Department of Endocrinology and Metabolism, Peninsula College of Medicine and Dentistry, Plymouth Campus, UK.
Int J Obes (Lond). 2009 Jul;33(7):716-26. doi: 10.1038/ijo.2009.97. Epub 2009 Jun 9.
Although some 40 years have passed since type I diabetes was first defined, its cause remains unknown. The autoimmunity paradigm of immune dysregulation has not offered an explanation for its rising incidence, nor means of preventing it, and there is arguably good reason to consider alternatives. The accelerator hypothesis is a singular, unifying concept that argues that type I and type II diabetes are the same disorder of insulin resistance, set against different genetic backgrounds. The hypothesis does not deny the role of autoimmuniy, only its primacy in the process. It distinguishes type I and type II diabetes only by tempo, the faster tempo reflecting the more susceptible genotype and (inevitably) earlier presentation. Insulin resistance is closely related to the rise in overweight and obesity, a trend that the hypothesis deems central to the rising incidence of all diabetes in the developed and developing world. Rather than overlap between the two types of diabetes, the accelerator hypothesis envisages overlay-each a subset of the general population differing from each other only by genotype. Indeed, it views type I and type II diabetes as a continuum, where the infinitely variable interaction between insulin resistance and genetic response determines the age at which beta-cell loss becomes critical. Adult diabetes is not viewed as an entity, but rather as diabetes presenting in adulthood. Childhood diabetes, similarly, is diabetes presenting in childhood. The increasing incidence of both is primarily the result of lifestyle change and the rise in body weight that has resulted.
尽管自 1 型糖尿病首次被定义以来已经过去了约 40 年，但它的病因仍不清楚。免疫失调的自身免疫范式既没有解释其发病率上升的原因，也没有预防的方法，因此有充分的理由考虑替代方案。加速器假说（accelerator hypothesis）是一个单一的、统一的概念，它认为 1 型和 2 型糖尿病是相同的胰岛素抵抗障碍，只是在不同的遗传背景下发生。该假说并不否认自身免疫的作用，只是认为它在这个过程中不是首要因素。它仅通过速度（tempo）来区分 1 型和 2 型糖尿病，速度越快反映出更易感的基因型，并且（不可避免地）发病更早。胰岛素抵抗与超重和肥胖的增加密切相关，而这种趋势正是该假说认为在发达国家和发展中国家所有糖尿病发病率上升的核心因素。加速器假说并不认为两种类型的糖尿病存在重叠，而是认为存在叠加——它们是一般人群的亚组，彼此之间仅因基因型不同而有所不同。实际上，它将 1 型和 2 型糖尿病视为一个连续体，其中胰岛素抵抗和遗传反应之间的无限可变相互作用决定了β细胞丧失变得至关重要的年龄。成人糖尿病不再被视为一种实体，而是成年后出现的糖尿病。同样，儿童糖尿病是指儿童时期出现的糖尿病。这两种疾病发病率的增加主要是生活方式改变和由此导致的体重增加的结果。
