orlistat and Metabolic-Syndrome

To conduct a systematic review and meta-analysis of relevant randomized clinical trials (RCTs) to ascertain the effect size of orlistat in modulating plasma levels of adipokines, ghrelin and C-reactive protein (CRP).. Medline, SCOPUS, Web of Science and Google Scholar databases were searched. A random-effects model and the generic inverse variance method were used for quantitative data synthesis. Heterogeneity was quantitatively assessed using I(2) index. Sensitivity analyses were conducted using the one-study remove approach. Random-effects meta-regression was performed using unrestricted maximum likelihood method to evaluate the impact of duration of treatment, percentage change in body mass index (BMI) and baseline BMI values as potential confounders of the estimated effect size.. Meta-analysis suggested a significant increase in plasma levels of adiponectin [weighted mean difference (WMD): 19.18%, 95% confidence interval (CI): 5.80, 32.57, p = 0.005] and significant reductions in plasma levels of leptin (WMD: -13.24%, 95% CI: -20.69, -5.78, p = 0.001) and CRP (WMD: -11.52%, 95% CI: -16.55, -6.49, p < 0.001) following treatment with orlistat. In meta-regression, changes in plasma concentrations of adiponectin, leptin and CRP were associated with duration of treatment, but not with either change in BMI or baseline BMI values.. Orlistat is effective in increasing plasma concentrations of adiponectin and decreasing those of leptin and CRP.

Topics: Adiponectin; Anti-Obesity Agents; Body Weight; C-Reactive Protein; Ghrelin; Humans; Lactones; Leptin; Metabolic Syndrome; Orlistat; Randomized Controlled Trials as Topic

Non-alcoholic fatty liver disease (NAFLD) is an umbrella term, which encompasses simple steatosis and non-alcoholic steatohepatitis (NASH). The entire spectrum of NAFLD has been associated with metabolic syndrome. NASH is associated with increased mortality compared with that of the general population. Many therapeutic options for NASH have been studied. However, there is very little evidence supporting the efficacy of most regimens for the treatment of NASH.. To provide a review focusing on the current therapeutic options available for patients with NASH as well as to briefly introduce possible future interventions.. A MEDLINE, Pubmed and Cochrane Review database search using a combination of keywords, which included non-alcoholic fatty liver disease, non-alcoholic hepatic steatosis, NAFLD, NASH, treatment, therapeutics, vitamin E, orlistat and bariatric surgery. An overall summary of the articles was developed for each section of discussion in this review.. NASH associated with metabolic syndrome can progress advanced fibrosis and cirrhosis. Weight loss and lifestyle modification have been shown to improve NASH. Other medications used for weight loss and metabolic syndrome have been evaluated, such as orlistat, metformin and thiazolidinediones. Alternative regimens using ursodeoxycholic acid, statins and probiotics as well as bariatric surgery have been evaluated, but have not been recommended as first-line treatment for NASH. Vitamin E for NASH patients without diabetes seems to be promising. The lack of effective treatment for NASH suggests the heterogeneity of patients presenting with the NASH phenotype. The best treatment strategy for these patients may be to identify their pathogenic target and develop personalised treatment protocols.. Currently, there are few options available for the management of NASH. Future targeted treatment strategies based on the pathogenic pathways may be needed to develop effective treatment for patients with NASH.

Topics: Bariatric Surgery; Fatty Liver; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lactones; Metabolic Syndrome; Metformin; Non-alcoholic Fatty Liver Disease; Orlistat; Precision Medicine; Thiazolidinediones; Ursodeoxycholic Acid; Vitamin E; Weight Loss

Topics: Anti-Obesity Agents; Appetite; Appetite Depressants; Benzazepines; Benzoxazines; Bupropion; Clinical Trials as Topic; Drug Approval; Drug Combinations; Drug Discovery; Energy Metabolism; Enzyme Inhibitors; Fructose; Glucagon-Like Peptide 1; Humans; Hypothalamus; Lactones; Lipase; Liraglutide; Metabolic Syndrome; Naltrexone; Obesity; Orlistat; Phentermine; Topiramate

Triglycerides participate in key metabolic functions such as energy storage, thermal insulation and as deposit for essential and non-essential fatty acids that can be used as precursors for the synthesis of structural and functional phospholipids. The liver is a central organ in the regulation of triglyceride metabolism, and it participates in triglyceride synthesis, export, uptake and oxidation. The metabolic syndrome and associated diseases are among the main concerns of public health worldwide. One of the metabolic syndrome components is impaired triglyceride metabolism. Diseases associated with the metabolic syndrome promote the appearance of hepatic alterations e.g., non-alcoholic steatosis, steatohepatitis, fibrosis, cirrhosis and cancer. In this article, we review the molecular actions involved in impaired triglyceride metabolism and its association with hepatic diseases. We discuss mechanisms that reconcile the chronic inflammation and insulin resistance, and new concepts on the role of intestinal micro-flora permeability and proliferation in fatty liver etiology. We also describe the participation of oxidative stress in the progression of events leading from steatosis to steatohepatitis and fibrosis. Finally, we provide information regarding the mechanisms that link fatty acid accumulation during steatosis with changes in growth factors and cytokines that lead to the development of neoplastic cells. One of the main medical concerns vis-a-vis hepatic diseases is the lack of symptoms at the onset of the illness and, as result, its late diagnosis. The understandings of the molecular mechanisms that underlie hepatic diseases could help design strategies towards establishing markers for their accurate and timely diagnosis.

Topics: Fatty Liver; Fibrosis; Humans; Insulin Resistance; Lactones; Liver Cirrhosis; Liver Diseases; Liver Neoplasms; Metabolic Syndrome; Non-alcoholic Fatty Liver Disease; Orlistat; Oxidative Stress; Triglycerides

Topics: Age Factors; Androgens; Dyslipidemias; Humans; Hypertension; Hypolipidemic Agents; Insulin Resistance; Kidney Failure, Chronic; Lactones; Metabolic Syndrome; Orlistat; Progesterone-Binding Globulin; Testosterone; Tumor Necrosis Factor-alpha; Tunica Intima

