly, A. G., Lin, D.-Y., Long, T., Penedo, F. J., Petty, L. E., … Avery, C. L. (2026). Evaluating associations of oxylipin metabolites and fatty acids with incident and prevalent type 2 diabetes in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). PLOS One, 21(10), e0360656. https://doi.org/10.1371/journal.pone.0360656

Image Credits: AI Generated

DOI: 10.1371/journal.pone.0360656

Keywords: type 2 diabetes, oxylipins, fatty acids, inflammation, lipid metabolites, Mendelian randomization, HCHS/SOL, Hispanic and Latino health, cohort study, diHETrE, epidemiology, Evaluating