LADA: Time for a New Definition

Abstract

In this issue of Diabetes , Zhou et al. (1) report on the prevalence and characteristics of latent autoimmune diabetes in adults (LADA) in China. Findings from this study underscore the profound need for a new definition of LADA. LADA, a slowly progressive form of autoimmune diabetes that develops in adults and does not require insulin therapy for some time after diagnosis, was first described over 25 years ago (2). Subsequently, clinical, metabolic, immunological, and genetic characteristics that are unique to LADA have been identified (3–6). For example, relative to patients with type 1 diabetes (T1D), those with LADA are more likely to be obese and have other elements of the metabolic syndrome. They are also more likely to retain greater β-cell function, express a single autoantibody (particularly GAD65) and certain GAD65 epitopes (7), and carry the transcription factor 7-like 2 ( TCF7L2 ) gene polymorphism, which is strongly associated with type 2 diabetes (T2D) (8). However, the rationale for the strict criteria that are most often used to define LADA, including age >30 years at diagnosis and insulin independence for at least 6 months after diagnosis (5), have been questioned repeatedly (9–13). Furthermore, there is substantial heterogeneity in LADA, with some cases closely resembling T1D (e.g., low BMI, association with other autoimmune diseases), and others that share many features with T2D (14–16). Many authors and clinicians question …