Metabolite biomarkers of type 2 diabetes mellitus and pre-diabetes: a systematic review and meta-analysis
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RESEARCH ARTICLE
Open Access
Metabolite biomarkers of type 2 diabetes mellitus and pre-diabetes: a systematic review and meta-analysis Jianglan Long1,2, Zhirui Yang1, Long Wang3, Yumei Han4, Cheng Peng2, Can Yan5* and Dan Yan1*
Abstract Background: We aimed to explore metabolite biomarkers that could be used to identify pre-diabetes and type 2 diabetes mellitus (T2DM) using systematic review and meta-analysis. Methods: Four databases, the Cochrane Library, EMBASE, PubMed and Scopus were selected. A random effect model and a fixed effect model were applied to the results of forest plot analyses to determine the standardized mean difference (SMD) and 95% confidence interval (95% CI) for each metabolite. The SMD for every metabolite was then converted into an odds ratio to create an metabolite biomarker profile. Results: Twenty-four independent studies reported data from 14,131 healthy individuals and 3499 patients with T2DM, and 14 included studies reported 4844 healthy controls and a total of 2139 pre-diabetes patients. In the serum and plasma of patients with T2DM, compared with the healthy participants, the concentrations of valine, leucine, isoleucine, proline, tyrosine, lysine and glutamate were higher and that of glycine was lower. The concentrations of isoleucine, alanine, proline, glutamate, palmitic acid, 2-aminoadipic acid and lysine were higher and those of glycine, serine, and citrulline were lower in prediabetic patients. Metabolite biomarkers of T2DM and pre-diabetes revealed that the levels of alanine, glutamate and palmitic acid (C16:0) were significantly different in T2DM and pre-diabetes. Conclusions: Quantified multiple metabolite biomarkers may reflect the different status of pre-diabetes and T2DM, and could provide an important reference for clinical diagnosis and treatment of pre-diabetes and T2DM. Keywords: Metabolite, Biomarker, Type 2 diabetes mellitus, Pre-diabetes; meta-analysis
Background Type 2 diabetes mellitus (T2DM) is a highly prevalent chronic disease that is associated with the development of complications including diabetic retinopathy, kidney disease and diabetic ketoacidosis [1, 2], which represent serious threats to human health. Between 1980 and 2014, the number of adults with diabetes increased from * Correspondence: [email protected]; [email protected] 5 Guangzhou University of Chinese Medicine, Guangzhou 510006, China 1 Beijing Key Laboratory and Joint Laboratory for International Cooperation of Bio-characteristic Profiling for Evaluation of Rational Drug Use, Capital Medical University Affiliated Beijing Shijitan Hospital, Beijing 100038, China Full list of author information is available at the end of the article
108 million to 422 million [3], with T2DM accounting for > 90% of these cases [4]. Recent studies have shown that diabetes has become one of the three major diseases in the world with the increasing global prevalence rate [5]. However, the symptoms of T2DM are not very obvious or only partially manifest in the early stages of the disease. Therefore, it is partic
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