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The long-term consequences of intra-uterine protein malnutrition for glucose metabolism

Published online by Cambridge University Press:  28 February 2007

Susan E. Ozanne  and
C. Nicholas Hales
Susan E. Ozanne
Affiliation:
Department of Clinical Biochemistry, University of Cambridge, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 2QR, UK
C. Nicholas Hales*
Affiliation:
Department of Clinical Biochemistry, University of Cambridge, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 2QR, UK
*
*Corresponding Author: Professor C. Nicholas Hales, fax +44 (0)1223 762563, email [email protected]
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Abstract

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Our initial observations, in epidemiological studies, linking indices of poor early (fetal and infant) growth to the subsequent development of poor glucose tolerance and the insulin resistance syndrome in adult life, have been confirmed in studies in a wide variety of populations around the world. These findings led us 5 years ago to propose the ‘thrifty phenotype’ hypothesis. Tests of this hypothesis in an animal model in which the pregnant and/or lactating rat dams are fed on an isoenergetic diet containing just under half the normal protein content are consistent with the ideas put forward. They have also allowed us to refine the hypothesis in the light of the new data as follows: (1) the growth of the fetus (and possibly infant) is quantitatively and qualitatively altered by its nutritional environment (which may include maternal diet-dependent changes in maternal hormones); (2) these changes serve to select between the growth rates of different tissues according to priorities which differ between males and females (nutritional thrift) and to alter organ function to constitute a thrifty offspring adapted to survival in poor nutritional circumstances (thrifty phenotype); (3) an individual so constituted suffers adverse consequences in adult life if he/she experiences good or supranormal nutrition; (4) both poor insulin secretion and insulin resistance can result from these adaptive processes; (5) the adverse consequences include loss of glucose tolerance and hypertension. The precise outcome of growth retardation during early life may vary according to the type and timing of the factors responsible for the retardation. It remains to be determined to what extent these potentially adverse effects can be delayed or prevented by a suitable postnatal diet. Experiments in animal models are largely consistent with the concepts proposed from human epidemiological studies. They show that the metabolism of the liver, muscle and adipose tissue may be programmed by maternal nutrition during gestation and lactation. The combination of early growth restriction and subsequent adult obesity reproduced in the rat are the main features of the insulin resistance syndrome.

Keywords

Fetal growthNon-insulin-dependent diabetes mellitusInsulin resistanceHypertension‘Thrifty phenotype’ hypothesis
Type
Symposium on ‘Functionality of nutrients and gene expression’
Information
Proceedings of the Nutrition Society , Volume 58 , Issue 3 , August 1999 , pp. 615 - 619
Copyright
Copyright © The Nutrition Society 1999

