Impact of Increased Growth Hormone Secretion on Carbohydrate Metabolism in Adolescents with Diabetes

Abstract

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 Gli, 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 Gil secretory episodes. In the subjects with diabetes, a direct link between the dawn rise in insulin requirements, increased concentrations of 9‐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, β‐hydroxybutyrate and IGF‐I despite normoglycaemia. The role of inappropriate insulin delivery in the development of these abnormalities is discussed.

The effects of recombinant human insulin‐like growth factor I on growth hormone secretion in adolescents with insulin dependent diabetes mellitus

“…Elevated GH concentrations in adolescents with IDDM may affect metabolic control by increasing insulin resistance (Dunger et al, 1991). It has been suggested that the increase in GH levels is due to altered feedback control from the reduced levels of IGF-I and reduced IGF-I bioactivity found in adolescents with IDDM (Dunger, 1992).…”

Does the long-term clinical course of type I diabetes mellitus differ in patients with prepubertal and pubertal onset? Results of the Berlin Retinopathy Study

“…According to clinical experience, adolescents with diabetes onset during or after puberty frequently do present a milder course of the disease, compared to those subjects with onset in earlier child-hood. During puberty, moreover, when insulin resistance due to the excess of hormonal anti-insulin activity [6] frequently complicates management in patients with long-term diabetes, those with onset near puberty present fewer diculties.…”

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

“…Overnight GH secretory profiles are characterized by increases in both pulse amplitude and baseline concentrations. These abnormalities have direct effects on insulin sensitivity (Dunger et al, 1991) which may lead to a worsening of metabolic control (Press et al, 1984).…”