|Reference : Improvement of insulin-induced glucose disposal in obese patients with NIDDM after 1-wk ...|
|Scientific journals : Article|
|Human health sciences : Pharmacy, pharmacology & toxicology|
Human health sciences : Endocrinology, metabolism & nutrition
|Improvement of insulin-induced glucose disposal in obese patients with NIDDM after 1-wk treatment with d-fenfluramine.|
|Scheen, André [Université de Liège - ULg > Département des sciences cliniques > Diabétologie, nutrition et maladie métaboliques - Médecine interne générale >]|
|Paolisso, G. [> > > >]|
|Salvatore, T. [> > > >]|
|Lefebvre, Pierre [Centre Hospitalier Universitaire de Liège - CHU > > Diabétologie,nutrition, maladies métaboliques >]|
|American Diabetes Association|
|[en] Adult ; Blood Glucose/drug effects/metabolism ; Body Mass Index ; Diabetes Mellitus/blood/drug therapy ; Diabetes Mellitus, Type 2/blood ; Double-Blind Method ; Female ; Fenfluramine/pharmacology ; Glucose Clamp Technique ; Humans ; Insulin/blood ; Male ; Middle Aged ; Obesity|
|[en] OBJECTIVE: To study the short-term effects of the serotoninergic anorectic drug d-fenfluramine on insulin-induced glucose disposal. RESEARCH DESIGN AND METHODS: A randomized double-blind placebo-controlled crossover trial with 1-wk treatment periods (2 x 15 mg/day d-fenfluramine) was conducted. Twenty obese subjects, 10 with normal oral glucose tolerance and 10 with non-insulin-dependent diabetes mellitus (NIDDM), were all treated with a weight-maintaining diet. Euglycemic-hyperinsulinemic glucose clamps with measurement of glucose kinetics with D-[3-3H]glucose were performed at either two (patients without NIDDM, 0.05 and 0.10 U.kg-1.h-1) or three (patients with NIDDM, 0.05, 0.10, and 0.50 U.kg-1.h-1) insulin delivery rates. RESULTS: In the nondiabetic subjects, no significant changes in any metabolic or hormonal parameter were measured in the basal state or during the clamp despite a slight reduction in body weight (-1.2 +/- 0.5 kg, P less than 0.05). In the diabetic patients, no significant changes in body weight or basal plasma insulin levels were observed, but fasting blood glucose levels (8.0 +/- 0.8 vs. 9.4 +/- 1.1 mM, P less than 0.005) and plasma free fatty acid concentrations (1150 +/- 227 vs. 1640 +/- 184 microM, P less than 0.05) were significantly reduced after d-fenfluramine compared with placebo. During the clamp, insulin metabolic clearance rate (MCR) was similar after both placebo and d-fenfluramine; endogenous (hepatic) glucose production was similarly and almost completely suppressed, whereas glucose disposal was remarkably enhanced after d-fenfluramine (average increase of glucose MCR 35 +/- 12%, P less than 0.02). CONCLUSIONS: Whatever the mechanism(s) involved, a 1-wk treatment with d-fenfluramine induces better blood glucose control and improves insulin sensitivity in obese patients with NIDDM independent of significant weight reduction; this last effect is not present in obese subjects with normal oral glucose tolerance.|
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