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.

慢性肾病（CKD）导致对胰岛素代谢效应的敏感性降低。本研究对95名非糖尿病成年人在空腹状态下的血浆代谢组进行了分析（其中58名患有中度至重度CKD，37名肾小球滤过率正常），其中60名在胰岛素高血糖clamp实验期间采集了血浆（40名患有CKD）。我们评估了胰岛素反应的异质性，以识别潜在的联系CKD与胰岛素抵抗的细胞代谢通路。在空腹状态下，CKD组和对照组之间存在显著差异，包括色氨酸代谢、辅酶Q10生物合成和三羧酸循环的显著异常。胰岛素输注显著降低了血浆代谢物水平，主要是氨基酸及其代谢物。CKD与胰岛素诱导的烟酰胺、花生四烯酸以及谷氨酰胺/谷氨酸代谢通路的减弱改变相关。这些发现提示，氨基酸代谢和线粒体功能的广泛紊乱可能是CKD中胰岛素合成作用受损的潜在机制或表现。