Reduction of Visceral Adipose Tissue and Improvement of Metabolic Indices: Effect of Dexfenfluramine in NIDDM

Abstract

Res. 1996;4:1-7. Increased visceral adipose tissue is thought to contribute to impaired glucose tolerance. We studied 10 men with non-insulin dependent diabetes (NIDDM) before and after a 12-week intervention study using dexfenfluramine. Subjects had a mean body mass index (BMI) of 26.4 ± 1.7 kg\m 2 and had an abdominal distribution of body fatness (waist-to hip ratio >0.9). Anthropometric indices, biochemistry, macronutrient intake from 7-day food records as well as a euglycaemic glucose clamp and magnetic resonance imaging (MRI) were performed at week 0 and week 12. Abdominal adipose tissue area measured by MRI was reduced from 854 ± 270 cm 2 to 666 ± 231 cm 2 (p=0.003) due mainly to a selective 32 % reduction in visceral fat area from 484 ± 230 cm 2 to 333 ± 72 cm 2 ( p=0.002). Insulin sensitivity improved from 0.29 ± 0.13 [min-1 (mUlL)] to 0.54 ± 0.21 [min-1 (mUlL)] (p=0.01) and C-peptide levels reduced from 0.77 ± 0.24 umol/L to 0.58 ± 0.15 umol/T, (p=0.002). The reductions in fasting glucose and glycated haemoglobin failed to achieve significance. Fasting total cholesterol and triglyceride levels significantly reduced (p=<0.001 and p=O.021 respectively). There was a reduction in total energy intake (p=0.005) due to a significant reduction in calories obtained from fat (p<0.001). Thus dexfenfluramine was shown to be a useful adjunct therapy for the reduction of visceral fat in abdominally-obese men with NIDDM with an associated improvement in insulin sensitivity.

Reduction of visceral adipose tissue during weight loss

“…The fact that men in the present study lost more fat from the VAT compartment than from the SAT depot is in accordance with other clinical trials which also used drug therapy to induce weight loss (Marks et al, 1996(Marks et al, ,1998. In the study of Marks et al, (1998) placebo-treated men lost significantly less VAT than men who received the dexfenfluramine treatment.…”

“…This observation is in accordance with two other recent studies that reported differences of the same magnitude (Goodpaster et al, 1999;Wirth & Steinmetz, 1998). However, it has been suggested that individuals who display large initial amounts of VAT are also characterized by a more substantial reduction of this depot during weight loss interventions Leenen et al, 1992;Marks et al, 1996Marks et al, ,1998. Since men in the present study displayed VAT levels that were higher than those measured in women, initial levels of VAT were also considered as a potential covariate of the changes of VAT which occurred in response to weight loss.…”

“…Moreover, it has also been reported that a lesser decrease in VAT is observed in women than in men in response to weight loss (Goodpaster et al, 1999;Wirth & Steinmetz, 1998). Since large initial levels of VAT seem to be associated with the reduction of fat from this compartment during weight loss Marks et al, 1996Marks et al, ,1998, these gender differences in VAT reduction are possibly attributable to higher initial levels of VAT in men. Accordingly, it has been recently demonstrated that, when pre-treatment VAT levels are taken into account, no difference in the reduction of fat from this compartment in response to weight loss could be observed between men and women (Janssen & Ross, 1999).…”

Preferential loss of omental-mesenteric fat during growth hormone therapy of HIV-associated lipodystrophy

“…INCREASED INTRA-ABDOMINAL ADIPOSE TISSUE (IAAT) has been linked to metabolic perturbations, especially hyperlipidemia and insulin resistance (21,23), and reduction of intra-abdominal fat has been shown to improve insulin sensitivity in both animals (2) and humans (17,26). A substantial proportion of human immunodeficiency virus (HIV)-infected individuals on highly active antiretroviral therapy (HAART) develop fat redistribution, or HIV lipodystrophy, which is characterized by increased IAAT and/or depletion of subcutaneous adipose tissue (3)(4)(5).…”

The impact of pharmacotherapy on weight management in type 2 diabetes

“…31 Another study demonstrated that dexfen¯ur-amine preferentially reduces abdominal fat and, therefore, may have a special potential in the treatment of obese subjects with the metabolic syndrome. 32 However, due to possible serious adverse effects on heart valves, fen¯uramine and dexfen¯uramine were withdrawn in 1997. 24 Fluoxetine selectively inhibits the central reuptake of serotonin and is widely used as an antidepressant drug.…”