Tolrestat in the Primary Prevention of Diabetic Neuropathy
- Dario Giugliano, MD,
- Rita Acampora, MD,
- Raffaele Marfella, MD,
- Giosué Di Maro, MD,
- Nicoletta De Rosa, MD,
- Lucio Misso, MD,
- Antonio Ceriello, MD,
- Antonio Quatraro, MD and
- Felice D'Onofrio, MD
- Department of Gerontology and Metabolic Diseases, Second University of Naples, and the Diabetic Clinic Lepanto Naples, Italy
- Address correspondence and reprint requests to Dario Giugliano, MD, Via Emilia 1, 80021 Afragola (NA), Italy.
Abstract
OBJECTIVE To compare the effects of tolrestat and placebo in patients with subclinical diabetic neuropathy.
RESEARCH DESIGN AND METHODS Non-insulin-dependent diabetes mellitus (NIDDM) patients with early involvement of the autonomic nervous system were identified by only one pathological (outside the 99% confidence interval of the normal population) squatting test (vagal or sympathetic). Fifty-seven patients entered a randomized, placebo-controlled, double-blind, parallel 52-week study of tolrestat at a dose of 200 mg/day. Cardiovascular reflex tests (squatting vagal and sympathetic tests, pressure gain, deep breathing, lying-to-standing, Valsalva maneuver, and orthostatic hypertension), vibration thresholds, tendon reflexes, and muscle strength were assessed throughout the study.
RESULTS At 12 months, nerve function significantly improved in patients receiving tolrestat and deteriorated in patients taking placebo. At baseline, the squatting vagal test was normal in 16 patients in the tolrestat group and in 15 patients in the placebo group. At 12 months, 25 patients taking tolrestat had a normalized squatting test, but only 6 patients taking placebo did (P = 0.02). Vibration perception threshold improved by a value of 6 ± 3 V in the tolrestat group (P < 0.001) and deteriorated by a value of 3 ± 1.8 V (P < 0.001) in the placebo group.
CONCLUSIONS Tolrestat may be useful in the primary prevention of diabetic neuropathy.
- Received May 9, 1994.
- Revision received November 17, 1994.
- Accepted November 17, 1994.
- Copyright © 1995 by the American Diabetes Association
