Evaluation of Rosiglitazone Administration on Cardiovascular Function in Severe Obesity

Abstract

Background: Obese patients have myocardial structural and functional alterations related to insulin resistance. Hypothesis: The purpose of the study was to analyze the effects of rosiglitazone, an insulin sensitizer agent, on cardiac morphometry and functioning. Methods: In 2 groups of sex-and age-matched, nondiabetic, obese patients (5 men and 7 women, age 19-51 y; group A: body mass index [BMI] 40.6±3.4 kg/m 2 ; group B: BMI 42.6±2.7 kg/m 2 ), we evaluated the basal insulin sensitivity index (HOMA[IS]), body composition by bioelectrical impedance analysis and 24-h blood pressure monitoring. Furthermore, all patients underwent conventional 2-Dimensional and color Doppler echocardiography, and pulsed-wave tissue Doppler imaging (TDI). After the baseline evaluation, all patients were put on a hypocaloric diet (70% basal metabolic rate) plus placebo if they were in group A, or plus rosiglitazone (4 mg twice daily; Avandia [GlaxoSmithKline plc., Brentford, Middlesex, United Kingdom]) if they were in group B, for 6 mo. Results: Significant decreases in body weight, total fat mass, BMI, and systolic blood pressure were registered in both groups. Rosiglitazone administration appeared more efficient in improving HOMA(IS) (mean difference: 0.30±0.19 versus 0.11±0.21, p<0.05). Left ventricular (LV) diastolic diameter (49.4±7.7 versus 52.3±5.4 mm, p<0.05) and E wave (0.89±0.18 versus 0.99±0.20 m/sec, p<0.05) increased in the rosiglitazone group due to a rise in preload and water content without peripheral edema. The increase in systolic (Sa) wave velocity in both groups was probably a result of the general improvement in insulin metabolism and the decrease in blood pressure. Conclusions: We confirmed the positive effect of rosiglitazone on glucose metabolism in obese, nondiabetic patients, but changes in insulin sensitivity did not explain the cardiac effects produced by further mechanisms.

Meta-analysis: Continuous Positive Airway Pressure Improves Insulin Resistance in Patients with Sleep Apnea without Diabetes

“…However, these association studies do not prove causality, and interventional studies using an effective treatment for OSA (such as CPAP) are needed to support this concept. The effect size of CPAP treatment on HOMA-IR is modest (20.44) when compared with the effect of the thiazolidinedione rosiglitazone, which has been reported to improve the HOMA-IR by 20.9 in nondiabetic obese patients or in those with the metabolic syndrome (34,35). Our study does not address whether OSA and the development of diabetes are causally linked.…”

Rosiglitazone, but Not Pioglitazone, Improves Myocardial Systolic Function in Type 2 Diabetic Patients: A Tissue Doppler Study

“…When rosiglitazone treatment was continued to 6 months, the increase in BNP levels became soft and statistically significant improvements were seen myocardial performance index 13 . In a study comparing the effects of rosiglitazone and the low calorie diet on LV echocardiographic parameters in nondiabetic obese patients with insulin resistance, an increase in Sm wave velocity in the treatment and the only low calorie diet group was obtained probably a result of the general improvement in insulin metabolism and the decrease in blood pressure 14 …”

“…There is only one study showing that rosiglitazone therapy caused an increase in Sm velocity, 14 whereas there is no study utilizing TDI for evaluation of the effects of pioglitazone therapy on LV function. In a study evaluating the effect of single dose of rosiglitazone and pioglitazone on isolated perfused rat hearts, only rosiglitazone, exerted positive inotropic, positive lusitropic, negative chronotropic, and coronary vasorelaxant effects 20 .…”

“…13 In a study comparing the effects of rosiglitazone and the low calorie diet on LV echocardiographic parameters in nondiabetic obese patients with insulin resistance, an increase in Sm wave velocity in the treatment and the only low calorie diet group was obtained probably a result of the general improvement in insulin metabolism and the decrease in blood pressure. 14 The abovementioned studies involved patients with normal systolic functions. Randomized studies investigating the effects of pioglitazone and rosiglitazone on LV systolic function in patients with type 2 diabetes, systolic dysfunction, and New York Heart Association (NYHA) functional classes I-III heart failure were also conducted.…”