The relentless rise in the prevalence of obesity predicts an exponential increase in the incidence of obesity-related complications. Medical and surgical treatments are necessary to prevent and treat obese co-morbidities, thereby avoiding disability and premature death. Interventions for obesity should be evaluated not by weight loss alone but against the new incidence in obesity-related co-morbidities, their remission or improvement. In combination with lifestyle measures, currently available pharmacological therapies -- rimonabant, orlistat and sibutramine -- achieve 5-10% weight loss, although a return to baseline is the norm after cessation of medication. All these agents demonstrate approximately 0.5% reduction in HbA1c in diabetic subjects; orlistat also reduces the new incidence of type 2 diabetes. Modest improvement in lipid profiles and reduced calculated cardiovascular risk is observed, but data on improvement of other co-morbidities are sparse. In contrast, surgical procedures that restrict food ingestion and/or curtail the absorptive surface area of the gut consistently achieve substantial weight loss, typically 20-35%, effect resolution of co-morbid conditions and improve quality of life. Although mortality is low, complications and hospitalisation are not uncommon after bariatric surgery. Intriguingly, surgical patients experience a reduction in appetite and report changes in food preference. Accentuation of the normal gastrointestinal hormonal response to food intake and possible changes in vagal afferent signalling are proposed to induce satiety. Increased understanding of body weight homeostasis and appetite regulation has provided an impressive list of potential targets for drug development, with the promise that single or combination therapy may ultimately challenge the supremacy of bariatric surgery.

Topics: Adipose Tissue; Amyloid; Anticonvulsants; Antidepressive Agents; Anxiety; Appetite Regulation; Bariatric Surgery; Body Mass Index; Bupropion; Cholecystokinin; Ciliary Neurotrophic Factor; Clinical Trials as Topic; Cyclobutanes; Depression; Diabetes Mellitus, Type 2; Female; Fluoxetine; Fructose; Ghrelin; Humans; Intra-Abdominal Fat; Islet Amyloid Polypeptide; Isoxazoles; Lactones; Leptin; Metabolic Syndrome; Metformin; Obesity; Obesity, Morbid; Orlistat; Oxyntomodulin; Peptide YY; Piperidines; Polycystic Ovary Syndrome; Pyrazoles; Rimonabant; Sertraline; Sleep Apnea, Obstructive; Surgical Procedures, Operative; Topiramate; Zonisamide

Excessive adipose tissue is associated with increased expression or suppression of cytokines and hormones, leading to inflammation and chronic disease. In particular, abdominal adiposity, as evidenced by a high waist circumference, is a component of the metabolic syndrome, a constellation of risk factors (e.g., high waist circumference, high blood pressure, elevated triglycerides, low high-density lipoprotein cholesterol, elevated fasting glucose) that increases the risk for type 2 diabetes and cardiovascular disease. Lifestyle modification is the first-line approach to the management of obesity and the metabolic syndrome. However, for patients who cannot achieve a reduction in weight (5% to 10% of initial body weight) and cardiometabolic risk factors with lifestyle modification alone, physicians should consider adjunctive long-term pharmacotherapy. A variety of approved and investigational pharmacologic agents have been shown to reduce weight and modify metabolic syndrome components, including sibutramine, orlistat, metformin, and rimonabant. Data from four phase 3 trials suggest that rimonabant, the first cannabinoid receptor inhibitor, modulates cardiometabolic risk factors, both through its impact on body weight and through direct pathways that are not related to weight loss.

Topics: Anti-Obesity Agents; Appetite Depressants; Cardiovascular Diseases; Cyclobutanes; Humans; Hypoglycemic Agents; Lactones; Metabolic Syndrome; Obesity; Orlistat; Practice Guidelines as Topic; Receptor, Cannabinoid, CB1; Weight Loss

The present article reviews the diagnostic criteria for pediatric obesity and its comorbidities. Treatment is also reviewed, including promotion of physical activity, and dietetic, pharmacologic and surgical treatment.

Topics: Anti-Obesity Agents; Appetite Depressants; Cardiovascular Diseases; Child; Combined Modality Therapy; Cyclobutanes; Fatty Liver; Gastric Bypass; Humans; Hypercholesterolemia; Hypertension; Insulin Resistance; Lactones; Metabolic Syndrome; Obesity; Orlistat; Risk Factors

The obesity epidemic is associated with numerous health-related sequelae, including alterations in glucose metabolism, dyslipidemia, and hypertension. These conditions, in turn, are associated with an increased incidence of type 2 diabetes mellitus and cardiovascular disease, which ultimately leads to increased morbidity and mortality. Abdominal obesity, in particular, has been identified as a key risk factor. Accordingly, therapeutic lifestyle change remains the cornerstone of treatment for patients with obesity. Therapeutic lifestyle change is effective; even moderate weight loss leads to clinical improvements. However, lifestyle change is often challenging to implement, and pharmacologic therapies may become necessary. Available pharmacologic and surgical treatment modalities for patients with obesity are fraught with challenges of their own, including poor patient adherence and presence of adverse events. The author outlines available modes of treatment and their consequences for patients with obesity.

Topics: Anti-Obesity Agents; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Humans; Intra-Abdominal Fat; Lactones; Life Style; Metabolic Syndrome; Obesity; Orlistat; Risk Factors

Obesity has reached global epidemic proportions because of an increasingly obesogenic environment. This review examines the association between obesity, and in particular visceral fat, as a risk factor for cardiovascular disease and mortality.. The World Health Organization defines obesity based on the body mass index. Recently the waist-to-hip ratio has been shown to be a significantly stronger predictor of cardiovascular events than body mass index. The metabolic syndrome and its evolving definition represent a cluster of metabolic risk factors which help predict cardiovascular disease and mortality. Although insulin resistance plays a central role in the pathophysiology of the metabolic syndrome, there is limited support for therapy with insulin sensitizers, thiazolidinediones, in patients with coronary artery disease. The current anti-obesity drugs, orlistat and sibutramine, have only a modest effect on weight loss. The blockade of the endocannabinoid system with rimonabant, however, may be a promising new strategy.. Obesity is associated with significant increase in cardiovascular risk. Lifestyle modification remains the cornerstone of management although anti-obesity medications may be indicated in high risk individuals with comorbid disease.

Topics: Appetite Depressants; Body Fat Distribution; Body Mass Index; Cardiovascular Diseases; Cyclobutanes; Humans; Inflammation; Insulin Resistance; Intra-Abdominal Fat; Lactones; Life Style; Lipid Metabolism; Metabolic Syndrome; Obesity; Orlistat; Piperidines; Pyrazoles; Rimonabant; Thiazolidinediones; Waist-Hip Ratio

Intervention in weight management should begin before the onset of the metabolic syndrome. Therapeutic lifestyle changes (e.g., diet and physical activity) comprise the cornerstone of care for overweight and obese patients. Behavior modification approaches are useful in facilitating adherence to specific dietary regimens. Pharmacotherapy is an option for patients with a BMI >30 kg/m(2) or for those with a BMI of 27 to 30 kg/m(2) and two or more risk factors, who have failed on diet and exercise alone. To date, the U.S. Food and Drug Administration has approved three weight loss agents: sibutramine, orlistat, and phentermine.

