Overweight and obesity affect treatment response in major depression.

BACKGROUND: Epidemiologic and clinical studies suggest comorbidity between major depressive disorder (MDD) and obesity. To elucidate the impact of weight on the course of depression beyond comorbidity, we investigated psychopathology, attention, neuroendocrinology, weight change, and treatment response in MDD patients, depending on their weight. METHODS: Four hundred eight inpatients with MDD participated in the Munich Antidepressant Response Signature Study, designed to discover biomarkers and genotypes that are predictive for clinical outcome. Psychopathology and anthropometric parameters were monitored weekly in 230 patients. In subsamples, combined dexamethasone-corticotropin-releasing hormone and attention tests were conducted at admission and discharge. One thousand twenty-nine diagnosed matched controls served for morphometric comparisons. RESULTS: Patients with MDD had a significantly higher body mass index (BMI) compared with healthy controls. Patients with high BMI (> or =25) showed a significantly slower clinical response, less improvement in neuroendocrinology and attention, and less weight gain than did patients with normal BMI (18.5 < or = BMI < 25) during antidepressant treatment. CONCLUSIONS: Our findings suggest that overweight and obesity characterize a subgroup of MDD patients with unfavorable treatment outcome.

Histamine H1-receptors differentially mediate the action of amylin on hypothalamic neurons in control and in overweight rats.

The hypothalamic arcuate, dorsomedial and paraventricular nuclei are involved in regulation of body weight and food intake and contain binding sites for the anorexigenic amylin. Effects of amylin on medial arcuate and paraventricular neurons studied in adult rats overweight through early postnatal overfeeding in small litters (SL) differed from those of control litters (CL). Now we observed that also dorsomedial neurons respond differentially to this satiety signal. They were significantly inhibited by amylin in SL but not CL rats. Since the histaminergic system seems to be involved in mediating effects of amylin, we studied the role of histamine H(1)-receptors. Single unit activity was recorded in brain slices of CL and SL rats in each of the three hypothalamic nuclei. The histamine H(1)-receptor antagonist pyrilamine differentially altered or reduced responses to amylin, not depending on the kind of litter but on the functional effect of the peptide. Pyrilamine prevented significant inhibition of medial arcuate neurons in controls as well as inhibition of dorsomedial and paraventricular neurons in SL rats. Searching for further mechanisms possibly contributing to the change of neuronal responses we found that in the presence of a GABA(A)-receptor antagonist amylin induced a significant inhibition of medial arcuate neurons in SL rats similar to that in CL without antagonist. Activation of medial arcuate neurons expressing the orexigenic neuropeptide Y and inhibition of dorsomedial and paraventricular neurons in SL rats may in vivo contribute to hyperphagia and overweight. Histamine H(1)-receptors and GABA(A)-receptors seem to be differentially involved in mediation of these effects.

Pharmacotherapeutic options for overweight adolescents.

OBJECTIVE: To evaluate the safety and efficacy of current pharmacotherapeutic options for weight loss in overweight adolescents. DATA SOURCES: Literature was obtained through MEDLINE Ovid (1996-April 2007) and EMBASE Drugs and Pharmacology (1991-2nd quarter 2007) searches and a bibliographic review of published articles. Key words included adolescents, overweight, obesity, anti-obesity agents, drug therapy, orlistat, sibutramine, and metformin. STUDY SELECTION AND DATA EXTRACTION: All studies published in the English language that evaluated the use of pharmacotherapy for the treatment of overweight adolescents were critically analyzed; pertinent articles were selected for this review. DATA SYNTHESIS: Orlistat has been approved for use in adolescents between the ages of 12 and 16 years. The most frequently reported adverse effects of orlistat were gastrointestinal; reduced concentrations of fat-soluble vitamins were also observed. Of the 6 clinical trials published, 5 have shown statistically significant reductions in body mass index (BMI) from baseline, ranging from 0.55 to 4.09 kg/m2; one small trial failed to demonstrate significant weight reduction compared with placebo. Sibutramine has also been evaluated for use in overweight adolescents in 6 trials. Trials demonstrated a statistically significant reduction in BMI up to 5.6 kg/m2 (from baseline). Of concern is evidence indicating that sibutramine therapy may be associated with elevated blood pressure, increased pulse rate, depression, and suicidal ideations. Lastly, metformin has recently been evaluated for weight loss in overweight adolescents; small, short-term trials demonstrate modest reductions in weight and BMI. CONCLUSIONS: Orlistat has been proven both safe and effective for weight reduction in overweight adolescents. Sibutramine has also been proven effective in reducing weight in this population; however, the potential for severe adverse effects requires further investigation. Metformin has demonstrated promising results in small trials; its role in the treatment of overweight adolescents will remain investigational until further research is conducted.

