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Serum metabolomic profile of incident diabetes.

TitleSerum metabolomic profile of incident diabetes.
Publication TypeJournal Article
Year of Publication2018
AuthorsRebholz CM, Yu B, Zheng Z, Chang P, Tin A, Köttgen A, Wagenknecht LE, Coresh JJ, Boerwinkle E
Secondary AuthorsSelvin E
JournalDiabetologia
Volume61
Issue5
Pagination1046-1054
Date Published2018 05
ISSN1432-0428
KeywordsAmino Acids, Branched-Chain, Asparagine, Atherosclerosis, Blood Glucose, Diabetes Mellitus, Type 2, Erythritol, Female, Glucose, Humans, Isoleucine, Lactic Acid, Leucine, Male, Maryland, Metabolome, Middle Aged, Minnesota, Mississippi, North Carolina, Prospective Studies, Risk Factors, Trehalose, Valine
Abstract

AIMS/HYPOTHESIS: Metabolomic profiling offers the potential to reveal metabolic pathways relevant to the pathophysiology of diabetes and improve diabetes risk prediction.

METHODS: We prospectively analysed known metabolites using an untargeted approach in serum specimens from baseline (1987-1989) and incident diabetes through to 31 December 2015 in a subset of 2939 Atherosclerosis Risk in Communities (ARIC) study participants with metabolomics data and without prevalent diabetes.

RESULTS: Among the 245 named compounds identified, seven metabolites were significantly associated with incident diabetes after Bonferroni correction and covariate adjustment; these included a food additive (erythritol) and compounds involved in amino acid metabolism [isoleucine, leucine, valine, asparagine, 3-(4-hydoxyphenyl)lactate] and glucose metabolism (trehalose). Higher levels of metabolites were associated with increased risk of incident diabetes (HR per 1 SD increase in isoleucine 2.96, 95% CI 2.02, 4.35, p = 3.18 × 10; HR per 1 SD increase in trehalose 1.16, 95% CI 1.09, 1.25, p = 1.87 × 10), with the exception of asparagine, which was associated with a lower risk of diabetes (HR per 1 SD increase in asparagine 0.78, 95% CI 0.71, 0.85, p = 4.19 × 10). The seven metabolites modestly improved prediction of incident diabetes beyond fasting glucose and established risk factors (C statistics 0.744 vs 0.735, p = 0.001 for the difference in C statistics).

CONCLUSIONS/INTERPRETATION: Branched chain amino acids may play a role in diabetes development. Our study is the first to report asparagine as a protective biomarker of diabetes risk. The serum metabolome reflects known and novel metabolic disturbances that improve prediction of diabetes.

DOI10.1007/s00125-018-4573-7
Alternate JournalDiabetologia
PubMed ID29556673
PubMed Central IDPMC5878141
Grant ListHHSN268201100012C / HL / NHLBI NIH HHS / United States
HHSN268201100009I / HL / NHLBI NIH HHS / United States
HHSN268201100010C / HL / NHLBI NIH HHS / United States
HHSN268201100008C / HL / NHLBI NIH HHS / United States
HHSN268201100005G / HL / NHLBI NIH HHS / United States
HHSN268201100008I / HL / NHLBI NIH HHS / United States
R01 DK089174 / DK / NIDDK NIH HHS / United States
HHSN268201100007C / HL / NHLBI NIH HHS / United States
K01 DK107782 / DK / NIDDK NIH HHS / United States
HHSN268201100011I / HL / NHLBI NIH HHS / United States
HHSN268201100011C / HL / NHLBI NIH HHS / United States
HHSN268201100006C / HL / NHLBI NIH HHS / United States
HHSN268201100005I / HL / NHLBI NIH HHS / United States
K24 DK106414 / DK / NIDDK NIH HHS / United States
U01 DK085689 / DK / NIDDK NIH HHS / United States
HHSN268201100009C / HL / NHLBI NIH HHS / United States
HHSN268201100005C / HL / NHLBI NIH HHS / United States
HHSN268201100007I / HL / NHLBI NIH HHS / United States