Are the beneficial cardiovascular effects of simvastatin and metformin also associated with a hormone-dependent mechanism improving insulin sensitivity?

In addition to lipid-lowering and cardiovascular protective actions, statins may have beneficial effects on insulin sensitivity. The objective of the present study was to evaluate the effect of simvastatin therapy on insulin resistance and on leptin, adiponectin, and C-reactive protein (CRP) levels, as compared to metformin, in overweight pre-diabetic subjects. Forty-one subjects with BMI >25 kg/m(2) and impaired fasting glucose or impaired glucose tolerance were randomized to take simvastatin, 20 mg/day (N = 20) or metformin, 1.7 g/day (N = 21) for 16 weeks. Blood samples for the determination of metabolic, hormonal, and inflammatory parameters were obtained at baseline and after each treatment. After metformin therapy, significant reductions in mean BMI and waist circumference were observed, and after simvastatin treatment LDL and triglyceride levels were significantly reduced. Insulin resistance determined by the homeostasis model assessment decreased only with metformin. Independently of the type of medication, a significant decrease in CRP levels was detected from baseline to the end of the study. CRP showed a mean reduction of 0.12 +/- 0.04 mg/dL (P = 0.002) over time. No change in leptin or adiponectin levels was induced by any therapy. The data suggest that a low dose of simvastatin does not affect insulin resistance in overweight pre-diabetic subjects and has no effect on leptin or adiponectin levels. Further studies including a larger sample size, higher doses of statins, and a placebo control group are necessary to confirm the present data.

Are the beneficial cardiovascular effects of simvastatin and metformin also associated with a hormone-dependent mechanism improving insulin sensitivity?

In addition to lipid-lowering and cardiovascular protective actions, statins may have beneficial effects on insulin sensitivity. The objective of the present study was to evaluate the effect of simvastatin therapy on insulin resistance and on leptin, adiponectin, and C-reactive protein (CRP) levels, as compared to metformin, in overweight pre-diabetic subjects. Forty-one subjects with BMI >25 kg/m² and impaired fasting glucose or impaired glucose tolerance were randomized to take simvastatin, 20 mg/day (N = 20) or metformin, 1.7 g/day (N = 21) for 16 weeks. Blood samples for the determination of metabolic, hormonal, and inflammatory parameters were obtained at baseline and after each treatment. After metformin therapy, significant reductions in mean BMI and waist circumference were observed, and after simvastatin treatment LDL and triglyceride levels were significantly reduced. Insulin resistance determined by the homeostasis model assessment decreased only with metformin. Independently of the type of medication, a significant decrease in CRP levels was detected from baseline to the end of the study. CRP showed a mean reduction of 0.12 ± 0.04 mg/dL (P = 0.002) over time. No change in leptin or adiponectin levels was induced by any therapy. The data suggest that a low dose of simvastatin does not affect insulin resistance in overweight pre-diabetic subjects and has no effect on leptin or adiponectin levels. Further studies including a larger sample size, higher doses of statins, and a placebo control group are necessary to confirm the present data.

Leptin is not associated independently with hypertension in Japanese-Brazilian women.

We evaluated the relationship of leptin with hypertension adjusted for body mass index (BMI) and/or waist circumference in a population of Japanese-Brazilian women aged > or = 30 years with centrally distributed adiposity. After excluding diabetic subjects, the study subjects--who participated in a population-based study on the prevalence of metabolic syndrome--showed prevalence rates of obesity (BMI > or = 25 kg/m2) and central adiposity (waist > or = 80 cm) of 32.0 and 37.8%, respectively. The hypertensive group (N = 162) was older, had higher BMI (24.9 +/- 4.2 vs 23.3 +/- 3.4 kg/m2, P < 0.001), waist circumference (81.1 +/- 10.1 vs 76.3 +/- 8.2 cm, P < 0.001) and insulin levels (8.0 +/- 6.2 vs 7.1 +/- 4.9 microU/mL, P < 0.05) than the normotensive group (N = 322) and showed an unfavorable metabolic profile (higher 2-h plasma glucose, C-reactive protein and non-HDL cholesterol levels). Leptin did not differ between groups (8.2 +/- 6.8 vs 7.2 +/- 6.6 ng/mL, P = 0.09, for hypertensive vs normotensive, respectively) and its levels correlated significantly with anthropometric variables but not with blood pressure. Logistic regression analysis indicated that age and waist were independently associated with hypertension but not with homeostasis model assessment of insulin resistance or leptin levels. The lack of an independent association of hypertension with metabolic parameters (2-h glucose, C-reactive protein and non-HDL cholesterol) after adjustment for central adiposity suggested that visceral fat deposition may be the common mediator of the disturbances of the metabolic syndrome. Our data indicate that age and waist are major determinants of hypertension in this population of centrally obese (waist > or = 80 cm) Japanese-Brazilian women, but do not support a role for leptin in the elevation of blood pressure.

