Myocardial triglyceride content is increased in uncomplicated T2DM and is associated with impaired left ventricular diastolic function, independently of age, BMI, heart rate, visceral fat, and diastolic blood pressure.

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Patients versus control subjects showed impaired LV diastolic function and altered myocardial substrate metabolism, but unchanged HEP metabolism. We found no direct relation between cardiac diastolic function and parameters of myocardial metabolism.

Background-Cardiac disease is the leading cause of mortality in type 2 diabetes mellitus (T2DM). Pioglitazone has been associated with improved cardiac outcome but also with an elevated risk of heart failure. We determined the effects of pioglitazone on myocardial function in relation to cardiac high-energy phosphate, glucose, and fatty acid metabolism and triglyceride content in T2DM patients. Methods and Results-Seventy-eight T2DM men without structural heart disease or inducible ischemia as assessed by dobutamine stress echocardiography were assigned to pioglitazone (30 mg/d) or metformin (2000 mg/d) and matching placebo for 24 weeks. The primary end point was change in cardiac diastolic function from baseline relative to myocardial metabolic changes, measured by magnetic resonance imaging, proton and phosphorus magnetic resonance spectroscopy, and [ 18 F]-2-fluoro-2-deoxy-D-glucose and [ 11 C]palmitate positron emission tomography. No patient developed heart failure. Both therapies similarly improved glycemic control, whole-body insulin sensitivity, and blood pressure. Pioglitazone versus metformin improved the early peak flow rate (Pϭ0.047) and left ventricular compliance. Pioglitazone versus metformin increased myocardial glucose uptake (PϽ0.001), but pioglitazone-related diastolic improvement was not associated with changes in myocardial substrate metabolism. Metformin did not affect myocardial function but decreased cardiac work relative to pioglitazone (Pϭ0.006), a change that was paralleled by a reduced myocardial glucose uptake and fatty acid oxidation. Neither treatment affected cardiac high-energy phosphate metabolism or triglyceride content. Only pioglitazone reduced hepatic triglyceride content (PϽ0.001). Conclusions-In T2DM patients, pioglitazone was associated with improvement in some measures of left ventricular diastolic function, myocardial glucose uptake, and whole-body insulin sensitivity. The functional changes, however, were not associated with myocardial substrate and high-energy phosphate metabolism.

Background-Magnetic resonance spectroscopy can quantify myocardial triglyceride content in type 2 diabetic patients.Its relation to alterations in left (LV) and right (RV) ventricular myocardial functions is unknown. Methods and Results-A total of 42 men with type 2 diabetes mellitus were recruited. Exclusion criteria included hemoglobin A 1c Ͼ8.5%, known cardiovascular disease, diabetes-related complications, or blood pressure Ͼ150/ 85 mm Hg. Myocardial ischemia was excluded by a negative dobutamine stress test. LV and RV volumes and ejection fraction were quantified by magnetic resonance imaging. LV global longitudinal and RV free wall longitudinal strain, systolic strain rate, and diastolic strain rate were quantified by echocardiographic speckle tracking analyses. Myocardial triglyceride content was quantified by magnetic resonance spectroscopy and dichotomized on the basis of the median value of 0.76%. The median age was 59 years (25th and 75th percentiles, 54 and 62 years). Median diabetes diagnosis duration was 4 years, and median glycohemoglobin level was 6.2% (25th and 75th percentiles, 5.9% and 6.8%). There were no differences in LV and RV end-diastolic and end-systolic volume indexes and ejection fraction between patients with high (Ն0.76%) and those with low (Ͻ0.76%) myocardial triglyceride content. However, patients with high myocardial triglyceride content had greater impairment of LV and RV myocardial strain and strain rate. The myocardial triglyceride content was an independent correlate of LV and RV longitudinal strain, systolic strain rate, and diastolic strain rate. Conclusions-High