Abstract
Metabolomic signatures of incident diabetes remain largely unclear for the U.S. Hispanic/Latino population, a group with high diabetes burden. We evaluated the associations of 624 known serum metabolites (measured by a global, untargeted approach) with incident diabetes in a subsample (n = 2,010) of the Hispanic Community Health Study/Study of Latinos without diabetes and cardiovascular disease at baseline (2008–2011). Based on the significant metabolites associated with incident diabetes, metabolite modules were detected using topological network analysis, and their associations with incident diabetes and longitudinal changes in cardiometabolic traits were further examined. There were 224 incident cases of diabetes after an average 6 years of follow-up. After adjustment for sociodemographic, behavioral, and clinical factors, 134 metabolites were associated with incident diabetes (false discovery rate–adjusted P < 0.05). We identified 10 metabolite modules, including modules comprising previously reported diabetesrelated metabolites (e.g., sphingolipids, phospholipids, branched-chain and aromatic amino acids, glycine), and 2 reflecting potentially novel metabolite groups (e.g., threonate, N-methylproline, oxalate, and tartarate in a plant food metabolite module and androstenediol sulfates in an androgenic steroid metabolite module). The plant food metabolite module and its components were associated with higher diet quality (especially higher intakes of healthy plant-based foods), lower risk of diabetes, and favorable longitudinal changes in HOMA for insulin resistance. The androgenic steroid module and its component metabolites decreased with increasing age and were associated with a higher risk of diabetes and greater increases in 2-h glucose over time. We replicated the associations of both modules with incident diabetes in a U.S. cohort of non-Hispanic Black and White adults (n = 1,754). Among U.S. Hispanic/Latino adults, we identified metabolites across various biological pathways, including those reflecting androgenic steroids and plant-derived foods, associated with incident diabetes and changes in glycemic traits, highlighting the importance of hormones and dietary intake in the pathogenesis of diabetes.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1338-1349 |
| Number of pages | 12 |
| Journal | Diabetes |
| Volume | 71 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 2022 |
Funding
The HCHS/SOL is a collaborative study supported by contracts from the National Heart, Lung, and Blood Institute (NHLBI) to the University of North Carolina (HHSN268201300001I/N01-HC-65233), University of Miami (HHSN268201300004I/N01-HC-65234), Albert Einstein College of Medicine (HHSN268201300002I/N01-HC-65235), University of Illinois at Chicago (HHSN268201300003I/N01-HC-65236 Northwestern University), and San Diego State University (HHSN268201300005I/N01-HC-65237). The following institutes, centers, and offices have contributed to HCHS/SOL through a transfer of funds to NHLBI: National Institute on Minority Health and Health Disparities, National Institute on Deafness and Other Communication Disorders, National Institute of Dental and Craniofacial Research, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, and National Institutes of Health (NIH) Office of Dietary Supplements. The ARIC study has been funded in whole or in part with federal funds from NHLBI, NIH, Department of Health and Human Services (contracts HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700004I, and HHSN268201700005I and R01HL087641, R01HL059367, and R01HL086694), National Human Genome Research Institute contract U01HG004402, and NIH contract HHSN268200625226C. Infrastructure was partly supported by grant UL1RR025005, a component of NIH and the NIH Roadmap for Medical Research. Metabolomics measurements were sponsored by the National Human Genome Research Institute (3U01HG004402-02S1). This work is supported by the National Institute of Diabetes and Digestive and Kidney Diseases grant R01DK119268, and other funding sources for this study include the National Human Genome Research Institute (UM1HG008898), NHLBI (K01HL129892, R01HL060712, R01HL140976, and R01HL136266), New York Regional Center for Diabetes Translation Research (R01DK120870), and National Institute of Diabetes and Digestive and Kidney Diseases (P30DK111022). E.S. was supported by NHLBI grant K24HL152440. C.M.R. was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (K01DK107782 and R03DK128386) and NHLBI (R56HL153178). Institute of Diabetes and Digestive and Kidney Diseases grant R01DK119268, and other funding sources for this study include the National Human Genome Research Institute (UM1HG008898), NHLBI (K01HL129892, R01HL060712, R01HL140976, and R01HL136266), New York Regional Center for Diabetes Translation Research (R01DK120870), and National Institute of Diabetes and Digestive and Kidney Diseases (P30DK111022). E.S. was supported by NHLBI grant K24HL152440. C.M.R. was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (K01DK107782 and R03DK128386) and NHLBI (R56HL153178). Duality of Interest. No potential conflicts of interest relevant to this article were reported. Author Contributions. J.C.C. and G.-C.C. prepared the tables and figures. J.C.C., G.-C.C., B.Y., and J.X. performed the statistical analyses. J.C.C., G.-C.C., B.Y., J.L., T.K., K.M.P., M.J.P., D.C.V., S.F.C., E.S., C.M.R., M.L.D., J.C., L.V.H., C.R.I., Q.S., M.H., X.X., E.B., R.C.K, and Q.Q. contributed to the interpretation of data, critically reviewed and revised the manuscript, and all authors approved the final manuscript. J.C.C. and Q.Q. designed the research and developed the analytical plan. G.-C.C. and Q.Q. had primary responsibility for writing the manuscript. Q.Q. directed the study. Q.Q. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Prior Presentation. Parts of this study were presented in abstract and oral form at the 79th Scientific Sessions of the American Diabetes Association, San Francisco, CA, 7–11 June 2019. Acknowledgments. The authors thank the staff and participants of HCHS/SOL and ARIC for important contributions. A complete list of HCHS/SOL staff and investigators can be found in Lavange et al. (18) or at https://sites. cscc.unc.edu/hchs/. Funding. The HCHS/SOL is a collaborative study supported by contracts from the National Heart, Lung, and Blood Institute (NHLBI) to the University of North Carolina (HHSN268201300001I/N01-HC-65233), University of Miami (HHSN268201300004I/N01-HC-65234), Albert Einstein College of Medicine (HHSN268201300002I/N01-HC-65235), University of Illinois at Chicago (HHSN268201300003I/N01-HC-65236 Northwestern University), and San Diego State University (HHSN268201300005I/N01-HC-65237). The following institutes, centers, and offices have contributed to HCHS/SOL through a transfer of funds to NHLBI: National Institute on Minority Health and Health Disparities, National Institute on Deafness and Other Communication Disorders, National Institute of Dental and Craniofacial Research, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, and National Institutes of Health (NIH) Office of Dietary Supplements. The ARIC study has been funded in whole or in part with federal funds from NHLBI, NIH, Department of Health and Human Services (contracts HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700004I, and HHSN268201700005I and R01HL087641, R01HL059367, and R01HL086694), National Human Genome Research Institute contract U01HG004402, and NIH contract HHSN268200625226C. Infrastructure was partly supported by grant UL1RR025005, a component of NIH and the NIH Roadmap for Medical Research. Metabolomics measurements were sponsored by the National Human Genome Research Institute (3U01HG004402-02S1). This work is supported by the National
ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism
