Effect of aldose reductase inhibition on cardiovascular reflex tests in patients with definite diabetic autonomic neuropathy over a period of 2 years.
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patients on tolrestat (8.6%) developed high transaminases levels (more than threefold the upper normal limit) and were withdrawn from the study.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.
Didangelos
T P
TP
Diabetes Center, Second Propedeutic Department of Internal Medicine, Aristotelian University, Hippocration Hospital, Thessaloniki, Greece.
Karamitsos
D T
DT
Athyros
V G
VG
Kourtoglou
G I
GI
D000328:Adult; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D001341:Autonomic Nervous System / Q000503:physiopathology*; D002319:Cardiovascular System / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000627:therapeutic use*; D011446:Prospective Studies; D012018:Reflex
D004791:Enzyme Inhibitors; D009281:Naphthalenes; C040550:tolrestat; D000449:Aldehyde Reductase