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Abstract
To test the potential effects of dexfenfluramine (dF) on enhancing free fatty acid
(FFA) turnover and oxidation rates, 11 obese female non—insulin-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/m2) received a primed-constant infusion of 1-14C-palmitate. The waist to hip ratio (WHR) was 0.91 ± 0.04. Fat body mass and lean
body mass, assessed by dual-energy x-ray densitometry, were 32.0 ± 1.5 and 49.30 ±
2.67 kg, respectively. All patients had an average hemoglobin A1 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,
indirect-calorimetry session. The protocol was a randomized, placebo-controlled, 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 the 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 administration resulted
in a significant increase in FFA oxidation, expressed 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 ± 1.48 μmol/kg/min [P < .05] and 11.92 ± 2.74 v 8.43 ± 1.86 μmol/kg/min [P < .05]). Serum FFA concentration during both acute and chronic dF administration
increased, but not significantly. Mean serum glucose 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 an important role in weight reduction. In addition,
dF shows a weight-independent effect on glucose metabolism, reducing serum glucose
levels without acting on insulin secretion.
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© 1995 Published by Elsevier Inc.
