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Effects of combined recombinant insulin-like growth factor (IGF)-I and IGF binding protein-3 in type 2 diabetic patients on glycemic control and distribution of IGF-I and IGF-II among serum binding protein complexes.
J Clin Endocrinol Metab. 2007 Jul; 92(7):2652-8.JC

Abstract

CONTEXT

Administration of recombinant human IGF-I (rhIGF-I)/recombinant human IGF binding protein-3 (rhIGFBP-3) to patients with type 2 diabetes improves blood glucose and enhances insulin sensitivity. The changes in various components of the IGF system that occur in response to rhIGF-I/rhIGFBP-3 as well as the minimum effective dose have not been determined.

OBJECTIVES

The aim was to determine the dose of rhIGF-I/rh-IGFBP-3 necessary to achieve a significant decrease in glucose and to determine the changes that occur in the IGF-II and acid labile subunit in response to treatment.

DESIGN

A total of 39 insulin-requiring type 2 diabetics were randomized to placebo or one of six groups that received different dosages of rhIGF-I/rhIGFBP-3. After 3 d in which insulin doses were adjusted to improve glucose control, a variable insulin dosage regimen was continued, and either placebo or one of six dosages (0.125-2.0 mg/kg.d) of rhIGF-I/rhIGFBP-3 was administered for 7 d. All subjects were hospitalized, and dietary intake as well as insulin dosage were controlled with instructions to treat to normal range targets.

RESULTS

Fasting glucose was reduced in the groups that received either 1 (32 +/- 5% reduction) or 2 mg/kg.d (40 +/- 6% reduction) of the complex. Mean daily glucose (four determinations) was reduced by 26 +/- 4% in the 1 mg/kg group and by 33 +/- 5% in the 2 mg/kg group compared with 18 +/- 4% in the placebo group. Total serum IGF-I increased between 2.0 +/- 0.3- and 5.7 +/- 1.3-fold by d 8. IGFBP-3 concentrations increased significantly only in the 2 mg/kg group. IGF-II concentrations declined to values that were between 27 +/- 4% and 64 +/- 7% below baseline. Acid labile subunit concentrations declined significantly in the three highest dose groups. The sum of the IGF-I + IGF-II concentrations was significantly increased at the two highest dosages. There were very few drug-associated adverse events reported in this study with the exception of hypoglycemia, which occurred in 15 subjects who had received rhIGF-I/rhIGFBP-3 treatment.

CONCLUSIONS

Administration of rhIGF-I/rhIGFBP-3 resulted in a redistribution of the amount of IGF-I and IGF-II that bound to IGFBP-3. Fasting and mean daily blood glucose were reduced significantly in the two highest dosage groups. The results suggest that both the total concentration of IGF-I as well as its distribution in blood may determine the extent to which insulin sensitivity is enhanced.

Authors+Show Affiliations

Division of Endocrinology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7170, USA. endo@med.unc.eduNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