A Dietary supplement containing standardized Phaseolus vulgaris extract influences body composition of overweight men and women.

BACKGROUND: More than one billion human adults worldwide are overweight and, therefore, are at higher risk of developing cardiovascular diseases, diabetes, and a variety of other chronic perturbations. Many believe that use of natural dietary supplements could aid in the struggle against obesity. So-called "starch blockers" are listed among natural weight loss supplements. Theoretically, they may promote weight loss by interfering with the breakdown of complex carbohydrates thereby reducing, or at least slowing, the digestive availability of carbohydrate-derived calories and/or by providing resistant starches to the lower gastrointestinal tract. AIMS: The present research study examines a dietary supplement containing 445 mg of Phaseolus vulgaris extract derived from the white kidney bean, previously shown to inhibit the activity of the digestive enzyme alpha amylase, on body composition of overweight human subjects. METHODS: A randomized, double-blinded, placebo-controlled study was conducted on 60 pre-selected, slightly overweight volunteers, whose weight had been essentially stable for at least six months. The volunteers were divided into two groups, homogeneous for age, gender, and body weight. The test product containing Phaseolus vulgaris extract and the placebo were taken one tablet per day for 30 consecutive days before a main meal rich in carbohydrates. Each subject's body weight, fat and non-fat mass, skin fold thickness, and waist/hip/thigh circumferences were measured. RESULTS: After 30 days, subjects receiving Phaseolus vulgaris extract with a carbohydrate-rich, 2000- to 2200-calorie diet had significantly (p<0.001) greater reduction of body weight, BMI, fat mass, adipose tissue thickness, and waist,/hip/ thigh circumferences while maintaining lean body mass compared to subjects receiving placebo. CONCLUSION: The results indicate that Phaseolus vulgaris extract produces significant decrements in body weight and suggest decrements in fat mass in the face of maintained lean body mass.

[Cardiometabolic effects of rimonabant in obese/overweight subjects with dyslipidaemia or type 2 diabetes]. / Effets cardio-métaboliques du rimonabant chez le sujet obèse ou en surpoids avec dyslipidémie ou diabète de type 2.

Rimonabant (Acomplia) is the first selective CB1 receptor blocker of the endocannabinoid system. It has been evaluated in the RIO ("Rimonabant In Obesity and related disorders") programme including above 6.600 overweight/obese patients with or without comorbidities followed for 1 to 2 years. Compared to placebo, rimonabant 20 mg/day consistently increases weight loss, reduces waist circumference, increases HDL cholesterol, lowers triglyceride levels, diminishes insulin resistance, and reduces the prevalence of metabolic syndrome. In patients with type 2 diabetes, rimonabant also diminishes HbA1c levels, an effect confirmed in the recent SERENADE trial. Almost half of the metabolic effects occurs beyond weight loss, suggesting direct peripheral effects of rimonabant. Rimonabant is indicated in Europe as an adjunct to diet and exercise for the treatment of obese patients, or overweight patients with associated risk factor(s), such as type 2 diabetes or dyslipidaemia.

[A nursing experience in a patient with antipsychotics-induced overweight].

