Pioglitazone Improves Left Ventricular Diastolic Function in Subjects With Diabetes

Diabetes Care. 2017 Nov;40(11):1530-1536. doi: 10.2337/dc17-0078. Epub 2017 Aug 28.

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.

MeSH terms

  • Adult
  • Blood Glucose / metabolism
  • Blood Pressure / drug effects
  • Body Mass Index
  • Cholesterol / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diastole / drug effects*
  • Female
  • Glucose Clamp Technique
  • Glycated Hemoglobin / metabolism
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Insulin Resistance
  • Male
  • Middle Aged
  • Myocardium / metabolism
  • Pioglitazone
  • Stroke Volume / drug effects
  • Systole / drug effects
  • Thiazolidinediones / administration & dosage*
  • Triglycerides / blood
  • Ventricular Function, Left / drug effects*

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Thiazolidinediones
  • Triglycerides
  • Cholesterol
  • Pioglitazone

Associated data

  • ClinicalTrials.gov/NCT01588470