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Effect of Pioglitazone Therapy on Myocardial and Hepatic Steatosis in Insulin-Treated Patients with Type 2 Diabetes
  1. Ivana Zib,
  2. Aris N. Jacob,
  3. Ildiko Lingvay,
  4. Karin Salinas,
  5. Jonathan M. McGavock,
  6. Philip Raskin,
  7. Lidia S. Szczepaniak
  1. From the Department of Internal Medicine, Division of Hypertension (J.M.M., L.S.S.), Division of Endocrinology, Diabetes and Metabolism (I.Z., A.N.J., I.L., K.S., P.R.), and Department of Radiology (L.S.S.), University of Texas Southwestern Medical Center at Dallas, Dallas, TX.
  1. L.S.S. was supported by K25 HL-68736 from the National Institutes of Health (NIH), Innovative Methodologies Award #7-04-IN-27 from the American Diabetes Association, and Takeda Pharmaceuticals North America Inc. I.Z. was supported by NIH Training Grant 5T3 DK 007307-25. I.L. was supported by a Departmental Clinical Scholars Award. J.M.M. was supported by a Target Obesity Postdoctoral Fellowship, the Heart and Stroke Foundation of Canada, the Canadian Institutes for Health Research, and the Canadian Diabetes Association.
  2. Address correspondence to: Dr. Lidia S. Szczepaniak, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd, Dallas, TX 75390-8899; e-mail: lidia.szczepaniak{at}


High levels of myocardial and hepatic triglyceride are common in obesity and type 2 diabetes. Monotherapy with thiazolidinedione agents reduces hepatic steatosis by up to 50% in patients with type 2 diabetes. It is not known if treatment with a thiazolidinedione added to insulin has a similar beneficial antisteatotic effect. The aim of our study was to determine whether the addition of pioglitazone to insulin treatment in patients with type 2 diabetes has antisteatotic action in the heart and the liver. Thirty-two patients were randomized to 6 months of treatment with insulin or insulin plus pioglitazone. In addition to blood tests, we evaluated myocardial and hepatic triglyceride content, as well as subcutaneous and visceral fat mass at the L2 level, by magnetic resonance spectroscopy and imaging, respectively. Despite weight and subcutaneous fat mass gain, hemoglobin A1c was significantly reduced by both treatments. Myocardial and hepatic triglyceride contents were reduced by the treatment with pioglitazone plus insulin (p = .02 and .03, respectively) but not by the treatment with insulin. Systolic and diastolic blood pressure and heart function remained unchanged in both groups. The addition of pioglitazone to insulin therapy reduced myocardial and hepatic steatosis, consistent with the reported ability of the thiazolidinedione agents to redistribute fat from nonadipose to subcutaneous adipose depots.

Key words
  • myocardial and hepatic steatosis
  • pioglitazone/insulin therapy
  • type 2 diabetes
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