Pioglitazone Improves Left Ventricular Diastolic Function in Subjects With Diabetes

Geoffrey D Clarke, Carolina Solis-Herrera, Marjorie Molina-Wilkins, Sandra Martinez, Aurora Merovci, Eugenio Cersosimo, Robert J Chilton, Patricia Iozzo, Amalia Gastaldelli, Muhammad Abdul-Ghani, Ralph A DeFronzo, Geoffrey D Clarke, Carolina Solis-Herrera, Marjorie Molina-Wilkins, Sandra Martinez, Aurora Merovci, Eugenio Cersosimo, Robert J Chilton, Patricia Iozzo, Amalia Gastaldelli, Muhammad Abdul-Ghani, Ralph A DeFronzo

Abstract

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 [18F]fluoro-2-deoxy-d-glucose and [15O]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 HbA1c 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 μmol/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.

Trial registration: ClinicalTrials.gov NCT01588470.

© 2017 by the American Diabetes Association.

Figures

Figure 1
Figure 1
Correlation between insulin-stimulated whole-body glucose disposal (glucose infusion rate) and MGU (A), transmitral E/A ratio (B), and PLVFR (C) in subjects with T2D before (●) and after (▴) pioglitazone treatment.
Figure 2
Figure 2
Correlation between the change in transmitral E/A ratio and change in HbA1c (A), MGU (B), and glucose infusion rate (GIR) (C) during insulin clamp after pioglitazone treatment.
Figure 3
Figure 3
Correlation between the change in PLVFR and change in HbA1c (A), MGU (B), and glucose infusion rate (GIR) (C) during insulin clamp after pioglitazone treatment.

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