The relationship between insulin secretion, the insulin‐like growth factor axis and growth in children with cystic fibrosis

Abstract

Impaired glucose tolerance was present in 20% of children with cystic fibrosis. Impaired insulin secretion was common (65%) even in children with normal glucose tolerance. The mean height SDS for the group was low and the height velocity was abnormally slow in 39%, yet nutritional status as measured by BMI was appropriate for age. Relative insulin deficiency rather than nutritional deprivation or poor clinical status thus appears to be implicated in the poor linear growth of these children with relatively stable lung disease. This was a small study and firm conclusions on this chronic suppurative disease as to the cause of poor growth are not possible. The causes of poor growth are likely to be complex; nevertheless, the apparent decrease in insulin secretion combined with the expected increased demands on insulin production during pubertal growth raises the question as to whether insulin therapy should be considered in children with cystic fibrosis before the onset of cystic fibrosis-related diabetes mellitus.

Inflammation is a modulator of the insulin-like growth factor (IGF)/IGF-binding protein system inducing reduced bioactivity of IGFs in cystic fibrosis

“…Taylor et al (28) described a progressive reduction of IGF-I and IGFBP-3 related to declining BMI, and deteriorating pulmonary function, and suggested that progressive insulin deficiency might be contributing to this. Ripa et al (29) further supported this hypothesis by showing a high frequency of insulin hyposecretion with increased serum IGFBP-1 levels, normal IGF-I and reduced growth velocity in CF. However, this group of patients had basal insulin levels similar or greater than controls.…”

“…IGFBP-3 serum concentrations were similar in the patients and controls although they tended to be lower in patients with the most severe clinical state, and we did not find any relationship with insulin at variance with previously published data (28,29). This helps to explain why the IGF-I/IGFBP-3 molar ratios were similar in CF and healthy subjects.…”

“…Serum IGF-I levels were significantly lower in CF patients than in controls. At variance with previous studies this did not seem to be dependent on malnutrition or anorexia (9,14,28,29) as the BMI values of these patients were normal and similar to those of controls, and total serum protein concentration was normal. Other authors have hypothesized that low serum IGF-I concentrations could be dependent on insulin hyposecretion in CF.…”

Decreased Lung Function in Female but not Male Subjects With Established Cystic Fibrosis–Related Diabetes

“…The cross-sectional nature of our analysis could have introduced selection bias, although comparison of our population profile with that of previously published studies (6,19,26,27) suggests otherwise. The higher proportion of female than male subjects with CFRD was consistent with previously published data by Yung and Hodson (27), and the higher proportion of female than male subjects with CFRD and chronic P. aeruginosa was also consistent with those of Demko et al (6).…”

Late Consequences of Chronic Pediatric Illness

“…This may result from a combination of poor nutrition, pancreatic insufficiency, chronic inflammatory lung disease, and intestinal disease. Even with vigorous treatment of these problems, including dietary interventions to provide calories and fat soluble vitamins in excess of usual recommended amounts [35], severe CF is associated with poor weight gain and slower growth [36]. Relative insulin deficiency rather than nutritional deprivation or poor clinical status may be implicated in the poor linear growth of children with relatively stable lung disease [36].…”