The growth hormone/insulin-like growth factor I axis in insulin-dependent diabetes mellitus during adolescence. Studies of recombinant human insulin-like growth factor I (rhIGF-I) administration.

Abstract

The fall in insulin sensitivity during adolescence is accentuated in insulin-dependent diabetes mellitus (IDDM) and has been linked to enhanced growth hormone (GH) secretion. The rise in GH release is related to low insulin-like growth factor I (IGF-I) levels and low IGF bioactivity. Abnormalities of the IGF binding proteins (IGFBP's), including low insulin-like growth factor binding protein-3 (IGFBP-3) and elevated insulin-like growth factor binding protein-1 (IGFBP-1) concentrations are also observed. The rise in GH concentrations may lead to increased insulin requirements that cannot easily be met by current treatment regimens and can result in deteriorating blood glucose control. GH release also enhances ketogenesis and has been linked to the development of microvascular complications. The impact of a subcutaneous injection of rhIGF-I (40 mug/kg) on GH concentrations, insulin sensitivity and the IGFBP's was studied in adolescents with IDDM (n=17). A control night was compared with a night when rhIGF-I was administered at 18.00h. Blood samples were taken regularly overnight and glucose concentrations controlled by a variable-rate insulin infusion. GH concentrations on the control night correlated with glycated haemoglobin levels. The administration of rhIGF-I led to a sustained increase in IGF-I levels, IGF bioactivity and reductions in GH secretion and the insulin infusion requirements to maintain euglycaemia. The change in GH secretion was due to reduced pulse amplitude rather than pulse frequency. The attributes assessing GH release correlated with free insulin concentations on control and rhIGF-I nights, and the reduction in GH release was related to the fall in insulin levels. The concentrations of IGFBP-3 did not fall after rhIGF-I as they did during the control study, but IGFBP-1 levels were unchanged. In longer term studies (n=6), daily rhIGF-I administration (40 ug/kg) for one month led to a reduced isophane insulin dose and a fall in glycated haemoglobin concentrations. GH levels were reduced and IGFBP-3 concentrations rose in 5 of the 6 subjects studied. The administration of rhIGF-I may have a therapeutic role in IDDM during adolescence by reducing GH concentrations and increasing insulin sensitivity