Effect of IGF-I therapy on VLDL apolipoprotein B100 metabolism in type 1 diabetes mellitus.
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.
Christ
Emanuel R
ER
Department of Endocrinology and Diabetology of the Adult, University Hospital of Bern, Inselspital, CH-3010 Bern, Switzerland. Emanuel.Christ@insel.ch
Carroll
Paul V
PV
Albany
Elaine
E
Umpleby
A Margot
AM
Lumb
Peter J
PJ
Wierzbicki
Anthony S
AS
Sönksen
Peter H
PH
Russell-Jones
David L
DL
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
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