Pioglitazone Ameliorates Endothelial Dysfunction in Those with Impaired Glucose Regulation among the First-Degree Relatives of Type 2 Diabetes Mellitus Patients

Abstract

Objective: To study the effects of pioglitazone on endothelial dysfunction of subjects with impaired glucose regulation (IGR) among the first-degree relatives of patients with type 2 diabetes mellitus (T2DM). Subjects and Methods: The first-degree relatives of T2DM patients were screened with oral glucose test and IGR was diagnosed. IGR subjects whose blood glucose was still above the level after 1-month exercise were randomized to receive pioglitazone (15 mg/day) or vehicle for 12 weeks. Endothelial function was assessed as endothelium-dependent and -independent vasodilation. Blood nitric oxide (NO), blood pressure, body mass index, insulin and serum lipids were also measured. Area under the curve of glucose (AUC_glu) and insulin (AUC_INS), homeostasis model assessment of insulin resistance (HOMA-IR), HOMA of β-cell function (HOMA-β) and early insulin secretion index (ΔI₃₀/ΔG₃₀) were calculated. Results: After pioglitazone treatment, fasting plasma, 2-hour plasma glucose, triglyceride (TG), fasting insulin, AUC_glu, HOMA-β and HOMA-IR, 2-hour insulin, AUC_INS and ΔI₃₀/ΔG₃₀ decreased. Endothelium-dependent vasodilation and NO were significantly improved in the treatment group. Furthermore, the changes of endothelium-dependent vasodilation were negatively correlated with changes in AUC_INS but positively with NO and HOMA-β. Stepwise multivariate regression analysis showed that changes in NO and HOMA-β were both independent parameters for improvement of endothelial dysfunction. Conclusion: Pioglitazone decreased blood glucose and TG, increased insulin sensitivity, and ameliorated endothelial dysfunction of IGR subjects among the first-degree relatives of T2DM patients. Increased NO production may be associated with the improvement of endothelial dysfunction.

Effects of Gold Nanoparticles Functionalized with Cornus mas L. Fruit Extract on the Aorta Wall in Rats with a High-Fat Diet and Experimental-Induced Diabetes Mellitus—An Imaging Study

“…These modifications were confirmed with the MRI investigation that recorded the highest descending aorta volume ( Figure 7 ). These findings were concordant with the study performed on persons with impaired glucose regulation by Yu et al, which showed the increase in nitric oxide levels after the administration of pioglitazone at a dose of 15 mg/day for 12 weeks [ 28 ]. The vasodilation may be also explained by the opening effect of pioglitazone on the smooth muscle K V (voltage-dependent K + ) and/or KIR (inward rectifier K + ) channels that was reported by Nomura et al in their study on the isolated rat aorta [ 29 ].…”

Metformin: An Old Drug for the Treatment of Diabetes but a New Drug for the Protection of the Endothelium

“…Collectively, these data strongly suggest that metformin protects the vasculature through mechanisms that are independent of IR. However, a study with another peroxisome proliferator-activated receptor γ ligand, pioglitazone, concluded that this thiazolidinedione did improve both insulin sensitivity and EDV as well as elevating blood levels of NO in patients with impaired glucose regulation [ 120 ].…”

Pioglitazone and Endothelial Dysfunction: Pleiotropic Effects and Possible Therapeutic Implications

“…In the recent randomized, double-blind, and prospective study of Yu et al (2013) [ 17 ], it has been determined that pioglitazone ameliorated ED in subjects with impaired glucose regulation among first-degree relatives of T2DM patients. The test group consisted of 107 first-degree relatives (30–59 years of age) that were diagnosed with impaired glucose regulation or impaired fasting glucose for the first time or before, but without treatment or already off of treatment for more than three months.…”

“…Macroangiopathy, as a pathological condition, is known to be directly correlated with atherosclerosis, which is in turn associated with vascular ED and reduced NO. Diabetic macroangiopathy, with the consequential peripheral vascular disease, stroke, or coronary heart disease, can be marked as the leading cause of mortality and disability due to T2DM [ 17 ]. This is supported by the fact that an accelerated progression of the atherosclerotic process can be detected in patients with T2DM [ 18 ].…”