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IGFs and binding proteins in short children with intrauterine growth retardation
Wayne S Cutfield1, Paul L Hofman, Mark Vickers
1Department of Pediatrics, University of Auckland, Auckland 92019, New Zealand. waynec@ahsl.co.nz
Insights
Short intrauterine growth retardation (IUGR) children exhibit elevated insulin-like growth factor (IGF) levels and IGF-binding protein 3 (IGFBP-3). This suggests potential hyperinsulinism and insulin resistance in IUGR, impacting the IGF-IGFBP axis.
Area of Science:
- Pediatric Endocrinology
- Growth and Development
- Metabolic Disorders
Background:
- The insulin-like growth factor (IGF) and IGF-binding protein (IGFBP) axis plays a crucial role in growth and metabolism.
- Intrauterine growth retardation (IUGR) is associated with altered postnatal growth and metabolic profiles.
- Understanding the interplay between the IGF-IGFBP axis and insulin secretion is vital in short IUGR children.
Purpose of the Study:
- To investigate the relationship between the IGF-IGFBP axis and insulin secretion in short children with IUGR.
- To compare IGF-I, IGF-II, IGFBP-3, and IGFBP-1 levels and insulin response in IUGR versus normal short children.
Main Methods:
- A frequently sampled intravenous glucose tolerance test (FSIGT) was administered to 15 short IUGR and 12 short normal prepubertal children.
- Plasma levels of glucose, insulin, IGF-I, IGF-II, IGFBP-3, and IGFBP-1 were measured.
- Fasting IGF-I and IGFBP-3 levels were also assessed in 29 nonobese, normal-height prepubertal subjects for comparison.
Main Results:
- Short IUGR children displayed significantly higher plasma IGF-I, IGF-II, IGFBP-3, fasting insulin, and acute insulin response (AIR) compared to short normal children.
- Nonobese, normal-height children had higher IGF-I and IGFBP-3 than the IUGR group.
- In normal short children, AIR correlated with a decrease in IGFBP-1; this relationship was absent in IUGR subjects.
Conclusions:
- Short IUGR children exhibit an altered IGF-IGFBP axis with elevated IGF-I, IGF-II, and IGFBP-3 compared to height-matched normal children.
- The findings suggest potential hyperinsulinism secondary to insulin resistance in IUGR children, influencing the IGF-IGFBP axis.
- Further research is warranted to elucidate the long-term metabolic implications of these alterations in IUGR.
Abstract:
The aim of this study was to examine the relationship between the IGF-IGF binding protein (IGFBP) axis and insulin secretion in short intrauterine growth retardation (IUGR) children. Fifteen IUGR and 12 normal short prepubertal subjects had a 90-min frequently sampled iv glucose tolerance test performed to measure plasma glucose, insulin, IGF-I, IGF-II, IGFBP-3, and IGFBP-1. In addition, 29 nonobese prepubertal subjects of normal height had fasting plasma IGF-I and IGFBP-3 levels measured. In comparison to short normal subjects, IUGR subjects had higher plasma values for IGF-I (42 +/- 10 vs. 77 +/- 31 microg/liter; P < 0.0001), IGF-II (291 +/- 76 vs. 370 +/- 66 microg/liter; P < 0.008), IGFBP-3 (1.66 +/- 0.28 vs. 2.07 +/- 0.48 mg/liter; P < 0.0005), fasting insulin (2 +/- 1 vs. 4 +/- 2 mU/liter; P < 0.004), and acute insulin response (AIR; 215 +/- 36 vs. 504 +/- 90 mU/liter; P = 0.008). Nonobese subjects of normal height had higher plasma IGF-I (117 +/- 9 microg/liter; P < 0.0001) and IGFBP-3 (2.34 +/- 0.12 mg/liter) values than the IUGR group (P < 0.0005). During the frequently sampled iv glucose tolerance test, the magnitude of the AIR in short normal subjects was related to the fall in IGFBP-1 levels (P = 0.03); however, no relationship was seen between AIR and fall in IGFBP-1 in IUGR subjects (P = 0.24). In conclusion, short IUGR children have higher plasma IGF-I, IGF-II, and IGFBP-3, when compared with normal children matched for height, weight, and pubertal status. We speculate that hyperinsulinism secondary to insulin resistance may have led to these changes to the IGF-IGFBP axis in the IUGR group.