Metabolic Effects Of Rosiglitazone Research Articles

A multicentre, randomized, double-blind placebo-controlled trial evaluating rosiglitazone for the prevention of atherosclerosis progression after coronary artery bypass graft surgery in patients with type 2 diabetes. Design and rationale of the VeIn-Coronary aTherOsclerosis and Rosiglitazone after bypass surgerY (VICTORY) trial

The number of patients with coronary artery disease and type 2 diabetes will increase dramatically over the next decade. Diabetes has been related to accelerated atherosclerosis and many patients with diabetes will require coronary artery bypass graft (CABG) surgery utilizing saphenous vein grafts. After CABG, accelerated atherosclerosis in saphenous vein grafts leads to graft failure in approximately 50% of cases over a 10-year period. Rosiglitazone, a peroxisome proliferator-activated receptor-gamma agonist, has been shown to improve multiple metabolic parameters in patients with type 2 diabetes. However, its role in the prevention of atherosclerosis progression is uncertain. VeIn-Coronary aTherOsclerosis and Rosiglitazone after bypass surgerY (VICTORY) is a cardiometabolic trial in which patients with type 2 diabetes, one to 10 years after CABG, will be randomly assigned to receive rosiglitazone (up to 8 mg/day) or a placebo after qualifying angiography and intravascular ultrasound of a segment of one vein graft with or without a native anastomosed coronary artery. A comprehensive set of athero-thrombo-inflammatory markers will be serially assessed during the 12-month follow-up period. Body fat distribution and body composition will be assessed by computed tomography and dual energy x-ray absorptiometry, respectively, at baseline, six months and 12 months follow-up. For atherosclerosis progression evaluation, repeat angiography and intravascular ultrasound will be performed after 12 months follow-up. The primary end point of the study will be the change in atherosclerotic plaque volume in a 40 mm or longer segment of one vein graft. The VICTORY trial is the first cardiometabolic study to evaluate the antiatherosclerotic and metabolic effects of rosiglitazone in post-CABG patients with type 2 diabetes.

The effect of cinnamon extract on insulin resistance parameters in polycystic ovary syndrome: a pilot study

Cinnamon extract has been shown to reduce insulin resistance in in vitro and in vivo studies by increasing phosphatidylinositol 3-kinase activity in the insulin signaling pathway and thus potentiating insulin action. Fifteen women with polycystic ovary syndrome (PCOS) were randomized to daily oral cinnamon and placebo for 8 weeks. Comparisons of post-treatment to baseline insulin sensitivity indices using fasting and 2-hour oral glucose tolerance tests showed significant reductions in insulin resistance in the cinnamon group but not in the placebo group. A larger trial is needed to confirm the findings of this pilot study and to evaluate the effect of cinnamon extract on menstrual cyclicity.

Endocrine and metabolic effects of rosiglitazone in overweight women with PCOS: a randomized placebo-controlled study

Endocrine and metabolic effects of rosiglitazone in overweight women with PCOS: a randomized placebo-controlled study

Endocrine and Metabolic Effects of Rosiglitazone in Overweight Women With PCOS: Placebo-Controlled Study

Rosiglitazone is a member of the thiazolidinedione group of drugs that have, along with metformin, been used to treat insulin resistance in women with polycystic ovary syndrome (PCOS). Unlike metformin, rosiglitazone is a true insulin sensitizer that affects the transcription of various genes having roles in carbohydrate and lipid homeostasis. It significantly lowers plasma glucose levels in diabetic individuals. This double-blind, placebo-controlled study enrolled 30 overweight women with PCOS whose body mass index exceeded 25 kg/m 2 and whose average age was 29 years. All had symptoms of PCOS and'were confirmed by vaginal ultrasonography as having polycystic ovaries. Participants were randomized to receive either rosiglitazone (ROSI) or placebo (PLA), the former in a dose of 4 mg once a day for 2 weeks followed by 4 mg twice daily for 4 months. The 2 groups were clinically and endocrinologically comparable at the outset. Menstrual cycles had become more regular after 4 months of active treatment. There were no changes in the waist-to-hip ratio or in hirsutism scores. Serum levels of sex hormone-binding globulin increased in the treatment group. At the same time, levels of androstenedione, 17-hydroxyprogesterone, dehydroepiandrosterone, and dehydroepiandrosterone sulfate all decreased. On oral glucose tolerance testing, tolerance improved in the ROSI group and the peripheral insulin response decreased. M values, reflecting insulin sensitivity, improved in the ROSI group from 33 to 40 μmol/kg/min. Serum levels of testosterone and follicle-stimulating hormone did not change in either the ROSI or the PLA group. Fasting serum free fatty acid levels decreased significantly in women treated with ROSI. Treatment over 4 months with rosiglitazone significantly improved insulin resistance and menstrual cyclicity and, to some extent, hyperandrogenism in these overweight women with PCOS. This drug offers an effective and well-tolerated alternative for anovulatory women with PCOS who do not want to become pregnant.

