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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.

TitleSerum Metabolomics of Incident Diabetes and Glycemic Changes in a Population With High Diabetes Burden: The Hispanic Community Health Study/Study of Latinos.
Publication TypePublication
Year2022
AuthorsChai JChoul, Chen G-C, Yu B, Xing J, Li J, Khambaty T, Perreira KM, Perera MJ, Vidot DC, Castañeda SF, Selvin E, Rebholz CM, Daviglus ML, Cai J, Van Horn L, Isasi CR, Sun Q, Hawkins M, Xue X, Boerwinkle E, Kaplan RC, Qi Q
JournalDiabetes
Volume71
Issue6
Pagination1338-1349
Date Published2022 06 01
ISSN1939-327X
KeywordsAdult, Diabetes Mellitus, Hispanic or Latino, Humans, Metabolomics, Public Health, Risk Factors, Steroids
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 diabetes-related 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.

DOI10.2337/db21-1056
Alternate JournalDiabetes
PubMed ID35293992
Grant ListK24 HL152440 / HL / NHLBI NIH HHS / United States
N01HC65234 / HL / NHLBI NIH HHS / United States
N01HC65235 / HL / NHLBI NIH HHS / United States
N01HC65236 / HL / NHLBI NIH HHS / United States
N01HC65237 / HL / NHLBI NIH HHS / United States
HHSN268201700001I / HL / NHLBI NIH HHS / United States
HHSN268201700002I / HL / NHLBI NIH HHS / United States
HHSN268201700003I / HL / NHLBI NIH HHS / United States
HHSN268201700004I / HL / NHLBI NIH HHS / United States
HHSN268201700005I / HL / NHLBI NIH HHS / United States
R01 HL087641 / HL / NHLBI NIH HHS / United States
R01 HL059367 / HL / NHLBI NIH HHS / United States
R01 HL086694 / HL / NHLBI NIH HHS / United States
U01 HG004402 / HG / NHGRI NIH HHS / United States
UL1 RR025005 / RR / NCRR NIH HHS / United States
U01 HG004402 / HG / NHGRI NIH HHS / United States
R01 DK119268 / DK / NIDDK NIH HHS / United States
UM1 HG008898 / HG / NHGRI NIH HHS / United States
K01 HL129892 / HL / NHLBI NIH HHS / United States
R01 HL060712 / HL / NHLBI NIH HHS / United States
R01 HL140976 / HL / NHLBI NIH HHS / United States
R01 HL136266 / HL / NHLBI NIH HHS / United States
R01 DK120870 / DK / NIDDK NIH HHS / United States
P30 DK111022 / DK / NIDDK NIH HHS / United States
K01 DK107782 / DK / NIDDK NIH HHS / United States
R03 DK128386 / DK / NIDDK NIH HHS / United States
R56 HL153178 / HL / NHLBI NIH HHS / United States
MS#: 
0689
Manuscript Lead/Corresponding Author Affiliation: 
Field Center: Bronx (Einstein College of Medicine)
ECI: 
Manuscript Affiliation: 
Field Center: Bronx (Einstein College of Medicine)
Manuscript Status: 
Published