Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Section of Epidemiology, Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Diabetologia. 2022 Nov;65(11):1804-1813. doi: 10.1007/s00125-021-05639-5. Epub 2022 Jan 7.
The past decades have seen a rapid global rise in the incidence of type 2 diabetes. This surge has been driven by diabetogenic environmental changes that may act together with a genetic predisposition to type 2 diabetes. It is possible that there is a synergistic gene-environment interaction, where the effects of the diabetogenic environment depend on the genetic predisposition to type 2 diabetes. Randomised trials have shown that it is possible to delay, or even prevent the development of type 2 diabetes in individuals at elevated risk through behavioural modification, focusing on weight loss, physical activity and diet. There is wide heterogeneity between individuals regarding the effectiveness of these interventions, which could, in part, be due to genetic differences. However, the studies of gene-environment interactions performed thus far suggest that behavioural modifications appear equally effective in reducing the incidence of type 2 diabetes from the stage of impaired glucose tolerance, regardless of the known underlying genetic predisposition. Recent studies suggest that there may be several subtypes of type 2 diabetes, which give new opportunities for gaining insight into gene-environment interactions. At present, the role of gene-environment interactions in the development of type 2 diabetes remains unclear. With many puzzle pieces missing in the general picture of type 2 diabetes development, the available evidence of gene-environment interactions is not ready for translation to individualised type 2 diabetes prevention based on genetic profiling.
过去几十年,全球 2 型糖尿病发病率迅速上升。这种增长是由可能与 2 型糖尿病遗传易感性共同作用的致糖尿病环境变化驱动的。可能存在协同的基因-环境相互作用,其中致糖尿病环境的影响取决于 2 型糖尿病的遗传易感性。随机临床试验表明,通过行为改变,专注于减肥、身体活动和饮食,可以延迟甚至预防处于高风险的个体发生 2 型糖尿病。个体之间在这些干预措施的有效性方面存在很大的异质性,部分原因可能是遗传差异。然而,迄今为止进行的基因-环境相互作用研究表明,无论已知的潜在遗传易感性如何,行为改变似乎同样有效地降低 2 型糖尿病从葡萄糖耐量受损阶段的发病率。最近的研究表明,2 型糖尿病可能存在几种亚型,这为深入了解基因-环境相互作用提供了新的机会。目前,基因-环境相互作用在 2 型糖尿病发展中的作用仍不清楚。由于 2 型糖尿病发展的总体情况中缺少许多拼图,因此基因-环境相互作用的现有证据还不足以根据遗传特征进行个体化 2 型糖尿病预防。