Rosiglitazone treatment alleviates inflammation and improves liver function in overweight women with polycystic ovary syndrome: a randomized placebo-controlled study

In a randomized, placebo-controlled study, we studied the effects of 4 months' treatment with rosiglitazone on low-grade inflammation, liver function, lipid levels, and blood pressure in 30 overweight women with polycystic ovary syndrome. Rosiglitazone significantly decreased serum C-reactive protein levels, white blood cell count, and alanine aminotransferase enzyme activity but did not affect lipid or blood pressure levels. Placebo had no effect on any parameters.

Endocrine and metabolic effects of rosiglitazone in overweight women with PCOS: a randomized placebo-controlled study

The objective of the study was to assess the therapeutic effects of rosiglitazone in overweight women with polycystic ovary syndrome (PCOS). A double-blind, placebo-controlled study was conducted on 30 (BMI > 25 kg/m2, mean age 29.1 +/- 1.2 years) overweight women with PCOS treated with rosiglitazone or placebo for 4 months. Waist-to-hip ratios (WHRs), serum concentrations of sex hormones and binding proteins, blood glucose, serum insulin and serum C-peptide during a 75-g oral glucose tolerance test (OGTT), first-phase insulin secretion as determined by an intravenous glucose tolerance test (IVGTT), M values (expressing insulin sensitivity using a euglycaemic clamp) and calorimetric data were assessed at 0 and 4 months of treatment. Rosiglitazone improved menstrual cyclicity, increased serum sex hormone-binding globulin (SHBG) levels and decreased serum levels of androstenedione, 17-hydroxyprogesterone (17-OHP), dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulphate (DHEA-S). Glucose tolerance [expressed as AUC(glucose) during the OGTT] improved (P = 0.002) and peripheral insulin response (expressed as AUC(insulin)) decreased (P = 0.004) in the rosiglitazone group (ROSI group). M value improved in the ROSI group from 33.4 +/- 3.27 to 40.0 +/- 5.51 micromol/kg min (P = 0.04). Rosiglitazone, by improving menstrual cyclicity, hyperandrogenism, insulin resistance and hyperinsulinaemia, represents an alternative treatment for overweight anovulatory women with PCOS and no pregnancy desire.

Endocrine and Metabolic Effects of Rosiglitazone in Non-obese Women with Polycystic Ovary Disease

We hypothesized that the administration of rosiglitazone, an insulin-sensitizing agent of the thiazolidinedione class, would improve the ovulatory dysfunction, hirsutism, hyperandrogenemia, and hyperinsulinemia of polycystic ovary syndrome (PCOS) patients. Forty women with PCOS and impaired glucose tolerance test (IGT) were randomly assigned to the 8-month treatment with rosiglitazone at either 2 mg/day or 4 mg/day. We compared changes in ovulatory function, hirsutism, hormonal levels (total and free testosterone, estradiol, estrone, androstenedione, LH and FSH), and measures of glycemic parameters (fasting and post-challenge levels of glucose and insulin, HOMA-IR, hemoglobin A1c), between the study groups. The patients' baseline characteristics were similar across all treatment arms. Fifteen of 20 women in the 2 mg group and 19 of 20 women in the 4 mg group achieved normal glucose tolerance; 14 of 20 women in the 2 mg group and 17 of 20 women in the 4 mg group achieved ovulatory menses at the end of the study period. The decreases of free testosterone levels were better in the 4 mg group than the 2 mg rosiglitazone group (-1.89+/-0.35 pg/ml vs. -2.21+/-0.39 pg/ml; P<0.01). There were neither any serious adverse events nor any liver enzyme elevations in our study patients during the treatment period. This study demonstrated that rosiglitazone improves the ovulatory dysfunction, hirsutism, hyperandrogenemia, and insulin resistance of PCOS in a dose-related fashion, with minimal adverse effects. This drug may be a good choice for lifetime treatment of patients with PCOS, especially for the ones who failed to show satisfactory results in metformin therapy.