The purpose of this article is to describe a nursing experience with a patient with schizophrenia who had antipsychotics-induced overweight. The authors assessed the patient's health condition and provided weight management to reduce her hallucinations as well as her body weight between May 1 and June 10, 2004. Three nursing problems had been identified as follows: disturbed sensory perception, imbalanced nutrition, and ineffective health maintenance. During the nursing process, the authors established a rapport relationship with the patient and her mother, educated them in skills for reducing hallucinations, and designed an individual body weight management program. After the interventions, the patient was able to positively face her illness, effectively use methods to reduce the impact of hallucinations, and successfully lose 5.5 kg. From this perspective, an individual body weight management program can be an effective intervention for nurses to care for this group of patients.

Overweight humans are resistant to the weight-reducing effects of melanocortin4-10.

CONTEXT: By enhancing energy expenditure and suppressing appetite, melanocortin peptides derived from proopiomelanocortin play a primary role in the hypothalamic regulation of body weight. In a recent study in normal-weight adults, the 6-wk intranasal administration of the MSH/ACTH(4-10) core fragment of proopiomelanocortin resulted in a distinct reduction of body weight and body fat, accompanied by significant decreases in leptin and insulin plasma concentrations. OBJECTIVE: The present study aimed to generalize this finding to overweight patients. DESIGN, SUBJECTS, AND INTERVENTION: MSH/ACTH(4-10) (0.5 mg) and placebo were intranasally administered once in the morning and once in the evening over a period of 12 wk in 23 overweight men (body mass index, mean +/- sem: 29.72 +/- 0.43 kg/m(2)). RESULTS: MSH/ACTH(4-10) did not induce any significant reduction in body weight, body fat, and plasma levels of insulin and leptin as compared with the effects of placebo. Melanocortin treatment was accompanied by reduced cortisol concentrations. CONCLUSIONS: We conclude that contrasting with normal-weight humans, overweight subjects are not susceptible to the effects of melanocortin administration on hypothalamic weight regulatory systems. In overweight subjects, a decreased sensitivity to ACTH/MSH peptides may derive from alterations at the level of the melanocortin receptor or at subsequent steps in the processing of the body fat signal.

Citrus aurantium and synephrine alkaloids in the treatment of overweight and obesity: an update.

Obesity is a major health problem facing the developed and developing world. Efforts by individuals, health professionals, educators, and policy makers to combat the escalating trend of growing obesity prevalence have been multifaceted and mixed in outcome. Various dietary supplements have been marketed to reduce obesity. These products have been suggested to accomplish this by decreasing energy intake and energy absorption, and/or increasing metabolic rate. Ephedra, one such supplement, was banned from sale in the US market because of concerns about adverse events. Another substance, Citrus aurantium, which contains several compounds including synephrine alkaloids, has been suggested as a safe alternative. This review examines the evidence for safety and efficacy of C. aurantium and synephrine alkaloids as examined in animal studies, clinical weight loss trials, acute physiologic studies and case reports. Although at least three reviews of C. aurantium have been published, our review expands upon these by: (i) distinguishing and evaluating the efficacy of C. aurantium and related compounds; (ii) including results from previously unreviewed research; (iii) incorporating recent case reports that serve to highlight, in an anecdotal way, potential adverse events related to the use of C. aurantium and related compounds; and (iv) offering recommendations to guide the design of future trials to evaluate the safety and efficacy of C. aurantium. While some evidence is promising, we conclude that larger and more rigorous clinical trials are necessary to draw adequate conclusions regarding the safety and efficacy of C. aurantium and synephrine alkaloids for promoting weight loss.

Phytosterols mixed with medium-chain triglycerides and high-oleic canola oil decrease plasma lipids in overweight men.