Topics: Caloric Restriction; Cardiovascular Diseases; Cyclobutanes; Diabetes Mellitus; Diet; Diet, Fat-Restricted; Diet, Mediterranean; Exercise; Feeding Behavior; Food, Formulated; Humans; Lactones; Metabolic Syndrome; Obesity; Orlistat; Phentermine; Prediabetic State; Risk Reduction Behavior; Weight Loss

The need for an effective and safe medical treatment of nonalcoholic fatty liver disease is urgent due to its high prevalence and progressive character. At the moment, therapeutic strategies are largely empirical and based on the control of associated clinical conditions (especially obesity, type 2 diabetes mellitus, and hypertriglyceridemia) and the use of some specific drugs (insulin sensitizing agents, cytoprotectives, antioxidants, and anticytokines) as an attempt to counteract known elements of the pathogenesis. None of these specifics measures have been found to display enough evidence to recommend their clinical use. It is indispensable to join efforts in coordinated networks to define, as soon as possible, the best treatment and the best time to start it.

Topics: Anti-Obesity Agents; Anticholesteremic Agents; Atorvastatin; Chromans; Diabetes Mellitus, Type 2; Fatty Liver; Heptanoic Acids; Humans; Hypoglycemic Agents; Insulin Resistance; Lactones; Metabolic Syndrome; Metformin; Obesity; Orlistat; Prevalence; Pyrroles; Rosiglitazone; Thiazolidinediones; Troglitazone

Cardiovascular disease (CVD) is the leading cause of death of men and women in the United States. The accumulation of visceral adipose tissue, as opposed to subcutaneous fat, increases the risk of developing CVD and metabolic disease. Because visceral adipose tissue uniquely contributes to the pathophysiology of CVD and insulin resistance, waist circumference is now being considered as a more useful marker of potential health risks associated with overweight and obesity than body mass index. Weight loss, particularly a reduction in waist circumference, improves insulin sensitivity, lipid profile, and serum adipocytokines, thereby reducing the risk of developing chronic disease and CVD.

Topics: Anti-Obesity Agents; Coronary Disease; Cyclobutanes; Exercise; Feeding Behavior; Humans; Intra-Abdominal Fat; Lactones; Metabolic Syndrome; Obesity; Orlistat; Piperidines; Pyrazoles; Rimonabant

Orlistat is an inhibitor of gastrointestinal lipases and, therefore, prevents the absorption of dietary fat. This agent reduces weight in obese adults and adolescents with or without comorbidities (including type 2 diabetes mellitus, hypercholesterolaemia, hypertension, metabolic syndrome) who received up to 4 years of therapy in conjunction with a hypocaloric diet. In obese patients, orlistat in combination with a hypocaloric diet improved metabolic risk factors and reduced the risk of developing type 2 diabetes. Furthermore, this agent was cost effective in patients with obesity, particularly those with type 2 diabetes. Orlistat is generally well tolerated, with gastrointestinal adverse events being most commonly reported. Orlistat, in addition to lifestyle and dietary intervention, is thus an attractive option for the treatment of patients with obesity, especially those with associated comorbidities or at risk of developing type 2 diabetes.

Topics: Anti-Obesity Agents; Caloric Restriction; Diabetes Mellitus, Type 2; Humans; Lactones; Metabolic Syndrome; Obesity; Orlistat; Randomized Controlled Trials as Topic; Risk Factors

The public health burden of type 2 diabetes mellitus has been dramatically increased worldwide. Not only its prevalence rate at present but the increase of its incidence in the near future can create a global health problem. The rapid increase of the total number of newly diagnosed diabetic patients proved to be associated with the increasing prevalence rate of obesity. The metabolic syndrome and type 2 diabetes can contribute to accelerated atherosclerosis and, therefore, the target organ damages can carry a serious problem for the individuals and also for the whole society. It is obvious, that the primary prevention of type 2 diabetes mellitus is of great importance. There is now substantial evidence that type 2 diabetes can be prevented or delayed by lifestyle interventions, i.e. diet and exercise should be the first choice in order to avoid weight gain when preventing diabetes. Pharmacological intervention should not be routinely used to prevent diabetes although results of large clinical trials with metformin and acarbose in subjects with impaired glucose tolerance are available. It is noteworthy that a decrease in the number of newly diagnosed diabetes was observed in prospective, double blind clinical studies evaluating the effect of new antihypertensive drugs (captopril, ramipril, lisinopril, nifedipine GITS, amlodipine, losartan) or lipid-lowering agents (pravastatin) on the cardiovascular morbidity and mortality in high risk patients. In these studies the relative risk reduction of newly diagnosed diabetes was evaluated in comparison to placebo or other drugs in a subgroup of non-diabetic patients at baseline. In addition, the incidence of newly diagnosed type 2 diabetes decreased parallel with weight loss in clinical trials with orlistat, an anti-obesity drug. Although new results were provided by evidence based clinical trials a lot of questions remained to be solved. Further research is necessary to understand better how to facilitate effective primary prevention of type 2 diabetes. Further data are needed to evaluate the clinical significance of currently used antidiabetic drugs and, in addition, the possible role of other drugs (antihypertensives, lipid lowering agents, anti-obesity drugs) should also be investigated in order to identify the optimal primary prevention policy of type 2 diabetes.

Topics: Acarbose; Angiotensin-Converting Enzyme Inhibitors; Anti-Obesity Agents; Antihypertensive Agents; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Exercise; Global Health; Humans; Hypoglycemic Agents; Hypolipidemic Agents; Incidence; Lactones; Life Style; Metabolic Syndrome; Metformin; Orlistat; Prevalence; Primary Prevention; Risk Factors

Patients with non-alcoholic fatty liver disease (NAFLD) exhibit features of metabolic syndrome, including a high body mass index, central obesity, high blood pressure, and abnormal lipid profile values. Orlistat, an intestinal lipase enzyme inhibitor, improves insulin resistance. We aimed to investigate the effects of short-term therapy with orlistat on the components of metabolic syndrome associated with NAFLD and explore its effect on liver fibrosis scores.. An open-label placebo-controlled clinical study using orlistat for 12 weeks was carried out on 50 patients with NAFLD. They were divided into a placebo group (Group I) and an orlistat treatment group (120 mg per day, Group II). The diagnosis of NAFLD was made by ultrasonography and laboratory investigations. Anthropometric and blood pressure measurements and hepatic liver enzymes, fasting lipids, and blood glucose levels were determined before and after treatment. Lipid indices including cholesterol (Chol-I), triglyceride (TG-I), triglyceride-glucose (TYG-I), and the scores for lipid fibrosis using the NAFLD fibrosis score (NFS) and Fibrosis-4 score (Fib-4) were also determined.. Orlistat significantly improved the anthropometric and metabolic indices (TG-I, TYG-I) and liver enzymes. Orlistat demonstrated a favorable impact on the NAS and Fib-4 scores for liver fibrosis.. Orlistat improves the components of metabolic syndrome, leading to the improvement of insulin resistance and thereby improves fatty infiltration of the liver. To a lesser extent, orlistat improved the liver fibrosis scores.

