The metabolic and cardiovascular complications associated with in-utero undernutrition have been identified during the past 10 years. Reduced fetal growth is independently associated with an increased risk of development of cardiovascular diseases, the insulin-resistance syndrome or one of its components (i.e., hypertension, dyslipidaemia, impaired glucose tolerance and type 2 diabetes). Insulin resistance appears to be a key component underlying these metabolic complications. Although the mechanism remains unclear, several pieces of evidence support an active role of adipose tissue in the emergence of insulin resistance (an abnormal growth pattern and repartition, hypersensitivity to catecholamines, regulation of leptin and adiponectin secretion and modulation of peroxisome proliferator-activated receptor γ). Among individuals born SGA, those who are more at risk of gaining excess adiposity are those who are thin at birth following a period of fetal growth restriction. This period of undernutrition is followed by a neonatal period of catch-up growth and renutrition. This pattern induces important modifications in adipose tissue, with long-term consequences, among which is a high risk of early development of insulin resistance. Not all individuals born SGA will show such modifications in adipose tissue, meaning that not all of those born SGA are at risk of insulin resistance and diabetes. From a broader point of view, several hypotheses have been proposed over the past 10 years to explain this unexpected association between being born SGA and the later development of disease. Each of them points to a detrimental fetal environment, to a genetic susceptibility or to interactions between these two components playing a critical role in this context. Although not confirmed, the hypothesis suggesting that this association could be the consequence of genetic/environmental interactions remains the most attractive.

Keywords:
Adipose tissue, Catch-up growth, Insulin resistance, Intrauterine growth retardation, Type 2 diabetes
1.
Barker DJ, Winter PD, Osmond C, Margetts B, Simmonds SJ: Weight in infancy and death from ischaemic heart disease. Lancet 1989;2:577–580.
2.
Hales CN, Barker DJ, Clark PM, Cox LJ, Fall C, Osmond C, Winter PD: Fetal and infant growth and impaired glucose tolerance at age 64. BMJ 1991;303:1019–1022.
3.
Lithell HO, McKeigue PM, Berglund L, Mohsen R, Lithell UB, Leon DA: Relation of size at birth to non-insulin dependent diabetes and insulin concentrations in men aged 50–60 years. BMJ 1996;312:406–410.
4.
McCance DR, Pettitt DJ, Hanson RL, Jacobsson LT, Knowler WC, Bennett PH: Birth weight and non-insulin dependent diabetes: thrifty genotype, thrifty phenotype, or surviving small baby genotype? BMJ 1994;308:942–945.
5.
Hales CN, Desai M, Ozanne SE: The Thrifty Phenotype hypothesis: how does it look after 5 years? Diabet Med 1997;14:189–195.
6.
Phillips DI, Barker DJ, Hales CN, Hirst S, Osmond C: Thinness at birth and insulin resistance in adult life. Diabetologia 1994;37:150–154.
7.
Jaquet D, Gaboriau A, Czernichow P, Levy-Marchal C: Insulin resistance early in adulthood in subjects born with intrauterine growth retardation. J Clin Endocrinol Metab 2000;85:1401–1406.
8.
Flanagan DE, Moore VM, Godsland IF, Cockington RA, Robinson JS, Phillips DI: Fetal growth and the physiological control of glucose tolerance in adults: a minimal model analysis. Am J Physiol Endocrinol Metab 2000;278:E700–E706.
9.
Bavdekar A, Yajnik CS, Fall CH, Bapat S, Pandit AN, Deshpande V, Bhave S, Kellingray SD, Joglekar C: Insulin resistance syndrome in 8-year-old Indian children: small at birth, big at 8 years, or both? Diabetes 1999;48:2422–2429.
10.
Beringue F, Blondeau B, Castellotti MC, Breant B, Czernichow P, Polak M: Endocrine pancreas development in growth-retarded human fetuses. Diabetes 2002;51:385–391.
11.
Phipps K, Barker DJ, Hales CN, Fall CH, Osmond C, Clark PM: Fetal growth and impaired glucose tolerance in men and women. Diabetologia 1993;36:225–228.
12.
Hofman PL, Cutfield WS, Robinson EM, Bergman RN, Menon RK, Sperling MA, Gluckman PD: Insulin resistance in short children with intrauterine growth retardation. J Clin Endocrinol Metab 1997;82:402–406.
13.
Veening MA, Van Weissenbruch MM, Delemarre-Van De Waal HA: Glucose tolerance, insulin sensitivity, and insulin secretion in children born small for gestational age. J Clin Endocrinol Metab 2002;87:4657–4661.
