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Articles in PresS, published online ahead of print January 2, 2002
Am J Physiol Endocrinol Metab, 10.1152/ajpendo.00470.2001
Submitted on October 18, 2001
Accepted on December 17, 2001
1 University Hospital of Bern, Department of Endocrinology and Diabetology of the Adult, Bern, BE, Switzerland
2 Department of Medicine, King's College London, St. Thomas' Hospital Campus, London, London, United Kingdom
3 Chemical Pathology, King's College London, St. Thomas' Hospital Campus, London, London, United Kingdom
* To whom correspondence should be addressed. E-mail: Emanuel.Christ{at}bluewin.ch.
Patients with type 1 diabetes mellitus are at increased risk of cardiovascular disease, which may partially be related to abnormal lipid metabolism. Secretion and clearance rates of VLDL apolipoprotein B100 (apoB) are determinants of plasma lipid concentrations. Type 1 diabetes mellitus is characterised by a disordered GH/IGF-I axis with decreased IGF-I concentrations and increased GH secretion. High dose IGF-I (100µg/kg/d) therapy has been shown to improve lipid profile in patients with type 1 diabetes mellitus. This study examined the effect of low dose (40µg/kg/d) IGF-I therapy on overnight VLDL apoB metabolism and VLDL composition during euglycaemia in patients with type 1 diabetes. In addition, GH secretion profile and insulin concentrations were assessed to determine relationship between these variables and VLDL apoB metabolism. VLDL apoB kinetics was estimated using a stable isotope technique before and after one week's IGF-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 VLDL-triglyceride/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 (p<0.03), and IGFBP-1 concentrations (p<0.001) and in a significant reduction in GH secretion due to a decrease in GH peak amplitude (p<0.02) and peak length (p<0.03). The mean overnight insulin concentrations to maintain euglycaemia decreased by 25% (p<0.05) following IGF-I therapy. The current results indicate that low dose IGF-I therapy restores the disordered GH/IGF-I axis in type 1 diabetes. IGF-I therapy does not significantly influence VLDL apoB kinetics but changes fasting triglyceride concentrations and the composition of VLDL particles probably due to an increase in insulin sensitivity.
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