References

Barker, DJP, Hales, CN, Fall, CHD, Osmond, C, Phipps, K & Clark, PMS (1993) Type 2 (non-insulin-dependent) diabetes mellitus, hypertension and hyperlipidaemia (syndrome X): relation to reduced fetal growth. Diabetologia 36, 62–67.CrossRefGoogle ScholarPubMed
Brown, DC, Byrne, CD, Clark, PMS, Cox, BD, Day, NE, Hales, CN, Shackleton, JR, Wang, TWM & Williams, DRR (1991) Height and glucose tolerance in adult subjects. Diabetologia 34, 531–533.CrossRefGoogle ScholarPubMed
Burns, SP, Desai, M, Cohen, RD, Hales, CN, Iles, RA, Germain, JP, Going, TC & Bailey, RA (1997) Gluconeogenesis, glucose handling, and structural changes in livers of the adult offspring of rats partially deprived of protein during pregnancy and lactation. Journal of Clinical Investigation 100, 1768–1774.CrossRefGoogle ScholarPubMed
Desai, M, Byrne, CD, Zhang, J, Petry, CL, Lucas, A & Hales, CN (1996) Programming of hepatic insulin-sensitive enzymes in offspring of rat dams fed a protein restricted diet. American Journal of Physiology 272, G1083–G1090.Google Scholar
Hales, CN & Barker, DJP (1992) Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis. Diabetologia 35, 595–601.CrossRefGoogle ScholarPubMed
Hales, CN, Barker, DJP, Clark, PMS, Cox, LJ, Fall, C, Osmond, C & Winter, PD (1991) Fetal and infant growth and impaired glucose tolerance at age 64 years. British Medical Journal 303, 1019–1022.CrossRefGoogle Scholar
Hales, CN, Desai, M, Ozanne, SE & Crowther, NJ (1996) Fishing in the stream of diabetes: From measuring insulin to the control of fetal organogenesis. Biochemical Society Transactions 24, 341–350.CrossRefGoogle Scholar
Keller, U, Schnell, U, Sonnenberg, GE, Gerber, PP & Stauffacher, W (1983) Role of glucagon in enhancing ketone body production in ketotic diabetic man. Diabetes 323, 387–391.CrossRefGoogle Scholar
Kurosu, H, Machama, T, Okada, T, Yamamoto, T, Hoshino, S, Fukui, Y, Ui, M, Hazeki, O & Katada, T (1997) Heterodimeric phosphoinositide 3-kinase consisting of p85 and p110β is synergistically activated by the βγ subunits of G proteins and phosphotyrosol peptide. Journal of Biological Chemistry 272, 24252–24256.CrossRefGoogle ScholarPubMed
Law, CM, Gordon, GS, Shiell, AW, Barker, DJP & Hales, CN (1995) Thinness at birth and glucose tolerance in seven-year-old children. Diabetic Medicine 12, 24–29.CrossRefGoogle ScholarPubMed
O’Dea, K (1991) Cardiovascular risk factors in Australian aborigines. Clinical and Experimental Pharmacology and Physiology 18, 85–88.CrossRefGoogle ScholarPubMed
Okada, T, Kawano, Y, Sakakibara, T, Hazeki, O & Ui, M (1994) Essential role of phosphatidyl inositol 3-kinase in insulin-induced glucose transport and antilipolysis in rat adipocytes. Studies with a selective inhibitor wortmannin. Journal of Biological Chemistry 269, 3568–3573.CrossRefGoogle Scholar
Ozanne, SE, Nave, BT, Wang, CL, Shepherd, PR, Prins, J & Smith, GD (1997) Poor fetal nutrition causes long term changes in expression of insulin signalling components in adipocytes. American Journal of Physiology 273, E46–E51.Google ScholarPubMed
Ozanne, SE, Smith, GD, Tikerpae, J & Hales, CN (1996 a) Altered regulation of hepatic glucose output in the male offspring of protein-malnourished rat dams. American Journal of Physiology 270, E559–E564.Google ScholarPubMed
Ozanne, SE, Wang, CL, Coleman, N & Smith, GD (1996 b) Altered muscle insulin sensitivity in the male offspring of protein-malnourished rats. American Journal of Physiology 271, E1128–E1134.Google ScholarPubMed
Ozanne, SE, Wang, CL, Dorling, MW & Petry, CJ (1998) Selective resistance to insulin in adipocytes from early growth retarded rats. Diabetologica 41, Suppl. 1, A44:166.Google Scholar
Petry, CJ, Desai, M, Ozanne, SE & Hales, CN (1997 a) Early and late nutritional windows for diabetes susceptibility. Proceedings of the Nutrition Society 56, 233–242.CrossRefGoogle ScholarPubMed
Petry, CJ, Ozanne, SE, Wang, CL & Hales, CN (1997 b) Early protein restriction and obesity independently induced hypertension in year old rats. Clinical Science 93, 147–152.CrossRefGoogle ScholarPubMed
Phillips, DIW, Barker, DJP, Hales, CN, Hirst, S & Osmond, C (1994) Thinness at birth and insulin resistance in adult life. Diabetologia 37, 150–154.CrossRefGoogle ScholarPubMed
Phillips, DIW & Hales, CN (1996) The intrauterine environment and susceptibility to non-insulin dependent diabetes and the insulin resistance syndrome. In The Diabetes Annual, vol. 10, pp. 1–13[Marshall, SM, Home, PD and Rizza, RA, editors]. Amsterdam: Elsevier.Google Scholar
Poulsen, P, Vaag, AA, Kyvik, KO, Moller, Jensen D & Beck-Nielsen, H (1997) Low birth weight is associated with NIDDM in discordant monozygotic and dizygotic twin pairs. Diabetologia 40, 439–446.CrossRefGoogle ScholarPubMed
Ravelli, ACJ, van der Meulen, JHP, Michels, RPJ, Osmond, C, Barker, DJP, Hales, CN & Bleker, OP (1998) Glucose tolerance in adults after prenatal exposure to the Dutch famine. Lancet 351, 173–177.CrossRefGoogle Scholar
Shepherd, PR, Crowther, NJ, Desai, M, Hales, CN & Ozanne, SE (1997) Altered adipocyte properties in the offspring of protein malnourished rats. British Journal of Nutrition 78, 121–129.CrossRefGoogle ScholarPubMed
Shepherd, PR, Withers, DJ & Siddle, K (1998) Phosphoinositide 3-kinase: the key switch mechanism in insulin signalling. Biochemical Journal 333, 471–490.CrossRefGoogle ScholarPubMed
Snoeck, A, Remacle, C, Reusens, B & Hoet, JJ (1990) Effect of a low protein diet during pregnancy on the fetal rat endocrine pancreas. Biology of the Neonate 57, 107–118.CrossRefGoogle ScholarPubMed
Yajnik, CS, Fall, CHD, Vaidya, U, Pandit, AN, Bavdekar, A, Bhat, DS, Osmond, C, Hales, CN & Barker, DJP (1995) Fetal growth and glucose and insulin metabolism in four year old Indian children. Diabetic Medicine 12, 330–336.CrossRefGoogle ScholarPubMed
World Health Organization (1985) Diabetes mellitus. A Report of a WHO Study Group. Technical Report Series no. 844, pp. 20–25. Geneva: WHO.Google Scholar