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

摘要

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.