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Diabetologia. 2019 Oct;62(10):1823-1834. doi: 10.1007/s00125-019-4942-x. Epub 2019 Aug 27.

Early-life factors contributing to type 1 diabetes.

Author information

1
School of Women's and Children's Health, University of New South Wales Faculty of Medicine, Sydney, NSW, Australia. m.craig@unsw.edu.au.
2
Institute of Endocrinology and Diabetes, Children's Hospital at Westmead, Locked Bag 4001, Westmead, Sydney, NSW, 2145, Australia. m.craig@unsw.edu.au.
3
Discipline of Child and Adolescent Health, University of Sydney, Sydney, NSW, Australia. m.craig@unsw.edu.au.
4
School of Women's and Children's Health, University of New South Wales Faculty of Medicine, Sydney, NSW, Australia.
5
Virology Research Laboratory, Prince of Wales Hospital Randwick, Sydney, NSW, Australia.
6
Robinson Research Institute, School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, SA, Australia.
7
Department of Endocrinology and Diabetes, Women's and Children's Hospital, Adelaide, SA, Australia.
8
University of Queensland Diamantina Institute, University of Queensland, Translational Research Institute, Brisbane, QLD, Australia.
9
Serology and Virology Division, NSW Health Pathology, Prince of Wales Hospital, Sydney, NSW, Australia.

Abstract

The incidence of type 1 diabetes has increased since the mid-twentieth century at a rate that is too rapid to be attributed to genetic predisposition alone. While the disease can occur at any age, mounting evidence from longitudinal cohort studies of at-risk children indicate that type 1 diabetes associated autoantibodies can be present from the first year of life, and that those who develop type 1 diabetes at a young age have a more aggressive form of the disease. This corroborates the hypothesis that environmental exposures in early life contribute to type 1 diabetes risk, whether related to maternal influences on the fetus during pregnancy, neonatal factors or later effects during infancy and early childhood. Studies to date show a range of environmental triggers acting at different time points, suggesting a multifactorial model of genetic and environmental factors in the pathogenesis of type 1 diabetes, which integrally involves a dialogue between the immune system and pancreatic beta cells. For example, breastfeeding may have a weak protective effect on type 1 diabetes risk, while use of an extensively hydrolysed formula does not. Additionally, exposure to being overweight pre-conception, both in utero and postnatally, is associated with increased risk of type 1 diabetes. Epidemiological, clinical and pathological studies in humans support a role for viral infections, particularly enteroviruses, in type 1 diabetes, but definitive proof is lacking. The role of the early microbiome and its perturbations in islet autoimmunity and type 1 diabetes is the subject of investigation in ongoing cohort studies. Understanding the interactions between environmental exposures and the human genome and metagenome, particularly across ethnically diverse populations, will be critical for the development of future strategies for primary prevention of type 1 diabetes.

KEYWORDS:

Child; Diet; Enterovirus; Gene–environment interaction; Life course development; Microbiome; Pregnancy; Review; Type 1 diabetes; Virus

PMID:
31451871
DOI:
10.1007/s00125-019-4942-x

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