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Insulin-like growth factor I, IGF binding protein 3, and IGFBP protease activity: relation to anthropometric indices
B M Brennan1, M Gill, L Pennells
1Department of Paediatric Oncology, Manchester Children's Hospitals, UK.
Insights
Children with malignancies have low insulin-like growth factor I (IGF-I), especially if malnourished. IGF-I levels correlate with arm measurements, indicating nutritional status, but IGFBP-3 interpretation is complex due to protease activity.
Area of Science:
- Pediatric Oncology
- Endocrinology
- Nutritional Science
Background:
- Childhood malignancies can impact growth and nutritional status.
- Insulin-like growth factor I (IGF-I) and its binding proteins are crucial for growth.
- IGFBP-3 protease activity may affect the measurement of IGF-I and IGFBP-3.
Purpose of the Study:
- To measure serum IGF-I and IGFBP-3 concentrations and IGFBP-3 protease activity in children with malignancies.
- To assess the relationship between these factors and auxological parameters/nutritional status.
Main Methods:
- Collected anthropometric data (height, weight, skinfold thickness, MUAC).
- Measured IGF-I and IGFBP-3 using radioimmunoassays.
- Assessed IGFBP-3 protease activity via [125I]-IGFBP-3 fragmentation.
Main Results:
- IGF-I SDS was significantly reduced in all patients, lower in malnourished children.
- IGFBP-3 SDS was mostly normal, but protease activity was elevated in all patients.
- IGF-I correlated with MUAC and subscapular skinfold SDS, not other anthropometric measures.
Conclusions:
- IGF-I is low in pediatric malignancies, particularly with malnutrition.
- Elevated IGFBP-3 protease activity complicates IGFBP-3 concentration interpretation.
- IGF-I serves as a nutritional index related to arm anthropometry in these children.
Objectives:
To measure the serum concentrations of insulin-like growth factor I (IGF-I) and IGF binding protein 3 (IGFBP-3), and the level of IGFBP-3 protease activity in 38 children presenting with malignancies, and to assess their relation with auxological parameters and nutritional status.
Methods:
Height, weight, skinfold thickness, and mid-upper arm circumference (MUAC) were recorded using standard techniques. IGF-I and IGFBP-3 were measured using specific radioimmunoassays. Serum IGFBPs were also visualised on western ligand blot. IGFBP-3 protease activity was assessed by the extent of fragmentation of recombinant [125I]-IGFBP-3, compared with that induced by pregnancy serum. Anthropometric and radioimmunoassay data were expressed as standard deviation scores (SDS).
Results:
The median (range) IGF-I SDS was significantly reduced in all patients (-1.1 (-5.1 to 1.2)) and lower in children who were malnourished (-2.5 (-3.9 to 0.1)). IGFBP-3 SDS was within the normal range for 31 of 38 patients but IGFBP-3 protease activity was raised in all patients. Neither IGFBP-3 concentration nor protease activity was affected by nutritional status. IGF-I correlated with MUAC (r = 0.41) and subscapular skinfold thickness SDS (r = 0.38), but not with weight, height, weight for height, or triceps skinfold thickness.
Conclusions:
IGF-I is low in children with malignancies, and even lower in those who are malnourished. IGFBP-3 concentrations were normal in most patients but interpretation is complicated by the presence of raised IGFBP-3 protease activity, which could lead to overestimating concentrations of intact peptide. IGF-I appears to relate to arm anthropometry as an index of nutritional status but not height, weight, or weight for height, as would be expected in normal children.