Skip to main content
SpringerLink
Log in

Low Birth Weight in the Pathophysiology of Type 2 Diabetes: A Focus on Metabolic and Epigenetic Aspects

  • Chapter
  • First Online:
Handbook of Growth and Growth Monitoring in Health and Disease

  • 240 Accesses

Abstract

The prevalence of diabetes is increasing worldwide and constitutes a major threat to global health. A number of novel type 2 diabetes susceptibility genes have been identified in recent genome-wide association studies (GWA). Nevertheless only up to 10% of the risk of type 2 diabetes can be explained by these genes, placing the focus on non-genetic environmental factors. It is well recognized that an adverse intrauterine environment leads to a compensatory programming of fetal metabolism that may be beneficial for short-term survival, but can be detrimental in the long term. This phenomenon is particularly detrimental if the prenatal nutrient restriction is followed by a postnatal nutrient abundance, leading to rapid catch-up growth and increased risk of later development of obesity and type 2 diabetes, including the metabolic syndrome. Many defects present in patients with overt type 2 diabetes are detectable at the age around 20 years in lean and otherwise healthy young men born with a low birth weight, strongly suggestive of an important role of intrauterine programming in the etiology and pathophysiology of type 2 diabetes. In this review we will focus on the complicated physiological and molecular mechanisms as well as abnormalities of metabolism linking low birth weight (LBW) with an increased risk of type 2 diabetes several decades later in life.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 429.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 549.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 549.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

BMI:

Body mass index

BPA:

Bisphenol A

CpG:

Cytidine–guanosine

DAG:

Diacylglycerol

DEXA:

Dual-energy X-ray absorptiometry

DOHaD:

Developmental Origins of Health and Disease

FFA:

Free fatty acids

GIP:

Glucose-dependent insulinotropic polypeptide

GLP-1:

Glucagon-like peptide-1

GLUT4:

Glucose transporter-4

GWA:

Genome-wide association

HPA:

Hypothalamic–pituitary–adrenal

IGF:

Insulin-like growth factor

IGT:

Impaired glucose tolerance

IMCL:

Intramyocellular lipids

IRS-1:

Insulin receptor substrate-1

IUGR:

Intrauterine growth restriction

LBW:

Low birth weight

NAFLD:

Nonalcoholic fatty liver disease

NBW:

Normal birth weight

OXPHOS:

Oxidative phosphorylation

PCB:

Polychlorinated biphenyls

PI3K:

Phophatidylinositol 3-kinase

PKCζ:

Protein kinase C zeta

31P-MRS:

31Phosphorus magnetic resonance spectroscopy

PPARGC1A:

Peroxisome proliferator-activated receptor-γ coactivator-1α

TCA:

The citric acid cycle

TG:

Triglycerides

References

  • Arias E, MacDorman MF, Strobino DM, Guyer B. Annual summary of vital statistics–2002. Pediatrics. 2003;112:1215–30.

    Article  PubMed  Google Scholar 

  • Barker DJ, Godfrey KM, Fall C, Osmond C, Winter PD, Shaheen SO. Relation of birth weight and childhood respiratory infection to adult lung function and death from chronic obstructive airways disease. BMJ 1991;303:671–5.

    Article  PubMed  CAS  Google Scholar 

  • 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;36:62–7.

    Article  PubMed  CAS  Google Scholar 

  • Barrès R, Osler ME, Yan J, Rune A, Fritz T, Caidahl K, Krook A, Zierath JR. Non-CpG methylation of the PGC-1[alpha] promoter through DNMT3B controls mitochondrial density. Cell Metab. 2009;10:189–98.

    Article  PubMed  Google Scholar 

  • Brøns C, Jacobsen S, Nilsson E, Rönn T, Jensen CB, Storgaard H, Poulsen P, Groop L, Ling C, Astrup A, Vaag A. DNA methylation and gene expression of PPARGC1A in human muscle is influenced by high-fat overfeeding in a birth weight dependent manner. J Clin Endocrinol Metab. 2010;95:3048–56.

    Article  PubMed  Google Scholar 

  • Brøns C, Jensen CB, Storgaard H, Alibegovic A, Jacobsen S, Nilsson E, Astrup A, Quistorff B, Vaag A. Mitochondrial function in skeletal muscle is normal and unrelated to insulin action in young men born with low birth weight. J Clin Endocrinol Metab. 2008;93:3885–92.

