Diabetes-Associated Metabolic Reprogramming in Early-Stage Chronic Kidney Disease: An NMR Metabolomics Approach

UPASNA GUPTA (Centre of Biomedical Research, SGPGIMS Campus, Lucknow, India)

LinkedIn: Upasna Gupta, X: @Upasnagupta30

Abstract: Type 2 diabetes mellitus (T2DM) exacerbates the progression of chronic kidney disease (CKD) by intensifying metabolic and oxidative stress, however the underlying biochemical mechanisms remain incompletely understood in early stage CKD. This study aimed to delineate early metabolic alterations in CKD and to investigate diabetes-associated metabolic reprogramming using serum NMR-based metabolomics. A cohort of 100 early-stage CKD patients was analyzed using multivariate and univariate statistical approaches combined with pathway enrichment analysis. Distinct metabolic profiles clearly separated diabetic CKD from non-diabetic CKD. Notably, decreased levels of citrate, serine, and methionine indicated impaired tricarboxylic acid (TCA) cycle activity and disrupted one-carbon metabolism, consistent with a shift in systemic energy handling. Pathway analysis further confirmed significant perturbations in amino acid metabolism and central carbon metabolism, collectively suggesting diabetes-driven metabolic reprogramming in early CKD. These findings identify potential early biomarkers and provide mechanistic insight into diabetes-associated metabolic reprogramming, offering avenues for improved risk stratification and precision therapeutic strategies.