Leptin is not associated independently with hypertension in Japanese-Brazilian women

We evaluated the relationship of leptin with hypertension adjusted for body mass index (BMI) and/or waist circumference in a population of Japanese-Brazilian women aged > or = 30 years with centrally distributed adiposity. After excluding diabetic subjects, the study subjects - who participated in a population-based study on the prevalence of metabolic syndrome - showed prevalence rates of obesity (BMI > or = 25 kg/m²) and central adiposity (waist > or = 80 cm) of 32.0 and 37.8 percent, respectively. The hypertensive group (N = 162) was older, had higher BMI (24.9 ± 4.2 vs 23.3 ± 3.4 kg/m², P < 0.001), waist circumference (81.1 ± 10.1 vs 76.3 ± 8.2 cm, P < 0.001) and insulin levels (8.0 ± 6.2 vs 7.1 ± 4.9 æU/mL, P < 0.05) than the normotensive group (N = 322) and showed an unfavorable metabolic profile (higher 2-h plasma glucose, C-reactive protein and non-HDL cholesterol levels). Leptin did not differ between groups (8.2 ± 6.8 vs 7.2 ± 6.6 ng/mL, P = 0.09, for hypertensive vs normotensive, respectively) and its levels correlated significantly with anthropometric variables but not with blood pressure. Logistic regression analysis indicated that age and waist were independently associated with hypertension but not with homeostasis model assessment of insulin resistance or leptin levels. The lack of an independent association of hypertension with metabolic parameters (2-h glucose, C-reactive protein and non-HDL cholesterol) after adjustment for central adiposity suggested that visceral fat deposition may be the common mediator of the disturbances of the metabolic syndrome. Our data indicate that age and waist are major determinants of hypertension in this population of centrally obese (waist > or = 80 cm) Japanese-Brazilian women, but do not support a role for leptin in the elevation of blood pressure.

Effects of sibutramine on abdominal fat mass, insulin resistance and blood pressure in obese hypertensive patients.

OBJECTIVE: The objective of this study is to assess the effects of sibutramine on body weight, body fat distribution, insulin resistance, plasma leptin, lipid profile and blood pressure profiles in hypertensive obese patients. METHODS: Eighty-six central obese hypertensive patients (BMI = 39 +/- 5 kg/m(2), 84% of women, 48 +/- 8.5 years old) were placed on a hypocaloric diet and placebo therapy for 4 weeks. They were then randomized to receive sibutramine (10 mg) or placebo for 24 weeks. Both, before therapy and at the end of the study, the waist and hip circumferences were measured and the waist/hip ratio (WHR) was calculated; abdominal ultrasonography was performed in order to estimate the amount of subcutaneous fat (SF) and visceral fat (VF), and the visceral/subcutaneous ratio. Beyond HOMA-r, another insulin resistance index (IRIp) was calculated by means of the formula: peak of blood glucose after oral glucose load x plasma insulin level/10(4). Fasting plasma leptin and lipid levels were also determined. RESULTS: Sibutramine induced greater weight reduction than placebo (6.7 vs. 2.5%, p < 0.001). Reductions in WHR (0.97 +/- 0.08 vs. 0.94 +/- 0.07, p < 0.01), IRIp (0.11 +/- 0.07 vs. 0.09 +/- 0.06 mmol mu/l(2)) and VF (6.4 +/- 2.4-6.0 +/- 2.4 cm, p < 0.01) were observed only with sibutramine. Plasma leptin decreased with placebo (24 +/- 15 vs. 18 +/- 10 UI/l, p < 0.01), but not with sibutramine (18.8 +/- 8.4 vs. 18.2 +/- 13.2 UI/l). No clinically significant change in lipid profile was observed in both groups. Moreover, office and 24-h blood pressure values did not change during placebo or sibutramine therapy, whereas a significant increase in office heart rate, from 78.3 +/- 7.3-82 +/- 7.9 b.p.m., p = 0.02, was observed with sibutramine. CONCLUSIONS: Sibutramine therapy induced greater body weight loss than placebo in hypertensive obese patients. This was associated with WHR reduction, decreases in VF and insulin resistance. The maintenance of leptin levels during sibutramine therapy may be important to avoid weight recovery, although this finding must be confirmed by other prospective studies.

Ultrasonography for the evaluation of visceral fat and cardiovascular risk.

Visceral fat accumulation is associated with increased cardiovascular risk. Clinical evaluation of visceral fat is limited because of the lack of reliable and low-cost methods. To assess the correlation between ultrasonography and computed tomography (CT) for the evaluation of visceral fat, 101 obese women, age 50.5+/-7.7 years with a body mass index of 39.2+/-5.4 kg/m(2), were submitted to ultrasonograph and CT scans. Visceral fat measured by ultrasonography, 1 cm above the umbilical knot, showed a high correlation with CT-determined visceral fat (r=0.67, P<0.0001). The ultrasonograph method showed good reproducibility with an intra-observer variation coefficient of <2%. Both ultrasonograph and CT visceral fat values were correlated with fasting insulin (r=0.29 and r=0.27, P<0.01) and plasma glucose 2 hours after oral glucose load (r=0.22 and r=0.34, P<0.05), indicating that ultrasonography is a useful method to evaluate cardiovascular risk. A significant correlation was also found between visceral fat by CT and serum sodium (r=0.18, P<0.05). A ultrasonograph-determined visceral-to-subcutaneous fat ratio of 2.50 was established as a cutoff value to define patients with abdominal visceral obesity. This value also identified patients with higher levels of plasma glucose, serum insulin and triglycerides and lower levels of HDL-cholesterol, which are metabolic abnormalities characteristic of the metabolic syndrome. Our data demonstrate that ultrasonography is a precise and reliable method for evaluation of visceral fat and identification of patients with adverse metabolic profile.