    Article  PubMed  Google Scholar 

  • Brøns C, Jensen CB, Storgaard H, Hiscock NJ, White A, Appel JS, Jacobsen S, Nilsson E, Larsen CM, Astrup A, Quistorff B, Vaag A. Impact of short-term high-fat feeding on glucose and insulin metabolism in young healthy men. J. Physiol. 2009;587:2387–97.

    Article  PubMed  Google Scholar 

  • Buhl ES, Neschen S, Yonemitsu S, Rossbacher J, Zhang D, Morino K, Flyvbjerg A, Perret P, Samuel V, Kim J, Cline GW, Petersen KF. Increased hypothalamic-pituitary-adrenal axis activity and hepatic insulin resistance in low-birth-weight rats. Am J Physiol Endocrinol Metab. 2007;293:E1451–8.

    Article  PubMed  CAS  Google Scholar 

  • Burns SP. Gluconeogenesis, glucose handling, and structural changes in livers of the adult offspring of rats partially deprived of protein during pregnancy and lactation. J Clin Investig. 1997;100:1768–74.

    Article  PubMed  CAS  Google Scholar 

  • Carlsson S, Persson PG, Alvarsson M, Efendic S, Norman A, Svanstrom L, Ostenson CG, Grill V. Low birth weight, family history of diabetes, and glucose intolerance in Swedish middle-aged men. Diab Care. 1999;22:1043–7.

    Article  CAS  Google Scholar 

  • Cooper C, Harvey N, Cole Z, Hanson M, Dennison E. Developmental origins of osteoporosis: the role of maternal nutrition. Adv Exp Med Biol. 2009;646:31–9.

    Article  PubMed  Google Scholar 

  • de Rooij SR, Painter RC, Phillips DIW, Osmond C, Michels RPJ, Bossuyt PMM, Bleker OP, Roseboom TJ. Hypothalamic-pituitary-adrenal axis activity in adults who were prenatally exposed to the Dutch famine. Eur J Endocrinol. 2006;155:153–60.

    Article  PubMed  Google Scholar 

  • Defronzo RA. Dysfunctional fat cells, lipotoxicity and type 2 diabetes. Int J Clin Pract. 2004;58:9–21.

    Article  Google Scholar 

  • DeFronzo RA. Pathogenesis of type 2 diabetes mellitus. Med Clin North Am. 2004;88:787–835.

    Article  PubMed  CAS  Google Scholar 

  • Defronzo RA, Ferrannini E, Simonson DC. Fasting hyperglycemia in non-insulin-dependent diabetes mellitus: contributions of excessive hepatic glucose production and impaired tissue glucose uptake. Metabolism. 1989;38:387–95.

    Article  PubMed  CAS  Google Scholar 

  • Dolinoy DC, Weidman JR, Jirtle RL. Epigenetic gene regulation: linking early developmental environment to adult disease. Reprod Toxicol. 2007;23:297–307.

    Article  PubMed  CAS  Google Scholar 

  • Esteller M. Epigenetics in Cancer. N Engl J Med. 2008;358:1148–59.

    Article  PubMed  CAS  Google Scholar 

  • Fraga MF, Ballestar E, Paz MF, Ropero S, Setien F, Ballestar ML, Heine-Suner D, Cigudosa JC, Urioste M, Benitez J, Boix-Chornet M, Sanchez-Aguilera A, Ling C, Carlsson E, Poulsen P, Vaag A, Stephan Z, Spector TD, Wu YZ, Plass C, Esteller M. Epigenetic differences arise during the lifetime of monozygotic twins. Proc Natl Acad Sci USA. 2005;102:10604–9.

    Article  PubMed  CAS  Google Scholar 

  • Gemma C, Sookoian S, Alvarinas J, Garcia SI, Quintana L, Kanevsky D, Gonzalez CD, Pirola CJ. Maternal pregestational BMI is associated with methylation of the PPARGC1A promoter in newborns. Obesity Res. 2009;17:1032–9.