17426090

Citation

Clemmons, D R., et al. "Effects of Combined Recombinant Insulin-like Growth Factor (IGF)-I and IGF Binding Protein-3 in Type 2 Diabetic Patients On Glycemic Control and Distribution of IGF-I and IGF-II Among Serum Binding Protein Complexes." The Journal of Clinical Endocrinology and Metabolism, vol. 92, no. 7, 2007, pp. 2652-8.
Clemmons DR, Sleevi M, Allan G, et al. Effects of combined recombinant insulin-like growth factor (IGF)-I and IGF binding protein-3 in type 2 diabetic patients on glycemic control and distribution of IGF-I and IGF-II among serum binding protein complexes. J Clin Endocrinol Metab. 2007;92(7):2652-8.
Clemmons, D. R., Sleevi, M., Allan, G., & Sommer, A. (2007). Effects of combined recombinant insulin-like growth factor (IGF)-I and IGF binding protein-3 in type 2 diabetic patients on glycemic control and distribution of IGF-I and IGF-II among serum binding protein complexes. The Journal of Clinical Endocrinology and Metabolism, 92(7), 2652-8.
Clemmons DR, et al. Effects of Combined Recombinant Insulin-like Growth Factor (IGF)-I and IGF Binding Protein-3 in Type 2 Diabetic Patients On Glycemic Control and Distribution of IGF-I and IGF-II Among Serum Binding Protein Complexes. J Clin Endocrinol Metab. 2007;92(7):2652-8. PubMed PMID: 17426090.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of combined recombinant insulin-like growth factor (IGF)-I and IGF binding protein-3 in type 2 diabetic patients on glycemic control and distribution of IGF-I and IGF-II among serum binding protein complexes. AU - Clemmons,D R, AU - Sleevi,M, AU - Allan,G, AU - Sommer,A, Y1 - 2007/04/10/ PY - 2007/4/12/pubmed PY - 2007/8/29/medline PY - 2007/4/12/entrez SP - 2652 EP - 8 JF - The Journal of clinical endocrinology and metabolism JO - J Clin Endocrinol Metab VL - 92 IS - 7 N2 - CONTEXT: Administration of recombinant human IGF-I (rhIGF-I)/recombinant human IGF binding protein-3 (rhIGFBP-3) to patients with type 2 diabetes improves blood glucose and enhances insulin sensitivity. The changes in various components of the IGF system that occur in response to rhIGF-I/rhIGFBP-3 as well as the minimum effective dose have not been determined. OBJECTIVES: The aim was to determine the dose of rhIGF-I/rh-IGFBP-3 necessary to achieve a significant decrease in glucose and to determine the changes that occur in the IGF-II and acid labile subunit in response to treatment. DESIGN: A total of 39 insulin-requiring type 2 diabetics were randomized to placebo or one of six groups that received different dosages of rhIGF-I/rhIGFBP-3. After 3 d in which insulin doses were adjusted to improve glucose control, a variable insulin dosage regimen was continued, and either placebo or one of six dosages (0.125-2.0 mg/kg.d) of rhIGF-I/rhIGFBP-3 was administered for 7 d. All subjects were hospitalized, and dietary intake as well as insulin dosage were controlled with instructions to treat to normal range targets. RESULTS: Fasting glucose was reduced in the groups that received either 1 (32 +/- 5% reduction) or 2 mg/kg.d (40 +/- 6% reduction) of the complex. Mean daily glucose (four determinations) was reduced by 26 +/- 4% in the 1 mg/kg group and by 33 +/- 5% in the 2 mg/kg group compared with 18 +/- 4% in the placebo group. Total serum IGF-I increased between 2.0 +/- 0.3- and 5.7 +/- 1.3-fold by d 8. IGFBP-3 concentrations increased significantly only in the 2 mg/kg group. IGF-II concentrations declined to values that were between 27 +/- 4% and 64 +/- 7% below baseline. Acid labile subunit concentrations declined significantly in the three highest dose groups. The sum of the IGF-I + IGF-II concentrations was significantly increased at the two highest dosages. There were very few drug-associated adverse events reported in this study with the exception of hypoglycemia, which occurred in 15 subjects who had received rhIGF-I/rhIGFBP-3 treatment. CONCLUSIONS: Administration of rhIGF-I/rhIGFBP-3 resulted in a redistribution of the amount of IGF-I and IGF-II that bound to IGFBP-3. Fasting and mean daily blood glucose were reduced significantly in the two highest dosage groups. The results suggest that both the total concentration of IGF-I as well as its distribution in blood may determine the extent to which insulin sensitivity is enhanced. SN - 0021-972X UR - https://www.unboundmedicine.com/medline/citation/17426090/Effects_of_combined_recombinant_insulin_like_growth_factor__IGF__I_and_IGF_binding_protein_3_in_type_2_diabetic_patients_on_glycemic_control_and_distribution_of_IGF_I_and_IGF_II_among_serum_binding_protein_complexes_ L2 - https://academic.oup.com/jcem/article-lookup/doi/10.1210/jc.2006-2699 DB - PRIME DP - Unbound Medicine ER -