C-peptide, insulin-like growth factors I and II, and insulin-like growth factor binding protein-1 in cord serum of twins: Genetic versus environmental regulation,☆☆,,★★

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Abstract

OBJECTIVE: Our purpose was to examine the regulation of fetal serum concentrations of insulin (C-peptide), insulin-like growth factor-I, insulin-like growth factor-II, and insulin-like growth factor binding protein-1, which are growth-regulating factors in the fetus, in monozygotic and dizygotic twin pairs. STUDY DESIGN: Cord serum samples were collected from 110 twin pairs and compared with 178 nonsibling singleton pairs with the same gestational age. Five twin pairs were excluded from the statistical analyses because of severe intrauterine growth restriction and placental abnormalities in one. Zygosity was assigned by histologic examination of the placenta and by a questionnaire sent to the mother when the twins were ≥6 months old. Analyses included the calculation of correlation coefficients, between-pair variation, and univariate genetic analysis. RESULTS: Cord serum C-peptide concentrations were highly correlated in monozygotic (r = 0.94) and dizygotic twins (r = 0.79) but not in singleton pairs (r = -0.05); the between-pair variation was also smaller in twins than in singletons. Genetic analysis demonstrated a large contribution of the common environment to the variance in C-peptide concentrations (80%) and a smaller genetic contribution (12%). Insulin-like growth factor-I concentrations were better correlated in monozygotic (r = 0.82) than in dizygotic twins (r = 0.42), with a smaller between-pair variation in the former group (22% ± 4% vs 51% ± 5%). Univariate genetic analysis indicated that insulin-like growth factor-I levels were regulated predominantly by genetic mechanisms (93% in boys and 77% in girls). The regulation of insulin-like growth factor-II was more complex, with a gender-specific genetic contribution (50% for both sexes combined, 63% for girls but only 5% for boys). Insulin-like growth factor binding protein-1 was regulated by genetic mechanisms (41%) and the common environment (32%) but also by the specific or unique environment of each fetus (27%). In all five twins with intrauterine growth restriction of one member, insulin-like growth factor binding protein-1 concentrations were markedly higher in the growth-restricted fetus. CONCLUSIONS: Insulin secretion in twin fetuses is determined primarily by their common, probably maternal, environment, whereas insulin-like growth factor-I production is predominantly genetically regulated. Insulin-like growth factor-II and insulin-like growth factor binding protein-1 are regulated by both genetic and environmental factors. Of these growth-regulating factors, insulin-like growth factor binding protein-1 appears to be the best marker of intrauterine growth restriction in the individual case. (Am J Obstet Gynecol 1996;175:1180-8.)

Section snippets

Cord blood samples and placental examination

One hundred ten cord blood samples of twin pairs with gestational ages between 22 and 39 completed weeks were collected, centrifuged as rapidly as possible, and stored at -20° C. The gestational age, gender, birth weight, length, and head circumference of the neonates were recorded. Sixty-one twin pregnancies had occurred spontaneously, 46 were the result of an ovulation induction procedure (including in vitro fertilization), and for 3 pregnancies this information was missing. Fifty-eight of

RESULTS

Table I shows the correlation coefficients of birth weight and the cord serum concentrations of the growth-regulating factors between 105 twin members and 178 pairs of nonsibling singletons with the same gestational age and with birth weights appropriate for gestational age (10th to 90th percentile). After correction for gestational age and gender, IGF-I concentrations but not birth weight or C-peptide and IGF-II concentrations were correlated in singletons; the r of IGF-I concentrations

COMMENT

The data of this study produce evidence that serum insulin concentrations in the fetus are largely determined by the maternal environment, whereas serum IGF-I concentrations in the fetus are almost exclusively genetically determined (Fig. 2). IGF-II and IGFBP-1 concentrations appear to be determined by both their genetic constitution and the maternal environment.

The birth weights and lengths of the twins were primarily determined by their common environment in this study, which probably

Acknowledgements

We thank F.A. Van Assche, MD, and the physicians and midwives of the labor ward for taking the cord blood samples and I. Vandewal for help with the analyses.

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    From the Department of Obstetrics and Gynecology,athe Laboratorium voor Experimentele Geneeskunde en Endocrinologie,band the Center for Human Genetics,cKatholieke Universiteit Leuven.

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    Supported by a grant for Fundamental Clinical Research No. G. 3C06.93 and research grant No. 3.0157.95 from the Belgian Nationaal Fonds voor Wetenschappelijk Onderzoek (J.V.).

    Reprint requests: J. Verhaeghe, MD, Department of Obstetrics and Gynecology, U.Z. Gasthuisberg, 49 Herestraat, 3000 Leuven, Belgium.

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