Latent autoimmune diabetes of the adult: current knowledge and uncertainty

Patients with adult-onset autoimmune diabetes have less Human Leucocyte Antigen (HLA)-associated genetic risk and fewer diabetes-associated autoantibodies compared with patients with childhood-onset Type 1 diabetes. Metabolic changes at diagnosis reflect a broad clinical phenotype ranging from diabetic ketoacidosis to mild non-insulin-requiring diabetes, also known as latent autoimmune diabetes of the adult (LADA). This latter phenotype is the most prevalent form of adult-onset autoimmune diabetes and probably the most prevalent form of autoimmune diabetes in general. Although LADA is associated with the same genetic and immunological features as childhood-onset Type 1 diabetes, it also shares some genetic features with Type 2 diabetes, which raises the question of genetic heterogeneity predisposing to this form of the disease. The potential value of screening patients with adult-onset diabetes for diabetes-associated autoantibodies to identify those with LADA is emphasized by their lack of clinically distinct features, their different natural history compared with Type 2 diabetes and their potential need for a dedicated management strategy. The fact that, in some studies, patients with LADA show worse glucose control than patients with Type 2 diabetes, highlights the need for further therapeutic studies. Challenges regarding classification, epidemiology, genetics, metabolism, immunology, clinical presentation and treatment of LADA were discussed at a 2014 workshop arranged by the Danish Diabetes Academy. The presentations and discussions are summarized in this review, which sets out the current ideas and controversies surrounding this form of diabetes. WHAT’S NEW? 1. Latent autoimmune diabetes of the adult (LADA) is an autoimmune diabetes defined by adult-onset, presence of diabetes associated autoantibodies, and no insulin treatment requirement for a period after diagnosis. . 2. Immunologically, glutamic acid decarboxylase 65 autoantibodies are by far the most common autoantibody in adult-onset diabetes. . 3. LADA is the most prevalent form of adult-onset autoimmune diabetes and probably the most prevalent form of autoimmune diabetes in general. . 4. LADA shares genetic features with both type 1 and type 2 diabetes. . 5. Phenotypically, LADA patients are often misdiagnosed as having type 2 diabetes. . 6. LADA patients generally have worse HbA1c levels than type 2 diabetes patients. . 7. Clinically, LADA patients tend to have a lower mean age at diabetes onset, lower body mass index and more frequent need for insulin treatment than patients with type 2 diabetes. . 8. Management of LADA may require a dedicated strategy, yet currently there is a paucity of randomized controlled trial data. .