Genetic, nongenetic and epigenetic risk determinants in developmental programming of type 2 diabetes

TY - JOUR

T1 - Genetic, nongenetic and epigenetic risk determinants in developmental programming of type 2 diabetes

AU - Vaag, Allan

AU - Brøns, Charlotte

AU - Gillberg, Linn

AU - Hansen, Ninna S

AU - Hjort, Line

AU - Arora, Geeti P

AU - Thomas, Nihal

AU - Broholm, Christa

AU - Ribel-Madsen, Rasmus

AU - Grunnet, Louise G

N1 - © 2014 Nordic Federation of Societies of Obstetrics and Gynecology.

PY - 2014/11/1

Y1 - 2014/11/1

N2 - Low birthweight (LBW) individuals and offspring of women with gestational diabetes mellitus (GDM) exhibit increased risk of developing type 2 diabetes (T2D) and associated cardiometabolic traits in adulthood, which for both groups may be mediated by adverse events and developmental changes in fetal life. T2D is a multifactorial disease occurring as a result of complicated interplay between genetic and both prenatal and postnatal nongenetic factors, and it remains unknown to what extent the increased risk of T2D associated with LBW or GDM in the mother may be due to, or confounded by, genetic factors. Indeed, it has been shown that genetic changes influencing risk of diabetes may also be associated with reduced fetal growth as a result of reduced insulin secretion and/or action. Similarly, increased risk of T2D among offspring could be explained by T2D susceptibility genes shared between the mother and her offspring. Epigenetic mechanisms may explain the link between factors operating in fetal life and later risk of developing T2D, but so far convincing evidence is lacking for epigenetic changes as a prime and direct cause of T2D. This review addresses recent literature on the early origins of adult disease hypothesis, with a special emphasis on the role of genetic compared with nongenetic and epigenetic risk determinants and disease mechanisms.

AB - Low birthweight (LBW) individuals and offspring of women with gestational diabetes mellitus (GDM) exhibit increased risk of developing type 2 diabetes (T2D) and associated cardiometabolic traits in adulthood, which for both groups may be mediated by adverse events and developmental changes in fetal life. T2D is a multifactorial disease occurring as a result of complicated interplay between genetic and both prenatal and postnatal nongenetic factors, and it remains unknown to what extent the increased risk of T2D associated with LBW or GDM in the mother may be due to, or confounded by, genetic factors. Indeed, it has been shown that genetic changes influencing risk of diabetes may also be associated with reduced fetal growth as a result of reduced insulin secretion and/or action. Similarly, increased risk of T2D among offspring could be explained by T2D susceptibility genes shared between the mother and her offspring. Epigenetic mechanisms may explain the link between factors operating in fetal life and later risk of developing T2D, but so far convincing evidence is lacking for epigenetic changes as a prime and direct cause of T2D. This review addresses recent literature on the early origins of adult disease hypothesis, with a special emphasis on the role of genetic compared with nongenetic and epigenetic risk determinants and disease mechanisms.

KW - Adult

KW - Diabetes Mellitus, Type 2

KW - Diabetes, Gestational

KW - Epigenesis, Genetic

KW - Female

KW - Fetal Development

KW - Genetic Predisposition to Disease

KW - Humans

KW - Pregnancy

KW - Prenatal Exposure Delayed Effects

KW - Risk Factors

U2 - 10.1111/aogs.12494

DO - 10.1111/aogs.12494

M3 - Journal article

C2 - 25179736

SN - 0001-6349

VL - 93

SP - 1099

EP - 1108

JO - Acta Obstetrica et Gynecologica

JF - Acta Obstetrica et Gynecologica

IS - 11

ER -