orlistat and Glucose-Intolerance

(1) Diabetes is a chronic disease whose incidence is increasing worldwide. The long-term complications of diabetes place a large health and economic burden onto individuals, their families and communities as a whole.(2) Guidelines on the prevention of diabetes recommend lifestyle changes such as smoking cessation and weight loss to decrease type 2 diabetes incidence in patients with impaired glucose tolerance or impaired fasting glucose.(3) The role of lifestyle changes and weight loss in preventing diabetes has been proven in large, randomized, controlled clinical trials. To date, the evidence in favor of pharmacological methods is less robust; however, encouraging results obtained so far suggest a promising future role for these agents.(4) Several oral hypoglycemic agents and the antiobesity drug orlistat have been shown to significantly decrease progression to diabetes. The role of other agents such as statins, oestrogen and antihypertensive agents remains to be clarified in additional well-designed studies of diabetes prevention.

Topics: Administration, Oral; Anti-Obesity Agents; Antihypertensive Agents; Blood Glucose; Diabetes Mellitus, Type 2; Estrogens; Fasting; Glucose Intolerance; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypoglycemic Agents; Lactones; Life Style; Orlistat

Four prospective randomised long-term studies have been recently completed and published (Diabetes Prevention Study, Diabetes Prevention Program, STOP-NIDDM trial, XENDOS Study). Both of them clearly demonstrate the possibility to delay and/or prevent the onset of type 2 diabetes in at high-risk subjects with impaired glucose tolerance, through changes in lifestyle (dietary intervention, weight reduction, increased physical activity) or drug treatment (metformin, acarbose, orlistat). These studies are reviewed and practical implications of their results are discussed.

Topics: Acarbose; Adult; Aged; Diabetes Mellitus, Type 2; Diet; Exercise; Female; Glucose Intolerance; Humans; Hypoglycemic Agents; Lactones; Life Style; Male; Metformin; Middle Aged; Orlistat; Prospective Studies; Randomized Controlled Trials as Topic; Risk Factors; Weight Loss

Orlistat has been shown to increase adiponectin and reduce progression to type 2 diabetes in obese Caucasians. Some effects of orlistat are thought to be independent of weight loss by altering gut flora and the production of endotoxin lipopolysaccharide (LPS). We studied the effect of dietary treatment with and without orlistat in South Asian individuals with impaired glucose tolerance (IGT) on adiponectin and inflammatory markers including LPS.. South Asian individuals were randomised to either dietary treatment with orlistat or dietary treatment alone. At the end of 12 months, a comparison was made between the two groups for differences in anthropomorphic measurements and serum markers.. Three hundred and five individuals underwent oral glucose tolerance test of whom 40 had IGT. Complete baseline and 1-year data was available for 31 patients. After 1 year, patients in the orlistat group demonstrated a greater but insignificant decrease in weight (4.5 +/- 0.1 kg), and a significant increase in adiponectin (6.73 +/- 3.2 microg/ml) and decrease in LPS (4.55 +/- 1.98 EU/ml) compared with- the diet-alone group. In the orlistat group the reduction in LPS was correlated with the increase in adiponectin (p < 0.005).. The increase in adiponectin levels in the orlistat group would suggest that orlistat may reduce the progression to type 2 diabetes in South Asian individuals by raising serum adiponectin. The finding that LPS levels are also reduced by orlistat and that this reduction correlates with the increase in adiponectin raises the possibility that the increase in adiponectin may be mediated via an effect on LPS levels.

Topics: Adipokines; Adult; Combined Modality Therapy; Female; Follow-Up Studies; Glucose Intolerance; Humans; Lactones; Lipids; Lipopolysaccharides; Male; Orlistat

To investigate the efficacy of orlistat on the maintenance of weight loss over 3 years following a major weight loss induced by very-low-energy diet (VLED) in obese patients with metabolic risk factors such as dyslipidemia, impaired fasting glucose, and diet-treated type 2 diabetes.. Initially, weight loss was induced by an 8-week VLED (600-800 kcal/day) in 383 patients with a mean BMI of 37.5 kg/m(2) (range 30.0-45.2). Those who lost > or = 5% of their body weight (309 of 383 patients) were then randomized to receive lifestyle counseling for 3 years together with either orlistat 120 mg t.i.d. or matching placebo capsules. Primary end points were the maintenance of > or = 5% weight loss after 3 years. Additionally, differences in the development of type 2 diabetes between orlistat and placebo were analyzed.. The VLED induced a mean weight loss of 14.4 +/- 2.0 kg among the subsequently randomized patients. The mean weight gain after 3 years was lower with orlistat than with placebo (4.6 +/- 8.6 vs. 7.0 +/- 7.1 kg; P < 0.02). The number of participants who achieved > or =5% weight loss also favored orlistat (67 vs. 56%; P = 0.037). Waist circumference was significantly more reduced in the orlistat group (P < 0.05), but no other differences in the risk factors were observed between the two groups. The incidences of new cases of type 2 diabetes were significantly reduced in the orlistat group (8 cases out of 153 subjects) versus placebo (17 cases out of 156 subjects) (P = 0.041).. The addition of orlistat to lifestyle intervention was associated with maintenance of an extra 2.4 kg weight loss after VLED for up to 3 years in obese subjects. The combination of orlistat and lifestyle intervention was associated with a reduced occurrence of type 2 diabetes.

Topics: Adult; Aged; Anti-Obesity Agents; Body Mass Index; Body Size; Combined Modality Therapy; Diabetes Complications; Diet, Reducing; Female; Glucose Intolerance; Humans; Lactones; Male; Middle Aged; Obesity; Orlistat; Placebos; Weight Gain

Obesity is a multi-factorial metabolic syndrome that increases the risk of cardiovascular diseases, diabetes, and cancer. We recently demonstrated the antiadipogenic efficacy of lutein using a 3 T3-L1 cell culture model. This study aimed to examine the antiobesity efficacy of lutein on high-fat (60% kcal fat) diet-induced C57BL/6J obese mice model. Lutein (300 and 500 μM), Orlistat (30 mg/kg body weight - positive control), and its combination (orlistat, 15 mg/kg body weight+lutein, 300 μM) were administered in high-fat diet (HFD)-fed mice every other day for 24 weeks. The effect on serum and hepatic lipid parameters was estimated using biochemical assay kits. The adipose tissue expression of adipocyte differentiation markers at gene and protein levels was analyzed by RT-PCR and western blotting, respectively. The results showed that lutein administration and drug significantly reduced epididymal and abdominal adipose tissue weights. Further, lutein reduced the serum cholesterol and LDL-C concentration compared to the HFD group. The HFD-induced elevation in the hepatic triglycerides and cholesterol levels were significantly blocked by lutein and its combination with the drug. Similarly, lutein and its drug combination efficiently lowered the HFD-mediated elevated blood glucose levels. Lutein downregulated the expression of CEBP-α, PPAR-γ, and FAS in the epididymal adipose tissue. Thus, supplementation of lutein may control diet-induced obesity and associated complications in the human population.

Topics: Adipose Tissue; Animals; Anti-Obesity Agents; Cholesterol; Diet, High-Fat; Fatty Liver; Glucose Intolerance; Humans; Liver; Lutein; Mice; Mice, Inbred C57BL; Obesity; Orlistat

Topics: Animals; Diet, High-Fat; Diet, Western; Glucose Intolerance; Lipase; Liver; Mice; Mice, Inbred C57BL; Obesity; Orlistat; Phalaris; Seeds; Weight Gain