Reduced heart rate variability predicts incident diabetic polyneuropathy
Objective To determine whether cardiovascular autonomic neuropathy (CAN) and reduced heart rate variability (HRV) predict the development of distal symmetrical polyneuropathy (DSPN) in individuals with diabetes mellitus (DM). Methods A total of 288 individuals with DM (mean age 58.1 ± 13.4 years, 41.3% women, 78.5% with type 2 diabetes) underwent baseline assessment of CAN using cardiovascular autonomic reflex tests and HRV indices (CVRR, rMSSD, high- and low-frequency power). DSPN was characterized using three definitions: (i) clinical criteria based on symptoms and signs, (ii) the sensory-loss phenotype derived from quantitative sensory testing, and (iii) the Toronto consensus definition requiring abnormal nerve conduction plus symptoms or signs. A total of 194 participants without DSPN at baseline were followed for 3.0 ± 1.3 years to assess incident DSPN. Results At baseline, CAN prevalence was 16.3%, and low HRV indices were present in 18.6–40.2% of participants. DSPN prevalence was 27.7%, 17.6%, and 20.8% for definitions (i), (ii), and (iii), respectively. Cross-sectionally, CAN and reduced HRV were associated with DSPN (unadjusted ORs 1.8–4.0), with associations largely persisting after adjustment. Incident DSPN occurred at 8.4, 5.7, and 3.3 per 100 person-years. Baseline CAN independently predicted incident DSPN (adjusted HRs 6.20, 3.30, and 7.33 across definitions). Lower rMSSD, HF power, and LF power predicted incident DSPN according to definitions (i) and (iii), whereas reduced CVRR predicted DSPN defined by criteria (ii). Conclusions Established CAN is a strong predictor of future DSPN. Reduced HRV provides a practical, accessible alternative marker for identifying individuals at elevated neuropathy risk.