Efficacy of rimonabant in obese patients with binge eating disorder.

In obesity, a dysregulation of the endocannabinoid system has been shown. The endocannabinoid receptor blockage by rimonabant demonstrated interesting metabolic effects. However, the role of rimonabant in weight loss of patients with binge eating disorder has not been investigated. Thus, our aim was to evaluate the effects of rimonabant on body weight in obese patients with binge eating disorders. This multicenter, randomized, double-blind, placebo-controlled study included 289 obese subjects (age 18-70 years, body mass index 30-45 kg/m(2)) with binge eating disorders. Subjects were randomized (1:1) to receive rimonabant 20 mg/day or placebo for 6 months. In total, 289 participants (age: 43.2±10.5 yrs, 91% of women) were randomized. The completer rate was similar (71%) in both treatment and placebo groups. Participants treated with rimonabant lost 4.7±5.2% of their initial body weight, vs. 0.4±4.5% in the placebo group (difference between both groups: 4.4±0.6 kg, p<0.0001). The rimonabant group showed a greater reduction on the binge eating scale total score (mean±SD - 40.9±35.2%) vs. placebo ( - 29.9±34.6%, p=0.02). The incidence of treatment emergent adverse events was comparable in both the rimonabant (82.5%) and placebo (76.0%) group. Discontinuations due to treatment emergent adverse events occurred in 13.3% rimonabant-treated vs. 6.2% placebo-treated participants. In conclusion, this is the only randomised, placebo-controlled, double-blind trial having assessed the effect of rimonabant in patients with binge eating disorders. The rimonabant treatment reduced body weight significantly more than placebo in obese subjects with binge eating. Trial registration number (clinicaltrials.gov): NCT00481975.

The effect of the triple monoamine reuptake inhibitor tesofensine on energy metabolism and appetite in overweight and moderately obese men.

BACKGROUND: Tesofensine (TE) is a new drug producing twice the weight loss in obese individuals as seen with currently marketed drugs. It inhibits the presynaptic reuptake of the neurotransmitters noradrenaline, dopamine and serotonin, and is thought to enhance the neurotransmission of all three monoamines. The mechanisms by which it produces weight loss in humans are unresolved. OBJECTIVE: The aim of this study is to investigate the mechanism(s) behind weight reduction by measuring energy expenditure and appetite sensations in overweight and obese individuals. DESIGN: Thirty-two healthy, overweight or moderately obese men were treated with 2.0 mg TE daily for 7 days followed by an additional 7 days with 1.0 mg TE daily or corresponding placebo (PL) in a randomized, controlled trial. They were instructed to maintain habitual food intake and physical activity throughout. Twenty-four-hour energy expenditure (24-h EE), fat oxidation and spontaneous physical activity were measured in a respiration chamber before and after treatment. Body composition was assessed by dual-energy X-ray absorption and appetite was evaluated by visual analogue scales in conjunction with a standardized dinner. RESULTS: Despite efforts to keep body weight and composition constant, TE induced a 1.8 kg weight loss above PL after 2 weeks' treatment (P<0.0001). TE also induced higher ratings of satiety and fullness and concomitantly lower prospective food intake than placebo. No significant effect of TE on total 24-h EE could be demonstrated compared with PL, but higher energy expenditure was observed during the night period (4.6%; P<0.05) when adjusted for changes in body composition. Furthermore, TE increased 24-h fat oxidation as compared with PL (18 g; P<0.001). CONCLUSION: TE has a pronounced effect on appetite sensations and a slight effect on energy expenditure at night-both effects can contribute to the strong weight-reducing effect of TE.

Visceral fat loss induced by a low-calorie diet: a direct comparison between women and men.

