Latent Autoimmune Diabetes

Excerpt

Diabetes mellitus (DM) is a disease spectrum ranging from classic insulinopenic type 1 diabetes (T1DM) at one end to classic insulin-resistant type 2 diabetes (T2DM) at the other. Latent autoimmune diabetes of adults (LADA) is a form of DM with features of both T1DM and T2DM and has therefore been termed Type 1.5 DM. In Japan, the synonym used is slowly progressive insulin-dependent type 1 diabetes mellitus (SPIDDM). The American Diabetes Association (ADA) lists LADA as T1DM that evolves more slowly than the classic disease and does not recognize it as a specific type of DM. The World Health Organization's term for LADA is 'slowly evolving immune-related diabetes.'

LADA is, by definition, a disease of adults. The Immunology for Diabetes Society (IDS) has specified three criteria for the diagnosis of LADA:

1. Age greater than 35 years

2. Positive autoantibodies to islet beta cells

3. Insulin independence for at least the initial 6 months after initial diagnosis

Although attractive, this set of criteria has been challenged, especially because the choice of insulin as a treatment is highly physician dependent. It is immunologically similar to T1DM as antibodies to islet beta cells are present, albeit at lower titers, and immune destruction progresses at a much slower rate when compared to classic T1DM. The majority of these patients present with hyperglycemia that is not dramatic like T1DM and is misdiagnosed and managed as T2DM. Only later is it realized that they have poor control with many conventional agents, especially sulfonylureas, and eventually require insulin therapy.

LADA itself is a heterogeneous disease where some patients have high antibody titers, a low BMI, and progress to insulin therapy faster, and others who have low antibody titers, features of insulin resistance like higher BMI, and progress more slowly to requiring insulin.

Early recognition of LADA is paramount so that appropriate strategies are employed to delay beta-cell destruction and reduce complications. This article reviews the advances in the pathophysiology of LADA and its implications in the evaluation and treatment.