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Cited by 291Growth Hormone and Insulin-like Growth FactorsDiabetes Treatment and ManagementDiabetes Management and Research

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Recombinant Human Insulin-Like Growth Factor I Increases Insulin Sensitivity and Improves Glycemic Control in Type II Diabetes

Moses, Alan C, Young, Simon CJ, Morrow, Linda A, O'Brien, Maureen, Clemmons, David R·1996·Diabetes
DOI 10.2337/diab.45.1.91
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Abstract

Insulin resistance is a major factor in the pathophysiology of type II diabetes and a major impediment to successful therapy. The identification of treatments that specifically target insulin resistance could improve diabetes management significantly. Since IGFs exert insulin-like actions and increase insulin sensitivity when administered at supraphysiological doses, we determined the effect of 6 weeks of recombinant human IGF-I (rhIGF-I) administration on insulin resistance and glycemic control in obese insulin-resistant patients with type II diabetes. A total of 12 patients with type II diabetes were recruited for the study. Subcutaneous administration of rhIGF-I (100 micrograms/kg b.i.d.) significantly lowered blood glucose. Fructosamine declined from 369 to 299 mumol/l by 3 weeks of administration and then declined further to 271 at the end of 5 weeks. Glycosylated hemoglobin, which was 10.4% pretreatment, declined to 8.1% at the end of therapy. Mean 24-h blood glucose during a modal day was 14.71 +/- 4.5 mmol/l pretreatment and declined to 9.1 +/- 3.21 mmol/l by the end of treatment. These improvements in glycemia were associated with a decrease in serum insulin levels. Mean insulin concentrations declined from 108.0 to 57.0 pmol/l during the modal day measurements and from 97.2 to 72.0 pmol/l during the mixed-meal tolerance test. Changes in glycemia were accompanied by a marked increase in insulin sensitivity. The insulin sensitivity index (SI) calculated from a frequently sampled intravenous glucose tolerance test (FSIVGTT) after the method of Bergman et al. (Bergman RN, Finegold DT, Ader M: Assessment of insulin sensitivity in vivo. Endocr Rev 6:45-86, 1985) increased 3.4-fold. Furthermore, the improvement in glycemic control was accompanied by a change in body composition with a 2.1% loss in body fat as calculated by dual energy x-ray absorptiometry without change in total body weight. Significant side effects were present in some subjects, although nine subjects were able to complete at least 4.5 weeks of the protocol and six subjects completed the entire 6 weeks. Supraphysiological IGF-I concentrations were maintained throughout the study, increasing from 206 micrograms/l in the control period to 849 micrograms/l at the end of 6 weeks of rhIGF-I treatment. The increase in IGF-I levels was accompanied by a significant increase in IGF binding protein-2 levels, a slight reduction in IGF binding protein-3 levels, and an increase in levels of IGF binding protein-1. In summary, IGF-I significantly lowered blood glucose as reflected by short-term and long-term indexes of glycemic control and increased insulin sensitivity. It remains to be determined whether a dosage can be administered that avoids significant side effects and still achieves reasonable glycemic control.

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Metadata

Authors
Moses, A. C., Young, S. C., Morrow, L. A., O'Brien, M., & Clemmons, D. R.
Affiliations
  • Harvard University (US)
  • University of North Carolina at Chapel Hill (US)
  • Divisions of Endocrinology and Geriatrics, Department of Medicine, Charles A. Dana Research Institute of the Harvard-Thorndike Laboratories, Beth Israel Hospital and the Geriatrics Research, Education, and Clinical Center, Brockton/West Roxbury Veterans Administration Hospital Boston, Massachusetts
ORCID
Venue
Diabetes
Publisher
American Diabetes Association
Published
1996-01-01
Volume
45
Issue
1
Pages
91-100
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
DOI
10.2337/diab.45.1.91
OpenAlex
W2153356008
Cited by
291
References
0
Citations by year
2026: 1 · 2024: 7 · 2023: 4 · 2022: 8 · 2021: 4 · 2020: 7 · 2019: 5 · 2018: 11 · 2017: 16 · 2016: 10 · 2015: 10 · 2014: 7 · 2013: 10 · 2012: 4
FWCI
9.31
Type
journal article
Language
en
Open access
closed
Locations
  • Diabetes (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • Genentech
  • National Center for Research Resources (M01-RR01302, M01RR000046)
  • NIH Clinical Center
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
Keywords
recombinant human insulin-like growth factor I, type 2 diabetes, insulin resistance, insulin sensitivity, glycemic control, obesity, insulin sensitivity index, fructosamine, HbA1c, fat loss, body composition, serum insulin, adverse effects, subcutaneous administration, glucose tolerance test, mixed meal tolerance test, frequently sampled intravenous glucose tolerance test
MeSH terms
Adult, Blood Glucose, Body Composition, Diabetes Mellitus, Type 2, Female, Glucose Tolerance Test, Glycated Hemoglobin, Hexosamines, Humans, Injections, Subcutaneous, Insulin, Insulin Resistance, Insulin-Like Growth Factor I, Lipids, Male, Middle Aged, Recombinant Proteins, Insulin-Like Growth Factor Binding Proteins, Fructosamine

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