Faculty, Staff and Student Publications

Publication Date

9-20-2022

Journal

Cell Reports Medicine

Abstract

Although previous studies suggest that amino acids (AAs) and microbiota-related metabolites (MRMs) are associated with type 2 diabetes mellitus (T2DM), the results remain unclear among normoglycemic populations. We test 28 serum AAs and 22 MRMs in 3,414 subjects with incident diabetes and matched normoglycemic controls from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. In fully adjusted logistic regression models, per SD increment of branched-chain AAs, aromatic AAs, asparagine, alanine, glutamic acid, homoserine, 2-aminoadipic acid, histidine, methionine, and proline are positively associated with incident T2DM. In the MRM panel, serum carnitines, N-acetyltryptophan, and uric acid are positively associated with incident T2DM. Causal mediation analyses indicate 34 significant causal mediation linkages, with 88.2% through obesity and lipids. Variances explained in the serum metabolites are modestly limited in the comprehensive catalog of risk factor-metabolite-diabetes associations. These findings reveal that systematic AAs and MRMs change profile before T2DM onset and support a potential role of metabolic alterations in the pathogenesis of diabetes.

Keywords

2-Aminoadipic Acid, Adult, Alanine, Amino Acids, Asparagine, Diabetes Mellitus, Type 2, Glutamic Acid, Histidine, Homoserine, Humans, Lipids, Methionine, Microbiota, Proline, Uric Acid

DOI

10.1016/j.xcrm.2022.100727

PMID

35998626

PMCID

PMC9512668

PubMedCentral® Posted Date

8-22-2022

PubMedCentral® Full Text Version

Post-print

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Graphical Abstract

Published Open-Access

yes

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