Phytosterols (PSs) have been recently added to various mediums. Nevertheless, matrices with functional properties, such as medium-chain triglycerides (MCTs), should be precisely examined for supplementary advantages. The objective of this study was to identify the existence of combined biological actions of a functional oil enriched in PSs within MCTs and high-oleic canola (HOC), relative to a control (olive oil), in overweight, hyperlipidemic men using a rigorously controlled dietary intervention. Twenty-three overweight, hyperlipidemic men consumed both types of oil in a randomized, crossover trial for 6 weeks each. Fasted plasma samples were collected on the first and last 2 days of each study period. Body weight decreased -1.22 +/- 0.35 kg (P = .0019) and -1.68 +/- 0.47 kg (P = .0016) after the 6-week study period in the olive oil and functional oil groups, respectively. The end points for total cholesterol and low-density lipoprotein cholesterol (LDL-C) in the functional oil group (P = .0006) were lower than in the olive oil group (P = .0002). Total cholesterol values decreased from comparable baseline to end point of 4.71 +/- 0.16 mmol/L (P < .0001) in the functional oil phase and 5.14 +/- 0.19 mmol/L (P = .0001) in the olive oil phase (P = .0592). In addition, LDL-C demonstrated a similar drop, to an end point of 3.12 +/- 0.16 mmol/L (P < .0001) and 3.54 +/- 0.18 mmol/L (P = .0002), for the functional oil and olive oil groups, respectively, with significant changes (P = .0221). High-density lipoprotein cholesterol levels did not change in either treatment. Triacylglycerol end points decreased in functional oil and olive oil groups (P = .0195 and .0105, respectively) to the same extent from baseline. Results indicate that PSs mixed within an MCT- and HOC-rich matrix lower plasma LDL-C, without significantly changing the high-density lipoprotein cholesterol concentrations, in hyperlipidemic, overweight men, and may therefore decrease the risk of cardiovascular events.

Low-dose orlistat effects on body weight of mildly to moderately overweight individuals: a 16 week, double-blind, placebo-controlled trial.

BACKGROUND: Lifestyle measures are considered the first line of therapy for treating overweight individuals, but many are unable to achieve a meaningful weight loss. OBJECTIVE: To determine the efficacy and safety of orlistat 60 mg, given 3 times daily, for weight loss in mildly to moderately overweight individuals. METHODS: A multicenter, 16 week, randomized, double-blind, placebo-controlled study was conducted in 391 overweight subjects at 20 US centers. The main outcome measure was change in weight from baseline to week 16; secondary measures included changes in body mass index, waist circumference, blood pressure, and fasting lipoprotein and glucose levels. RESULTS: Subjects in both groups lost weight over the treatment period; however, orlistat-treated subjects lost significantly more weight than placebo-treated subjects beyond 2 weeks of treatment. Weight loss from baseline to week 16 was significantly greater in participants receiving orlistat versus those receiving placebo (3.05 vs 1.90 kg; p < 0.001, intent-to-treat analysis). Orlistat-treated subjects who completed 16 weeks of treatment lost 4.8 +/- 0.35% (mean +/- SE) of baseline weight compared with 3.1 +/- 0.38% for the placebo group (p < 0.001). Orlistat-treated subjects, compared with those receiving placebo, also demonstrated a greater relative reduction in total (-4.4% vs 0.0%; p = 0.004) and low-density lipoprotein cholesterol (-7.2% vs -0.6%; p = 0.005) and both diastolic (-3.9% vs -0.5%; p = 0.001) and systolic blood pressure (-4.7% vs -1.8%; p = 0.004). Both groups showed a similar safety profile; gastrointestinal events were significantly more common in the orlistat-treated subjects. CONCLUSIONS: The use of orlistat 60 mg by mildly to moderately overweight individuals produced significant weight loss in conjunction with a reduced calorie diet and self-instructional materials. This amount of weight loss was associated with improvements in several weight-related risk factors. Orlistat 60 mg may be a useful adjunct to lifestyle measures and has the potential to contribute significantly to weight and risk factor improvement for overweight individuals.

Rimonabant for overweight or obesity.

