Sudomotor dysfunction is an early manifestation of diabetic neuropathy, but markers associated with progression of small-fiber dysfunction remain limited. A retrospective real-world cohort study published in Diabetes Metabolism Research and Reviews evaluated whether recovery in fasting C-peptide (ΔFCP) was associated with progression of sudomotor small-fiber dysfunction in adults with diabetes.

The analysis included 288 hospitalized adults with diabetes who underwent repeated fasting C-peptide testing and serial assessment of sudomotor small-fiber function using Sudoscan electrochemical skin conductance (ESC). Deterioration in sudomotor function was defined as worsening foot ESC. Progression of large-fiber neuropathy (LFN) and diabetic kidney disease (DKD) was assessed using nerve conduction and kidney outcomes. Cox proportional hazards models, restricted cubic splines, and subgroup, landmark, and sensitivity analyses were performed.

Findings

• Over a median follow-up of 2.2 years, higher ΔFCP was independently associated with lower risk of sudomotor small-fiber deterioration.
• Compared with the lowest ΔFCP tertile, the highest tertile was associated with lower risk of sudomotor deterioration (adjusted HR 0.31; 95% CI, 0.14-0.69; p<0.001).
• An optimal ΔFCP cutoff of 126.8 pmol/L was identified, and ΔFCP ≥126.8 pmol/L was associated with a 66% lower risk of sudomotor deterioration (HR 0.34; 95% CI, 0.17-0.69; p<0.001).
• Associations remained consistent in landmark and sensitivity analyses.
• No significant association was observed between ΔFCP and progression of LFN or DKD.
• Baseline C-peptide levels mediated only a small proportion of the observed association.

Higher fasting C-peptide recovery was associated with lower risk of progression of sudomotor small-fiber dysfunction, while no significant associations were observed for LFN or DKD progression.