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Am J Physiol Endocrinol Metab 282: E1154-E1162, 2002. First published January 2, 2002; doi:10.1152/ajpendo.00470.2001
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Vol. 282, Issue 5, E1154-E1162, May 2002

Effect of IGF-I therapy on VLDL apolipoprotein B100 metabolism in type 1 diabetes mellitus

Emanuel R. Christ1, Paul V. Carroll2, Elaine Albany2, A. Margot Umpleby2, Peter J. Lumb3, Anthony S. Wierzbicki3, Peter H. Sönksen2, and David L. Russell-Jones2

1 Department of Endocrinology and Diabetology of the Adult, University Hospital of Bern, Inselspital, CH-3010 Bern, Switzerland; and Departments of 2 Medicine and 3 Chemical Pathology, King's College London, St. Thomas' Hospital Campus, London SE1 7EH, United Kingdom

Abnormal lipid metabolism may be related to the increased cardiovascular risk in type 1 diabetes. Secretion and clearance rates of very low density lipoprotein (VLDL) apolipoprotein B100 (apoB) determine plasma lipid concentrations. Type 1 diabetes is characterized by increased growth hormone (GH) secretion and decreased insulin-like growth factor (IGF) I concentrations. High-dose IGF-I therapy improves the lipid profile in type 1 diabetes. This study examined the effect of low-dose (40 µg · kg-1 · day-1) IGF-I therapy on VLDL apoB metabolism, VLDL composition, and the GH-IGF-I axis during euglycemia in type 1 diabetes. Using a stable isotope technique, VLDL apoB kinetics were estimated before and after 1 wk of IGF-I therapy in 12 patients with type 1 diabetes in a double-blind, placebo-controlled trial. Fasting plasma triglyceride (P < 0.03), VLDL-triglyceride concentrations (P < 0.05), and the VLDL-triglyceride-to-VLDL apoB ratio (P < 0.002) significantly decreased after IGF-I therapy, whereas VLDL apoB kinetics were not significantly affected by IGF-I therapy. IGF-I therapy resulted in a significant increase in IGF-I and a significant reduction in GH concentrations. The mean overnight insulin concentrations during euglycemia decreased by 25% after IGF-I therapy. These results indicate that low-dose IGF-I therapy restores the GH-IGF-I axis in type 1 diabetes. IGF-I therapy changes fasting triglyceride concentrations and VLDL composition probably because of an increase in insulin sensitivity.

type 1 diabetes mellitus; insulin-like growth factor I; growth hormone secretion; very low density lipoprotein apolipoprotein B turnover study; stable isotope technique


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