    Article  CAS  Google Scholar 

  • Hales CN, Barker DJP. Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis. Diabetologia. 1992;35:595–601.

    Article  PubMed  CAS  Google Scholar 

  • Hales CN, Barker DJP. The thrifty phenotype hypothesis: type 2 diabetes. Br Med Bull. 2001;60:5–20.

    Article  PubMed  CAS  Google Scholar 

  • 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;303:1019–22.

    Article  PubMed  CAS  Google Scholar 

  • Hanson MA, Gluckman PD. Developmental origins of health and disease: new insights. Basic Clin Pharmacol Toxicol. 2008;102:90–93.

    Article  PubMed  CAS  Google Scholar 

  • Heijmans BT, Tobi EW, Stein AD, Putter H, Blauw GJ, Susser ES, Slagboom PE, Lumey LH. Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc Natl Acad Sci USA 2008;105:17046–9.

    Article  PubMed  CAS  Google Scholar 

  • Hermann TS, Rask-Madsen C, Ihlemann N, Dominguez H, Jensen CB, Storgaard H, Vaag AA, Kober L, Torp-Pedersen C. Normal insulin-stimulated endothelial function and impaired insulin-stimulated muscle glucose uptake in young adults with low birth weight. J Clin Endocrinol Metab. 2003;88:1252–7.

    Article  PubMed  CAS  Google Scholar 

  • Højlund K, Beck-Nielsen H. Impaired glycogen synthase activity and mitochondrial dysfunction in skeletal muscle: markers or mediators of insulin resistance in type 2 diabetes? Curr Diabetes Rev. 2006;2:375–95.

    PubMed  Google Scholar 

  • Isganaitis E, Jimenez-Chillaron J, Woo M, Chow A, DeCoste J, Vokes M, Liu M, Kasif S, Zavacki AM, Leshan RL, Myers MG, Patti ME. Accelerated postnatal growth increases lipogenic gene expression and adipocyte size in low-birth weight mice. Diabetes. 2009;58:1192–200.

    Article  PubMed  CAS  Google Scholar 

  • Jensen CB, Martin-Gronert MS, Storgaard H, Madsbad S, Vaag A, Ozanne SE. Altered PI3-kinase/Akt signalling in skeletal muscle of young men with low birth weight. PLoS One 2008;3:e3738.

    Article  PubMed  Google Scholar 

  • Jensen CB, Storgaard H, Dela F, Holst JJ, Madsbad S, Vaag AA. Early Differential defects of insulin secretion and action in 19-year-old caucasian men who had low birth weight. Diabetes. 2002;51:1271–80.

    Article  PubMed  CAS  Google Scholar 

  • Jensen CB, Storgaard H, Madsbad S, Richter EA, Vaag AA. Altered skeletal muscle fiber composition and size precede whole-body insulin resistance in young men with low birth weight. J Clin Endocrinol Metab. 2007;92:1530–34.

    Article  PubMed  CAS  Google Scholar 

  • Kahn SE. The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of Type 2 diabetes. Diabetologia. 2003;46:3–19.

    Article  PubMed  CAS  Google Scholar 

  • Kim JK, Youn JH. Prolonged suppression of glucose metabolism causes insulin resistance in rat skeletal muscle. Am J Physiol. 1997;272:E288–96.

    PubMed  CAS  Google Scholar 

  • King H, Aubert RE, Herman WH. Global burden of diabetes, 1995–2025: prevalence, numerical estimates, and projections. Diab Care. 1998;21:1414–31.

    Article  CAS  Google Scholar 

  • Konishi K, Sasaki S, Kato S, Ban S, Washino N, Kajiwara J, Todaka T, Hirakawa H, Hori T, Yasutake D, Kishi R. Prenatal exposure to PCDDs/PCDFs and dioxin-like PCBs in relation to birth weight. Environ Res. 2009;109:906–13.

    Article  PubMed  CAS  Google Scholar 

  • Leunissen RWJ, Oosterbeek P, Hol LKM, Hellingman AA, Stijnen T, Hokken-Koelega ACS. Fat mass accumulation during childhood determines insulin sensitivity in early adulthood. J Clin Endocrinol Metab. 2008;93:445–51.

