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)

BACKGROUND: Inflammation is a common pathological feature underlying type 2 diabetes (T2D) risk and progression. Determining the roles of fatty acids and bioactive lipid oxylipin inflammatory mediators could inform T2D preventative efforts and therapeutic targets. METHODS: Leveraging the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), we evaluated cross-sectional and prospective associations of 81 oxylipins and polyunsaturated, monounsaturated, and saturated fatty acids with T2D. We assessed whether fatty acid levels differed at visit 2 by visit 1-prevalent T2D status and prioritized likely causal metabolites using Bayesian model averaging Mendelian randomization (MR-BMA). RESULTS: Fifty-four fatty acids and oxylipins were associated with prevalent T2D at visit 1 (15,138 participants; 2,962 T2D cases), four of which (adrenic, dihomo-gamma-linolenic, tricosanoic, and lignoceric acids) were also associated with incident T2D by visit 2 (8,548 participants; 1,376 T2D events), though effects were attenuated for adrenic and dihomo-gamma-linolenic acids upon further adjustment for impaired glucose tolerance. Sixteen out of 28 fatty acids were significantly different at visit 2 between those with and without prevalent T2D at visit 1 (9,115 participants; 2,151 T2D cases), holding visit 1-measured fatty acid levels constant. MR-BMA prioritized one diHETrE oxylipin as a likely causal risk factor for T2D. CONCLUSIONS: Fatty acids and oxylipins showed complex patterns of association with T2D, including more associations likely reflecting overt disease processes in prevalent T2D, than incident risk-enhancing associations.

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Publication Details

Journal
PLoS ONE
Published
2026-10-26
DOI
https://doi.org/10.1371/journal.pone.0360656
Primary Topic
Fatty Acid Research and Health
Type
article
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0.00

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article

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)

Christina Cordero, Tasneem Khambaty, Frank J. Penedo, Lauren E. Petty et al.
PLoS ONE
Fatty Acid Research and Health
article

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)

Christina Cordero, Tasneem Khambaty, Frank J. Penedo, Lauren E. Petty, Adam G. Lilly, Jennifer Elizabeth Below, Barrett M. Welch, Robert M. Kaplan, Christy L. Avery, Olga Garcia‐Bedoya, Carolina G Downie, Mercedes R. Carnethon, Kari E. North, Bharat Thyagarajan, Mona Alotaibi, Tali Elfassy, Martha L. Daviglus, Heather M. Highland, Tao Long, Annie Green Howard, Hsiao Chuan Tien, Mohit Jain, Yilun Li, Susan Cheng, Dan-Yu Lin
article en

Abstract

BACKGROUND: Inflammation is a common pathological feature underlying type 2 diabetes (T2D) risk and progression. Determining the roles of fatty acids and bioactive lipid oxylipin inflammatory mediators could inform T2D preventative efforts and therapeutic targets. METHODS: Leveraging the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), we evaluated cross-sectional and prospective associations of 81 oxylipins and polyunsaturated, monounsaturated, and saturated fatty acids with T2D. We assessed whether fatty acid levels differed at visit 2 by visit 1-prevalent T2D status and prioritized likely causal metabolites using Bayesian model averaging Mendelian randomization (MR-BMA). RESULTS: Fifty-four fatty acids and oxylipins were associated with prevalent T2D at visit 1 (15,138 participants; 2,962 T2D cases), four of which (adrenic, dihomo-gamma-linolenic, tricosanoic, and lignoceric acids) were also associated with incident T2D by visit 2 (8,548 participants; 1,376 T2D events), though effects were attenuated for adrenic and dihomo-gamma-linolenic acids upon further adjustment for impaired glucose tolerance. Sixteen out of 28 fatty acids were significantly different at visit 2 between those with and without prevalent T2D at visit 1 (9,115 participants; 2,151 T2D cases), holding visit 1-measured fatty acid levels constant. MR-BMA prioritized one diHETrE oxylipin as a likely causal risk factor for T2D. CONCLUSIONS: Fatty acids and oxylipins showed complex patterns of association with T2D, including more associations likely reflecting overt disease processes in prevalent T2D, than incident risk-enhancing associations.

PLoS ONEVol. 21(10)
Northwestern University (US), University of North Carolina at Chapel Hill (US), American Heart Association (US), Cedars-Sinai Medical Center (US), Albert Einstein College of Medicine (US), University of Minnesota (US), University of Nevada, Reno (US), University of Miami (US), University of California San Diego (US), University of Illinois Chicago (US), Cedars-Sinai Smidt Heart Institute (US), Sylvester Comprehensive Cancer Center (US), University of Maryland, Baltimore County (US), Vanderbilt University Medical Center (US), The University of Texas Health Science Center at Houston (US)
Office of Dietary Supplements, University of Miami, Northwestern University, San Diego State University, National Institutes of Health, University of Illinois at Urbana-Champaign, Gillings School of Public Health, National Heart, Lung, and Blood Institute, National Institute on Deafness and Other Communication Disorders, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute on Minority Health and Health Disparities
Openalex Percentile: Top 13%
Fatty Acid Research and Health
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