Effects Of N-3 Fatty Acids Supplements On Urine Metabolites In Patients With Type 2 Diabetes

Aims:The present study aimed to investigate the effects of n-3 fatty acids supplements on urine metabolites profiling and their relationship with type 2 diabetes(T2D)risk factors in T2D patients.Methods:A double-blind randomized controlled trial was conducted in 59 patients with T2D,who were randomized to receive either fish oil(FO),flaxseed oil(FSO)or corn oil(CO,served as a control group)capsules for 180 days.Morning urine samples were collected before and after the intervention and were analyzed for metabolomics by UHPLC-Q-Exactive Orbitrap/MS in positive and negative ionization modes.Results:A total of 51 participants were included in the urine metabolomics analysis.In the FO group,levels of 2-hexenoylcarnitine(C6:1)(p<0.001)and 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid(CMPF)(p=0.004)were significantly increased while hydroxyisovaleroyl carnitine(C5:OH)(p<0.001)were significantly decreased compared with CO group.In addition,geranylacetone(p=0.023)and citronellyl propionate(p=0.038)levels were significantly elevated,while dihydrojasmonic acid(p=0.003)was significantly reduced in the FSO compared with CO group.Moreover,increased C6:1 was correlated with decreased serum triglycerides(r=-0.340,p=0.020).Change of C5:OH was positively correlated with BUN and APOB(r=0.327,p=0.025;r=0.386,p=0.015).Change of urine CMPF showed inverse correlation with BUN(r=-0.338,p=0.020).Besides,change of serum CMPF was positively correlated with urine CMPF(r=0.646,p<0.001).Conclusions:The present study confirmed that CMPF is a strong biomarker of fish oil,indicated that increased level of CMPF may have a positive effect on glucose and lipid metabolism in Chinese T2D patients and marine n-3 PUFA intake might has a beneficial effect on lipid metabolism and renal function in patients with T2D.