Comparison of bare metal stent with pioglitazone versus sirolimus-eluting stent for percutaneous coronary intervention in patients with Type 2 diabetes mellitus.

BACKGROUND: Drug-eluting stents (DESs) have been shown to decrease restenosis as compared with bare-metal stents. Recently, thiazolidinediones effectively reduced restenosis and the risk of repeat target vessel revascularization. We conducted a study to compare the performance of a DES with that of a bare-metal stent with pioglitazone in patients with Type 2 diabetes mellitus (DM). METHODS: The study was a prospective cohort trial involving 38 Type 2 diabetic patients referred for coronary stenting who were assigned to either the sirolimus-eluting stent (SES) group or the pioglitazone group. Quantitative coronary angiography was performed at study entry and at 6 months of follow-up to evaluate in-stent late luminal loss and the percentage of the luminal diameter and the rate of restenosis. We also analyzed major adverse cardiac events (MACE) at 12 months. RESULTS: There were no significant differences in glycemic control levels or in lipid levels in the two groups at follow up. The insulin and homeostasis model assessment insulin resistance at follow-up were significantly lower in the pioglitazone group than in the SES group. The percentage of restenosis was similar between the SES group and the pioglitazone group. The incidence of MACE at 1 year tended to be lower in the pioglitazone group than in the SES group. CONCLUSIONS: The bare-metal stent with pioglitazone is not inferior to the SES in the present study and is one of therapeutic strategies of percutaneous coronary intervention for patients with DM.

The effect of pioglitazone on nitric oxide synthase in patients with type 2 diabetes mellitus.

The aim of this study was to evaluate the effect of pioglitazone on nitric oxide in patients with type 2 diabetes and coronary artery disease. Twenty-seven patients with coronary artery disease and diabetes mellitus who had received coronary stenting were eligible for the study. They were assigned to the no insulin resistance (NIR) group, the insulin resistance (IR) group, and the pioglitazone group (30 mg once a day). Endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-alpha), interleukin-6, leptin, and adiponectin were measured. In the pioglitazone group, eNOS, iNOS, and leptin were significantly lower and adiponectin was significantly higher than those in the IR group. Stepwise multiple regression analyses showed that eNOS correlated with TNF-alpha and iNOS correlated with leptin and TNF-alpha. Leptin was the strongest predictor of iNOS. Treatment with pioglitazone significantly reduced eNOS and iNOS by improving adipocytokine levels.

Insulin resistance in nondiabetic patients with acute myocardial infarction.

BACKGROUND: Recent studies have shown that insulin resistance (IR) is an independent predictor of early restenosis after coronary stenting. The aim of this study was to examine the effects of IR and its linkage to late loss with bare metal stenting in nondiabetic patients with acute myocardial infarction (AMI). MATERIALS AND METHODS: We enrolled 61 nondiabetic patients with AMI who have undergone coronary stenting. Quantitative analyses of coronary angiographic data before and after the procedure and at 4 months were performed. Fasting plasma glucose (FPG) and insulin were measured every week until the subjects' hospital discharge. Stress hormones, endothelial nitric oxide synthase, tumor necrosis factor alpha, interleukin-6, leptin, and adiponectin were measured on admission and at 4 months after coronary stenting. RESULTS: Simple linear regression analyses showed a relationship between FPG and insulin [IR group: r=0.297, P=.0428; no insulin resistance (NIR) group: r=0.539, P=.0466] and that late loss was associated with the homeostasis model assessment of IR (HOMA-IR) at 4 months (r=0.435, P=.03). At multiple regression analyses, HOMA-IR on admission in the IR group significantly correlated with thyroid-stimulating hormone, glucagon, and cortisol. The HOMA-IR at 4 months correlated with leptin. CONCLUSIONS: Nondiabetic patients with AMI can be classified into two groups: the IR group and the NIR group. The IR consisted of the transient IR, which correlated with stress hormones, and the continuous IR, which correlated with leptin and contributed to restenosis after coronary stenting.

A randomized comparison of pioglitazone to inhibit restenosis after coronary stenting in patients with type 2 diabetes.

