Sarcopenia is a novel complication of type 2 diabetes mellitus (T2DM), the incidence of which is rapidly increasing. Therefore, early detection and diagnosis of diabetic sarcopenia is important to improve the quality of life of patients.Differentially expressed genes (DEGs) were identified from GEO datasets GSE76895 and GSE1428. GO and KEGG pathway analyses were conducted using DAVID and KOBAS. Hub gene of metabolic pathways were validated using gene expression and ROC curves. Hub gene expression was then validated in mouse models and human populations, and therapeutic potential was assessed.The metabolic pathway is an important pathophysiological feature of T2DM and sarcopenia, with 17 genes co-enriched in this pathway. We focused on the PGK1, stained by immunofluorescence and western blot analysis revealed significantly lower expression of PGK1 in pancreatic islets and skeletal muscles of T2DM mice, with a negative correlation with the diabetic cycle. Similarly, serum levels of PGK1 were lower in T2DM patients than in healthy individuals. Overexpression of PGK1 alleviates metabolic stress and improves skeletal muscle function in diabetic sarcopenia, highlighting its potential as a therapeutic target.These results suggest that PGK1 may serve as a novel biomarker and potential target for diabetic sarcopenia.© The Author(s) 2025. Published by Oxford University Press on behalf of the Association of Physicians.