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Effect of Insulin Versus Triple Oral Therapy on the Progression of Hepatic Steatosis in Type 2 Diabetes
  1. Ildiko Lingvay, MD, MPH, MSCS*†,
  2. Erin D. Roe, MD, MBA*†,
  3. Jonathan Duong, MD,
  4. David Leonard, PhD,
  5. Lidia S. Szczepaniak, PhD§
  1. From the *Division of Endocrinology, †Department of Internal Medicine, and ‡Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX; and §Magnetic Resonance Spectroscopy for Translational Clinical Research, Cedars-Sinai Medical Center, Los Angeles, CA.
  1. Received April 4, 2012, and in revised form May 16, 2012.
  2. Accepted for publication May 22, 2012.
  3. Reprints: Ildiko Lingvay, MD, MPH, MSCS, Division of Endocrinology, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-8857. E-mail: ildiko.lingvay{at}
  4. The parent study was supported by an investigator-initiated trial grant from NovoNordisk, Inc. I.L. was supported by NIH K23RR024470 and 3UL1 RR024982-05S1. L.S. was supported by National Heart, Lung, and Blood Institute Grants K08 HL083101.
  5. The authors have no potential conflicts of interest to disclose.


Background Hyperinsulinemia has been associated with hepatic fat deposition and ensuing insulin resistance. It is unknown if treatment with exogenous insulin in patients with type 2 diabetes, who are most prone to hepatic fat accumulation, would promote the occurrence or worsening of nonalcoholic fatty liver disease.

Methods Patients with treatment-naive type 2 diabetes (N = 16) were treated with insulin and metformin for a 3-month lead-in period, then assigned triple oral therapy (metformin, glyburide, and pioglitazone) or continued treatment with insulin and metformin. Hepatic triglyceride content (HTC)—measured by magnetic resonance spectroscopy, serum lipids, glucose, liver function tests, and inflammatory and thrombotic biomarkers were followed for a median of 31 months.

Results The 45% decline in HTC during the lead-in period persisted through the follow-up period with no difference between treatment groups at the end of the study (5.26 ± 4.21% in the triple oral therapy vs 7.47 ± 7.40% for insulin/metformin), whereas glycemic control was comparable.

Conclusions Improvements in HTC with initial insulin/metformin therapy persisted through the median 31-month follow-up period regardless of the treatment. More importantly, insulin-based treatment did not appear to promote or worsen nonalcoholic fatty liver disease.

Key Words
  • hepatic steatosis
  • type 2 diabetes
  • insulin
  • triglyceride

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