The relationship between insulin, IGF-I and weight gain in cystic fibrosis.

OBJECTIVE: In cystic fibrosis, reduced body mass is related to low levels of IGF-I and changes in the IGF binding proteins. Our aim was to determine whether these abnormalities are linked to pancreatic endocrine dysfunction. PATIENTS AND DESIGN: We measured serum levels of insulin, IGF-I, IGFBP-I, IGFBP-3 and IGF bioactivity in 77 fasting subjects (43 male) mean age 9.6 years (range 2.99-17.98 years). Data were analysed with respect of body mass, puberty and stature and compared with control data established in the same laboratory. RESULTS: The mean height standard deviation score (SDS (SD)) was -0.54 (0.97) and the body mass index SDS -0.24 (1.09). Both body mass index SDS (r = -0.40, P = 0.0003) and IGF-I SDS (r = - 0.32, P = 0.009) declined with age. Insulin levels were also low and correlated with IGF-I and IGFBP-3 (r = 0.42, P = 0.0004, and r = 0.45, P = 0.0002, respectively) whereas levels of IGFBP-I were inversely related to those of IGF-I and insulin (r = - 0.43, P = 0. 0004, r = - 0.52, P < 0.0001). IGF bioactivity was reduced and inversely related to IGFBP-I (r = - 0.31, P = 0.009). In multiple regression analysis, body mass index SDS was negatively related to age (P < 0.0001) and positively related to insulin and IGF-I (P = 0. 04, P = 0.03, respectively). Height SDS was correlated with IGF bioactivity (P = 0.003) and negatively with IGFBP-I (P = 0.01). CONCLUSIONS: We conclude that progressive insulin deficiency may result in reduced IGF-I levels and IGF-bioactivity and may determine weight gain and statural growth in cystic fibrosis.

Relation between insulin-like growth factor-I, body mass index, and clinical status in cystic fibrosis.

OBJECTIVES: Despite improved nutrition and intensive treatment, subjects with cystic fibrosis have difficulty in maintaining anabolism during intercurrent infections, which can result in reduced body mass index and impaired skeletal growth. Insulin-like growth factor-I (IGF-I) and its binding protein IGFBP3 are sensitive to changes in nutritional status. The aim of this study was to determine the relation between circulating concentrations of these peptides, body mass index, and clinical status in cystic fibrosis. METHODS: Serum concentrations of IGF-I and IGFBP3 were measured in 197 subjects (108 males, 89 females; mean age 9.69 years, range 0.41-17.9 years) and these data were analysed with respect to body mass index, pubertal stage, and clinical status as assessed by Shwachman score and forced expiratory volume in one second (FEV1). RESULTS: The mean height SD score of the children studied was -0.2 (SD 1.14) and the body mass index SD score -0.26 (1.4). The body mass index SD score declined with increasing age (r = -0.18) and paralleled changes in IGF-I concentrations, which also declined. The IGF-I SD score (calculated from control data) correlated with age (r = -0.53). The abnormalities were most obvious during late puberty, when IGF-I and IGFBP3 concentrations were significantly reduced compared with those in control subjects matched for pubertal stage. The IGF-I SD score correlated with height SD score (r = 0.14) and the decline in IGF-I concentrations with the fall in body mass index SD score (r = 0.42). IGF-I SD scores also correlated with the Shwachman score (r = 0.33) and FEV1 (r = 0.17). CONCLUSIONS: The close relation between declining IGF-I and IGFBP3 concentrations and body mass index in patients with cystic fibrosis may simply reflect poor nutritional status and insulin hyposecretion. Nevertheless, IGF-I deficiency could also contribute towards the catabolism observed in these patients, and IGF-I SD scores correlated with other measures of clinical status such as the Shwachman score and FEV1.