Topics: Humans; Insulin Resistance; Liver Cirrhosis; Metabolic Syndrome; Non-alcoholic Fatty Liver Disease; Orlistat

Orlistat is a lipase inhibitor that reduces the intestinal absorption of fat and may enhance the effects of dietary and behavioural therapy on weight loss and maintenance. The present study examined the effect of orlistat on dietary intake, especially fat intake, during long-term weight maintenance.. Subjects comprised 44 men and women (aged 18-63 years; body mass index 37.5 +/- 4.3 kg m(-2)) included in the Scandinavian Multicenter study of Obese subjects with the metabolic syndrome, a 3-year clinical trial of orlistat or placebo following an 8-week, very low energy diet (VLED). Two months after the end of the trial when the use of orlistat was optional, 33 subjects remained in the study. A dietary interview based on a validated food frequency questionnaire was conducted before the VLED, after 1 year of treatment with orlistat or placebo and 2 months after the end of the trial.. At 1 year, dietary intake did not differ between the orlistat and placebo group. Energy percent (E%) fat was reduced and E% carbohydrate was increased within both groups. Two months after the end of the trial, E% fat was 32.6% (SD 6.2%) in subjects that chose to take orlistat and 27.7% (SD 5.5%) in subjects not taking orlistat [between group difference -5.0% (95% confidence interval -9.2 to -0.7); P = 0.021].. The use of orlistat compared with placebo in a lifestyle modification programme does not appear to influence dietary intake. Subjects that chose to take orlistat after the end of the programme did not comply with dietary recommendations and this may hamper the effect of the drug.

Topics: Adolescent; Adult; Anti-Obesity Agents; Combined Modality Therapy; Diet, Reducing; Dietary Fats; Energy Intake; Female; Humans; Lactones; Lipid Metabolism; Male; Metabolic Syndrome; Middle Aged; Obesity; Orlistat; Patient Compliance; Treatment Outcome; Weight Loss; Young Adult

Adipose tissue is an active endocrine organ that secretes signaling molecules involved in the regulation of insulin sensitivity, food intake and inflammation. Apelin is a peptide secreted by adipose tissue that has been shown to modulate cardiovascular tone in animals. The aim of this study was to measure abdominal fat, blood pressure and circulating apelin, adiponectin, leptin, ghrelin, TNF-alpha and IL-6 levels in patients with the metabolic syndrome after a diet-induced weight loss.. 35 obese individuals with the metabolic syndrome underwent an 8-week very-low-calorie diet (VLCD) and a 6-month weight maintenance period (WM) with 120mg orlistat or placebo administered 3 times daily. VLCD and WM (-15.1+/-1.0kg) decreased mean arterial pressure (MAP), insulin, leptin, triglycerides and visceral and subcutaneous adipose tissue. Moreover, adiponectin increased in response to the weight loss. However, the overall changes in plasma apelin, TNF-alpha and IL-6 were non-significant. A correlation between plasma apelin and TNF-alpha was observed at baseline (0.41, p<0.05), and the minor changes in plasma apelin levels were associated with changes in BMI during VLCD and MAP and TNF-alpha during VLCD and WM periods.. Despite reductions in BMI, body adiposity, MAP and enhancement of glucose metabolism and adiponectin in response to weight loss, no significant changes in plasma apelin, TNF-alpha and IL-6 were observed. However, apelin significantly correlated with TNF-alpha and MAP. These results suggest that apelin may not be that strongly correlated with the fat mass as an adipokine like the more abundant adipokines adiponectin or leptin and it might be involved in the regulation of inflammation and cardiovascular tone.

Topics: Adiponectin; Adipose Tissue; Anti-Obesity Agents; Apelin; Biomarkers; Blood Glucose; Body Mass Index; Combined Modality Therapy; Diet, Reducing; Female; Ghrelin; Humans; Insulin; Intercellular Signaling Peptides and Proteins; Interleukin-6; Lactones; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Orlistat; Placebos; Tumor Necrosis Factor-alpha; Weight Loss

We assessed the effect of orlistat and fenofibrate, alone or in combination, on plasma high-density lipoprotein (HDL) subfractions and plasma pre-beta1-HDL levels in overweight and obese subjects with metabolic syndrome (MetS).. Patients (n = 89) were prescribed a low-fat low-calorie diet and were randomly allocated to receive orlistat 120 mg three times daily (O group), micronized fenofibrate 200 mg/day (F group) or both (OF group) for 6 months. HDL subfractions were determined using a polyacrylamide gel tube electrophoresis method and pre-beta1-HDL levels using enzyme-linked immunoabsorbent assay.. We observed a significant change of high-density lipoprotein cholesterol (HDL-C) levels only in the F group (+3%, p < 0.05). Large HDL-C levels were significantly increased and small HDL-C levels were significantly reduced with O administration. In F group we observed a significant increase of small HDL-C levels. No significant change of large or small HDL-C levels was observed with combination treatment. We observed a significant increase of pre-beta1-HDL levels in all groups, which was significantly greater in OF group compared with O or F monotherapy.. OF combination increased the antiatherogenic pre-beta1-HDL levels in overweight and obese patients with MetS. Furthermore, OF combination counterbalanced the reduction of small HDL-C levels observed with orlistat monotherapy.