    Article  PubMed  CAS  Google Scholar 

  • Ling C, Del Guerra S, Lupi R, Rönn T, Granhall C, Luthman H, Masiello P, Marchetti P, Groop L, Del Prato S. Epigenetic regulation of PPARGC1A in human type 2 diabetic islets and effect on insulin secretion. Diabetologia. 2008;51:615–22.

    Article  PubMed  CAS  Google Scholar 

  • Ling C, Poulsen P, Carlsson E, Ridderstråle M, Almgren P, Wojtaszewski J, Beck-Nielsen H, Groop L, Vaag A. Multiple environmental and genetic factors influence skeletal muscle PGC-1alpha and PGC-1beta gene expression in twins. J Clin Invest. 2004;114:1518–26.

    PubMed  CAS  Google Scholar 

  • McGarry JD. Banting lecture 2001: dysregulation of fatty acid metabolism in the etiology of type 2 diabetes. Diabetes. 2002;51:7–18.

    Article  PubMed  CAS  Google Scholar 

  • Meas T, Deghmoun S, Armoogum P, Alberti C, Levy-Marchal C. Consequences of being born small for gestational age on body composition: an 8-year follow-up study. J Clin Endocrinol Metab. 2008;93:3804–9.

    Article  PubMed  CAS  Google Scholar 

  • Mootha VK, Lindgren CM, Eriksson KF, Subramanian A, Sihag S, Lehar J, Puigserver P, Carlsson E, Ridderstrale M, Laurila E, Houstis N, Daly MJ, Patterson N, Mesirov JP, Golub TR, Tamayo P, Spiegelman B, Lander ES, Hirschhorn JN, Altshuler D, Groop LC. PGC-1á-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet. 2003;34:267–73.

    Article  PubMed  CAS  Google Scholar 

  • Morino K, Petersen KF, Shulman GI. Molecular mechanisms of insulin resistance in humans and their potential links with mitochondrial dysfunction. Diabetes. 2006;55 Suppl 2:S9–15.

    Article  PubMed  CAS  Google Scholar 

  • Morino K, Petersen KF, Dufour S, Befroy D, Frattini J, Shatzkes N, Neschen S, White MF, Bilz S, Sono S, Pypaert M, Shulman GI. Reduced mitochondrial density and increased IRS-1 serine phosphorylation in muscle of insulin-resistant offspring of type 2 diabetic parents. J Clin Invest. 2005;115:3587–93.

    Article  PubMed  CAS  Google Scholar 

  • Ozanne S, Jensen C, Tingey K, Martin-Gronert M, Grunnet L, Brons C, Storgaard H, Vaag A. Decreased protein levels of key insulin signalling molecules in adipose tissue from young men with a low birthweight Г⍰Çô potential link to increased risk of diabetes? Diabetologia. 2006;49:2993–9.

    Article  PubMed  CAS  Google Scholar 

  • Ozanne SE, Dorling MW, Wang CL, Nave BT. Impaired PI 3-kinase activation in adipocytes from early growth-restricted male rats. Am J Physiol Endocrinol Metab. 2001;280:E534–9.

    PubMed  CAS  Google Scholar 

  • Ozanne SE, Jensen CB, Tingey KJ, Storgaard H, Madsbad S, Vaag AA. Low birthweight is associated with specific changes in muscle insulin-signalling protein expression. Diabetologia. 2005;48:547–52.

    Article  PubMed  CAS  Google Scholar 

  • Ozanne SE, Nave BT, Wang CL, Shepherd PR, Prins J, Smith GD. Poor fetal nutrition causes long-term changes in expression of insulin signaling components in adipocytes. Am J Physiol Endocrinol Metab. 1997;273:E46–51.

    CAS  Google Scholar 

  • Ozanne SE, Wang CL, Coleman N, Smith GD. Altered muscle insulin sensitivity in the male offspring of protein-malnourished rats. Am J Physiol Endocrinol Metab. 1996;271:E1128–34.

    CAS  Google Scholar 

  • Ozanne SE, Wang CL, Dorling MW, Petry CJ. Dissection of the metabolic actions of insulin in adipocytes from early growth-retarded male rats. J Endocrinol. 1999;162:313–9.

