This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints, Permissions and Rights Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Juurinen, L. Articles by Yki-Järvinen, H. Search for Related Content PubMed PubMed Citation Articles by Juurinen, L. Articles by Yki-Järvinen, H. Related Collections Diabetes and Insulin Metabolism

Rosiglitazone Reduces Liver Fat and Insulin Requirements and Improves Hepatic Insulin Sensitivity and Glycemic Control in Patients with Type 2 Diabetes Requiring High Insulin Doses

Department of Medicine (L.J., A.K., H.Y.-J.), Division of Diabetes, University of Helsinki, Minerva Medical Research Institute (L.J., A.K.), and Department of Internal Medicine (M.G.), Division of Cardiology, Helsinki University Central Hospital, FIN-00290 Helsinki, Finland

Address all correspondence and requests for reprints to: Anna Kotronen, M.B., Department of Medicine, Division of Diabetes, University of Helsinki, P.O. Box 700, Room C418B, FIN-00029 HUCH Helsinki, Finland. E-mail: anna.kotronen{at}helsinki.fi.

Background: Liver fat is an important determinant of insulin requirements during insulin therapy. Peroxisome proliferator-activated receptor (PPAR)- agonists reduce liver fat. We therefore hypothesized that type 2 diabetic patients using exceptionally high doses of insulin might respond well to addition of a PPAR agonist.

Methods: We determined the effect of the PPAR agonist rosiglitazone on liver fat and directly measured hepatic insulin sensitivity in 14 patients with type 2 diabetes (aged 51 ± 3 yr, body mass index 36.7 ± 1.1 kg/m²), who were poorly controlled (glycosylated hemoglobin A_1c (HbA_1c) 8.9 ± 0.4%) despite using high doses of insulin (218 ± 22 IU/d) in combination with metformin. Liver fat content (¹H-magnetic resonance spectroscopy), hepatic insulin sensitivity [6 h hyperinsulinemic euglycemic clamp (insulin 0.3 mU/kg·min) combined with [3-³H]glucose], body composition (magnetic resonance imaging), substrate oxidation rates (indirect calorimetry), clinical parameters, and liver enzymes were measured before and after rosiglitazone treatment (8 mg/d) for 8 months.

Results: During rosiglitazone, HbA_1c decreased from 8.9 ± 0.4% to 7.8 ± 0.3% (P = 0.007) and insulin requirements from 218 ± 22 to 129 ± 20 IU/d (P = 0.002). Liver fat content decreased by 46 ± 9% from 20 ± 3% to 11 ± 3% (P = 0.0002). Hepatic insulin sensitivity, measured from the percent suppression of endogenous glucose production by insulin, increased from –40 ± 7% to –89 ± 12% (P = 0.001). The percent change in liver fat correlated with the percent decrease in HbA_1c (r = 0.53, P = 0.06), insulin dose (r = 0.66, P = 0.014), and suppression of endogenous glucose production (r = 0.76, P = 0.003).

Conclusions: Our results suggest that rosiglitazone may be particularly effective in type 2 diabetic patients who are poorly controlled despite using high insulin doses. The mechanism is likely to involve reduced liver fat and enhanced hepatic insulin sensitivity.

This article has been cited by other articles:

				L. C. Chao, K. Wroblewski, Z. Zhang, L. Pei, L. Vergnes, O. R. Ilkayeva, S. Y. Ding, K. Reue, M. J. Watt, C. B. Newgard, et al. Insulin Resistance and Altered Systemic Glucose Metabolism in Mice Lacking Nur77 Diabetes, December 1, 2009; 58(12): 2788 - 2796. [Abstract] [Full Text] [PDF]

				A. Fraser, N. Sattar, S. Ebrahim, and D.A. Lawlor Is Serum-Glutamylatransferase a Biomarker of Xenobiotics Which Are Conjugated by Glutathione? Arterioscler Thromb Vasc Biol, April 1, 2008; 28(4): e29 - e29. [Full Text] [PDF]