Metabolite biomarkers of type 2 diabetes mellitus and pre-diabetes: a systematic review and meta-analysis

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.

A Preliminary Study Showing the Impact of Genetic and Dietary Factors on GC–MS-Based Plasma Metabolome of Patients with and without PROX1-Genetic Predisposition to T2DM up to 5 Years Prior to Prediabetes Appearance

“…Metabolomics has already allowed the identification of metabolites that can serve as potential biomarkers for the diagnosis or treatment of T2DM [12]. The relationships between metabolites level and insulin resistance [13,14], prediabetes [15,16] and T2DM [4,17] have been evaluated in several studies using mass spectrometry (MS) coupled with gas (GC) or liquid (LC) chromatography.…”

Metabolic Dysfunction Biomarkers as Predictors of Early Diabetes

“…All manuscripts were carefully studied, and biomarkers were identified and counted. The analysis of the results identified two approaches to novel prediabetic biomarkers: metabolomics [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ], and microRNA studies [ 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ]. The results are shown in Figure 1 .…”

Branched chain amino acids—friend or foe in the control of energy substrate turnover and insulin sensitivity?

“…Recent study conducted on 1,321 individuals with different risks for type 2 diabetes (i.e., from ADDITION-PRO cohort) did not provide genetic evidence for the causative role of BCAA in the development of insulin resistance, but suggested that insulin resistance itself can evoke higher plasma fasting BCAA concentrations (Mahendran et al 2017). Nevertheless, the elevation in plasma BCAA and BCKA levels predicted type 2 diabetes development in various study cohorts and preceded the disease by over 10 years (Long et al 2020;Arany and Neinast 2018;Wang et al 2011). Therefore, BCAA are valuable biomarkers for early detection and diagnosis of insulin resistance in non-diabetic obese patients and strong indicators of the later risk of type 2 diabetes (Zhao et al 2016) as well as potential biomarkers in the diagnosis of diabetes complications (Del Coco et al 2019).…”