    Article  PubMed  CAS  Google Scholar 

  • Painter RC, de Rooij SR, Bossuyt PM, Simmers TA, Osmond C, Barker DJ, Bleker OP, Roseboom TJ. Early onset of coronary artery disease after prenatal exposure to the Dutch famine. Am J Clin Nutr. 2006;84:322–7.

    PubMed  CAS  Google Scholar 

  • Park JH, Stoffers DA, Nicholls RD, Simmons RA. Development of type 2 diabetes following intrauterine growth retardation in rats is associated with progressive epigenetic silencing of Pdx1. J Clin Invest. 2008;118:2316–24.

    Article  PubMed  CAS  Google Scholar 

  • Park KS, Kim SK, Kim MS, Cho EY, Lee JH, Lee KU, Pak YK, Lee HK. Fetal and early postnatal protein malnutrition cause long-term changes in rat liver and muscle mitochondria. J Nutr. 2003;133:3085–90.

    PubMed  CAS  Google Scholar 

  • Park YW, Chang Y, Sung KC, Ryu S, Sung E, Kim WS. The sequential changes in the fasting plasma glucose levels within normoglycemic range predict type 2 diabetes in healthy, young men. Diab Res Clin Pract. 2006;73:329–35.

    Article  CAS  Google Scholar 

  • Patandin S, Koopman-Esseboom C, De Ridder MAJ, Weisglas-Kuperus N, Sauer PJJ. Effects of environmental exposure to polychlorinated biphenyls and dioxins on birth size and growth in Dutch children. Pediatr Res. 1998;44:538–45.

    Article  PubMed  CAS  Google Scholar 

  • Patti ME, Butte AJ, Crunkhorn S, Cusi K, Berria R, Kashyap S, Miyazaki Y, Kohane I, Costello M, Saccone R, Landaker EJ, Goldfine AB, Mun E, DeFronzo R, Finlayson J, Kahn CR, Mandarino LJ. Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: potential role of PGC1 and NRF1. Proc Natl Acad Sci USA. 2003;100:8466–71.

    Article  PubMed  CAS  Google Scholar 

  • Petersen KF, Dufour S, Befroy D, Garcia R, Shulman GI. Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes. N Engl J Med. 2004;350:664–71.

    Article  PubMed  CAS  Google Scholar 

  • Peterside IE, Selak MA, Simmons RA. Impaired oxidative phosphorylation in hepatic mitochondria in growth-retarded rats. Am J Physiol Endocrinol Metab. 2003;285:E1258–66.

    PubMed  CAS  Google Scholar 

  • Phillips DI, Hirst S, Clark PM, Hales CN, Osmond C. Fetal growth and insulin secretion in adult life. Diabetologia. 1994;37:592–6.

    Article  PubMed  CAS  Google Scholar 

  • Poulsen P, Vaag A. The intrauterine environment as reflected by birth size and twin and zygosity status influences insulin action and intracellular glucose metabolism in an age- or time-dependent manner. Diabetes. 2006;55:1819–25.

    Article  PubMed  CAS  Google Scholar 

  • Poulsen P, Levin K, Beck-Nielsen H, Vaag A. Age-dependent impact of zygosity and birth weight on insulin secretion and insulin action in twins. Diabetologia. 2002;45:1649–57.

    Article  PubMed  CAS  Google Scholar 

  • Randle PJ, Kerbey AL, Espinal J. Mechanisms decreasing glucose oxidation in diabetes and starvation: role of lipid fuels and hormones. Diab Metab Rev. 1988;4:623–38.

    Article  CAS  Google Scholar 

  • Rasmussen EL, Malis C, Jensen CB, Jensen JE, Storgaard H, Poulsen P, Pilgaard K, Schou JH, Madsbad S, Astrup A, Vaag A. Altered fat tissue distribution in young adult men who had low birth weight. Diab Care. 2005;28:151–3.

    Article  Google Scholar 

  • Ravelli AC, van der Meulen JH, Osmond C, Barker DJ, Bleker OP. Infant feeding and adult glucose tolerance, lipid profile, blood pressure, and obesity. Arch Dis Child. 2000;82:248–52.

