Institute of Biomedical and Clinical Science, College of Medicine and Health, University of Exeter, Exeter, U.K
MacLeod Diabetes and Endocrine Centre, Royal Devon and Exeter NHS Foundation Trust, Exeter, U.K.
Diabetes Care. 2021 Jun;44(6):1243-1251. doi: 10.2337/dc20-2834. Epub 2021 May 20.
Latent autoimmune diabetes of adults (LADA) is typically defined as a new diabetes diagnosis after 35 years of age, presenting with clinical features of type 2 diabetes, in whom a type 1 diabetes-associated islet autoantibody is detected. Identifying autoimmune diabetes is important since the prognosis and optimal therapy differ. However, the existing LADA definition identifies a group with clinical and genetic features intermediate between typical type 1 and type 2 diabetes. It is unclear whether this is due to ) true autoimmune diabetes with a milder phenotype at older onset ages that initially appears similar to type 2 diabetes but later requires insulin, ) a disease syndrome where the pathophysiologies of type 1 and type 2 diabetes are both present in each patient, or ) a heterogeneous group resulting from difficulties in classification. Herein, we suggest that difficulties in classification are a major component resulting from defining LADA using a diagnostic test-islet autoantibody measurement-with imperfect specificity applied in low-prevalence populations. This yields a heterogeneous group of true positives (autoimmune type 1 diabetes) and false positives (nonautoimmune type 2 diabetes). For clinicians, this means that islet autoantibody testing should not be undertaken in patients who do not have clinical features suggestive of autoimmune diabetes: in an adult without clinical features of type 1 diabetes, it is likely that a single positive antibody will represent a false-positive result. This is in contrast to patients with features suggestive of type 1 diabetes, where false-positive results will be rare. For researchers, this means that current definitions of LADA are not appropriate for the study of autoimmune diabetes in later life. Approaches that increase test specificity, or prior likelihood of autoimmune diabetes, are needed to avoid inclusion of participants who have nonautoimmune (type 2) diabetes. Improved classification will allow improved assignment of prognosis and therapy as well as an improved cohort in which to analyze and better understand the detailed pathophysiological components acting at onset and during disease progression in late-onset autoimmune diabetes.
成人隐匿性自身免疫性糖尿病（LADA）通常定义为 35 岁以后新诊断的糖尿病，表现为 2 型糖尿病的临床特征，检测到 1 型糖尿病相关胰岛自身抗体。识别自身免疫性糖尿病很重要，因为预后和最佳治疗方法不同。然而，现有的 LADA 定义确定了一组具有介于典型 1 型和 2 型糖尿病之间的临床和遗传特征的患者。尚不清楚这是由于（1）在老年发病时表现出更轻微表型的真正自身免疫性糖尿病，最初类似于 2 型糖尿病，但后来需要胰岛素，（2）一种疾病综合征，其中 1 型和 2 型糖尿病的病理生理学均存在于每个患者中，还是（3）由于分类困难导致的异质性群体。在这里，我们认为，在使用诊断性检测 - 胰岛自身抗体测量 - 特异性不完全且应用于低患病率人群的情况下定义 LADA 时，分类困难是一个主要组成部分。这产生了一个由真正阳性（自身免疫性 1 型糖尿病）和假阳性（非自身免疫性 2 型糖尿病）组成的异质性群体。对于临床医生来说，这意味着在没有提示自身免疫性糖尿病临床特征的患者中不应进行胰岛自身抗体检测：在没有 1 型糖尿病临床特征的成年患者中，单个阳性抗体很可能代表假阳性结果。这与具有提示 1 型糖尿病特征的患者形成对比，在这些患者中假阳性结果将很少见。对于研究人员来说，这意味着目前的 LADA 定义不适合研究晚年的自身免疫性糖尿病。需要提高测试特异性或自身免疫性糖尿病的先验可能性的方法，以避免纳入患有非自身免疫性（2 型）糖尿病的参与者。改进分类将有助于更好地分配预后和治疗，以及更好地分析和更好地理解在晚年发病的自身免疫性糖尿病发病和疾病进展过程中起作用的详细病理生理成分。
