Effect of Aldose Reductase Inhibition on Cardiovascular Reflex Tests in Patients with Definite Diabetic Autonomic Neuropathy Over a Period of 2 Years

• Published in: Journal of diabetes and its complications Vol. 12; no. 4; pp. 201 - 207
• Main Authors: Didangelos, Triantaffilos P., Karamitsos, Dimitrios T., Athyros, Vasilios G., Kourtoglou, Georgios I.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.07.1998; Elsevier Science
• Subjects: Adult; Aldehyde Reductase - antagonists & inhibitors; Autonomic Nervous System - physiopathology; Biological and medical sciences; Cardiovascular System - physiopathology; Diabetic Neuropathies - drug therapy; Diabetic Neuropathies - epidemiology; Diabetic Neuropathies - physiopathology; Enzyme Inhibitors - therapeutic use; Female; Hormones. Endocrine system; Humans; Male; Medical sciences; Middle Aged; Naphthalenes - therapeutic use; Pharmacology. Drug treatments; Prospective Studies; Reflex; Greece; Europe; Endocrinopathy; Human; Immunopathology; Nervous system diseases; Enzyme; Treatment efficiency; Enzyme inhibitor; Autoimmune disease; Non insulin dependent diabetes; Long term; Heart rate; Chemotherapy; Valsalva maneuver; Treatment; Diseases of the autonomic nervous system; Aldehyde reductase; Insulin dependent diabetes; Adult; Complication; Oxidoreductases; Postural fitting; Tolrestat; Comparative study
• ISSN: 1056-8727; 1873-460X
• DOI: 10.1016/S1056-8727(97)00121-9

The potential of the aldose reductase inhibitor tolrestat to ameliorate definite diabetic autonomic neuropathy (DAN), as defined by standard cardiovascular autonomic function tests, was evaluated in 35 patients over a period of 2 years, with repeated measurements at 3-month intervals. The effect of tolrestat (200 mg a day) was compared with that of placebo on 35 controls with diabetes mellitus, of similar age, gender, and glycemic control. In the placebo group, a significant deterioration of the indices, with the exception of Valsalva ratio, was recorded, while tolrestat induced a significant beneficial change in the values of most standard cardiovascular reflex tests, in comparison to baseline and placebo. The deep breathing tests (expiration–inspiration ratio, standard deviation, and mean circular resultant of R-R intervals), postural index, and postural hypotension were favorably affected. Three of 35 patients on tolrestat (8.6%) developed high transaminases levels (more than threefold the upper normal limit) and were withdrawn from the study. In conclusion, tolrestat improved autonomic nervous system function in patients with definite DAN, in comparison to baseline and placebo. The clinical importance of this finding needs further investigation.