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Insulin-Like Growth Factor-1 Therapy in Diabetes: Physiologic Basis, Clinical Benefits, and Risks

Jerzy W. Kolaczynski, MD; and Jose F. Caro, MD
[+] Article and Author Information

From the Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania. Requests for Reprints: Jose F. Caro, MD, Department of Medicine, Jefferson Medical College, College Building, Suite 821, 1025 Walnut Street, Philadelphia, PA 19107-5083. Acknowledgments: The authors thank Drs. Barry Goldstein, Marshall Goldberg, and Robert Considine for careful review of the manuscript; Drs. Gary G. Carpenter and Ewa Surmacz for valuable discussions; and Mrs. Francine Holak for preparation of figures and Mrs. Diane Miller for the typing of the manuscript. Grant Support: In part by grant RO1 DK45592 from the National Institute of Health.


Copyright ©2004 by the American College of Physicians


Ann Intern Med. 1994;120(1):47-55. doi:10.7326/0003-4819-120-1-199401010-00009
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Purpose: To review the effects of insulin-like growth factor-1 (IGF-1) and to discuss the clinical benefits and risks of using it in patients with diabetes.

Data Sources: Recent publications identified through a MEDLINE search using relevant keywords.

Study Selection: Selected studies on the metabolic effects and kinetic mechanisms of in vitro IGF-1 and existing literature on the effects of IGF-1 on glucose and lipid metabolism in vivo with special emphasis on data from humans.

Data Synthesis: The substantial stimulatory effect of IGF-1 on glucose uptake suggests that, in selected clinical situations, the drug may be an alternative to standard treatment of diabetes. Metabolic control in patients with extreme insulin resistance is improved after using IGF-1. Moreover, patients with type II (non–insulin-dependent) diabetes who receive IGF-1 have improved glucose tolerance and decreased hyperinsulinemia and hypertriglyceridemia. The complications associated with long-term administration of IGF-1 are unknown but might include the progression of certain neoplasms and diabetic complications, such as nephropathy and retinopathy.

Conclusions: Insulin-like growth factor-1 may be a useful adjunct for treatment of diabetes and may even be the drug of choice in some patients with extreme insulin resistance who have metabolic emergencies. However, further data are needed to evaluate the risks and benefits of IGF-1 use in diabetes and in other states associated with impaired insulin action.

Figures

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Figure 1.
Kinetics of insulin-like growth factor-1 in vivo.1.2.3.4.5.6.

The circulating 150-kd complex consisting of insulin-like growth factor-1 (IGF-1), binding protein-3 (BP-3), and a 85-kd acid-labile subunit, is the major storage form of IGF-1 in the body. IGF-1 free or bound to other binding proteins (BP) can cross the vascular barrier to reach the intercellular space. Free IGF-1 interacts with IGF type I, type II, or insulin receptors. Binding proteins associated with cells have a modulatory effect on cell growth and metabolism. Numerous cell types can generate IGF-1 to exert paracrine or autocrine effects. Numerous cells can also produce binding proteins.

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Figure 2.
Effect of insulin-like growth factor-1 in syndromes of extreme insulin resistance.[9]

Recombinant human insulin-like growth factor-1 (IGF-1) was administered in two (at 0 and at 120 min) 100 µg/kg intravenous bolus injections. The effect of IGF-1 on plasma glucose, insulin, and C-peptide levels is shown in three patients with acanthosis nigricans and insulin resistance. Bars represent values from each patient, black squares represent means. Adapted from Schoenle and colleagues with permission.

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Figure 3.
Effect of insulin-like growth factor-1 administration in a patient with insulin-dependent diabetes mellitus and severe insulin resistance.[10]

An intravenous bolus dose of insulin-like growth factor-1 (IGF-1), 500 µg/kg, was given at 1530 hours. The hatched area indicates the period in which the serum IGF-1 concentration was more than 1100 µg/L and the serum free insulin concentrations were not detectable and thus the period when changes to serum glucose could be attributed to IGF-1. Adapted from Usala and colleagues , with permission.

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Figure 4.
Effects of recombinant human insulin-like growth factor-1 in type II diabetic patients.*P[11]

Fasting glucose, insulin, C-peptide, and triglyceride levels in eight type II diabetic patients before (coarsely hatched bars, control), during (white bars), and after (grey bars) treatment with two subcutaneous doses of IGF-1 daily (120 µg/kg). Statistically ( < 0.05) different when compared with control (days 1 to 5). Adapted from Zenobi and colleagues , with permission.

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