Three-year clinical outcome in type 2 diabetic patients with drug-eluting stents versus bare-metal stents with pioglitazone.

AIMS: The aim of this study was to examine outcome subsequent to implantation of bare-metal stents (BMS) with pioglitazone, which are novel insulin-sensitizing agents, and drug-eluting stents (DES) in patients with diabetes. METHODS AND RESULTS: A total of 139 consecutive Type 2 diabetic patients treated with stent were followed up for 3 years. Data on death, myocardial infarction (MI), target lesion revascularization (TLR), and stent thrombosis were ascertained from January 2003 to January 2006. Eighty-nine patients were treated with a BMS with pioglitazone, and 50 patients were treated with a DES. The incidence of MI was 1.1% in the BMS with pioglitazone group, 4.0% in the DES group [relative risk RR):0.52; 95% CI: 0.10-2.56]. The incidence of TLR was 22.5% in the BMS with pioglitazone group, 28.0% in the DES group (RR 0.89; 95% CI: 0.65-1.22). The incidence of stent thrombosis was 1.0% in the BMS with pioglitazone group, 4.0% in the DES group (RR 0.52; 95% CI: 0.10-2.56). Overall 3-year mortality was similar in the two groups (RR 0.77; 95% CI: 0.34-1.74). CONCLUSIONS: During 3 years of follow-up, patients treated with BMS with pioglitazone had similar risks of death, TLR, MI, and stent thrombosis compared with patients treated with DES.

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.

Nocturnal oxygen therapy prevents progress of congestive heart failure with central sleep apnea.

BACKGROUND: Sleep disordered breathing has been reported to be associated with congestive heart failure (CHF). Nocturnal oxygen has been shown to abolish apnea. The aim of this study is to examine whether nocturnal oxygen reduces sympathetic nerve activity, and prevents progress of CHF. METHODS: 93 patients with left ventricular ejection fractions < 60%, were examined with overnight saturation monitoring for an oxygen desaturation index. Subjects with oxygen desaturation of 4% > or = 4/h were examined with polysomnography. Apnea-hypopnea index (AHI) was calculated as the total number of episodes of apnea and hypopnea per hour of sleep. We started nocturnal oxygen for the patients with AHI > or = 20. Urinary and plasma catecholamines concentrations, serum brain natriuretic peptide, human atrial natriuretic peptide, and endothelial nitric oxide synthase levels were measured before and after starting oxygen. RESULTS: Compared among the three groups, CHF with central sleep apnea (CHF-CSA) group had significantly higher 24-h urinary adrenaline (CHF-CSA: 4.411+/-2.940 micromol/day, CHF with obstructive sleep apnea (CHF-OSA): 2.686+/-1.084 micromol/day, CHF without apnea (CHF-N): 3.178+/-1.778 micromol/day, P<0.05). Oxygen therapy significantly decreased AHI and 4 serum BNP levels (from 91.75+/-80.35 pg/ml to 52.75+/-45.70 pg/ml, mean change=33.85 pg/ml, P=0.0208). Serum eNOS levels were lower in CHF-CSA group and CHF-OSA group than in CHF-N group (CHF-CSA: 15.89+/-10.75 pg/ml, CHF-OSA: 7.46+/-3.91 pg/ml, CHF-N: 27.33+/-14.83 pg/ml, P<0.05). CONCLUSIONS: Nocturnal oxygen may prevent progress of CHF with central sleep apnea.

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.