Influence of long-term aldose reductase inhibitor therapy on autonomic dysfunction of urinary bladder, stomach and cardiovascular systems in diabetic patients.
The effects of the aldose reductase inhibitor (ARI) sorbinil (250 mg/day) were tested in an open-label pilot study over 1 year, in eight diabetics with peripheral neuropathy, seven of whom had symptomic autonomic neuropathy (AN). Autonomic function studies of the urinary bladder, stomach and cardiovascular system were performed at baseline, 6 and 12 months. Six patients reported improvement in symptoms of AN by 6 months which was maintained or further improved by 12 months. Bladder sensation, as measured by cystometrographic parameters, improved at 6 months (P less than 0.02- less than 0.04), but by 12 months had reverted to baseline. Residual urine volume decreased at 6 months (P less than 0.06) and 12 months (P less than 0.06). Vagally mediated gastric acid secretion improved at 6 months (P less than 0.06); the subgroup of patients with subnormal secretion showed improvement to the normal range at 6 months (P less than 0.03). Gastric emptying of solid food was normal in six of eight subjects and showed no significant change at 6 months. Both patients with delayed emptying normalized. No change in beat-to-beat variability in heart rate with respiration was noted. Resting minimum heart rate decreased at 12 months (P less than 0.05). Glycohemoglobin levels showed no statistically significant changes. No toxic reactions were observed. These data suggest a beneficial effect of ARI treatment on symptomatic and asymptomatic manifestations of diabetic autonomic neuropathy and indicate a need for large controlled trials.
D000328:Adult; D000368:Aged; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D001342:Autonomic Nervous System Diseases / Q000188:drug therapy* / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000294:innervation* / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D048289:Imidazolidines; D008297:Male; D013270:Stomach / Q000294:innervation* / Q000503:physiopathology; D013401:Sugar Alcohol Dehydrogenases / Q000037:antagonists & inhibitors*; D001743:Urinary Bladder / Q000294:innervation* / Q000503:physiopathology
D007093:Imidazoles; D048289:Imidazolidines; D013401:Sugar Alcohol Dehydrogenases; D000449:Aldehyde Reductase; C026411:sorbinil