No evidence for anti-islet autoimmunity in diabetes mellitus associated with chronic hepatitis C infection

✍ Scribed by Ilana Harman-Boehm; Leonid Zingman; Nir Hilzenrat

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 17 KB
• Volume: 30
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.510300128

✦ Synopsis

rats treated with acarbose alone showed a 5% body weight reduction as compared with controls. The Phase I enzymes were broadly but moderately induced, especially CYP 2E1, as measured by chlorzoxazone hydroxylation. Epoxide hydrolase was also slightly induced. No indication was found for an induction of oxidative stress or depletion of glutathione by acarbose treatment. In the glucose-supplemented group, no effects were seen on body weight gain. The effects of acarbose on the liver parameters almost completely disappeared. It can be concluded that-even at maximum exposure to acarbose and its metabolites-CYP 2E1 or other subtype-related toxicological effects in SD rats are only mediated by the carbohydrate deficiency in this experimental model.

Taking these data into consideration, the question arises whether the effects observed in the rat model under the specific conditions of malnutrition caused by carbohydrate depletion might be relevant for patients under acarbose treatment. Significant body weight reduction or other indicators of malnutrition have never been observed in the large number of clinical trials with healthy and diabetic subjects. 7 In a specially designed study, total caloric intake as well as the used portions of fat, protein, and particularly carbohydrate were unaffected by acarbose. 8 There was also no relevant caloric loss with feces under acarbose treatment. 9 This indicates that, under therapeutic use, acarbose only changed the rate of carbohydrate digestion but not its extent. Therefore, we conclude that a condition corresponding to that in rats treated with high doses of acarbose does not exist in patients. Thus, the potentiation of acetaminophen hepatotoxicity by acarbose can be considered as an effect specific to the rat model. An extrapolation of these findings to humans is not supported by the available data.