Pioglitazone Improves Left Ventricular Diastolic Function in Subjects With Diabetes.

OBJECTIVE To examine the effect of pioglitazone on myocardial insulin sensitivity and left ventricular (LV) function in patients with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS Twelve subjects with T2D and 12 with normal glucose tolerance received a euglycemic insulin clamp. Myocardial glucose uptake (MGU) and myocardial perfusion were measured with [F-18]fluoro-2-deoxy-d-glucose and [O-15]H2O positron emission tomography before and after 24 weeks of pioglitazone treatment. Myocardial function and transmitral early diastolic relation/atrial contraction (E/A) flow ratio were measured with magnetic resonance imaging. RESULTS Pioglitazone reduced HbA(1c) by 0.9%; decreased systolic and diastolic blood pressure by 7 +/- 2 and 7 +/- 2 mmHg, respectively (P < 0.05); and increased whole-body insulin-stimulated glucose uptake by 71% (3.4 +/- 1.3 to 5.8 +/- 2.1 mg/kg.min; P < 0.01) in subjects with T2D. Pioglitazone enhanced MGU by 75% (0.24 +/- 0.14 to 0.42 +/- 0.13 mu mol/min.g; P < 0.01) and myocardial perfusion by 16% (0.95 +/- 0.16 to 1.10 +/- 0.25 mL/min.g; P < 0.05). Measures of diastolic function, E/A ratio (1.04 +/- 0.3 to 1.25 +/- 0.4) and peak LV filling rate (349 +/- 107 to 433 +/- 99 mL/min), both increased (P < 0.01). End-systolic volume, end-diastolic volume, peak LV ejection rate, and cardiac output trended to increase (P not significant), whereas the ejection fraction (61 +/- 6 to 66 +/- 7%) and stroke volume increased significantly (71 +/- 20 to 80 +/- 20 L/min; both P < 0.05). CONCLUSIONS Pioglitazone improves whole-body and myocardial insulin sensitivity, LV diastolic function, and systolic function in T2D. Improved myocardial insulin sensitivity and diastolic function are strongly correlated.