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Diabetologia. 2019 Oct;62(10):1789-1801. doi: 10.1007/s00125-019-4951-9. Epub 2019 Aug 27.

Intrauterine programming of obesity and type 2 diabetes.

Author information

1
Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Addenbrooke's Hospital, Level 4, Box 289, Addenbrooke's Treatment Centre, Cambridge, CB2 0QQ, UK.
2
Department of Endocrinology, the Diabetes and Bone-metabolic Research Unit, Rigshospitalet, Copenhagen, Denmark.
3
Department of Obstetrics, Center for Pregnant Women with Diabetes, Rigshospitalet, Copenhagen, Denmark.
4
Murdoch Children's Research Institute, Royal Children's Hospital, Flemington Road, Parkville, VIC, 3052, Australia.
5
Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Addenbrooke's Hospital, Level 4, Box 289, Addenbrooke's Treatment Centre, Cambridge, CB2 0QQ, UK. seo10@cam.ac.uk.
6
Murdoch Children's Research Institute, Royal Children's Hospital, Flemington Road, Parkville, VIC, 3052, Australia. Richard.saffery@mcri.edu.au.

Abstract

The type 2 diabetes epidemic and one of its predisposing factors, obesity, are major influences on global health and economic burden. It is accepted that genetics and the current environment contribute to this epidemic; however, in the last two decades, both human and animal studies have consolidated considerable evidence supporting the 'developmental programming' of these conditions, specifically by the intrauterine environment. Here, we review the various in utero exposures that are linked to offspring obesity and diabetes in later life, including epidemiological insights gained from natural historical events, such as the Dutch Hunger Winter, the Chinese famine and the more recent Quebec Ice Storm. We also describe the effects of gestational exposure to endocrine disruptors, maternal infection and smoking to the fetus in relation to metabolic programming. Causal evidence from animal studies, motivated by human observations, is also discussed, as well as some of the proposed underlying molecular mechanisms for developmental programming of obesity and type 2 diabetes, including epigenetics (e.g. DNA methylation and histone modifications) and microRNA interactions. Finally, we examine the effects of non-pharmacological interventions, such as improving maternal dietary habits and/or increasing physical activity, on the offspring epigenome and metabolic outcomes.

KEYWORDS:

Developmental programming; Epigenetic variation; Intrauterine programming; Life course development; Maternal exposures; MicroRNAs; Obesity; Paternal exposures; Review; Type 2 diabetes

PMID:
31451874
PMCID:
PMC6731191
DOI:
10.1007/s00125-019-4951-9

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