Topics: Anti-Obesity Agents; Body Mass Index; Cholesterol, HDL; Drug Therapy, Combination; Female; Fenofibrate; Greece; High-Density Lipoproteins, Pre-beta; Humans; Hypolipidemic Agents; Lactones; Lipoproteins, HDL; Male; Metabolic Syndrome; Middle Aged; Obesity; Orlistat; Overweight

To examine the effect of orlistat on dietary restraint, disinhibition, hunger, and binge eating and to understand the relation between changes in eating behavior and weight maintenance.. Subjects were 306 women and men (age: 19-45 years; BMI: 37.5 +/- 4.1 kg/m(2)) included in the Scandinavian Multicenter study of Obese subjects with the Metabolic Syndrome, a 3-year clinical trial of orlistat or placebo following an 8-week very low energy diet (VLED). Outcomes were changes in weight and in the Three Factor Eating Questionnaire (TFEQ) and Binge Eating Scale (BES) between screening and 17 and 33 months after randomization. As reported previously, weight gain following VLED was lower in subjects treated with orlistat than with placebo.. Compared to screening results, dietary restraint was increased and disinhibition, hunger, and binge eating were decreased in both groups. These changes were similar in both groups with the exception of the hunger score at month 33 that was reduced more in the placebo than in the orlistat group (difference between groups -1.1 (95% CI (-2.0, -0.2)) P = 0.014). In multivariate analyses, scores for restraint, disinhibition and binge eating were associated with weight loss after adjustment for BMI, gender, age, and treatment (all P < or = 0.002, model R (2) = 0.12-0.17).. Orlistat did not affect eating behavior differently in any substantial way than the placebo did in this long-term weight maintenance trial. The results indicate that increased restraint and decreased disinhibition and binge eating are important for sustained weight maintenance in obese subjects with the metabolic syndrome.

Topics: Adult; Anti-Obesity Agents; Body Weight; Bulimia; Energy Intake; Feeding Behavior; Female; Humans; Lactones; Longitudinal Studies; Male; Metabolic Syndrome; Middle Aged; Multivariate Analysis; Obesity; Orlistat; Regression Analysis; Scandinavian and Nordic Countries; Weight Loss

Increased concentration of small dense LDL cholesterol (sdLDL-C) and activity of lipoprotein-associated phospholipase A2 (Lp-PLA(2)) are considered as emerging cardiovascular risk factors and are commonly encountered in subjects with metabolic syndrome (MetS).. The primary endpoint of this study was the effect of orlistat and fenofibrate, alone or in combination, on Lp-PLA(2) activity and LDL phenotype in overweight and obese patients (body mass index>28 kg/m(2)) with MetS.. Patients (n=89) were prescribed a low-fat low-calorie diet and were randomly allocated to receive orlistat 120 mg three times daily (O group), micronized fenofibrate 200mg/day (F group) or both (OF group) for 6 months.. Significant reductions of sdLDL-C levels were observed in all treatment groups. Groups F and OF experienced a greater reduction in sdLDL-C levels (p<0.05) together with a greater increase in LDL particle diameter (p<0.05) compared with group O. Total plasma Lp-PLA(2) activity significantly decreased in all treatment groups. The reduction of Lp-PLA(2) was more pronounced with OF administration compared with each monotherapy (p<0.05).. Orlistat and fenofibrate exhibited favorable effects on Lp-PLA(2) activity and LDL phenotype in overweight and obese patients with MetS. Importantly, combination treatment had a more favorable effect on these risk factors.

Topics: 1-Alkyl-2-acetylglycerophosphocholine Esterase; Adult; Anti-Obesity Agents; Cardiovascular Diseases; Cholesterol, LDL; Drug Therapy, Combination; Female; Fenofibrate; Humans; Hypolipidemic Agents; Lactones; Male; Metabolic Syndrome; Middle Aged; Obesity; Orlistat; Overweight; Phospholipases A2; Risk Factors

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome (MetS). There is no established treatment for NAFLD.. To evaluate a multifactorial intervention in the treatment of NAFLD.. A prospective, open-label, randomised study in non-diabetic patients (n = 186) with MetS (follow-up: 54 weeks). All patients had both biochemical and ultrasonographic evidence of NAFLD at baseline. Other causes of liver disease were excluded. Patients received lifestyle advice and treatment for hypertension (mainly inhibitors of the renin-angiotensin system), impaired fasting glucose (metformin), obesity (orlistat) and dyslipidaemia [randomly allocated to atorvastatin 20 mg/day (n = 63) or micronised fenofibrate 200 mg/day (n = 62) or both drugs (n = 61)]. Liver ultrasonography was assessed at baseline and at the end of the study.. At the end of treatment, 67% of patients on atorvastatin, 42% on fenofibrate and 70% on combination treatment no longer had biochemical plus ultrasonographic evidence of NAFLD (p < 0.05 vs. baseline for all comparisons). The percentage of patients who no longer had evidence of NAFLD was significantly higher (p < 0.009) in the atorvastatin and combination groups compared with the fenofibrate group. This effect was independently related to drug treatment, as well as to reductions in high-sensitivity C-reactive protein, waist circumference, body weight, triglycerides, low-density lipoprotein-cholesterol, total cholesterol, systolic blood pressure and glucose. Four patients discontinued treatment because of adverse effects.. Multifactorial intervention in MetS patients with both biochemical and ultrasonographic evidence of NAFLD offsets surrogate markers of NAFLD (i.e. elevated aminotransferase plus echogenic liver).

Topics: Anti-Obesity Agents; Atorvastatin; Diet, Fat-Restricted; Drug Therapy, Combination; Dyslipidemias; Fatty Liver; Female; Fenofibrate; Heptanoic Acids; Humans; Hypolipidemic Agents; Lactones; Male; Metabolic Syndrome; Middle Aged; Orlistat; Prevalence; Prospective Studies; Pyrroles; Risk Factors; Treatment Outcome; Ultrasonography; Weight Loss

To investigate the effects of a pharmacotherapy (orlistat) plus lifestyle management (OLM) intervention on weight loss in Mexican American women with and without metabolic syndrome (MS).. One hundred and seven female participants aged 21-65 years and of Mexican origin were randomized to either OLM or a wait-list control group (WLC) for one year. The lifestyle interventions were tailored to exhibit features of the Mexican culture. Within each group, subjects with MS were compared to those without MS to assess whether its presence mitigates weight loss. Risk factors for MS also were assessed.. Participants with MS in the OLM group experienced significant decreases in weight and body mass index (BMI) as compared to participants without MS. Participants with MS in the OLM group and who completed the study lost 9.3+/-7.5 kg (20.5+/-16.5 lb) as compared to participants with MS in the WLC group, who only lost 0.2+/-3.1 kg (0.4+/-6.8 lb). Further, participants with MS in the OLM group who completed the study experienced a 3.1+/-3.9 kg/m2 decrease in BMI whereas participants with MS in the WLC group only experienced a 0.1+/-1.2 kg/m2 decrease in BMI. No changes in other MS risk factors were significant.. Patients with MS experienced significant weight loss and decreases in BMI as a result of a lifestyle and pharmacotherapy intervention.