Metabolic Effects of Rosiglitazone in HIV Lipodystrophy

Patients with HIV infection who are treated with antiretroviral agents often lose subcutaneous fat and have metabolic abnormalities, including insulin resistance and reduced adiponectin levels, which may be related to disrupted subcutaneous adipogenesis and altered peroxisome proliferator-activated receptor-gamma signaling. To investigate the effects of rosiglitazone (4 mg/d), a peroxisome proliferator-activated receptor-gamma agonist, in HIV-infected men and women with hyperinsulinemia and lipoatrophy. A randomized, double-blind, placebo-controlled, 3-month study. University hospital. 28 HIV-infected men and women with hyperinsulinemia and lipoatrophy. Insulin sensitivity measured by euglycemic hyperinsulinemic clamp testing; subcutaneous leg fat area measured by computed tomography; adiponectin, free fatty acid, and lipid levels; and safety variables. Rosiglitazone, when compared with placebo, improved insulin sensitivity (mean [+/-SD] change, 1.5 +/- 2.1 mg of glucose/kg of lean body mass per minute vs. -0.4 +/- 1.6 mg/kg per minute; P = 0.02), increased adiponectin levels (mean [+/-SD], 2.2 +/- 2.2 micro g/mL vs. 0.1 +/- 1.1 microg/mL; P = 0.006), and reduced free fatty acid levels (mean [+/-SD], -0.09 +/- 0.1 mmol/L vs. 0.01 +/- 0.1 mmol/L; P = 0.02). Mean percentage (+/-SD) of body fat (1.38% +/- 3.03% vs. -0.83% +/- 2.76%; P = 0.03) and subcutaneous leg fat area (2.3 +/- 8.4 cm2 vs. -0.9 +/- 1.9 cm2; P = 0.02) increased significantly with rosiglitazone compared with placebo. Mean total cholesterol levels (+/-SD) also increased with rosiglitazone compared with placebo (0.6 +/- 1.0 mmol/L [25 +/- 37 mg/dL] vs. -0.4 +/- 0.6 mmol/L [-15 +/- 25 mg/dL]; P = 0.007). The study was relatively small and of short duration. The authors demonstrated positive effects of rosiglitazone on lipoatrophy; insulin sensitivity; and metabolic indices, including adiponectin levels, in HIV-infected patients with lipoatrophy and insulin resistance. Peroxisome proliferator-activated receptor-gamma agonists may correct the metabolic abnormalities associated with disrupted adipogenesis in this population. Further studies must determine the clinical utility of such agents in HIV-infected patients.

Are the metabolic effects of rosiglitazone influenced by baseline glycaemic control?

SUMMARYObjective: To compare the metabolic effects of rosiglitazone, an antidiabetic agent of the thiazolidinedione class, in patients with type 2 diabetes with fair to moderate glycaemic control (glycosylated haemoglobin (HbA1c) < 9%) and poor glycaemic control (HbA1c > 9%).Research design and methods: Data were pooled from two 26-week, randomised, placebo-controlled, double-blind studies of rosiglitazone (4 and 8 mg/day).Results: After 26 weeks of treatment, HbA1c was significantly reduced (p < 0.05) compared with baseline and placebo in patients taking rosiglitazone 8mg/day for both HbA1c stratifications, with greater reductions in patients with baseline HbA1c >9%. After 26 weeks of treatment, reductions in fasting plasma glucose (FPG) were significant (p < 0.05) compared with baseline and placebo in both rosiglitazone treatment groups for both HbA1c stratifications, with greater reductions in the group with poor glycaemic control. Rosiglitazone significantly improved insulin sensitivity (p < 0.05) compared with baseline in patients with baseline HbA1c <9%. Rosiglitazone significantly improved beta-cell function (p < 0.05) compared with baseline with more improvement in the group with baseline HbA1c >9%. These improvements were statistically significant compared with placebo, regardless of HbA1c stratification.Conclusion: Rosiglitazone significantly improved HbA1c and FPG levels in patients with type 2 diabetes, with the greatest improvements observed in patients with baseline HbA1c levels >9%.