Impact of increased growth hormone secretion on carbohydrate metabolism in adolescents with diabetes

Growth hormone (GH) and fasting insulin concentrations rise during puberty in normal subjects. Any increase in GH secretion in adolescents with insulin-dependent diabetes mellitus (IDDM) might be expected to lead to further insulin resistance and metabolic disturbance. Despite the high incidence of delayed growth in IDDM, the relationship between GH, insulin-like growth factor I (IGF-I) and IGF binding protein 1 (IGFBP-1) has not been clearly established. Twenty-six adolescents with IDDM and 34 healthy siblings underwent measurement of their overnight GH secretory profiles (20.00-08.00 hours, 15-minute sampling). The diabetic subjects were studied either on their normal insulin regimen (n = 15) or during a euglycaemic clamp (n = 26). A second clamp study was undertaken (n = 7) with addition of pirenzepine to suppress GH secretion. GH profiles in the diabetic subjects were characterized by increases in both pulse amplitude and baseline GH concentrations. Deconvolution analysis also revealed an increase in the frequency of GH secretory episodes. In the subjects with diabetes, a direct link between the dawn rise in insulin requirements, increased concentrations of beta-hydroxybutyrate and the elevated concentrations of GH was established. These abnormalities were reversed by the suppression of GH pulse amplitude following pirenzepine. Serum IGF-I concentrations and IGF-I bioactivity in the diabetic subjects were low and were positively correlated with mean GH concentrations. In conclusion, well controlled adolescents with IDDM show persisting abnormalities of GH, beta-hydroxybutyrate and IGF-I despite normoglycaemia. The role of inappropriate insulin delivery in the development of these abnormalities is discussed.