Topics: Adult; Aged; Anti-Obesity Agents; Body Mass Index; Combined Modality Therapy; Exercise; Female; Humans; Lactones; Life Style; Metabolic Syndrome; Mexican Americans; Middle Aged; Obesity; Orlistat; Overweight; Risk Factors; Weight Loss

To specify changes in clinicolaboratory parameters in reduction of obesity in patients with diabetes mellitus type 2 (DM-2).. Antropometry, densitometry of fat tissue (FT) were made and parameters of fat and carbohydrate metabolism (lipidogram, glycated hemoglobin, immunoreactive insulin), FT secretory activity (leptin, adiponectin, TNF-alpha) were studied in 75 obese DM-2 patients. After the above primary examination all the patients were randomized into 2 groups: group 1 (n = 55) received xenical (120 mg 3 times a day) and kept moderate hypocaloric diet; group 2 (n = 20) received only the above diet therapy. Active treatment lasted 24 weeks.. In addition to symptoms of metabolic syndrome (MS) the patients were found to have secretory disturbances of FT activity: elevation of leptin and TNF-alpha levels, subnormal adiponectin. These alterations directly correlated with body mass, FT mass gain, increase in waist circumference. Hyperleptinemia, hyperinsulinemia and hypoadiponectinemia were considered as markers of insulin resistance (IR) and related conditions. Xenical promoted a significant weight loss resulting in a positive trend in the parameters of adipokines, fat and carbohydrate metabolism, in reduction of IR.. Xenical is beneficial for patients with DM-2 and obesity because it improves metabolic processes.

Topics: Adiponectin; Adipose Tissue; Anthropometry; Anti-Obesity Agents; Biomarkers; Body Weight; Caloric Restriction; Carbohydrate Metabolism; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Insulin; Insulin Resistance; Lactones; Leptin; Lipids; Male; Metabolic Syndrome; Middle Aged; Obesity; Orlistat; Tumor Necrosis Factor-alpha

To study effects of body mass loss due to orlistat on carbohydrate and lipid metabolism, insulin resistance, 24-h profile of arterial pressure (AP), left ventricular myocardial hypertrophy, brain perfusion in patients with metabolic syndrome (MS).. Thirty middle-aged patients with MS entered the trial. They received orlistat in a dose 120 mg twice a day for 24 weeks. Before and after the treatment the patients' carbohydrate and lipid metabolism, insulin resistance were studied, 24-h monitoring of arterial pressure, echo-cardiography were made. Brain perfusion was studied with single-photon emission computed tomography in 18 patients. Results. All the patients lost much weight. This was accompanied with improved indices of AP profile, metabolism of carbohydrates and lipids, insulin resistance, left ventricular hypertrophy, brain perfusion. Conclusion. Orlistat treatment weakens basic factors of cardiovascular risk.

Topics: Adult; Anti-Obesity Agents; Blood Glucose; Cardiovascular Diseases; Cerebral Angiography; Female; Humans; Insulin; Insulin Resistance; Lactones; Lipid Metabolism; Lipids; Male; Metabolic Syndrome; Orlistat; Risk Factors; Weight Loss

Topics: Antihypertensive Agents; Atorvastatin; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Drug Therapy, Combination; Fenofibrate; Fibrinogen; Heptanoic Acids; Humans; Hypolipidemic Agents; Inflammation; Lactones; Leukocyte Count; Metabolic Syndrome; Metformin; Orlistat; Prospective Studies; Pyrroles; Treatment Outcome

Obesity is becoming increasingly common worldwide and is strongly associated with the metabolic syndrome (MetS). MetS is considered to be a cluster of risk factors that increase the risk of vascular events.. In an open-label randomised study (the FenOrli study) we assessed the effect of orlistat and fenofibrate treatment, alone or in combination on reversing the diagnosis of the MetS (primary end-point) as well as on anthropometric and metabolic parameters (secondary end-points) in overweight and obese patients with MetS but no diabetes.. Overweight and obese patients (N = 89, body mass index (BMI) > 28 kg/m2) with MetS [as defined by the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III criteria] participated in the study. Patients were prescribed a low-calorie low-fat diet and were randomly allocated to receive orlistat 120 mg three times a day (tid) (O group), micronised fenofibrate 200 mg/day (F group), or orlistat 120 mg tid plus micronised fenofibrate 200 mg/day (OF group). Body weight, BMI, waist circumference, blood pressure, serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, triglyceride, creatinine (SCr) and uric acid (SUA) levels, as well as homeostasis model assessment (HOMA) index and liver enzyme activities were measured at baseline and after 3 months of treatment.. Of the 89 patients enrolled, three (one in each group) dropped out during the study due to side effects. After the 3-month treatment period, 43.5% of patients in the O group, 47.6% in the F group and 50% in the OF group no longer met the MetS diagnostic criteria (primary end-point, p < 0.0001 vs. baseline in all treatment groups). No significant difference in the primary end-point was observed between the three treatment groups. Significant reductions in body weight, BMI, waist circumference, blood pressure, TC, LDL-C, non-HDL-C, triglyceride and SUA levels, as well as gamma-glutamyl transpeptidase activity and HOMA index were observed in all treatment groups. In the OF group a greater decrease in TC (-26%) and LDL-C (-30%) was observed compared with that in the O and F groups (p < 0.01) and a more pronounced reduction of triglycerides (-37%) compared with that in the O group (p < 0.05). SUA levels and alkaline phosphatase activity decreased more in the F and OF groups compared with the O group (p < 0.05). Moreover, SCr significantly increased and estimated creatinine clearance decreased in the F and OF groups but they were not significantly altered in the O group (p < 0.01 for the comparison between O and either F or OF groups). Glucose (in groups O and OF), as well as insulin levels and HOMA index (in all groups), were significantly reduced after treatment (p < 0.05 vs. baseline).. The combination of orlistat and micronised fenofibrate appears to be safe and may further improve metabolic parameters in overweight and obese patients with MetS compared with each monotherapy.

