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The Journal of Clinical Endocrinology & Metabolism Vol. 82, No. 4 1181-1187
Copyright © 1997 by The Endocrine Society

Clinical Studies

Dual Hormonal Replacement Therapy with Insulin and Recombinant Human Insulin-Like Growth Factor (IGF)-I in Insulin-Dependent Diabetes Mellitus: Effects on the Growth Hormone/IGF/IGF-Binding Protein System1

Kathryn Thrailkill, Teresa Quattrin, Lester Baker, Jean Litton, Karen Dwigun, Melissa Rearson, Mary Poppenheimer3, Debbie Kotlovker3, David Giltinan3, Neil Gesundheit2 and Paul Martha, Jr.3

Department of Pediatrics, Duke University Medical Center (K.T., J.L.), Durham, North Carolina 27710; Department of Pediatrics, Children’s Hospital of Buffalo (T.Q., K.D.), Buffalo, New York 14222; and Department of Pediatrics, Children’s Hospital of Philadelphia (L.B., M.R.), Philadelphia, Pennsylvania 19104.

Address all correspondence and requests for reprints to: Kathryn Thrailkill, University of Kentucky, J465 Kentucky Clinic, 740 South Limestone Avenue, Lexington, Kentucky 40536-0284. E-mail: Thrail{at}pop.uky.edu

Patients with insulin-dependent diabetes mellitus (IDDM) exhibit abnormalities in the GH/insulin-like growth factor (IGF) axis, including GH hypersecretion, low serum IGF-I and IGF-binding protein-3 (IGFBP-3) levels, and elevated IGFBP-1 levels. We recently demonstrated that in IDDM, dual hormonal replacement therapy with insulin plus recombinant human IGF-I (rhIGF-I) improves glycemic control better than insulin alone. To determine whether the addition of rhIGF-I therapy to insulin therapy also corrects GH/IGF/IGFBP abnormalities, we examined the effects of chronic combined rhIGF-I/insulin therapy on key components of the somatotropin axis. Forty-three pediatric IDDM patients were randomly assigned to groups receiving daily, fasting subcutaneous injections of placebo or rhIGF-I (80 µg•kg•day) for 28 days, while continuing to receive split-mix insulin therapy and intensive outpatient management. rhIGF-I therapy corrected IGF-I deficiency, suppressed IGFBP-1 levels (P < 0.01), and induced a trend toward lower circulating GH levels throughout the study. rhIGF-I therapy also induced an approximate 50% decrease in IGF-II levels (P < 0.001) and an approximate 70% increase in IGFBP-2 levels (P < 0.05). Serum IGFBP-3 levels, normal before treatment, remained normal during rhIGF-I administration. All effects were apparent during the first week of rhIGF-I therapy and persisted throughout treatment. Because improvements in the GH/IGF axis abnormalities and in glycemic control were greater in subjects receiving combined rhIGF-I and insulin, these data strongly support the concept that dual hormonal replacement in IDDM may offer distinct therapeutic advantages over insulin monotherapy.




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