AIM: No studies have assessed if changes in visceral adipose tissue (VAT) during weight loss differ between women and men with comparable amounts of VAT at baseline. The aim of this study was to assess if changes in VAT induced by a low-calorie diet (LCD) differ between women and men. METHODS: In this post hoc analysis of an existing database, abdominal adipose tissue was evaluated before and after an 8-week LCD (800-1000 kcal/day) by a single-slice magnetic resonance scan performed at the abdominal level. Body composition was measured by dual X-ray energy absorptiometry. RESULTS: Data from 111 obese subjects (85 women and 26 men) were available. Relative changes in VAT were found to be more pronounced in men [mean (95% CI): -32.6% (-38.7 to -26.6)] than in women [-21.9% (-25.0 to -18.8)] (p = 0.003) after correction for relative changes in fat mass (FM). When analysing only the data from a subgroup of 23 women and 23 men who were matched for similar visceral to abdominal subcutaneous fat ratio at baseline, these differences could not be observed anymore: the change in VAT was -33.7% (-38.7 to -28.7) in men and -26.8% (-31.8 to -21.8) in women (p = 0.07). CONCLUSIONS: This study suggests that relative changes in VAT during a LCD may be greater in men than in women even after taking relative changes in FM into account. However, these differences disappear when properly matching the subjects for baseline amounts of VAT.

A critical review of the cannabinoid receptor as a drug target for obesity management.

The discovery of cannabinoids, with the well-known stimulatory effect of Cannabis sativa on appetite, has offered a new drug target for obesity treatment. Cannabinoids act on two different receptors: CB1 receptors which are sited in the brain and many peripheral tissues, and CB2 receptors which are primarily found in immune system cells. Cannabinoid receptor antagonists act centrally by blocking CB1 receptors, thereby reducing food intake. Moreover, they probably also act peripherally by increasing thermogenesis and therefore energy expenditure, as has been suggested by animal experiments. Despite these promising mechanisms of action, recent clinical studies examining the effect of the two CB1 receptor antagonists rimonabant and taranabant showed that the attained weight loss did not exceed that attained with other currently approved anti-obesity medications. Moreover, potentially severe psychiatric adverse effects limit their clinical use. As several new CB1 receptor antagonists are presently undergoing development, it remains to be elucidated to what extent they differ in terms of efficacy and safety. This review primarily discusses how close cannabinoid receptor antagonists are to the ideal anti-obesity drug, with respect to their mechanisms of action, clinical effectiveness and safety.

[Oral antidiabetic agents: which role in 2006?]. / Les antidiabétiques oraux: quelle place en 2006?

This article offers a review of the five classes of oral antidiabetics which are currently available, and focuses on practical considerations about the daily use of these drugs. Based on data from recent studies, it addresses several frequently asked questions. Which treatment to choose for which patient? How to adapt the treatment facing the progression of type 2 diabetes, which most often necessitates an intensification of the therapeutic means over time? Usually there are several initial therapeutic options for a given patient. The glycemic control over the following months allows to verify the efficiency of the treatment chosen. In case of a persistant glycemic imbalance, early intensification of the treatment is recommended.

[Nutritional follow-up after gastric bypass]. / Le suivi nutritionnel après bypass gastrique.

Roux-en-Y gastric bypass has become one of the main bariatric procedures. This surgical operation shows excellent results in weight evolution and quality of life and allows a decrease of mortality. However, it leads, relatively often, to nutritional deficiencies which need an effective post-operative follow-up. This follow-up includes not only medical and dietetic encounters but also regular blood analyses made every 3 months during the first post-operative year, every 6 months the second year, then each year. The most frequent deficiencies are those in vitamin B12, iron and folic acid. The secondary hyperparathyroidism characterized by an increase of PTH associated to a low vitamin D and a normal calcium, is quite frequent.

Changes in body composition, metabolic profile and nutritional status 24 months after gastric banding.