Topics: Adult; Aged; Cholesterol, HDL; Cholesterol, LDL; Drug Therapy, Combination; Female; Fenofibrate; Humans; Lactones; Male; Metabolic Syndrome; Middle Aged; Obesity; Orlistat; Overweight

Metabolic syndrome (MetSyn) is associated with a marked increase in the risk of cardiovascular disease, especially in patients with type 2 diabetes mellitus (DM).. To investigate the effect of orlistat plus hypocaloric diet (HCD) vs HCD alone on the cardiovascular risk profile in patients with both MetSyn (National Cholesterol Educational Program--NCEP--Adult Treatment Panel III definition) and type 2 DM.. This was a prospective, multicentre, open-label, randomized, controlled study. One hundred and twenty-six patients, free of cardiovascular disease at baseline, were included in the final analysis. Ninety-four (73%) patients were treated with orlistat (360 mg/day) and HCD for a 6-month period, while 34 (27%) were on HCD alone. Analysis of covariance was used to assess differences between the treatment groups over time.. Components of the MetSyn criteria assessed were: waist circumference; systolic and diastolic blood pressure; fasting glucose, triglycerides; high-density lipoprotein cholesterol (HDL-C) plus body mass index; glycosylated haemoglobin (HbA1C); homeostasis model for assessment of insulin resistance (HOMA) index; and total and low-density lipoprotein cholesterol (LDL-C).. By protocol, all patients had MetSyn at baseline. After a 6 month treatment period there were significant differences between the orlistat plus HCD vs the HCD-alone groups in body weight (p = 0.0001), waist circumference (p < 0.0001), fasting glucose (p < 0.0001), HbA(1C) (p < 0.0001), systolic blood pressure (p = 0.024), total cholesterol (p < 0.0001), LDL-C (p = 0.034), and HOMA index (p = 0.022), while there were no significant differences in triglycerides and HDL-C. Orlistat was well tolerated. By the end of the study, 65% of the patients on orlistat plus HCD were still meeting the MetSyn criteria and 41% had four to five MetSyn components vs 91% (p < 0.0001) and 53% (p = 0.017), respectively, of those on HCD alone.. Orlistat plus HCD favourably modified several cardiovascular risk factors in patients with both MetSyn and type 2 DM. These effects might partly offset the excess cardiovascular risk and improve outcome in this patient population.

Topics: Anti-Obesity Agents; Blood Glucose; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diet, Reducing; Female; Humans; Lactones; Lipase; Male; Metabolic Syndrome; Middle Aged; Obesity; Orlistat; Risk Factors

Obesity is an abnormal fat accumulation disorder in the metabolic syndrome constellation, and a risk factor for diabetes, cardiovascular disorders, non-alcoholic fatty liver disease (NAFLD), and cancer. Nuclear receptors (Peroxisome proliferator-activated receptor, PPAR) are implicated in metabolic syndrome and NAFLD, and have potential for therapeutic targeting. Nuclear receptors are ligand-dependent transcription factors that have diverse roles in metabolism, including regulating genes involved in lipid and glucose metabolism, modulating inflammatory genes, and are crucial for maintaining metabolic flexibility. PPAR activates adipose triglyceride lipase, which then releases fatty acids as ligands for PPAR, indicating the interdependency of nuclear receptors and lipases. Here, molecular docking was performed with selected phytochemical ligands that can bind with PPAR-α/γ (PDB ID: 2ZNN and 2ATH, respectively) using Glide module of Schrodinger software followed by molecular dynamics simulation study using Desmond module, and ADMET analysis. Interestingly, orlistat which is a well-known lipase and fatty acid synthase inhibitor also demonstrated favorable binding affinity with both PPAR-α/γ (-10.96 kcal/mol against PPARα and -10.26 kcal/mol against PPARγ). The highest docking scores were however shown by the flavonoids - rutin (-14.88 kcal/mol against PPARα and -13.64 kcal/mol against PPARγ), and its aglycone, quercetin (-10.08 kcal/mol in PPARα and -9.89 kcal/mol in PPARγ). The other phytochemicals (genistein, esculin, daidzin, naringenin, daidzein, dihydroxy coumarin, hydroquinone) showed lower binding affinity as dual agonists. The anti-obesity effects were experimentally validated in cultured adipocytes, which revealed better lipid inhibition by rutin and quercetin than orlistat (quercetin > rutin > orlistat) pointing to their strong potential in anti-obesity treatment.

Topics: Anti-Obesity Agents; Humans; Ligands; Lipids; Metabolic Syndrome; Molecular Docking Simulation; Non-alcoholic Fatty Liver Disease; Obesity; Orlistat; Phytochemicals; PPAR alpha; PPAR gamma; Quercetin; Rutin

To determine the efficacy of Corchorus olitorius (C. olitorius) leaf extract in the prevention of metabolic syndrome induced in rats by high-fat diet (HFD) and compare it with that of orlistat.. Phytochemical analysis was performed. Effect of orlistat and C. olitorius extract on lipase activity and acute food intake were investigated. Body weight, biochemical parameters and histopathological examination were demonstrated.. Corchorus olitorius extract inhibited the pancreatic lipase activity, but orlistat was more potent. Cumulative food intake has not changed by the tested agents. In obese rats, C. olitorius or orlistat significantly decreased weight gain and visceral white adipose tissue. They exhibited a significant reduction in serum glucose, total cholesterol, triglycerides, low density lipoprotein cholesterol, free fatty acids, IL-1β, tumour necrosis factor-α (TNF-α), insulin and leptin levels of obese rat groups while high density lipoprotein cholesterol and adiponectin levels were significantly increased by them. Histopathological examination of the liver revealed that C. olitorius was more effective than orlistat in the alleviating of steatosis and adipocyte hypertrophy shown in obese control rats.. Corchorus olitorius is effective as orlistat in preventing obesity, hyperlipidaemia, steatosis and insulin resistance. These actions may be mediated by inhibiting of lipase activity, TNF-α, IL-1β and leptin resistance along with increasing of adiponectin.

