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Serum Metabolomics of Incident Diabetes and Glycemic Changes in a Population With High Diabetes Burden: the Hispanic Community Health Study/Study of Latinos
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posted on 2022-03-16, 15:22 authored by Jin Choul Chai, Guo-Chong Chen, Bing Yu, Jiaqian Xing, Jun Li, Tasneem Khambaty, Krista M. Perreira, Marisa J Perera, Denise C. Vidot, Sheila F. Castaneda, Elizabeth Selvin, Casey M. Rebholz, Martha L. Daviglus, Jianwen Cai, Linda Van Horn, Carmen R Isasi, Qi Sun, Meredith Hawkins, Xiaonan Xue, Eric Boerwinkle, Robert C. Kaplan, Qibin QiMetabolomic signatures of incident
diabetes remain largely unclear for US Hispanics/Latinos, 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 = 2010) of the Hispanic Community Health Study/Study of Latinos
without diabetes and cardiovascular disease at baseline (2008-2011). On the
basis of 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 on average 6 years of follow-up. After
adjustment for sociodemographic,
behavioral and clinical factors,
134 metabolites were associated with incident diabetes (FDR-adjusted P<0.05). We identified 10 metabolite
modules, including modules comprised of previously reported diabetes-related metabolites
(e.g., sphingolipids, phospholipids, branched-chain and aromatic amino acids, and
glycine) and two 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-IR. The androgenic-steroid module and
its component metabolites decreased with increasing age and were associated
with 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 US
cohort of non-Hispanic Blacks and Whites (n = 1754). Among US Hispanics/Latinos
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.