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Dose-dependent effects of recombinant human insulin-like growth factor (IGF)-I/IGF binding protein-3 complex on overnight growth hormone secretion and insulin sensitivity in type 1 diabetes.
J Clin Endocrinol Metab. 2004 Sep; 89(9):4634-41.JC

Abstract

GH hypersecretion in type 1 diabetes has been implicated in the pathogenesis of insulin resistance, and microangiopathic complications, and may result from reduced circulating IGF levels. We examined the effects of recombinant human (rh)IGF-I [complexed in equimolar ratio with rhIGF binding protein (BP)-3 (rhIGF-I/IGFBP-3)] replacement on overnight GH levels and insulin sensitivity in type 1 diabetes. Fifteen subjects, 13-24 yr old (10 male), were given rhIGF-I/IGFBP-3 or placebo as a daily sc injection for 2 d. After the second injection overnight, insulin requirements for euglycemia were determined (0400-0800 h), followed by a 4-h, two-step (insulin, 0.6 and 1.5 mU/kg.min) hyperinsulinemic euglycemic [90 mg/dl (5 mmol/liter)] clamp. In each subject, the protocol was repeated on three occasions in random order. Seven subjects received placebo and rhIGF-I/IGFBP-3 (0.1 mg/kg.d and 0.4 mg/kg.d), and eight subjects received placebo and rhIGF-I/IGFBP-3 (0.2 mg/kg.d and 0.8 mg/kg.d). We found dose-dependent increases in circulating IGF-I and IGFBP-3 concentrations after rhIGF-I/IGFBP-3. These were paralleled by significant reductions in mean overnight GH levels and GH pulse amplitude. We also observed dose-dependent effects of rhIGF-I/IGFBP-3 on overnight insulin requirements for euglycemia, with reductions of up to 41%. Insulin sensitivity, defined by M-values, was improved with rhIGF-I/IGFBP-3 (0.4 and 0.8 mg/kg.d). Thus, restoration of circulating IGF-I and IGFBP-3 levels with rhIGF-I/IGFBP-3 suppresses GH secretion in adolescents with type 1 diabetes, leading to reduced insulin requirements and improvements in insulin sensitivity.

Authors+Show Affiliations

Department of Paediatrics, University of Cambridge, Box 116, Level 8, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, United Kingdom.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15356074

Citation

Saukkonen, Tero, et al. "Dose-dependent Effects of Recombinant Human Insulin-like Growth Factor (IGF)-I/IGF Binding Protein-3 Complex On Overnight Growth Hormone Secretion and Insulin Sensitivity in Type 1 Diabetes." The Journal of Clinical Endocrinology and Metabolism, vol. 89, no. 9, 2004, pp. 4634-41.
Saukkonen T, Amin R, Williams RM, et al. Dose-dependent effects of recombinant human insulin-like growth factor (IGF)-I/IGF binding protein-3 complex on overnight growth hormone secretion and insulin sensitivity in type 1 diabetes. J Clin Endocrinol Metab. 2004;89(9):4634-41.
Saukkonen, T., Amin, R., Williams, R. M., Fox, C., Yuen, K. C., White, M. A., Umpleby, A. M., Acerini, C. L., & Dunger, D. B. (2004). Dose-dependent effects of recombinant human insulin-like growth factor (IGF)-I/IGF binding protein-3 complex on overnight growth hormone secretion and insulin sensitivity in type 1 diabetes. The Journal of Clinical Endocrinology and Metabolism, 89(9), 4634-41.
Saukkonen T, et al. Dose-dependent Effects of Recombinant Human Insulin-like Growth Factor (IGF)-I/IGF Binding Protein-3 Complex On Overnight Growth Hormone Secretion and Insulin Sensitivity in Type 1 Diabetes. J Clin Endocrinol Metab. 2004;89(9):4634-41. PubMed PMID: 15356074.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dose-dependent effects of recombinant human insulin-like growth factor (IGF)-I/IGF binding protein-3 complex on overnight growth hormone secretion and insulin sensitivity in type 1 diabetes. AU - Saukkonen,Tero, AU - Amin,Rakesh, AU - Williams,Rachel M, AU - Fox,Charles, AU - Yuen,Kevin C, AU - White,Martin A, AU - Umpleby,A Margot, AU - Acerini,Carlo L, AU - Dunger,David B, PY - 2004/9/10/pubmed PY - 2004/10/8/medline PY - 2004/9/10/entrez SP - 4634 EP - 41 JF - The Journal of clinical endocrinology and metabolism JO - J Clin Endocrinol Metab VL - 89 IS - 9 N2 - GH hypersecretion in type 1 diabetes has been implicated in the pathogenesis of insulin resistance, and microangiopathic complications, and may result from reduced circulating IGF levels. We examined the effects of recombinant human (rh)IGF-I [complexed in equimolar ratio with rhIGF binding protein (BP)-3 (rhIGF-I/IGFBP-3)] replacement on overnight GH levels and insulin sensitivity in type 1 diabetes. Fifteen subjects, 13-24 yr old (10 male), were given rhIGF-I/IGFBP-3 or placebo as a daily sc injection for 2 d. After the second injection overnight, insulin requirements for euglycemia were determined (0400-0800 h), followed by a 4-h, two-step (insulin, 0.6 and 1.5 mU/kg.min) hyperinsulinemic euglycemic [90 mg/dl (5 mmol/liter)] clamp. In each subject, the protocol was repeated on three occasions in random order. Seven subjects received placebo and rhIGF-I/IGFBP-3 (0.1 mg/kg.d and 0.4 mg/kg.d), and eight subjects received placebo and rhIGF-I/IGFBP-3 (0.2 mg/kg.d and 0.8 mg/kg.d). We found dose-dependent increases in circulating IGF-I and IGFBP-3 concentrations after rhIGF-I/IGFBP-3. These were paralleled by significant reductions in mean overnight GH levels and GH pulse amplitude. We also observed dose-dependent effects of rhIGF-I/IGFBP-3 on overnight insulin requirements for euglycemia, with reductions of up to 41%. Insulin sensitivity, defined by M-values, was improved with rhIGF-I/IGFBP-3 (0.4 and 0.8 mg/kg.d). Thus, restoration of circulating IGF-I and IGFBP-3 levels with rhIGF-I/IGFBP-3 suppresses GH secretion in adolescents with type 1 diabetes, leading to reduced insulin requirements and improvements in insulin sensitivity. SN - 0021-972X UR - https://www.unboundmedicine.com/medline/citation/15356074/Dose_dependent_effects_of_recombinant_human_insulin_like_growth_factor__IGF__I/IGF_binding_protein_3_complex_on_overnight_growth_hormone_secretion_and_insulin_sensitivity_in_type_1_diabetes_ L2 - https://academic.oup.com/jcem/article-lookup/doi/10.1210/jc.2004-0243 DB - PRIME DP - Unbound Medicine ER -