Topics: Adiponectin; Animals; Anti-Obesity Agents; Corchorus; Cytokines; Diet, High-Fat; Hyperlipidemias; Insulin; Insulin Resistance; Leptin; Lipase; Male; Metabolic Syndrome; Obesity; Orlistat; Plant Extracts; Plant Leaves; Rats; Rats, Sprague-Dawley; Weight Gain

Lipoprotein lipase (LPL) is a multifunctional protein and a key enzyme involved in the regulation of lipoprotein metabolism. We determined the lipoproteins to which LPL is bound in the pre-heparin and post-heparin plasma.. Tetrahydrolipstatin (THL), a potent inhibitor of serine lipases, was used to block the lipolytic activity of LPL, thereby preventing changes in the plasma lipoproteins due to ex vivo lipolysis. Gel filtration was performed to obtain the LPL elution profiles in plasma and the isolated remnant lipoproteins (RLP).. When ex vivo lipolytic activity was inhibited by THL in the post-heparin plasma, majority of the LPL was found in the VLDL elution range, specifically in the RLP as inactive dimers. However, in the absence of THL, most of the LPL was found in the HDL elution range as active dimers. Furthermore, majority of the LPL in the pre-heparin plasma was found in the RLP as inactive form, with broadly diffused lipoprotein profiles in the presence and absence of THL.. It is suggested that during lipolysis in vivo, the endothelial bound LPL dimers generates RLP, forming circulating RLP-LPL complexes in an inactive form that subsequently binds and initiates receptor-mediated catabolism.

Topics: Adult; Aged; Diabetes Mellitus, Type 2; Female; Humans; Lactones; Lipoprotein Lipase; Lipoproteins; Male; Metabolic Syndrome; Middle Aged; Orlistat; Young Adult

Topics: Anti-Obesity Agents; Bariatric Surgery; Behavior Therapy; Body Mass Index; Caloric Restriction; Clinical Trials as Topic; Consensus Development Conferences as Topic; Diet Records; Dietary Carbohydrates; Dietary Fats; Dietary Proteins; Exercise; Female; Humans; Lactones; Male; Metabolic Syndrome; Obesity; Orlistat; Physical Exertion; Practice Guidelines as Topic; Time Factors; Waist Circumference; Weight Loss

Overweight and obesity are major factors contributing to the development of type 2 diabetes mellitus (DM) and cardiovascular disease (CVD). In addition to the many physical and metabolic consequences of obesity, there are also mental health consequences, in particular, the risk for depression. Depression can lead to poor self-care, poor treatment compliance, and possible increased morbidity and mortality from such illnesses as type 2 DM and CVD. Lifestyle modification for the treatment of overweight and obesity is rarely successful over the long term, and use of surgery is limited by eligibility criteria; therefore, researchers and clinicians continue to explore pharmacotherapy, with intense efforts being directed toward the development of agents that, optimally, will reduce weight and simultaneously reduce or eliminate modifiable cardiovascular and metabolic risk factors. Among the promising new agents are the CB(1) receptor antagonists. These agents target receptors of the endocannabinoid system, a neuromodulatory system recently found to influence energy balance, eating behavior, and metabolic homeostasis via central and peripheral mechanisms. In animal and clinical studies, antagonism of CB(1) receptors has resulted in meaningful weight loss and improvement of lipid and glycemic profiles. Thus, these agents may provide a rational and effective approach for the management of not only overweight and obesity but also their metabolic and cardiovascular sequelae.

Topics: Amides; Anti-Obesity Agents; Cannabinoid Receptor Modulators; Cyclobutanes; Depression; Endocannabinoids; Humans; Lactones; Life Style; Metabolic Syndrome; Obesity; Orlistat; Piperidines; Pyrazoles; Pyridines; Rimonabant; Risk

Weight loss improves metabolic abnormalities and reduces cardiovascular risk in obese hypertensive patients. To evaluate the impact of a sustained weight loss on coronary risk, 181 hypertensive patients with metabolic syndrome underwent to orlistat therapy, 120 mg, t.i.d., plus diet for 36 weeks. During therapy, Framingham risk scores (FRS) were calculated for determination of coronary heart disease risk in ten years. Body mass index decreased from 35.0 +/- 4.2 to 32.6 +/- 4.5 kg/m(2) (p< 0.0001) and waist circumference from 108.1 +/- 10.1 to 100.5 +/- 11.1 cm (p< 0.0001), at the end of the study period (week 36). Systolic and diastolic blood pressure showed reductions after the two first weeks, which were maintained up to the end of the study. A clear shift to the left in FRS distribution curve occurred at the end of the study, compared to baseline, indicating a reduction in coronary risk. Over all patients at risk, 49.2% moved to a lower risk category. A weight loss > 5% occurred in 64.6% of all patients, associated with improvement in glucose metabolism. Among those with abnormal glucose metabolism, 38 out 53 patients (71.7%) improved their glucose tolerance (p< 0.0005). In conclusion, long-term orlistat therapy helps to reduce and maintain a lower body weight, decreasing risk of coronary disease and improving glucose metabolism, thus protecting against type 2 diabetes.

Topics: Adult; Aged; Anti-Obesity Agents; Blood Pressure; Body Mass Index; Female; Follow-Up Studies; Humans; Hypertension; Lactones; Male; Metabolic Syndrome; Middle Aged; Obesity; Orlistat; Waist-Hip Ratio; Weight Loss

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Anti-Obesity Agents; Female; Humans; Hypoglycemic Agents; Lactones; Metabolic Syndrome; Orlistat; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Ramipril; Sulfonylurea Compounds

Impaired vascular endothelial function may be an important mechanism linking obesity to increased cardiovascular risk. We investigated whether short-term weight loss improves conduit artery endothelial dysfunction in overweight adults. Forty-three otherwise healthy overweight patients with a body mass index > or =27 kg/m(2) completed an open-label 3-month trial consisting of a calorie-restricted diet and 120 mg of orlistat taken 3 times daily with meals. Endothelial function and parameters of the metabolic syndrome were measured before and after intervention. Subjects lost 6.6 +/- 3.4% of their body weight. Low-density lipoprotein cholesterol, low-density lipoprotein concentration, fasting insulin, and leptin decreased significantly (all p <0.009), and C-reactive protein decreased (p = 0.22). Conduit vascular function did not change as assessed by flow-mediated dilation (3.86 +/- 3.54 vs 3.74 +/- 3.78%, p = 0.86) and nitroglycerin-mediated dilation (17.18 +/- 5.89 vs 18.87 +/- 7.11%, p = 0.13) of the brachial artery. A moderate degree of weight reduction over 3 months improved the metabolic syndrome profile but not the vascular dysfunction associated with uncomplicated obesity.

Topics: Adolescent; Adult; Anti-Obesity Agents; C-Reactive Protein; Cholesterol, LDL; Diet, Reducing; Endothelium, Vascular; Female; Humans; Insulin; Lactones; Leptin; Lipoproteins, LDL; Male; Metabolic Syndrome; Middle Aged; Obesity; Orlistat; Weight Loss

Topics: Anti-Obesity Agents; Diabetes Mellitus, Type 2; Humans; Lactones; Metabolic Syndrome; Orlistat