The thrifty phenotype hypothesis revisited

A A Vaag, L G Grunnet, G P Arora, C Brøns, A A Vaag, L G Grunnet, G P Arora, C Brøns

Abstract

Twenty years ago, Hales and Barker along with their co-workers published some of their pioneering papers proposing the 'thrifty phenotype hypothesis' in Diabetologia (4;35:595-601 and 3;36:62-67). Their postulate that fetal programming could represent an important player in the origin of type 2 diabetes, the metabolic syndrome and cardiovascular disease (CVD) was met with great scepticism.More recently, their observations have been confirmed and expanded in many epidemiological and animal experimental studies, and human integrative physiological studies have provided insights into some of the underlying molecular mechanisms. Type 2 diabetes is a multiple-organ disease, and developmental programming, with its idea of organ plasticity, is a plausible hypothesis for a common basis for the widespread organ dysfunctions in type 2 diabetes and the metabolic syndrome. Only two among the 45 known type 2 diabetes susceptibility genes are associated with low birthweight, indicating that the association between low birthweight and type 2 diabetes is mainly non-genetic. Prevention programmes targeting adult lifestyle factors seems unable to stop the global propagation of type 2 diabetes, and intensive glucose control is inadequate to reduce the excess CVD mortality in type 2 diabetic patients. Today, the thrifty phenotype hypothesis has been established as a promising conceptual framework for a more sustainable intergenerational prevention of type 2 diabetes.

Figures

Fig. 1
Fig. 1
The developmental origin of type 2 diabetes provides a conceptual framework to explain the multiple organ defects in type 2 diabetes

References

    1. Yalow RS, Berson SA. Plasma insulin concentrations in nondiabetic and early diabetic subjects. Determinations by a new sensitive immuno-assay technic. Diabetes. 1960;9:254–260.
    1. Barnett AH, Eff C, Leslie RD, Pyke DA. Diabetes in identical twins. A study of 200 pairs. Diabetologia. 1981;20:87–93. doi: 10.1007/BF00262007.
    1. 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. doi: 10.1007/BF00399095.
    1. Hales CN, Barker DJ. Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis. Diabetologia. 1992;35:595–601. doi: 10.1007/BF00400248.
    1. Forsdahl A. Are poor living conditions in childhood and adolescence an important risk factor for arteriosclerotic heart disease? Br J Prev Soc Med. 1977;31:91–95.
    1. Phillips DI, Barker DJ, Hales CN, Hirst S, Osmond C. Thinness at birth and insulin resistance in adult life. Diabetologia. 1994;37:150–154. doi: 10.1007/s001250050086.
    1. Ahlqvist E, Ahluwalia TS, Groop L. Genetics of type 2 diabetes. Clin Chem. 2011;57:241–254. doi: 10.1373/clinchem.2010.157016.
    1. DeFronzo RA. Banting lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes. 2009;58:773–795. doi: 10.2337/db09-9028.
    1. Clausen TD, Mathiesen ER, Hansen T, et al. High prevalence of type 2 diabetes and pre-diabetes in adult offspring of women with gestational diabetes mellitus or type 1 diabetes: the role of intrauterine hyperglycemia. Diabetes Care. 2008;31:340–346. doi: 10.2337/dc07-1596.
    1. Pilgaard K, Færch B, Carstensen PP, et al. Low birthweight and premature birth are both associated with type 2 diabetes in a random sample of middle-aged Danes. Diabetologia. 2010;53:2526–2530. doi: 10.1007/s00125-010-1917-3.
    1. 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;45:1649–1657. doi: 10.1007/s00125-002-0983-6.
    1. Poulsen P, Vaag AA, Kyvik KO, Moller JD, Beck-Nielsen H. Low birth weight is associated with NIDDM in discordant monozygotic and dizygotic twin pairs. Diabetologia. 1997;40:439–446. doi: 10.1007/s001250050698.
    1. Poulsen P, Grunnet LG, Pilgaard K, et al. Increased risk of type 2 diabetes in elderly twins. Diabetes. 2009;58:1350–1355. doi: 10.2337/db08-1714.
    1. Petersen I, Nielsen MM, Beck-Nielsen H, Christensen K. No evidence of a higher 10 year period prevalence of diabetes among 77,885 twins compared with 215,264 singletons from the Danish birth cohorts 1910–1989. Diabetologia. 2011;54:2016–2024. doi: 10.1007/s00125-011-2128-2.
    1. Vielwerth SE, Jensen RB, Larsen T, et al. The effect of birthweight upon insulin resistance and associated cardiovascular risk factors in adolescence is not explained by fetal growth velocity in the third trimester as measured by repeated ultrasound fetometry. Diabetologia. 2008;51:1483–1492. doi: 10.1007/s00125-008-1037-5.
    1. 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;118:2316–2324. doi: 10.1172/JCI32011.
    1. 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;48:547–552. doi: 10.1007/s00125-005-1669-7.
    1. Ferland-McCollough D, Fernandez-Twinn DS, Cannell IG et al (2012) Programming of adipose tissue miR-483-3p and GDF-3 expression by maternal diet in type 2 diabetes. Cell Death Differ 19:1003–1012
    1. Innes KE, Byers TE, Marshall JA, Baron A, Orleans M, Hamman RF. Association of a woman’s own birth weight with subsequent risk for gestational diabetes. JAMA. 2002;287:2534–2541. doi: 10.1001/jama.287.19.2534.
    1. Griffin SJ, Borch-Johnsen K, Davies MJ, et al. Effect of early intensive multifactorial therapy on 5-year cardiovascular outcomes in individuals with type 2 diabetes detected by screening (ADDITION-Europe): a cluster-randomised trial. Lancet. 2011;378:156–167. doi: 10.1016/S0140-6736(11)60698-3.
    1. Hemmingsen B, Lund SS, Gluud C, et al. Intensive glycaemic control for patients with type 2 diabetes: systematic review with meta-analysis and trial sequential analysis of randomised clinical trials. BMJ. 2011;343:d6898. doi: 10.1136/bmj.d6898.

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