Serum metabolomics profiles in response to n-3 fatty acids in Chinese patients with type 2 diabetes: a double-blind randomised controlled trial.

Key Findings

Type 2 diabetes (T2D) is characterized by insulin resistance and impaired β -cell function. There remains differences in the results of mechanistic studies and human studies with regard to how n-3 PUFA might influence the pathogenesis of T2D. A multi-centre double-blind parallel randomised controlled trial (n = 185) was conducted to investigate the effects of n-3 PUFA supplements (both marine [fish oil] and plant source [flaxseed oil]) on glycaemic traits in Chinese patients with T2D. Using a metabolomics approach, it was found that both the plant-based and marine-based PUFA interventions led to significant changes in metabolite patterns. The concentration of serum 3-carboxy-4-methyl-5-propyl-2-furanpropanoate (CMPF) significantly increased in response to the intervention of marine-based PUFA. In the case-control comparison at baseline, CMPF was substantially higher in the healthy controls than in the T2D patients. In previous research, CMPF was elevated in the plasma of patients with gestational diabetes, impaired glucose-tolerance or T2D. In addition, a rodent experiment demonstrated that CMPF could directly affect β -cell function, impair mitochondrial function, decrease glucose-induced ATP accumulation and induce oxidative The authors concluded that the overall association of CMPF with glycaemic traits was not clear, and research with larger sample sizes is needed.

Abstract

We aimed to investigate the change of serum metabolomics in response to n-3 fatty acid supplements in Chinese patients with type 2 diabetes (T2D). In a double-blind parallel randomised controlled trial, 59 Chinese T2D patients were randomised to receive either fish oil (FO), flaxseed oil (FSO) or corn oil capsules (CO, served as a control group) and followed up for 180 days. An additional 17 healthy non-T2D participants were recruited at baseline for cross-sectional comparison between cases and non-cases. A total of 296 serum metabolites were measured among healthy controls and T2D patients before and after the intervention. Serum 3-carboxy-4-methyl-5-propyl-2-furanpropanoate (CMPF) (P interaction = 1.8 × 10 (-7)) was the most significant metabolite identified by repeated-measures ANOVA, followed by eicosapentaenoate (P-interaction = 4.6 × 10(-6)), 1-eicosapentaenoylglycerophosphocholine (P-interaction = 3.4 × 10(-4)), docosahexaenoate (P-interaction = 0.001), linolenate (n-3 or n-6, P-interaction = 0.005) and docosapentaenoate (n-3, P-interaction = 0.021). CMPF level was lower in T2D patients than in the healthy controls (P = 0.014) and it was significantly increased in the FO compared with CO group (P = 1.17 × 10(-7)). Furthermore, change of CMPF during the intervention was negatively correlated with change of serum triglycerides (P = 0.016). In conclusion, furan fatty acid metabolite CMPF was the strongest biomarker of fish oil intake. The association of CMPF with metabolic markers warrants further investigation.