BACKGROUND: Laparoscopic adjustable gastric banding (LAGB) causes significant weight loss in morbidly obese adults. However, its consequences on nutritional status still remain unclear. This study aimed to investigate the effects of LAGB on body composition, metabolic profile and nutritional status in obese, premenopausal women. METHODS: 36 obese, premenopausal women (age 24-52 years; mean BMI 43.8 kg/m2) who underwent LAGB were included. Body composition was measured using dual-X-ray absorptiometry at baseline, 6, 12 and 24 months after surgery. Blood pressure, total cholesterol, HDL-cholesterol, triglycerides, glucose, uric acid, total proteins, iron, ferritin, vitamin B12, folic acid, hemoglobin and mean corpuscular volume were measured at baseline, 6, 12, 18 and 24 months after surgery. RESULTS: All patients lost weight over 24 months (range 16.0-71.9 kg): there was a significant loss of fat mass (-51.4%; P<0.0001) as well as of fat-free mass (-13.1%; P<0.0001). There was a significant improvement in blood pressure, glucose, total cholesterol, HDL-cholesterol, triglycerides and urates during the first year; during the second year, a further significant decline was noted only in glucose and urates. According to ATP III criteria, 21 of our patients (58%) had a metabolic syndrome before surgery, but only 9 of them (25%) after 12 months and 1 of them (3%) after 24 months. No nutritional deficiency was noted, except for a significant decrease in serum folate (44.1%; P<0.0001 between baseline and month 24). CONCLUSION: LAGB allows significant improvements in metabolic profile, especially during the first postoperative year, without causing major nutritional deficiencies, except for folates.

Gastric banding induces negative bone remodelling in the absence of secondary hyperparathyroidism: potential role of serum C telopeptides for follow-up.

OBJECTIVE: Data about the consequences of laparoscopic adjustable gastric banding (LAGB) on phospho-calcic and bone metabolism remain scarce. SUBJECTS: We studied a group of 37 obese premenopausal women (age: 24-52 y; mean BMI = 43.7 kg/m2) who underwent LAGB. METHODS: Serum calcium, phosphate, alkaline phosphatase, parathormone (PTH), vitamin D3, serum C-telopeptides, IGFBP-3 and IGF-1 were measured at baseline, 6, 12, 18 and 24 months after surgery. Body composition, bone mineral content (BMC) and density (BMD) were measured using dual-X-ray absorptiometry (DXA) at baseline, 6, 12 and 24 months after surgery. RESULTS: There was no clinically significant decrease of calcemia; PTH remained stable. Serum telopeptides increased by 100% (P < 0.001) and serum IGFBP-3 decreased by 16% (P < 0.001) during the first 6 months, and then stabilized, whereas IGF-1 remained stable over the 2 y. BMC and BMD decreased, especially at the femoral neck; this decrease was significantly correlated with the decrease of waist and hip circumference. CONCLUSIONS: We concluded that there was no evidence of secondary hyperparathyroidism 24 months after LAGB. The observed bone resorption could be linked to the decrease of IGFBP-3, although this decrease could be attributable to other confounding factors. Serum telopeptides seem to be a reliable marker of bone metabolism after gastric banding. DXA must be interpreted cautiously during major weight loss, because of the artefacts caused by the important variation of fat tissue after LAGB.

Metabolic impact of body fat distribution.

Many studies have shown that fat distribution influences metabolism independently of the effects of total body fat stores. The accumulation of fat in the abdominal area, particularly in the visceral fat compartment, seems to be associated with an increased risk to display complications such as insulin resistance, diabetes, dyslipidemias and atherosclerosis. As reviewed in this paper, the mechanisms explaining this impact of fat distribution is not clearly established, although evidence suggests that free-fatty acids, leptin, TNF-alpha, PPAR-gamma, and F are directly or indirectly involved in this process. Despite a lot of research has yet to be performed to mechanistically characterize the impact of visceral fat on the metabolic profile, there is enough consensus in the literature about its effect to justify its consideration in a clinical setting. In this regard, the use of waist circumference as a clinical marker of variations in visceral fat is highly relevant and should be encouraged. This review also presents an evolutionary perspective according to which body fat gain would have been and may still remain an adaptation that helps to deal with stress and inflammation.