SUGAR metabolomics dataset

Chronic kidney disease (CKD) leads to decreased sensitivity to the metabolic effects of insulin. We examined the plasma metabolome in 95 adults without diabetes in the fasted state (58 with moderate-severe CKD, 37 with normal glomerular filtration rate) of whom 60 had plasma collected during a hyperinsulinemic-euglycemic clamp (40 with CKD). We assessed heterogeneity in the response to insulin to identify potential cellular metabolic pathways linking CKD with insulin resistance. In the fasting state, differences between CKD and control subjects included significant abnormalities in tryptophan metabolism, ubiquinone biosynthesis, and the TCA cycle. Insulin infusion markedly decreased plasma metabolite levels, predominantly amino acids and their metabolites. CKD was associated with attenuated insulin-induced changes in nicotinamide, arachidonic acid, and glutamine/glutamate metabolic pathways. These findings suggest that broad disruption in amino acid metabolism and mitochondrial function as putative mechanisms or manifestations of the impaired anabolic effects of insulin in CKD.