LOSS OF THE NORMAL RELATIONSHIPS BETWEEN GROWTH-HORMONE, GROWTH HORMONE-BINDING PROTEIN AND INSULIN-LIKE GROWTH-FACTOR-I IN ADOLESCENTS WITH INSULIN-DEPENDENT DIABETES-MELLITUS

OBJECTIVE It has been proposed that the dissociation between growth ho rmone secretion and insulin-like growth factor-I (IGF-I) concentration s in insulin-dependent diabetes mellitus arises because of partial res istance at the GH receptor. In order to explore this hypothesis furthe r we have examined the relations between IGF-I, GH-binding protein (GH BP), and GH secretion in normal subjects and patients with diabetes du ring puberty. DESIGN AND SUBJECTS Blood samples for the estimation of IGF-I and GHBP levels were obtained from 104 patients with diabetes an d 89 puberty matched controls. Thirty-four of the controls and 42 of t he patients with diabetes also underwent an overnight GH secretory pro file with measurements of GH every 15-20 minutes between 2000 and 0800 h. RESULTS In multivariate analysis using sex, puberty stage, and pre sence or absence of diabetes as dependent variables, diabetes was asso ciated with increased GH levels (F = 23.04, P < 0.001), reduced IGF-I (F = 10.89, P < 0.001), and reduced GHBP levels (F = 31.36, P < 0.001) . A negative relation between GH and GHBP levels (r = -0.44, P < 0.01) was found in normal subjects but this was absent in those with diabet es. Both GHBP and IGF-I levels in the diabetic subjects were correlate d with total insulin dose (r = 0.4, P < 0.001, and r = 0.46, P < 0.001 , respectively). Yet there was no direct correlation between GHBP and IGF-I concentrations. The variation in IGF-I levels was also related t o glycosylated haemoglobin levels in the diabetics (r = -0.27, P = 0.0 1). In a stepwise multiple regression analysis insulin dose contribute d 23%, HbA(1) 4.4% and C-peptide levels 3.7% to the variation in IGF-I levels. CONCLUSIONS In adolescents with insulin dependent diabetes me llitus, the elevated GH concentrations are associated with low circula ting IGF-I and GHBP concentrations and the normal reciprocal relation between GHBP and GH is no longer evident. Although IGF-I and GHBP are both related to insulin dose, there is no direct correlation between t hese variables. This may indicate that GHBP reflects GH receptor numbe rs but not necessarily post receptor events, and the weak positive cor relation between GH and IGF-I indicates that increased growth hormone secretion may compensate for reduced receptor numbers.