    Article  PubMed  CAS  Google Scholar 

  • Ravelli ACJ, van der Meulen JHP, Michels RPJ, Osmond C, Barker DJP, Hales CN, Bleker OP. Glucose tolerance in adults after prenatal exposure to famine. Lancet. 1998;351:173–7.

    Article  PubMed  CAS  Google Scholar 

  • Ravelli G, Stein ZA, Susser MW. Obesity in young men after famine exposure in utero and early infancy. N Engl J Med. 1976;295:349–53.

    Article  PubMed  CAS  Google Scholar 

  • Raychaudhuri N, Raychaudhuri S, Thamotharan M, Devaskar SU. Histone code modifications repress glucose transporter 4 expression in the intrauterine growth-restricted offspring. J Biol Chem. 2008;283:13611–26.

    Article  PubMed  CAS  Google Scholar 

  • Ritov VB, Menshikova EV, He J, Ferrell RE, Goodpaster BH, Kelley DE. Deficiency of subsarcolemmal mitochondria in obesity and type 2 diabetes. Diabetes. 2005;54:8–14.

    Article  PubMed  CAS  Google Scholar 

  • Rosmond R, Bjørntorp P. The hypothalamic-pituitary-adrenal axis activity as a predictor of cardiovascular disease, type 2 diabetes and stroke. J Intern Med. 2000;247:188–97.

    Article  PubMed  CAS  Google Scholar 

  • Samuel VT, Liu ZX, Qu X, Elder BD, Bilz S, Befroy D, Romanelli AJ, Shulman GI. Mechanism of hepatic insulin resistance in non-alcoholic fatty liver disease. J Biol Chem. 2004;279:32345–53.

    Article  PubMed  CAS  Google Scholar 

  • Sanyal AJ, Campbell-Sargent C, Mirshahi F, Rizzo WB, Contos MJ, Sterling RK, Luketic VA, Shiffman ML, Clore JN. Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities. Gastroenterology. 2001;120:1183–92.

    Article  PubMed  CAS  Google Scholar 

  • Schlotz W, Phillips DIW. Fetal origins of mental health: evidence and mechanisms. Brain Behav Immun. 2009;23:905–16.

    Article  PubMed  Google Scholar 

  • Schou JH, Pilgaard K, Vilsboll T, Jensen CB, Deacon CF, Holst JJ, Volund A, Madsbad S, Vaag AA. Normal secretion and action of the gut incretin hormones glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide in young men with low birth weight. J Clin Endocrinol Metab. 2005;90:4912–19.

    Article  PubMed  CAS  Google Scholar 

  • Simmons RA, Templeton LJ, Gertz SJ. Intrauterine growth retardation leads to the development of type 2 diabetes in the rat. Diabetes. 2001;50:2279–86.

    Article  PubMed  CAS  Google Scholar 

  • Singhal A, Fewtrell M, Cole TJ, Lucas A. Low nutrient intake and early growth for later insulin resistance in adolescents born preterm. Lancet. 2003;361:1089–97.

    Article  PubMed  CAS  Google Scholar 

  • Taylor DJ, Thompson CH, Kemp GJ, Barnes PRJ, Sanderson AL, Radda GK, Phillips DIW. A relationship between impaired fetal growth and reduced muscle glycolysis revealed by 31P magnetic resonance spectroscopy. Diabetologia. 1995;38:1205–12.

    Article  PubMed  CAS  Google Scholar 

  • Tobi EW, Lumey LH, Talens RP, Kremer D, Putter H, Stein AD, Slagboom PE, Heijmans BT. DNA methylation differences after exposure to prenatal famine are common and timing- and sex-specific. Hum Mol Genet. 2009;18:4046–53.

    Article  PubMed  CAS  Google Scholar 

  • Vaag AA, Holst JJ, Volund A, Beck-Nielsen H. Gut incretin hormones in identical twins discordant for non-insulin-dependent diabetes mellitus (NIDDM)–evidence for decreased glucagon-like peptide 1 secretion during oral glucose ingestion in NIDDM twins. Eur J Endocrinol. 1996;135:425–32.

    Article  PubMed  CAS  Google Scholar 

  • Vilsbøll T, Krarup T, Deacon CF, Madsbad S, Holst JJ. Reduced postprandial concentrations of intact biologically active glucagon-like peptide 1 in type 2 diabetic patients. Diabetes. 2001;50:609–13.