BACKGROUND: Worldwide, the prevalence of obesity and overweight in industrialized countries and in a substantial number of developing countries is increasing at an alarming rate. Rimonabant is a selective cannabinoid-1 receptor antagonist that has been investigated for its efficacy in reducing body weight and associated risk factors in obese people. Phase III trials are now under way to test the use of rimonabant for long-term weight-loss. Given the prevalence of overweight and obesity, it is important to establish the efficacy and safety of rimonabant. OBJECTIVES: To assess the effects of rimonabant in overweight and obese people. SEARCH STRATEGY: MEDLINE, EMBASE, The Cochrane Library, LILACS, databases of ongoing trials and reference lists were used to identify relevant trials. The last search was conducted in June 2006. SELECTION CRITERIA: Randomised controlled trials comparing rimonabant with placebo or other weight loss interventions in overweight or obese adults. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed all potentially relevant citations for inclusion and methodological quality. The primary outcome measures were weight loss change, morbidity and adverse effects occurrence. MAIN RESULTS: Four studies evaluating rimonabant 20 mg versus rimonabant 5 mg versus placebo in addition to a hypocaloric diet lasting at least one year were included. Compared with placebo, rimonabant 20 mg produced a 4.9 kg greater reduction in body weight in trials with one-year results. Improvements in waist circumference, high-density lipoprotein cholesterol, triglyceride levels and systolic and diastolic blood pressure were also seen. However, the results with rimonabant 5 mg demonstrated a weight reduction which was only 1.3 kg greater when compared with placebo. No clinically relevant effects on plasma lipids and blood pressure were found. Rimonabant 20 mg caused significant more adverse effects both of general and serious nature, especially of nervous system, psychiatric or gastro-intestinal origin. Attrition rates were approximately 40% at the end of one year. AUTHORS' CONCLUSIONS: The use of rimonabant after one year produces modest weight loss of approximately 5%. Even modest amounts of weight loss may be potentially beneficial. The observed results should be interpreted with some caution, though, since the evaluated studies presented some deficiencies in methodological quality. Studies with longer follow-ups after the end of treatment and of more rigorous quality should be done before definitive recommendations can be made regarding the role of this new medication in the management of overweight or obese patients.

The use of a Cissus quadrangularis formulation in the management of weight loss and metabolic syndrome.

AIM: Once considered a problem of developed countries, obesity and obesity-related complications (such as metabolic syndrome) are rapidly spreading around the globe. The purpose of the present study was to investigate the use of a Cissus quadrangularis formulation in the management of metabolic syndrome, particularly weight loss and central obesity. METHODS: The study was a randomized, double-blind, placebo-controlled design involving 123 overweight and obese persons (47.2% male; 52.8% female; ages 19-50). The 92 obese (BMI >30) participants were randomized into three groups; placebo, formulation/no diet, and formulation/diet (2100-2200 calories/day). The 31 overweight participants (BMI = 25-29) formed a fourth (no diet) treatment group. All participants received two daily doses of the formulation or placebo and remained on a normal or calorie-controlled diet for 8 weeks. RESULTS: At the end of the trial period, statistically significant net reductions in weight and central obesity, as well as in fasting blood glucose, total cholesterol, LDL-cholesterol, triglycerides, and C-reactive protein were observed in participants who received the formulation, regardless of diet. CONCLUSION: Cissus quadrangularis formulation appears to be useful in the management of weight loss and metabolic syndrome.

Antihypertensive and lipid lowering treatment in 70-74 year old individuals--predictors for treatment and blood-pressure control: a population based survey. The Hordaland Health Study (HUSK).

BACKGROUND: In an elderly, community based population we aimed at investigating antihypertensive and lipid lowering medication use in relation to own and familiar cardiovascular morbidity and diabetes mellitus, as well as to lifestyle factors and general health. We also examined levels of blood pressure in untreated and treated residents, to investigate factors correlating with blood pressure control. METHODS: A health survey carried out in 1997-9 in the county of Hordaland, Norway included a self-administered questionnaire mailed to 4,338 persons born in 1925-7. Drug use the day prior to filling in the questionnaire was reported. A health check-up was carried out, where their systolic and diastolic blood pressure (SBP and DBP), body mass index (BMI), and serum-cholesterol level were recorded. RESULTS: One third of respondents used one or more antihypertensive drugs, while 13% of men and women were treated with a statin. Diabetes mellitus, own or relatives'cardiovascular disease, having quit smoking, physical inactivity, and overweight correlated with antihypertensive treatment. Mean blood pressure was lower in respondents not on treatment. Among those on treatment, 38% of men and 29% of women had reached a target BP-level of lower than 140/90 mm Hg. Own cardiovascular disease and a low BMI correlated with good BP-control. CONCLUSION: One third of 70-74 year old individuals living in the community used one or more antihypertensive drugs. Only around one third of those treated had reached a target BP-level of less than 140/90 mm Hg. Own cardiovascular disease and a low BMI correlated with good BP-control.

