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.

慢性肾脏病（Chronic kidney disease, CKD）可降低机体对胰岛素代谢效应的敏感性。本研究针对95名无糖尿病的空腹成人开展血浆代谢组分析，其中58名为中重度CKD患者，37名为肾小球滤过率正常者；该队列中60名受试者接受了高胰岛素正糖钳夹试验（hyperinsulinemic-euglycemic clamp）下的血浆采集，其中40名为CKD患者。本研究评估了胰岛素应答的异质性，以识别将CKD与胰岛素抵抗相关联的潜在细胞代谢通路。空腹状态下，CKD患者与对照组受试者的差异主要体现为色氨酸代谢、泛醌生物合成以及三羧酸循环（TCA cycle）存在显著异常。胰岛素输注可显著降低血浆代谢物水平，其主要影响氨基酸及其代谢产物。CKD与胰岛素诱导的烟酰胺、花生四烯酸以及谷氨酰胺/谷氨酸代谢通路的变化减弱相关。上述研究结果表明，氨基酸代谢与线粒体功能的广泛紊乱，或为CKD患者胰岛素合成代谢效应受损的潜在机制或表现形式。