
<ArticleTitle>The role of IGF-binding proteins in mediating the effects of recombinant human <prot>IGF-I</prot> on insulin requirements in type 1 diabetes mellitus.</ArticleTitle>
<AbstractText>To determine the role of IGF-binding proteins in mediating the direct effects of recombinant human <prot>IGF-I</prot> on insulin requirements in type 1(insulin-dependent) diabetes mellitus, overnight changes in <prot>IGF-I</prot>, <prot>IGF-II</prot>, and <prot>IGF-binding protein-1</prot>, -2, and -3, collected under euglycemic conditions, were compared in nine subjects after double blind, randomized, sc administration of recombinant human <prot>IGF-I</prot> (40 microg/kg) or placebo at 1800 h. On both nights a somatostatin analog infusion (300 ng/kg x h) suppressed endogenous GH production, and three timed discrete GH pulses (total, 0.029 IU/kg x night) ensured identical GH levels. After recombinant human <prot>IGF-I</prot> administration, <prot>IGF-I</prot> levels and the <prot>IGF-I</prot>/<prot>IGF-binding protein-3</prot> ratio increased [mean +/- SEM:IGF-I, 401 +/- 22 ng/ml; placebo, 256 +/- 20 ng/ml (P = 0.0002); IGF-I, 0.108 +/- 0.006; placebo, 0.074 +/- 0.004 (P = 0.0003), respectively], and insulin requirements decreased (<prot>IGF-I</prot>, 0.12 +/- 0.03; placebo, 0.23 +/- 0.03 U/kg x min; P = 0.008). The normal within-individual inverse relationships between insulin and IGF-binding protein-1 levels were observed (lag time 2 h: r = -0.34; P &#60; 0.01). Yet despite reduced free insulin levels (8.5 +/- 1.5; placebo, 12.2 +/- 1.2 mU/liter; P = 0.03), <prot>IGF-binding protein-1</prot> levels were reduced after recombinant human <prot>IGF-I</prot> administration (53.7 +/- 6.8; placebo, 82.2 +/- 11.8 ng/ml; P = 0.008). The largest reductions in free insulin levels after recombinant human IGF-I and thus putative improvement in insulin sensitivity occurred in subjects with the smallest increase in the plasma<prot> IGF-I</prot>/<prot>IGF-binding protein-3</prot> ratio (r = 0.7; P = 0.03). Taken together, these data are consistent with the hypothesis that transcapillary movement of <prot>IGF-I</prot> (perhaps mediated by <prot>IGF-binding protein-1</prot>), out of the circulation facilitates altered insulin sensitivity. These data have important implications for risk-benefit assessment of recombinant human <prot>IGF-I</prot> therapy in type 1 diabetes mellitus.</AbstractText>