Efficacy of 12 weeks supplementation of a botanical extract-based weight loss formula on body weight, body composition and blood chemistry in healthy, overweight subjects--a randomised double-blind placebo-controlled clinical trial.

OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of composite extracts in reducing weight, as the main outcome measure. Secondary measures of the study were body composition change. DESIGN: Randomised, double blind, placebo-controlled clinical trial. SETTING: Tertiary university clinic. SUBJECTS: hundred and five subjects, 5 of them withdrawn consent, 2 drop-outs not related to study preparation. INTERVENTION: two tablet per meal concept supposed to generate a "psychological" therapy-like approach during 12 weeks supported by measured physical activity. The tablets 1 (one hour before meals, comprises extracts of Asparagus, Green tea, Black tea, Guarana, Mate and Kidney beans) and 2 (taken half an hour after meals, comprises extracts of Kidney bean pods, Garcinia cambogia, and Chromium yeast) are taken twice daily with two main meals. RESULTS: A significant change of the Body Composition Improvement Index (BCI) was observed in the active extract group compared to placebo (p = 0.012). Weight, BMI, waist-to-hip ratio was not statistically different between groups. Body fat loss was greater in active group (p = 0.011) compared to placebo. A weight loss parameter corrected for exercise was introduced and found to be higher in active group (p = 0.046) than in placebo, meaning that the formula was more efficacious, due to a concurrently performed exercise program--a recommended strategy for life style modification. CONCLUSIONS: A significant change of the Body Composition Improvement Index and the decrease in body fat was statistically significant in active extract subjects compared to placebo. A change in some outcome measures like: weight, BMI failed to produce significant difference between groups.

Effect of rimonabant, a cannabinoid-1 receptor blocker, on weight and cardiometabolic risk factors in overweight or obese patients: RIO-North America: a randomized controlled trial.

CONTEXT: Rimonabant, a selective cannabinoid-1 receptor blocker, may reduce body weight and improve cardiometabolic risk factors in patients who are overweight or obese. OBJECTIVE: To compare the efficacy and safety of rimonabant with placebo each in conjunction with diet and exercise for sustained changes in weight and cardiometabolic risk factors over 2 years. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled trial of 3045 obese (body mass index > or =30) or overweight (body mass index >27 and treated or untreated hypertension or dyslipidemia) adult patients at 64 US and 8 Canadian clinical research centers from August 2001 to April 2004. INTERVENTION: After a 4-week single-blind placebo plus diet (600 kcal/d deficit) run-in period, patients were randomized to receive placebo, 5 mg/d of rimonabant, or 20 mg/d of rimonabant for 1 year. Rimonabant-treated patients were rerandomized to receive placebo or continued to receive the same rimonabant dose while the placebo group continued to receive placebo during year 2. MAIN OUTCOME MEASURES: Body weight change over year 1 and prevention of weight regain during year 2. Additional efficacy measures included changes in waist circumference, plasma lipid levels, and other cardiometabolic risk factors. RESULTS: At year 1, the completion rate was 309 (51%) patients in the placebo group, 620 (51%) patients in the 5 mg of rimonabant group, and 673 (55%) patients in the 20 mg of rimonabant group. Compared with the placebo group, the 20 mg of rimonabant group produced greater mean (SEM) reductions in weight (-6.3 [0.2] kg vs -1.6 [0.2] kg; P<.001), waist circumference (-6.1 [0.2] cm vs -2.5 [0.3] cm; P<.001), and level of triglycerides (percentage change, -5.3 [1.2] vs 7.9 [2.0]; P<.001) and a greater increase in level of high-density lipoprotein cholesterol (percentage change, 12.6 [0.5] vs 5.4 [0.7]; P<.001). Patients who were switched from the 20 mg of rimonabant group to the placebo group during year 2 experienced weight regain while those who continued to receive 20 mg of rimonabant maintained their weight loss and favorable changes in cardiometabolic risk factors. Use of different imputation methods to account for the high rate of dropouts in all 3 groups yielded similar results. Rimonabant was generally well tolerated; the most common drug-related adverse event was nausea (11.2% for the 20 mg of rimonabant group vs 5.8% for the placebo group). CONCLUSIONS: In this multicenter trial, treatment with 20 mg/d of rimonabant plus diet for 2 years promoted modest but sustained reductions in weight and waist circumference and favorable changes in cardiometabolic risk factors. However, the trial was limited by a high drop-out rate and longer-term effects of the drug require further study. Clinical Trials Registration ClinicalTrials.gov Identifier: NCT00029861.

