title: rhIGF-I administration reduces insulin requirements, decreases growth hormone secretion, and improves the lipid profile in adults with IDDM.
abstract: IDDM is associated with elevated circulating levels of growth hormone (GH) and reduced insulin-like growth factor I (IGF-I). GH antagonizes the action of insulin-increasing insulin requirements in IDDM. The effects of subcutaneously administered rhIGF-I on glycemic control, insulin requirements, and GH secretion were studied in eight adults with IDDM. Patients received either placebo or rhIGF-I (50 microg/kg b.i.d.) for 19 days in a randomized, double-blind, parallel-design, placebo-controlled trial. Overnight GH, plasma glucose, free insulin, IGF-I, fructosamine, and lipid profiles were assessed during this period. rhIGF-I therapy increased IGF-I concentration from 117.1 +/- 14.2 (mean +/- SE) ng/ml (baseline) to 310.5 +/- 40.6 and 257.1 +/- 41.2 ng/ml on day 5 (P < 0.01 vs. baseline) and day 20 (P < 0.01 vs. baseline), respectively. After 19 days of rhIGF-I treatment, fructosamine concentrations were unchanged compared with baseline (439 +/- 32 vs. 429 +/- 35 micromol/l, day -1 vs. day 20, respectively), yet insulin requirements were decreased by approximately 45% (0.67 +/- 0.08 vs. 0.36 +/- 0.07 U x kg(-1) x day(-1), day -1 vs. day 19, respectively, P < 0.005). After 4 days of rhIGF-I therapy, there was a decrease in free insulin levels (8.38 +/- 1.47 vs. 4.98 +/- 0.84 mU/l, P < 0.05), mean overnight GH concentration (12.6 +/- 3.3 vs. 3.8 +/- 2.1 mU/l, P = 0.05), and total cholesterol and triglycerides (4.68 +/- 0.31 vs. 4.25 +/- 0.35 mmol/l, P < 0.05, 1.27 +/- 0.19 vs. 0.95 +/- 0.21 mmol/l, P < 0.001, respectively). There was no change in any variable in the placebo-treated patients. This study demonstrates that subcutaneous administration of rhIGF-I decreases insulin requirements and improves the plasma lipid profile while maintaining glycemic control in adults with IDDM. The excess nocturnal release of GH, characteristic of IDDM, is also decreased by rhIGF-I therapy.
authors.affiliation: Division of Medicine, St. Thomas' Hospital, London, U.K. p.carroll@umds.ac.uk
authors.forename: P V
authors.initials: PV
authors.lastname: Carroll
authors.forename: M
authors.initials: M
authors.lastname: Umpleby
authors.forename: G S
authors.initials: GS
authors.lastname: Ward
authors.forename: S
authors.initials: S
authors.lastname: Imuere
authors.forename: E
authors.initials: E
authors.lastname: Alexander
authors.forename: D
authors.initials: D
authors.lastname: Dunger
authors.forename: P H
authors.initials: PH
authors.lastname: Sönksen
authors.forename: D L
authors.initials: DL
authors.lastname: Russell-Jones
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D004734:Energy Metabolism; D005260:Female; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000008:administration & dosage*; D007334:Insulin-Like Growth Factor I / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood*; D008297:Male
chemical_list: D001786:Blood Glucose; D007328:Insulin; D008055:Lipids; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I