This paper is only available as a PDF. To read, Please Download here.
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.
To read this article in full you will need to make a payment
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to Metabolism - Clinical and Experimental
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
- d-Fenfluramine selectively suppresses carbohydrate snacking by obese subjects.Int J Eating Disord. 1985; 4: 89-99
- Model system for investigating the actions of anorectic drugs: Effects of dexfenfluramine.in: Ferrari E Brambilla F Disorders of Eating Behaviour: A Psychoneuronendocrine Approach. Pergamon, New York, NY1986: 377-389
- Serotoninergic modulation of the pattern of eating and the profile of hunger-satiety in humans.Int J Obes. 1987; 11: 141-155
- Serotonin manipulations and structure of feeding behaviour.Appetite. 1986; 7: 39-56
- Effect of d-fenfluramine on basal glucose turnover and fat-feeding-induced insulin resistance in rats.Diabetes. 1989; 38: 499-503
- Acute and chronic effects of dexfenfluramine on glucose and insulin response to intravenous glucose in diabetic and non-diabetic obese subjects.Diabetes Res. 1992; 19: 165-176
- Improvement of insulin-induced glucose disposal in obese patients with NIDDM after 1-wk treatment with d-fenfluramine.Diabetes Care. 1991; 14: 325-332
- The effects of dexfenfluramine on blood glucose control in patients with type 2 diabetes.Diabetic Med. 1992; 9: 341-343
- Fenfluramine increases insulin action in patients with NIDDM.Diabetes Care. 1989; 12: 252-258
- Hypoglycemic effect of fenfluramine in insulin-treated diabetics.Clin Invest Med. 1986; 9: 12-14
- Lipostatic and ischymetric mechanisms originate dexfenfluramine-induced anorexia.Pharmacol Biochem Behav. 1988; 30: 89-99
- Correlation between metabolic and behavioral effects of dexfenfluramine treatment.Clin Neuropharmacol. 1988; 11 (suppl): S93-S96
- Turnover and oxidation rates of plasma free fatty acids in obese patients treated with dexfenfluramine.Ann Nutr Metab. 1993; 37: 237-244
- Dual photon absorptiometry: Validation of mineral and fat measurements.Basic Life Sci. 1990; 55: 327-337
- Free fatty acid mobilization and oxidation during total parenteral nutrition in trauma and infection.Ann Surg. 1983; 198: 725-735
- Collection of CO2.in: Liss AR Tracers in Metabolic Research. Raven, New York, NY1984
- Effect of carbohydrate and fat intake on nitrogen excretion during total intravenous feeding.Am Surg. 1977; 185: 417-422
- An application of high performance liquid chromatography to analysis of lipids in archeological samples.J Lipid Res. 1981; 22: 778-784
- Influences of glucose loading and of injected insulin on hepatic glucose output.Ann NY Acad Sci. 1959; 82: 420-430
- Influence of body fat distribution on free fatty acid metabolism in obesity.J Clin Invest. 1989; 83: 1168-1173
- Relationship of body fat topography to insulin sensitivity and metabolic profiles in premenopausal women.Metab Clin Exp. 1984; 33: 68-75
- Relationship between skeletal muscle, insulin resistance, insulin-mediated glucose disposal, and insulin binding: Effects of obesity and body topography.J Clin Invest. 1984; 74: 1515-1525
- The glucose—fatty acid cycle: Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus.Lancet. 1963; 1: 785-789
- Effect of fatty acids on glucose production and utilization in man.J Clin Invest. 1983; 72: 1737-1747
- Sustained decreases in weight and serum insulin, glucose, triacylglycerol and cholesterol in JCR: LA-corpulent rats treated with d-fenfluramine.Br J Pharmacol. 1992; 105: 579-685
- Neuroendocrine regulation and obesity.Int J Obes. 1992; 16 (suppl): S73-S79
© 1995 Published by Elsevier Inc.