School of Women's and Children's Health, University of New South Wales Faculty of Medicine, Sydney, NSW, Australia.
Institute of Endocrinology and Diabetes, Children's Hospital at Westmead, Locked Bag 4001, Westmead, Sydney, NSW, 2145, Australia.
Diabetologia. 2019 Oct;62(10):1823-1834. doi: 10.1007/s00125-019-4942-x. Epub 2019 Aug 27.
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.
自 20 世纪中叶以来，1 型糖尿病的发病率呈上升趋势，其上升速度之快不能仅归因于遗传易感性。虽然这种疾病可发生于任何年龄，但来自高危儿童的纵向队列研究的大量证据表明，1 型糖尿病相关自身抗体可从生命的第一年开始出现，而且在年轻时发病的 1 型糖尿病患者具有更具侵袭性的疾病形式。这证实了这样一种假设，即在生命早期暴露于环境因素会增加 1 型糖尿病的风险，无论是与怀孕期间母体对胎儿的影响、新生儿因素还是婴儿期和幼儿期后期的影响有关。迄今为止的研究表明，一系列环境触发因素在不同时间点起作用，提示 1 型糖尿病发病机制中的遗传和环境因素存在多因素模型，这整体上涉及免疫系统和胰腺β细胞之间的对话。例如，母乳喂养可能对 1 型糖尿病风险有微弱的保护作用，而使用高度水解配方则没有。此外，受孕前超重，无论是在子宫内还是出生后，都与 1 型糖尿病风险增加有关。人类的流行病学、临床和病理学研究支持病毒感染，特别是肠道病毒，在 1 型糖尿病中的作用，但缺乏确凿的证据。早期微生物组及其在胰岛自身免疫和 1 型糖尿病中的扰动作用是正在进行的队列研究的主题。了解环境暴露与人类基因组和宏基因组之间的相互作用，特别是在不同种族的人群中，对于制定未来的 1 型糖尿病一级预防策略至关重要。
