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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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