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Rh/IGF-I/rhIGFBP-3 administration to patients with type 2 diabetes mellitus reduces insulin requirements while also lowering fasting glucose.
Growth Horm IGF Res. 2005 Aug; 15(4):265-74.GH

Abstract

Administration of insulin-like growth factor-I to patients with diabetes enhances insulin action and reduces the degree of hyperglycemia but it is associated with a high rate of adverse events. Infusion of the combination of rhIGFBP-3 (the principal binding protein for IGF-I in plasma) with rhIGF-I to patients with type I diabetes improved insulin sensitivity and was associated with a low incidence in side effects. In this study, 52 patients with insulin-treated type 2 diabetes received recombinant human IGF-I plus rhIGFBP-3 in one of four dosage regimens for 14 days. The four groups were: (1) continuous subcutaneous infusion of 2 mg/kg/day; (2) the same 2 mg/kg dose infused subcutaneously over 6 h between 2000 and 0200 h; (3) 1 mg/kg twice a day by bolus subcutaneous injection; (4) a single bedtime subcutaneous injection of 1 mg/kg. Across these four groups rhIGF-I/rhIGFBP-3 decreased insulin requirements between 54% and 82%. Fasting glucose decreased by 32-37%. Mean daily blood glucose (4 determinations per day) declined in all 4 groups (range 9-23% decrease). Frequent sampling for total IGF-I, free IGF-I and IGFBP-3 was performed on days 0,1,7,14 and 15. The peak total IGF-I values were increased to 4.0-4.8-fold at 16-24 h. For free IGF-I the increase varied between 7.1 and 8.2-fold and peak values were attained at 16-20 h after administration. Both the time to maximum concentration (Tmax) and the maximum free IGF-I levels (Cmax) on day 1 for all groups were substantially less than previously published studies, wherein lower doses of rhIGF-I were given without IGFBP-3. The improvement in glucose values and the degree of reduction in insulin requirement were the greatest in groups 2 and 3 and the patients in those groups had the highest free IGF-I levels. The frequency of side effects such as edema, jaw pain and arthralgias was 4% which is less than that has been reported in previous studies wherein IGF-I was administered without IGFBP-3. We conclude that rhIGF-I/rhIGFBP-3 significantly lowers insulin requirements yet improves glucose values and these changes may reflect improvement in insulin sensitivity. Coadministration of IGFBP-3 with IGF-I produces lower free IGF-I (Tmax and Cmax) levels compared to administration of IGF-I alone and is associated with relatively low incidence of side effects during 2 weeks of administration.

Authors+Show Affiliations

Division of Endocrinology, Department of Medicine, University of North Carolina, 6111A Thurston-Bowles, CB 7170, Chapel Hill, NC 27599, USA. endo@med.unc.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16005252

Citation

Clemmons, D R., et al. "Rh/IGF-I/rhIGFBP-3 Administration to Patients With Type 2 Diabetes Mellitus Reduces Insulin Requirements While Also Lowering Fasting Glucose." Growth Hormone & IGF Research : Official Journal of the Growth Hormone Research Society and the International IGF Research Society, vol. 15, no. 4, 2005, pp. 265-74.
Clemmons DR, Moses AC, Sommer A, et al. Rh/IGF-I/rhIGFBP-3 administration to patients with type 2 diabetes mellitus reduces insulin requirements while also lowering fasting glucose. Growth Horm IGF Res. 2005;15(4):265-74.
Clemmons, D. R., Moses, A. C., Sommer, A., Jacobson, W., Rogol, A. D., Sleevi, M. R., & Allan, G. (2005). Rh/IGF-I/rhIGFBP-3 administration to patients with type 2 diabetes mellitus reduces insulin requirements while also lowering fasting glucose. Growth Hormone & IGF Research : Official Journal of the Growth Hormone Research Society and the International IGF Research Society, 15(4), 265-74.
Clemmons DR, et al. Rh/IGF-I/rhIGFBP-3 Administration to Patients With Type 2 Diabetes Mellitus Reduces Insulin Requirements While Also Lowering Fasting Glucose. Growth Horm IGF Res. 2005;15(4):265-74. PubMed PMID: 16005252.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Rh/IGF-I/rhIGFBP-3 administration to patients with type 2 diabetes mellitus reduces insulin requirements while also lowering fasting glucose. AU - Clemmons,D R, AU - Moses,A C, AU - Sommer,A, AU - Jacobson,W, AU - Rogol,A D, AU - Sleevi,M R, AU - Allan,G, PY - 2005/01/25/received PY - 2005/04/05/revised PY - 2005/05/02/accepted PY - 2005/7/12/pubmed PY - 2005/10/21/medline PY - 2005/7/12/entrez SP - 265 EP - 74 JF - Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society JO - Growth Horm IGF Res VL - 15 IS - 4 N2 - Administration of insulin-like growth factor-I to patients with diabetes enhances insulin action and reduces the degree of hyperglycemia but it is associated with a high rate of adverse events. Infusion of the combination of rhIGFBP-3 (the principal binding protein for IGF-I in plasma) with rhIGF-I to patients with type I diabetes improved insulin sensitivity and was associated with a low incidence in side effects. In this study, 52 patients with insulin-treated type 2 diabetes received recombinant human IGF-I plus rhIGFBP-3 in one of four dosage regimens for 14 days. The four groups were: (1) continuous subcutaneous infusion of 2 mg/kg/day; (2) the same 2 mg/kg dose infused subcutaneously over 6 h between 2000 and 0200 h; (3) 1 mg/kg twice a day by bolus subcutaneous injection; (4) a single bedtime subcutaneous injection of 1 mg/kg. Across these four groups rhIGF-I/rhIGFBP-3 decreased insulin requirements between 54% and 82%. Fasting glucose decreased by 32-37%. Mean daily blood glucose (4 determinations per day) declined in all 4 groups (range 9-23% decrease). Frequent sampling for total IGF-I, free IGF-I and IGFBP-3 was performed on days 0,1,7,14 and 15. The peak total IGF-I values were increased to 4.0-4.8-fold at 16-24 h. For free IGF-I the increase varied between 7.1 and 8.2-fold and peak values were attained at 16-20 h after administration. Both the time to maximum concentration (Tmax) and the maximum free IGF-I levels (Cmax) on day 1 for all groups were substantially less than previously published studies, wherein lower doses of rhIGF-I were given without IGFBP-3. The improvement in glucose values and the degree of reduction in insulin requirement were the greatest in groups 2 and 3 and the patients in those groups had the highest free IGF-I levels. The frequency of side effects such as edema, jaw pain and arthralgias was 4% which is less than that has been reported in previous studies wherein IGF-I was administered without IGFBP-3. We conclude that rhIGF-I/rhIGFBP-3 significantly lowers insulin requirements yet improves glucose values and these changes may reflect improvement in insulin sensitivity. Coadministration of IGFBP-3 with IGF-I produces lower free IGF-I (Tmax and Cmax) levels compared to administration of IGF-I alone and is associated with relatively low incidence of side effects during 2 weeks of administration. SN - 1096-6374 UR - https://www.unboundmedicine.com/medline/citation/16005252/Rh/IGF_I/rhIGFBP_3_administration_to_patients_with_type_2_diabetes_mellitus_reduces_insulin_requirements_while_also_lowering_fasting_glucose_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1096-6374(05)00055-9 DB - PRIME DP - Unbound Medicine ER -