Growth And The Growth Hormone-Insulin Like Growth Factor 1 Axis In Children With Chronic Inflammation:Current Evidence, Gaps In Knowledge And Future Directions

Growth failure is frequently encountered in children with chronic inflammatory conditions like juvenile idiopathic arthritis, inflammatory bowel disease and cystic fibrosis. Delayed puberty and attenuated pubertal growth spurt is often seen during adolescence. The underlying inflammatory state mediated by pro-inflammatory cytokines, prolonged use of glucocorticoid and suboptimal nutrition contribute to growth failure and pubertal abnormalities. These factors can impair growth by their effects on the growth hormone-insulin like growth factor axis and also directly at the level of the growth plate via alterations in chondrogenesis and local growth factor signaling. Recent studies on the impact of cytokines and glucocorticoid on the growth plate studies further advanced our understanding of growth failure in chronic disease and provided a biological rationale of growth promotion. Targeting cytokines using biologic therapy may lead to improvement of growth in some of these children but approximately one third continue to grow slowly. There is increasing evidence that the use of relatively high dose recombinant human growth hormone may lead to partial catch up growth in chronic inflammatory conditions, although long term follow-up data is currently limited. In this review, we comprehensively review the growth abnormalities in children with juvenile idiopathic arthritis, inflammatory bowel disease and cystic fibrosis, systemic abnormalities of the growth hormone-insulin like growth factor axis and growth plate perturbations. We also systematically reviewed all the current published studies of recombinant human growth hormone in these conditions and discuss the role of recombinant human insulin like growth factor-1

Carbohydrate and fat metabolism related to blood lactate in boys and male adolescents

The half maximal constant (k (el)) of the relative rate of carbohydrate oxidation (relCHO) was individually approximated (relCHO = 100/(1 + k (el)/BLC(2)) as a function of the blood lactate concentration (BLC) in 11 pre-pubertal boys and 11 male adolescents (age: 11.6 +/- A 0.1 vs. 16.4 +/- A 0.2 years, height: 151.6 +/- A 1.7 vs. 182.4 +/- A 2.3 cm, body mass: 38.2 +/- A 1.1 vs. 68.7 +/- A 2.3 kg, all P < 0.001) during incremental cycle ergometry. k (el) explained 89.0 +/- A 2.2 and 91.9 +/- A 2.2% of the variance of the reliance on CHO in boys and adolescents respectively (both P < 0.001). No difference in k (el) [1.34 +/- A 0.40 vs. 1.48 +/- 0.30 (mmol l(-1))(2)] was found between boys and adolescents. The BLC was lower (P < 0.05) in boys when relCHO was higher than 91.2 +/- A 2.1 and 92.1 +/- A 1.3% in boys and adolescents respectively. This seems to explain why the reliance on CHO and the BLC are independent of maturation in the moderate and heavy exercise intensity domain and the BLC but not the relCHO which is higher under severe and maximal exercise conditions in more mature subjects

Hemoglobin oxygen affinity in patients with cystic fibrosis.

In patients with cystic fibrosis lung damages cause arterial hypoxia. As a typical compensatory reaction one might expect changes in oxygen affinity of hemoglobin. Therefore position (standard half saturation pressure P50st) and slope (Hill's n) of the O2 dissociation curve as well as the Bohr coefficients (BC) for CO2 and lactic acid were determined in blood of 14 adult patients (8 males, 6 females) and 14 healthy controls (6 males, 8 females). While Hill's n amounted to approximately 2.6 in all subjects, P50st was slightly increased by 1 mmHg in both patient groups (controls male 26.7 ± 0.2, controls female 27.0 ± 0.1, patients male 27.7 ± 0.5, patients female 28.0 ± 0.3 mmHg; mean and standard error, overall p<0.01). Main cause was a rise of 1-2 µmol/g hemoglobin in erythrocytic 2,3-biphosphoglycerate concentration. One patient only, clearly identified as an outlier and with the mutation G551D, showed a reduction of both P50st (24.5 mmHg) and [2,3-biphosphoglycerate] (9.8 µmol/g hemoglobin). There were no differences in BCCO2, but small sex differences in the BC for lactic acid in the controls which were not detectable in the patients. Causes for the right shift of the O2 dissociation curve might be hypoxic stimulation of erythrocytic glycolysis and an increased red cell turnover both causing increased [2,3-biphosphoglycerate]. However, for situations with additional hypercapnia as observed in exercising patients a left shift seems to be a more favourable adaptation in cystic fibrosis. Additionally when in vivo PO2 values were corrected to the standard conditions they mostly lay left of the in vitro O2 dissociation curve in both patients and controls. This hints to unknown fugitive factors influencing oxygen affinity