OBJECTIVE: Recent studies have demonstrated that the treatment with thiazolidinediones reduces in-stent restenosis. The aim of this study was to elucidate the mechanism of the efficacy of pioglitazone for preventing in-stent restenosis in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: We conducted a prospective, randomized trial involving 54 type 2 diabetic patients referred for coronary stenting who were randomly assigned to either the control or the pioglitazone group. Quantitative coronary angiography was performed at study entry and at 6 months follow-up. Endothelial nitric oxide synthase (eNOS), tumor necrosis factor alpha, interleukin-6, leptin, and adiponectin were measured at study entry and at 6 months follow-up. RESULTS: A total of 28 patients were randomly assigned to the control group, and 26 patients were assigned to the pioglitazone group. There were no significant differences in glycemic control levels or in lipid levels in the two groups at baseline or at follow-up. Insulin, homeostasis model assessment of insulin resistance, eNOS, and leptin at follow-up were significantly reduced in the pioglitazone group compared with the control group. The late luminal loss and in-stent restenosis were significantly less in the pioglitazone group than in the control group. Leptin independently correlated with late luminal loss at multiple regression analysis. CONCLUSIONS: The treatment with pioglitazone in type 2 diabetic patients significantly reduced leptin. This decreased leptin improved insulin resistance and endothelial function with the reduction of insulin. The improved endothelial function affected the reduction of in-stent restenosis.

Insulin resistance as a predictor for restenosis after coronary stenting.

PURPOSE: The rationale of this study was to determine whether insulin resistance is an independent risk factor for restenosis after coronary stenting. BACKGROUND: Previous studies suggested that hyperinsulinemia may be an important risk factor for ischemic heart disease. Restenosis after coronary stenting is neointimal tissue proliferation and de-novo stenosis is atherosclerosis from the point of view of histology. However, it has not been determined whether insulin resistance is independently related to restenosis after coronary stenting. METHODS: Clinical variables of unselected population of 110 patients were analyzed in multivariate logistic regression analyses for both restenosis and de-novo stenosis. Clinical, lesion-related, and procedural variables were analyzed by chi-square analysis, and relative risk. RESULTS: Multivariate logistic regression analysis showed that homeostasis model assessment insulin resistance (HOMA-IR) and HbA1c were associated with restenosis after coronary stenting (HOMA-IR; P=0.0447, HbA1c; P=0.0462), and HbA1c and low-density lipoprotein cholesterol (LDL-C) were associated with de-novo stenosis (HbA1c; P=0.0201, LDL-C; P=0.0204). Restenosis was influenced by insulin resistance [Relative Risk (RR) 2.06; 95 percent confidence interval (95%CI) 1.20 to 3.56], diabetes mellitus (DM: RR 1.92; 95%CI 1.25 to 2.95), and final minimal lumen diameter (RR 2.83; 95%CI 1.32 to 6.06). CONCLUSIONS: HOMA-IR and DM are the predictors of restenosis after coronary stenting, and HbA1c and LDL-C are the predictors of de-novo stenosis. These results may be reflected in histological differences between neointimal tissue proliferation as restenosis and atherosclerosis as de-novo stenosis.

Production of hydrogen peroxide in situ in cardiac myocytes during hypoxia-reoxygenation as assessed with cerium.

Free radicals have been implicated in myocardial reperfusion injury. Hydrogen peroxide (H(2)O(2)) is one possible source of reactive oxygen intermediates. We studied the formation and toxicity of H(2)O(2) in isolated myocytes during hypoxia-reoxygenation with the use of cerium. This method involves formation of an electron-dense precipitate when H(2)O(2) reacts with cerium chloride (CeCl(3)). Single myocytes were obtained from rat hearts by collagenase digestion. Isolated myocytes were reoxygenated for 15 min after 30 min of hypoxia. The cells were treated with digitonin to increase the permeability of the plasma membrane, and CeCl(3) was added to detect intracellular H(2)O(2) on electron microscopy. In the nonhypoxia control group, the ultrastructure of cells was well preserved, and no dense deposits were found in myocytes. In the hypoxia-reoxygenation group, precipitates, i.e., Ce-H(2)O(2) reaction products, were found inside and along swollen mitochondria, and cell viability was reduced to 72.3% of control. These results indicate that endogenous H(2)O(2) is generated by mitochondria and that its release into the cytosol may lead to myocyte death under pathological situations such as hypoxia-reoxygenation.