EFFECTS OF DEXFENFLURAMINE ON FREE FATTY-ACID TURNOVER AND OXIDATION IN OBESE PATIENTS WITH TYPE-2 DIABETES-MELLITUS

To test the potential effects of dexfenfluramine (df) on enhancing fre e fatty acid (FFA) turnover and oxidation rates, 11 obese female non-i nsulin-dependent diabetes mellitus (NIDDM) outpatients (age, 52.5 +/- 1.5 years; weight, 81.3 +/- 3.2 kg; height, 158 +/- 3.04 cm; body mass index, 32.4 +/- 0.7 kg/m(2)) received a primed constant infusion of 1 -C-14-palmitate. The waist to hip ratio (WHR) was 0.91 +/- 0.04. Fat b ody mass and lean body mass, assessed by dual-energy x-ray densitometr y, were 32.0 +/- 1.5 and 49.30 +/- 2.67 kg, respectively. All patients had an average hemoglobin Al of 6.3% +/- 0.3% in the month preceding the study and had not received oral hypoglycemic agents. Gas exchange was measured both basally and during a ventilated-hood system, indirec t calorimetry session. The protocol was a randomized, placebo-controll ed, single blind design. Subjects received dF 30 mg acutely (n = 6) or a placebo (n = 5). A dose of dF 15 mg twice daily or placebo was then administered over 15 days (chronic). To obtain serum peak level of th e drug, dF was administered 2 hours before starting palmitate infusion . A free diet was allowed throughout the study, and the group treated with dF lost approximately 0.5 kg body weight. Acute and chronic dF ad ministration resulted in a significant increase in FFA oxidation, expr essed as a percentage of the dose of radiocarbon (respectively, 11.47% +/- 0.46% v 9.50% +/- 0.46% [P < .01] and 12.06% +/- 0.71% v 9.88% +/ - 0.62% [P < .01]). FFA turnover rate was higher after both acute and chronic dF administration (respectively, 10.71 +/- 2.18 v 7.79 +/- 1.4 8 mu mol/kg/min [P < .05] and 11.92 +/- 2.74 v 8.43 +/- 1.86 mu mol/kg /min [P < .05]). Serum FFA concentration during both acute and chronic dF administration increased, but not significantly. Mean serum glucos e level decreased after acute dF from 114.3 +/- 8.6 to 86.5 +/- 5.1 mg /dL (P < .001) and after chronic dF from 120.3 +/- 7.3 to 89.8 +/- 5.8 mg/dL (P < .001). Serum insulin was not affected by dF administration . In conclusion, oral acute and chronic dF administration increase FFA turnover and oxidation rates in NIDDM obese patients. This may play a n important role in weight reduction. In addition, dF shows a weight-i ndependent effect on glucose metabolism, reducing serum glucose levels without acting on insulin secretion. Copyright (C) 1995 by W.B. Saund ers Company