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IGFs and Binding Proteins in Short Children with Intrauterine Growth Retardation

Department of Pediatrics (W.S.C., P.L.H.), Research Centre for Developmental Medicine and Biology (M.V., B.B.), and the Health Research Council Biostatistics Unit, Department of Community Health (E.M.R.), University of Auckland, Auckland 92019, New Zealand; and Lilly Deutschand GmBH (W.F.B.), Bad Homburg 61350, Germany

Address all correspondence and requests for reprints to: Dr. Wayne Cutfield, Department of Pediatrics, University of Auckland, Private Bag 92019, Auckland, New Zealand. E-mail: waynec{at}ahsl.co.nz

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 µg/liter; P < 0.0001), IGF-II (291 ± 76 vs. 370 ± 66 µg/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 µg/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.

This work was supported by grants from the Auckland Medical Research Foundation and Pharmacia \|[amp ]\| Upjohn, Inc.

Abbreviations: AIR, Acute insulin response; IGFBP, IGF binding protein; IUGR, intrauterine growth retardation; WLI, weight for length index.

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