Latent autoimmune diabetes in adults: a guide for the perplexed

Abstract

Diabetes rejoices in silly names. Maturity-onset diabetes of the young (MODY) is no doubt the silliest, but—for reasons that will emerge—latent autoimmune diabetes in adults (LADA) comes close. There is, however, one important difference between the two conditions: MODY can be defined at a molecular level and LADA is hard to define at all. LADA, as discussed in this issue of Diabetologia [1], exists somewhere in the borderland between type 1 and type 2 diabetes, and exemplifies the difficulties we have in telling the two conditions apart. From a historical perspective, it is easy to see how these difficulties arose. Idiopathic diabetes was long considered a single disease, despite mounting evidence of heterogeneity. Once formulated, however, the concept of two major disorders with distinct phenotypes, genetic determinants and aetiology won almost immediate acceptance [2] and now rules our thinking, just as the one-disease concept did in the past. For this reason it is rarely acknowledged that the methods we use are of limited value in telling the two conditions apart [3]. So how do we distinguish between them? Early-onset type 1 diabetes differs from type 2 diabetes in—among other things—age distribution, rapidly progressive insulin deficiency resulting in a need for insulin therapy, associations with the HLA system, and the presence of circulating islet autoantibodies. These distinguishing features become less helpful with increasing age, and our ignorance of the role of immune-mediated beta cell failure in people who develop diabetes over the age of 30 represents an embarrassing gap in our understanding of the condition. Type 2 diabetes, meanwhile, has no distinctive genetic or serological features, and tends to be defined by the absence of markers associated with type 1 diabetes. The relative prevalence of the two conditions (assuming there really are two conditions) in middle and later life therefore depends upon how you choose to draw a line between them. Let us consider some of the ways in which this line might be drawn.