EFFECT OF ALDOSE REDUCTASE INHIBITION ON HEART-RATE-VARIABILITY IN PATIENTS WITH SEVERE OR MODERATE DIABETIC AUTONOMIC NEUROPATHY

Patients with diabetic autonomic neuropathy (DAN) have an increased ca rdiovascular mortality rate compared with diabetic patients without DA N. Heart rate variability (HRV) time and frequency domain indices are strong predictors of malignant arrhythmias and sudden cardiac death. T his prospective, randomised, double-blind, placebo-controlled study an alysed the long-term effect of an aldose reductase inhibitor, tolresta t, on HRV time and frequency domain variables in 45 patients with diab etes mellitus (DM) and DAN. Patients were randomised into tolrestat (n = 22) and placebo (n = 23) groups. Tolrestat (200 mg/day) or placebo were administered, respectively, for a period of 12 months. HRV was as sessed at months 0, 3, 6, 9 and 12. The HRV level of the 45 patients w as compared with that of 20 patients with DEVI, with analogous glycaem ic control, without DAN and 20 healthy controls, of similar age and ge nder. At the twelfth month, tolrestat, compared with placebo, had a be neficial effect on HRV indices related to vagal tone. Compared with ba seline, HRV time and frequency domain indices showed no significant im provement. Moreover, at the twelfth month of tolrestat administration, HRV indices remained less than that of patients with DM but without D AN, and healthy controls. The 12 patients of the 22 with moderate DAN benefited more than the 10 patients of the 22 with severe DAN. At the twelfth month no patient showed deterioration in HRV indices with tolr estat as was seen with placebo. Our data suggest that tolrestat slows down the progression of DAN compared with placebo. This effect of an a ldose reductase inhibitor may contribute to a reduction in risk for ma lignant ventricular arrhythmias. The early detection of DAN is imperat ive for successful intervention.