14.
Jaquet D, Deghmoun S, Chevenne D, Collin D, Czernichow P, Levy-Marchal C: Dynamic change in adiposity from fetal to postnatal life is involved in the metabolic syndrome associated with reduced fetal growth. Diabetologia 2005;48:849–855.
15.
Léger J, Levy-Marchal C, Bloch J, Pinet A, Chevenne D, Porquet D, Collin D, Czerni chow P: Reduced final height and indications for insulin resistance in 20 year olds born small for gestational age: regional cohort study. BMJ 1997;315:341–347.
16.
Soto N, Bazaes RA, Pena V, Salazar T, Avila A, Iniguez G, Ong KK, Dunger DB, Mericq MV: Insulin sensitivity and secretion are related to catch-up growth in small-for-gestational-age infants at age 1 year: results from a prospective cohort. J Clin Endocrinol Metab 2003;88:3645–3650.
17.
Yajnik CS, Fall CH, Vaidya U, Pandit AN, Bavdekar A, Bhat DS, Osmond C, Hales CN, Barker DJ: Fetal growth and glucose and insulin metabolism in four-year-old Indian children. Diabet Med 1995;12:330–336.
18.
Yajnik CS, Lubree HG, Rege SS, Naik SS, Deshpande JA, Deshpande SS, Joglekar CV, Yudkin JS: Adiposity and hyperinsulinemia in Indians are present at birth. J Clin Endocrinol Metab 2002;87:5575–5580.
19.
Whincup PH, Cook DG, Adshead F, Taylor SJ, Walker M, Papacosta O, Alberti KG: Childhood size is more strongly related than size at birth to glucose and insulin levels in 10–11-year-old children. Diabetologia 1997;40:319–326.
20.
Barker DJ, Hales CN, Fall CH, Osmond C, Phipps K, Clark PM: Type 2 (non-insulin-dependent) diabetes mellitus, hypertension and hyperlipidaemia (syndrome X): relation to reduced fetal growth. Diabetologia 1993;36:62–67.
21.
Valdez R, Athens MA, Thompson GH, Bradshaw BS, Stern MP: Birthweight and adult health outcomes in a biethnic population in the USA. Diabetologia 1994;37:624–631.
22.
Dunger DB, Ong KK, Huxtable SJ, Sherriff A, Woods KA, Ahmed ML, Golding J, Pembrey ME, Ring S, Bennett ST, Todd JA: Association of the INS VNTR with size at birth. ALSPAC Study Team. Avon Longitudinal Study of Pregnancy and Childhood. Nat Genet 1998;19:98–100.
23.
Lindsay RS, Hanson RL, Wiedrich C, Knowler WC, Bennett PH, Baier LJ: The insulin gene variable number tandem repeat class I/III polymorphism is in linkage disequilibrium with birth weight but not Type 2 diabetes in the Pima population. Diabetes 2003;52:187–193.
24.
Eriksson JG, Forsen T, Tuomilehto J, Winter PD, Osmond C, Barker DJ: Catch-up growth in childhood and death from coronary heart disease: longitudinal study. BMJ 1999;318:427–431.
25.
Dulloo AG: Regulation of fat storage via suppressed thermogenesis: a thrifty phenotype that predisposes individuals with catch-up growth to insulin resistance and obesity. Horm Res 2006;65(suppl 3):88–95.
26.
Lapillonne A, Braillon P, Claris O, Chatelain PG, Delmas PD, Salle BL: Body composition in appropriate and in small for gestational age infants. Acta Paediatr 1997;86:196–200.
27.
Petersen S, Gotfredsen A, Knudsen FU: Lean body mass in small for gestational age and appropriate for gestational age infants. J Pediatr 1988;113:886–889.
28.
Ong K: Size at birth, postnatal growth and risk of obesity. Horm Res 2006;65(suppl 3):64–68.
29.
Jaquet D, Gaboriau A, Czernichow P, Levy-Marchal C: Relatively low serum leptin levels in adults born with intra-uterine growth retardation. Int J Obes Relat Metab Disord 2001;25:491–495.
30.
Boiko J, Jaquet D, Chevenne D, Rigal O, Czernichow P, Levy-Marchal C: In situ lipolytic regulation in subjects born small for gestational age. Int J Obes Relat Metab Disord 2005;29:565–570.
31.
Jaquet D, Léger J, Czernichow P, Levy-Marchal C: The effect of in-utero undernutrition on the insulin resistance syndrome. Curr Diab Rep 2002;2:77–82.
© 2006 S. Karger AG, Basel
2006
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.