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
Graphical Abstract
Published Open-Access
yes
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Genetic Phenomena Commons, Medical Genetics Commons, Oncology Commons