Metabolic signatures and risk of type 2 diabetes in a Chinese population: an untargeted metabolomics study using both LC-MS and GC-MS

Abstract

Aims/hypothesis Metabolomics has provided new insight into diabetes risk assessment. In this study we characterised the human serum metabolic profiles of participants in the Singapore Chinese Health Study cohort to identify metabolic signatures associated with an increased risk of type 2 diabetes. Methods In this nested case-control study, baseline serum metabolite profiles were measured using LC-MS and GC-MS during a 6-year follow-up of 197 individuals with type 2 diabetes but without a history of cardiovascular disease or cancer before diabetes diagnosis, and 197 healthy controls matched by age, sex and date of blood collection. Results A total of 51 differential metabolites were identified between cases and controls. Of these, 35 were significantly associated with diabetes risk in the multivariate analysis after false discovery rate adjustment, such as increased branchedchain amino acids (leucine, isoleucine and valine), nonesterified fatty acids (palmitic acid, stearic acid, oleic acid and linoleic acid) and lysophosphatidylinositol (LPI) species Conclusions/interpretation Our findings show that branched-chain amino acids and NEFA are potent predictors of diabetes development in Chinese adults. Our results also indicate the potential of lysophospholipids for predicting diabetes.Electronic supplementary material The online version of this article

Plasma branched chain/aromatic amino acids, enriched Mediterranean diet and risk of type 2 diabetes: case-cohort study within the PREDIMED Trial

“…The pooled RR per SD of each amino acid ranged from 1.26 (95% CI 1.10, 1.44) to 1.36 (95% CI 1.24, 1.48) [6]. However, none of these studies or subsequent studies [7–13] used repeated measurements of these amino acids over time nor evaluated how dietary interventions can influence changes in the levels of these plasma amino acids and risk of type 2 diabetes. This more dynamic assessment is important because a decreased uptake and an increased release of amino acids from skeletal muscle can also be a consequence of increased protein catabolism with underlying insulin resistance [14].…”

Targeting BCAA Catabolism to Treat Obesity-Associated Insulin Resistance

“…The three branched-chain amino acids (BCAAs) are leucine, isoleucine, and valine. A strong association between elevated plasma BCAAs and insulin resistance (IR) has been repeatedly observed in human and rodent models (1)(2)(3)(4)(5)(6)(7)(8)(9). Moreover, longitudinal studies suggest that a high plasma BCAA level is predictive of the future onset of diabetes (10)(11)(12)(13).…”

3‐carboxy‐4‐methyl‐5‐propyl‐2‐furanpropanoic acid (CMPF): A metabolite identified after consumption of fish oil and fish

“…In the past few years, there have been a number of publications implicating CMPF as a compound with functions related to the causality of type 2 diabetes (Prentice et al 2014;Koppe & Poitout 2016;Liu et al 2016). However, the subject is still very controversial as there are other studies that do not support such associations Lu et al 2016;Retnakaran et al 2016;Zheng et al 2016). In none of these studies on CMPF and type 2 diabetes did the authors report whether the subjects' renal function was impaired and this may have confounded results.…”