Altered Caffeine Metabolism Is Associated With Recurrent Hypoglycemia in Type 2 Diabetes Mellitus: A UPLC–MS-Based Untargeted Metabolomics Study

Autor: Wang Lijing, Ke Sujie, Wang Linxi, Huang Lishan, Qi Liqin, Zhan Zhidong, Wu Kejun, Zhang Mengjun, Liu Xiaoying, Liu Xiaohong, Liu Libin
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Frontiers in Endocrinology, Vol 13 (2022)
Druh dokumentu: article
ISSN: 1664-2392
DOI: 10.3389/fendo.2022.843556
Popis: BackgroundRecurrent hypoglycemia (RH) is well known to impair awareness of hypoglycemia and increase the risk of severe hypoglycemia; the underlying mechanism requires further understanding. We aimed to investigate the metabolic characteristic profile for RH in type 2 diabetes mellitus (T2DM) patients and explore the potential metabolic mechanism and prevention strategies.MethodsWe screened 553 community-based T2DM patients. T2DM with RH (DH group, n=40) and T2DM without hypoglycemia (DC group, n=40) were assigned in the case-control study, matched by propensity score matching. Non-targeted, global metabolite profiling was conducted using ultra-high performance liquid chromatography-mass spectrometry. Principal component analysis and supervised projections to latent structures-discriminant analysis were constructed to evaluate the potential biomarkers. Metabolites with a fold change of >2.0 or 1 were identified as significantly differential metabolites. MetaboAnalyst was performed to analyze the related metabolic pathways.ResultsWe identified 12 significantly distinct metabolites as potential biomarkers of RH, which were enriched in five pathways; the caffeine metabolic pathway was the most dominant related one. Caffeine and its main downstream metabolites (theophylline and paraxanthine, all q
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