Insulin resistance, growth factors and cytokine levels in overweight women with breast cancer before and after chemotherapy.

OBJECTIVE: To evaluate insulin values, insulin resistance, growth factors and cytokine levels in women suffering from breast cancer and the effect of chemotherapy on these parameters. DESIGN: In a prospective study, glucose and insulin values were determined in ten previously undiagnosed diabetic postmenopausal women with stage IV breast cancer (hepatic metastases excluded) during an oral glucose tolerance test (OGTT) carried out after a glucose load of 75 g. At baseline, leptin, Interleukin-1 (IL-1), Interleukin-6 (IL-6), Interleukin-8 (IL-8), Insulin-Growth Factor-1 (IGF-1), Tumor-Necrosis-Factor-alpha (TNF-alpha), Vascular Endothelial Growth Factor (VEGF) and Platelet Derived Growth Factor (PDGF) levels were also determined using appropriate methodolody. Insulin resistance and beta-cell function were calculated (HOMA-model). All women were evaluated prior to and after chemotherapy applied for 6 months. RESULTS: 1) Insulin levels at 120 minutes of the OGTT were higher before compared to post-chemotherapy (Mean+/-SD: 170.39+/-78.07 vs 111.75+/-76.19, p=0.037). 2) Body mass index (BMI) was an important predictor of post-glucose load insulin levels both before (coefficient=1.051, p=0.004) and after chemotherapy (coefficient=0.711, p=0.003). 3) Before chemotherapy BMI values were positively related to PDGF levels (rs=0.685, p=0.029), while after chemotherapy this relationship became non-significant (rs=0.188, p=0.603). Before chemotherapy there was a negative relationship between VEGF and waist circumference (coefficient= -0.542, p=0.023). CONCLUSIONS: Post-glucose load insulin values significantly decrease after chemotherapy. There is a positive relationship between BMI and post-glucose load insulin before and after chemotherapy. The contribution of the reduction in insulin, a known growth factor, to the outcome of chemotherapy in these patients remains speculative at present.

[Rimonabant improves cardiometabolic risk profile in obese or overweight subjects: overview of RIO studies]. / Le rimonabant améliore le profit de risque cardio-métabolique chez le sujet obèse ou en surpoids: synthèse des etudes "RIO".

RIO (Rimonabant In Obesity and related disorders) is a large phase 3 programme (>6600 patients) evaluating the efficacy and safety of rimonabant (5 or 20 mg/day), a CBI receptor antagonist of endocannabinoid system, in obese or overweight patients with or without comorbidities (RIO-Europe and RIO-North America), with untreated dyslipidaemia (RIO-Lipids) or with type 2 diabetes treated with metformin or sulfonylurea (RIO-Diabetes). Compared to placebo, rimonabant 20 mg/day consistently increases weight loss, reduces waist circumference, increases HDL cholesterol, lowers triglyceride levels, diminishes insulin resistance, and reduces the prevalence of metabolic syndrome. Almost half of the metabolic effects, including adiponectin increase, occur beyond weight loss, suggesting a direct peripheral effect of rimonabant.

Efficacy and safety of sibutramine in 2225 subjects with cardiovascular risk factors: short-term, open-label, observational study.

