Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Endocr Rev. 2010 Apr;31(2):183-93. doi: 10.1210/er.2009-0029. Epub 2009 Dec 10.
The pathophysiology of latent autoimmune diabetes in adults (LADA) is considered less understood than its much better characterized counterparts of type 1 and type 2 diabetes (T1D and T2D), where its clinical presentation exhibits some features of each of these two main diseases, earning it a reputation as being "type 1.5 diabetes". The etiology of LADA remains unknown, but a genetic component has been implicated from recent reports of T1D and T2D genes playing a role in its pathogenesis. One way to shed much needed light on the classification of LADA is to determine the discrete genetic factors conferring risk to the pathogenesis of this specific phenotype and to determine to what extent LADA shares genetic similarities with T1D and T2D. For instance, no conclusive support for a role of the T1D-associated INS gene has been reported in T2D; conversely, but similarly, no evidence has been found for the role of the T2D-associated genes IDE/HHEX, SLC30A8, CDKAL1, CDKN2A/B, IGF2BP2, FTO, and TCF7L2 in T1D. However, and somewhat at odds with current thinking, TCF7L2, the most strongly associated gene with T2D to date, is strongly associated with LADA, a disorder considered by the World Health Organization to be a slowly progressing form of T1D. In this review, we address recent advances in the genetics of T1D and T2D and how such discoveries have in turn shed some light on the genetics of LADA as being potentially at the "genetic intersection" of these two major diseases.
成人隐匿性自身免疫性糖尿病（LADA）的病理生理学被认为不如 1 型和 2 型糖尿病（T1D 和 T2D）那么清楚，因为它的临床表现具有这两种主要疾病的一些特征，因此被称为“1.5 型糖尿病”。LADA 的病因尚不清楚，但最近有报道称 T1D 和 T2D 基因在其发病机制中起作用，这表明其病因可能与遗传有关。阐明 LADA 分类的一种方法是确定赋予这种特定表型发病风险的离散遗传因素，并确定 LADA 在多大程度上与 T1D 和 T2D 具有遗传相似性。例如，在 T2D 中，没有确凿的证据表明 T1D 相关 INS 基因在其中起作用；相反，但类似地，在 T1D 中也没有发现 T2D 相关基因 IDE/HHEX、SLC30A8、CDKAL1、CDKN2A/B、IGF2BP2、FTO 和 TCF7L2 的作用证据。然而，与当前的思维方式有些矛盾的是，TCF7L2 是迄今为止与 T2D 关联最强的基因，与 LADA 强烈相关，而 LADA 被世界卫生组织认为是 T1D 的一种缓慢进展形式。在这篇综述中，我们将讨论 T1D 和 T2D 的遗传学最新进展，以及这些发现如何反过来阐明 LADA 的遗传学，认为其可能处于这两种主要疾病的“遗传交叉点”。
