Latent autoimmune diabetes in adults (LADA)—more than a name

Abstract

In a recent editorial [1], Edwin Gale questioned the rationale for the designation of latent autoimmune diabetes in adults (LADA) [2] as a distinct aetiological entity. The reasons given for this were that measurements of antibodies to GAD are imprecise and cut-off levels are arbitrary, and that the clinical value of a diagnosis of LADA has not been demonstrated. We, however, think that there are persuasive reasons for retention of LADA as a subgroup of diabetes. The classification of diabetes into two main groups, type 1 and type 2, has led to the belief that all patients can be allocated to one or other of these two categories. However, when we apply distinct criteria for classification, it becomes clear that many patients do not fit readily into either group, and that there is a significant grey area between the two, as evident in epidemiological studies. LADA has provided a much better understanding of this grey area and has shown that there are patients with features of both types of diabetes. At this time, only genetically defined forms of MODY can be considered as aetiologically distinct entities; all other forms of diabetes are ‘self-imposed’ categories (including type 1 and type 2) based upon arbitrary cut-off levels for various indices. We can indeed consider diabetes as a continuum ranging from autoimmune inflammatory-mediated beta cell attrition at one pole to metabolic beta cell damage at the other, with LADA somewhere in between. It is often questioned why we do not simply refer to type 1 diabetes in adults, and whether we really need a ‘silly name’ such as LADA to designate a particular group of patients with autoimmune diabetes. We, however, see good clinical reason for this. It has never been a problem to distinguish these patients from type 1 diabetes, but rather from type 2 diabetes, since, prior to the more widespread use of GAD antibody measurements, these patients were generally misclassified as having type 2 diabetes. In our original report [3] we called this condition latent type 1 diabetes in patients over 35 years, and, later, autoimmune diabetes in adults [4]. On the other hand, we still recognise adult patients with an onset of rapidly progressing autoimmune diabetes who share all the clinical and metabolic features of classical type 1 diabetes in younger patients. This was the rationale for reinstating the word ‘latent’ to distinguish the slow-onset cases from classical adult type 1 diabetes [2]. We agree with Gale and the authors of an accompanying review [5] that the specifications for the diagnosis of LADA are currently imprecise, i.e. the presence of GAD antibodies in a patient with age at onset of diabetes of >30 years (or 35 years, as we previously proposed), and insulin independence for at least 6 months after diagnosis. Clearly, each of these cut-off values is arbitrary, and the definition of GAD antibody positivity will influence not only the prevalence but also the phenotype of LADA [6]. As Gale points out, GAD antibodies are continuously distributed throughout the population, but this applies to Diabetologia (2006) 49:1996–1998 DOI 10.1007/s00125-006-0345-x