Metabolite deficits and microbial disruption marked the earliest signals of DPNS. Diabetes, Metabolic Syndrome and Obesity published this trial investigating metabolic and microbial alterations linked to muscle loss in diabetic neuropathy.

This cross-sectional analysis evaluated 151 individuals with diabetic neuropathy using metabolomics and 16S rRNA sequencing. Metabolic profiles, microbial composition, and pathway enrichment were compared between DPNS and DPN groups to identify early biological alterations.

A total of 376 differential metabolites were identified. DPNS presented lower glycerophosphocholine, taurine, and succinic acid. Levels of 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine and sphingosine were higher. Microbial diversity was reduced, with fewer Faecalibacterium and Bacteroides and more Streptococcus. Enrichment analysis highlighted necroptosis, sphingolipid metabolism, the mTOR pathway, ABC transporters, and bile secretion as key pathways.

These results indicate combined metabolic and microbial disruption in DPNS. The identified signatures strengthen the biological link between neuropathy and muscle loss. Such mechanisms highlight opportunities for earlier diagnosis and precision therapy in affected individuals.