    Article  PubMed  Google Scholar 

  • Whincup PH, Kaye SJ, Owen CG, Huxley R, Cook DG, Anazawa S, Barrett-Connor E, Bhargava SK, Birgisdottir BE, Carlsson S, de Rooij SR, Dyck RF, Eriksson JG, Falkner B, Fall C, Forsen T, Grill V, Gudnason V, Hulman S, Hypponen E, Jeffreys M, Lawlor DA, Leon DA, Minami J, Mishra G, Osmond C, Power C, Rich-Edwards JW, Roseboom TJ, Sachdev HS, Syddall H, Thorsdottir I, Vanhala M, Wadsworth M, Yarbrough DE. Birth weight and risk of type 2 diabetes: a systematic review. JAMA 2008;300:2886–97.

    Article  PubMed  CAS  Google Scholar 

  • Wilson MR. The effect of maternal protein deficiency during pregnancy and lactation on glucose tolerance and pancreatic islet function in adult rat offspring. J Endocrinol. 1997;154:177–85.

    Article  PubMed  CAS  Google Scholar 

  • Yajnik C, Deshmukh U. Maternal nutrition, intrauterine programming and consequential risks in the offspring. Rev Endocr Metab Disord. 2008;9:203–11.

    Article  PubMed  CAS  Google Scholar 

  • Zandi-Nejad K, Luyckx VA, Brenner BM. Adult hypertension and kidney disease: the role of fetal programming. Hypertension. 2006;47:502–8.

    Article  PubMed  CAS  Google Scholar 

  • Zeggini E, Scott LJ, Saxena R, Voight BF, Marchini JL, Hu T, de Bakker PI, Abecasis GR, Almgren P, Andersen G, Ardlie K, Bostrom KB, Bergman RN, Bonnycastle LL, Borch-Johnsen K, Burtt NP, Chen H, Chines PS, Daly MJ, Deodhar P, Ding CJ, Doney ASF, Duren WL, Elliott KS, Erdos MR, Frayling TM, Freathy RM, Gianniny L, Grallert H, Grarup N, Groves CJ, Guiducci C, Hansen T, Herder C, Hitman GA, Hughes TE, Isomaa B, Jackson AU, Jorgensen T, Kong A, Kubalanza K, Kuruvilla FG, Kuusisto J, Langenberg C, Lango H, Lauritzen T, Li Y, Lindgren CM, Lyssenko V, Marvelle AF, Meisinger C, Midthjell K, Mohlke KL, Morken MA, Morris AD, Narisu N, Nilsson P, Owen KR, Palmer CN, Payne F, Perry JRB, Pettersen E, Platou C, Prokopenko I, Qi L, Qin L, Rayner NW, Rees M, Roix JJ, Sandbaek A, Shields B, Sjogren M, Steinthorsdottir V, Stringham HM, Swift AJ, Thorleifsson G, Thorsteinsdottir U, Timpson NJ, Tuomi T, Tuomilehto J, Walker M, Watanabe RM, Weedon MN, Willer CJ, Illig T, Hveem K, Hu FB, Laakso M, Stefansson K, Pedersen O, Wareham NJ, Barroso I, Hattersley AT, Collins FS, Groop L, McCarthy MI, Boehnke M, Altshuler D. Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes. Nat Genet. 2008;40:638–45.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Steno Diabetes Center, 2820, Gentofte, Denmark

    Charlotte Brøns & Allan Vaag

Authors
  1. Charlotte Brøns
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Allan Vaag
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Allan Vaag .

Editor information

Editors and Affiliations

  1. Dept. Nutrition & Dietetics, King's College, Stamford St. 150, London, SE1 9NH, United Kingdom

    Victor R. Preedy

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Brøns, C., Vaag, A. (2012). Low Birth Weight in the Pathophysiology of Type 2 Diabetes: A Focus on Metabolic and Epigenetic Aspects. In: Preedy, V. (eds) Handbook of Growth and Growth Monitoring in Health and Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1795-9_20

Download citation

  • DOI: https://doi.org/10.1007/978-1-4419-1795-9_20

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4419-1794-2

  • Online ISBN: 978-1-4419-1795-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation