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

Patients with insulin-dependent diabetes mellitus (IDDM) exhibit abnor malities in the GW/insulin-like growth factor (IGF) axis, including GH hypersecretion, low serum IGF-I and IGF-binding protein-3 (IGFBP-3) l evels, and elevated IGFBP-1 levels. We recently demonstrated that in I DDM, dual hormonal replacement therapy with insulin plus recombinant h uman IGF-I (rhIGF-I) improves glycemic control better than insulin alo ne. To determine whether the addition of rhIGF-I therapy to insulin th erapy also corrects GH/IGF/ IGFBP abnormalities, we examined the effec ts of chronic combined rhIGF-I/insulin therapy on key components of th e somatotropin axis. Forty-three pediatric IDDM patients were randomly assigned to groups receiving daily, fasting subcutaneous injections o f placebo or rhIGF-I (80 mu g . kg . day) for 28 days, while continuin g to receive splitmix insulin therapy and intensive outpatient managem ent. rhIGF-I therapy corrected IGF-I deficiency, suppressed IGFBP-1 le vels (P < 0.01), and induced a trend toward lower circulating GH level s throughout the study. rhIGF-I therapy also induced an approximate 50 % decrease in IGF-II levels (P < 0.001) and an approximate 70% increas e in IGFBP-2 levels (P < 0.05). Serum IGFBP-3 levels, normal before tr eatment, remained normal during rhIGF-I administration. All effects we re apparent during the first week of rhIGF-I therapy and persisted thr oughout treatment. Because improvements in the GH/ IGF axis abnormalit ies and in glycemic control were greater in subjects receiving combine d rhIGF-I and insulin, these data strongly support the concept that du al hormonal replacement in IDDM may offer distinct therapeutic advanta ges over insulin monotherapy.