Pioglitazone Improves Left Ventricular Diastolic Function in Subjects With Diabetes
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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.
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Pioglitazone improves diastolic and systolic function in T2DM patients without clinical CV disease, and this amelioration is closely related to improved myocardial insulin sensitivity.
“In a clinical study, treatment with pioglitazone in patients with T2DM without clinical CV disease improved both diastolic and systolic function assessed with CMR, and this amelioration was closely related to improved myocardial insulin sensitivity evaluated after euglycemic insulin clamp with PET [166].”
From Dysregulated epicardial adipose tissue as a risk factor and potential therapeutic target of heart failure with preserved ejection fraction in diabetes (2022) · cites this paper as [166]
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- Authors
- Clarke, G. D., Solis-Herrera, C., Molina-Wilkins, M., Martinez, S., Merovci, A., Cersosimo, E., Chilton, R. J., Iozzo, P., Gastaldelli, A., Abdul-Ghani, M., & DeFronzo, R. A.
- Affiliations
- The University of Texas at San Antonio Health Science Center (US)
- Diabetes Division, University of Texas Health Science Center, San Antonio, TX
- Istituto di Fisiologia Clinica (IT)
- Corresponding author
- DeFronzo, Ralph A.
- ORCID
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2017-08-28
- Volume
- 40
- Issue
- 11
- Pages
- 1530-1536
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- PMC
- PMC5652586
- OpenAlex
- W2748954699
- Cited by
- 63
- References
- 48
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 8 · 2023: 8 · 2022: 5 · 2021: 14 · 2020: 5 · 2019: 9 · 2018: 6 · 2017: 3
- FWCI
- 4.86
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Diabetes Care (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK-2409333)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- pioglitazone, type 2 diabetes, left ventricular diastolic function, myocardial glucose uptake, myocardial perfusion, hyperinsulinemic-euglycemic clamp, ejection fraction, blood pressure reduction, HbA1c, PPARγ agonists, cardiac remodeling, left ventricular filling rate, E/A ratio, stroke volume
- MeSH terms
- Pioglitazone, Adult, Blood Glucose, Blood Pressure, Cholesterol, Diabetes Mellitus, Type 2, Diastole, Female, Glycated Hemoglobin, Humans, Hypoglycemic Agents, Insulin Resistance, Male, Middle Aged, Myocardium, Stroke Volume, Systole, Triglycerides, Glucose Clamp Technique, Body Mass Index, Ventricular Function, Left, Thiazolidinediones
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