title: Impact of fetal and neonatal environment on beta cell function and development of diabetes.
abstract: The global epidemic of diabetes is a serious threat against health and healthcare expenses. Although genetics is important it does not explain the dramatic increase in incidence, which must involve environmental factors. Two decades ago the concept of the thrifty phenotype was introduced, stating that the intrauterine environment during pregnancy has an impact on the gene expression that may persist until adulthood and cause metabolic diseases like obesity and type 2 diabetes. As the pancreatic beta cells are crucial in the regulation of metabolism this article will describe the influence of normal pregnancy on the beta cells in both the mother and the fetus and how various conditions like diabetes, obesity, overnutrition and undernutrition during and after pregnancy may influence the ability of the offspring to adapt to changes in insulin demand later in life. The influence of environmental factors including nutrients and gut microbiota on appetite regulation, mitochondrial activity and the immune system that may affect beta cell growth and function directly and indirectly is discussed. The possible role of epigenetic changes in the transgenerational transmission of the adverse programming may be the most threatening aspect with regard to the global diabetes epidemics. Finally, some suggestions for intervention are presented.
authors.affiliation: Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark; Center for Fetal Programming, Copenhagen, Denmark.
authors.forename: Jens H
authors.initials: JH
authors.lastname: Nielsen
authors.forename: Tobias N
authors.initials: TN
authors.lastname: Haase
authors.forename: Caroline
authors.initials: C
authors.lastname: Jaksch
authors.forename: Amarnadh
authors.initials: A
authors.lastname: Nalla
authors.forename: Birgitte
authors.initials: B
authors.lastname: Søstrup
authors.forename: Anjana A
authors.initials: AA
authors.lastname: Nalla
authors.forename: Louise
authors.initials: L
authors.lastname: Larsen
authors.forename: Morten
authors.initials: M
authors.lastname: Rasmussen
authors.forename: Louise T
authors.initials: LT
authors.lastname: Dalgaard
authors.forename: Louise W
authors.initials: LW
authors.lastname: Gaarn
authors.forename: Peter
authors.initials: P
authors.lastname: Thams
authors.forename: Hans
authors.initials: H
authors.lastname: Kofod
authors.forename: Nils
authors.initials: N
authors.lastname: Billestrup
mesh_terms: D016640:Diabetes, Gestational / Q000503:physiopathology*; D044127:Epigenesis, Genetic / Q000235:genetics / Q000502:physiology; D005260:Female; D047109:Fetal Development / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D039382:Maternal Nutritional Physiological Phenomena; D009765:Obesity / Q000235:genetics / Q000503:physiopathology*; D010641:Phenotype; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics* / Q000503:physiopathology*; D039401:Prenatal Nutritional Physiological Phenomena; D012307:Risk Factors
keywords: Diabetes; beta cells; epigenetics; fetal programming; gut microbiota; mitochondria; nutrition; pregnancy