Pioglitazone Improves Left Ventricular Diastolic Function in Subjects With Diabetes

• Published in: Diabetes care Vol. 40; no. 11; pp. 1530 - 1536
• Main Authors: Clarke, Geoffrey D., Solis-Herrera, Carolina, Molina-Wilkins, Marjorie, Martinez, Sandra, Merovci, Aurora, Cersosimo, Eugenio, Chilton, Robert J., Iozzo, Patricia, Gastaldelli, Amalia, Abdul-Ghani, Muhammad, DeFronzo, Ralph A.
• Format: Journal Article
• Language: English
• Published: United States American Diabetes Association 01.11.2017
• Subjects: Adult; Blood Glucose - metabolism; Blood pressure; Blood Pressure - drug effects; Body Mass Index; Cardiac output; Cholesterol - blood; Contraction; Diabetes; Diabetes mellitus; Diabetes Mellitus, Type 2 - drug therapy; Diastole - drug effects; Female; Glucose; Glucose Clamp Technique; Glucose tolerance; Glycated Hemoglobin - metabolism; Heart diseases; Heart rate; Humans; Hypoglycemic Agents - administration & dosage; Insulin; Insulin Resistance; Magnetic resonance imaging; Male; Middle Aged; Myocardium - metabolism; Pathophysiology/Complications; Perfusion; Pioglitazone; Positron emission; Positron emission tomography; Research design; Sensitivity; Stroke; Stroke volume; Stroke Volume - drug effects; Systole - drug effects; Thiazolidinediones - administration & dosage; Triglycerides - blood; Ventricle; Ventricular Function, Left - drug effects
• ISSN: 0149-5992; 1935-5548; 1935-5548
• DOI: 10.2337/dc17-0078

To examine the effect of pioglitazone on myocardial insulin sensitivity and left ventricular (LV) function in patients with type 2 diabetes (T2D). 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]fluoro-2-deoxy-d-glucose and [ O]H O 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. Pioglitazone reduced HbA by 0.9%; decreased systolic and diastolic blood pressure by 7 ± 2 and 7 ± 2 mmHg, respectively ( < 0.05); and increased whole-body insulin-stimulated glucose uptake by 71% (3.4 ± 1.3 to 5.8 ± 2.1 mg/kg · min; < 0.01) in subjects with T2D. Pioglitazone enhanced MGU by 75% (0.24 ± 0.14 to 0.42 ± 0.13 μmol/min · g; < 0.01) and myocardial perfusion by 16% (0.95 ± 0.16 to 1.10 ± 0.25 mL/min · g; < 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 ( < 0.01). End-systolic volume, end-diastolic volume, peak LV ejection rate, and cardiac output trended to increase ( not significant), whereas the ejection fraction (61 ± 6 to 66 ± 7%) and stroke volume increased significantly (71 ± 20 to 80 ± 20 L/min; both < 0.05). 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.