title: 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 system.
abstract: 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 micrograms.kg.day) for 28 days, while continuing to receive splitmix 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.
authors.affiliation: Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27710, USA. Thrail@pop.uky.edu
authors.forename: K
authors.initials: K
authors.lastname: Thrailkill
authors.forename: T
authors.initials: T
authors.lastname: Quattrin
authors.forename: L
authors.initials: L
authors.lastname: Baker
authors.forename: J
authors.initials: J
authors.lastname: Litton
authors.forename: K
authors.initials: K
authors.lastname: Dwigun
authors.forename: M
authors.initials: M
authors.lastname: Rearson
authors.forename: M
authors.initials: M
authors.lastname: Poppenheimer
authors.forename: D
authors.initials: D
authors.lastname: Kotlovker
authors.forename: D
authors.initials: D
authors.lastname: Giltinan
authors.forename: N
authors.initials: N
authors.lastname: Gesundheit
authors.forename: P
authors.initials: P
authors.lastname: Martha
mesh_terms: D000293:Adolescent; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D019382:Human Growth Hormone / Q000097:blood*; D006801:Humans; D007328:Insulin / Q000627:therapeutic use*; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000627:therapeutic use*; D008297:Male; D011994:Recombinant Proteins; D013002:Somatomedins / Q000378:metabolism*
chemical_list: D007328:Insulin; D018969:Insulin-Like Growth Factor Binding Proteins; D011994:Recombinant Proteins; D013002:Somatomedins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I