Pioglitazone Restores Endothelial Function in Patients with Type 2 Diabetes Treated with Insulin

Abstract

The primary aim of this study was to evaluate the effect of pioglitazone on endothelial function, as assessed by flow-mediated dilatation (FMD) nitroglycerine-induced dilatation (NID) in patients with type 2 diabetes mellitus treated with insulin. A randomized double-blind placebo-controlled trial involved 20 patients with insulin-treated type 2 diabetes. Patients received either pioglitazone 30 mg or placebo for 4 months. FMD, NID, and HbA1c were measured before and after 4 months of treatment. HbA1c decreased from 10.0 (+/- 2.3) to 8.4 (+/- 2.0) in the pioglitazone group, a statistically significant improvement in glycemic control (p = 0.018). HbA1c was unchanged in the placebo group (p = 0.477). Endothelial function as assessed by FMD significantly improved from 10.1 (+/- 4.0)% to 14.6 (+/- 6.2)% in the pioglitazone group (p = 0.036) as compared to the placebo group (p = 0.705). There was a trend towards improvement in the NID in the pioglitazone group (from 13.3 +/- 8.0% to 18.9 +/- 5.4%; p = 0.056). In insulin-treated patients with type 2 diabetes, the addition of pioglitazone improves endothelial function, as measured by FMD. Addition of pioglitazone to insulin in type 2 diabetes patients may favorably impact vascular function in diabetes, even after many years of insulin resistance and hyperglycemia.

Newer agents for blood glucose control in type 2 diabetes: systematic review and economic evaluation

“…Of these, eight fulfilled the inclusion criteria and compared pioglitazone plus insulin with insulin. [231][232][233][234][235][236][237][238] One compared pioglitazone plus insulin with pioglitazone. The remaining trials were excluded because they did not examine the comparison of interest, and one was the uncontrolled extension of a trial that seemed relevant but could not be identified (shown in Table 24).…”

“…For four 231,233,234,238 of the eight trials, randomisation was adequate, whereas for the remaining four trials the randomisation procedure was not reported or unclear. Three trials 231,233,238 had adequate allocation concealment, whereas the rest of the trials did not report on allocation concealment.…”

“…Five trials used ITT analysis. 231,[233][234][235][236] Five trials reported on follow-up rates 231,[233][234][235]238 and in those trials, between 77% and 92% of participants completed the trial, without any significant differences between comparison groups. Six of the eight trials reported that they had carried out a power calculation.…”

Rosiglitazone improves endothelial function in patients with type 2 diabetes treated with insulin

“…[5][6][7][8]10,11 This was the first study to evaluate the effect of rosiglitazone on endothelium in patients with advanced diabetes treated with insulin, although previous studies using pioglitazone in addition to insulin treatment have also shown improvement in endothelial function. 9,12 The low-dose regimen of rosiglitazone used in this study (i.e. 4 mg/day) has been previously associated with improved endothelial function only in non-diabetic populations.…”

Mechanisms of dysfunction endothelium and methods of pathogenetic correction of diabetes

“…Положительное влияние метформина на функцию эндотелия было от-мечено в клинических условиях у женщин, стра-дающих поликистозом яичников, что связыва-лось с уменьшением уровня тестостерона и 17-гидроксипрогестерона [48]. При наблюдении больных СД 2-го типа, находившихся на инсу-линотерапии, лечение которых было дополнено препаратом тиазолидинового ряда -пиоглитазо-ном, через 4 месяца было отмечено улучшение эндотелиальной функции на фоне увеличения потокопосредованной вазодилатации [28]. Ис-пользуемые при лечении больных СД ингиби-торы ангиотензинпревращающего фермента (иАПФ), препятствующие разрушению брадики-нина, уменьшают образование ангиотензина II и оказывают прямое влияние на активность NO-продуцирующего фермента.…”