title: Effect of IGF-I therapy on VLDL apolipoprotein B100 metabolism in type 1 diabetes mellitus.
abstract: 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 microg.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.
authors.affiliation: Department of Endocrinology and Diabetology of the Adult, University Hospital of Bern, Inselspital, CH-3010 Bern, Switzerland. Emanuel.Christ@insel.ch
authors.forename: Emanuel R
authors.initials: ER
authors.lastname: Christ
authors.forename: Paul V
authors.initials: PV
authors.lastname: Carroll
authors.forename: Elaine
authors.initials: E
authors.lastname: Albany
authors.forename: A Margot
authors.initials: AM
authors.lastname: Umpleby
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Lumb
authors.forename: Anthony S
authors.initials: AS
authors.lastname: Wierzbicki
authors.forename: Peter H
authors.initials: PH
authors.lastname: Sönksen
authors.forename: David L
authors.initials: DL
authors.lastname: Russell-Jones
mesh_terms: D000328:Adult; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000097:blood*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D019382:Human Growth Hormone / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000097:blood; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage* / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000097:blood*; D008297:Male; D014280:Triglycerides / Q000097:blood
chemical_list: D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D007328:Insulin; D018969:Insulin-Like Growth Factor Binding Proteins; D008079:Lipoproteins, VLDL; D014280:Triglycerides; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I