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

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 (ΔI(30)/ΔG(30)) 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 ΔI(30)/ΔG(30) 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.