This study aims to determine the efficacy and tolerability of sibutramine hydrochloride in overweight and obese patients with cardiovascular risk factors. This was a 12-week, open-label, observational trial carried out in primary care settings. Patients' data were obtained from questionnaires received from 153 physicians. A total of 2225 overweight and obese (BMI> or =27 kg/m2) patients received sibutramine in single daily doses of 10 and/or 15 mg. The study population included patients in general good health and with controlled hypertension (41.2%), type II diabetes mellitus (15.6%), hyperlipidaemia (45.5%), and who were chronic tobacco users (smokers) (37.0%). The main outcome measures were changes in body weight, blood pressure and heart rate, and evaluation of reported adverse events. Reduction of body weight of at least >5% from baseline to week 12 was achieved in 2030 (91%) patients and >10% was achieved in 987 (44%) patients. Baseline differences in the percentages of male and female patients, presence or absence of hyperlipidaemia or smoking status did not appear to affect the rate of weight change. Weight loss was less in patients with type II diabetes mellitus and/or controlled systolic hypertension at baseline compared to those patients without these conditions. Mean systolic and diastolic blood pressure and heart rate decreased from baseline to week 12. Overall, sibutramine was well tolerated. In conclusions, treatment with sibutramine resulted in clinically significant weight loss during short-term therapy in obese adults with a range of cardiovascular risk factors..

The cost effectiveness of orlistat in a 1-year weight-management programme for treating overweight and obese patients in Sweden : a treatment responder approach.

OBJECTIVE: To calculate the cost effectiveness (from the Swedish healthcare perspective) of orlistat plus diet for an obese and overweight population in a 1-year weight-management responder programme versus a 1-year weight-management programme based on diet only. As a reference, orlistat plus diet and diet only were also compared with a no-diet alternative. METHOD: Costs and effectiveness were calculated in a decision-tree model by means of Monte Carlo simulation. Efficacy was derived from a pooled analysis of the orlistat clinical trial programme. Acquisition costs for orlistat (euro, 2003 prices), healthcare costs for visits to doctors and dieticians related to weight management, and costs related to the difference in diabetes mellitus incidence between treatment arms were included in the analysis. The health benefit of temporary weight loss was measured in the number of quality-adjusted life-years (QALYs) gained. RESULTS: The number of responding (those with >5% weight loss) patients at month 3 was almost twice as high with orlistat compared with diet only: 48.9% versus 26.3%. Responding orlistat patients had a weight loss of 15.5% at month 12 compared with 7.9% for all patients on diet only. The incremental cost-effectiveness ratio (ICER) per QALY gained versus diet only was estimated to be 13,125 euro for the average patient starting on orlistat. When orlistat was compared with no diet, the cost effectiveness was improved. However, comparing diet only with no diet gave a slightly higher ICER, indicating that orlistat had an extended dominance over the diet-only alternative. CONCLUSION: Our estimates indicated that orlistat in a 12-month dietary responder programme increased the number of QALYs and reduced the cumulative incidence of diabetes compared with diet only. Patients starting on orlistat in addition to a dietary programme achieved an ICER that was similar to many other well accepted healthcare treatment programmes. In order to improve the precision of our calculations, we need to confirm the key assumptions regarding temporary weight loss and utility gains, and the relationship between temporary weight loss and diabetes, as well as other co-morbidities, and to have better knowledge of the long-term impact of weight-management programmes in clinical practice, such as changes in weight-controlling behaviours and sustainability of weight loss.

The 'expert patient': empowerment or medical dominance? The case of weight loss, pharmaceutical drugs and the Internet.

Do 'informed' or 'expert' patients challenge dominant traditions in biomedicine or simply adopt these as conventional ways of thinking about body shape and size, illness and health? This paper examines this question in relation to the use of the weight-loss drug Xenical by participants in an Internet forum for obese and overweight people. Ethnographic and interview data from the forum provides evidence that participants share information and support each other as they use Xenical, and in the process emerge as 'expert patients' in relation to their body shape and its treatment. However, it is argued that while an 'expert patient' can be perceived as desirable, enabling the democratisation of healthcare, it can also be constraining. The exchanges between the users in the forum perpetuate a biomedical model of overweight as a condition to be overcome. The discussion critically considers a number of options for the development of the expert patient, including the emergence of an 'informed consumer'.