Autoimmune diabetes in adults: lessons from the UKPDS

Abstract

Latent autoimmune diabetes in adults (LADA) is characterised by a relatively mild diabetes onset, autoantibody positivity and eventual requirement for insulin therapy. Twelve per cent of newly diagnosed, UK Prospective Diabetes Study (UKPDS) patients were positive for autoantibodies to GAD65 (GADA) and/or insulinoma-associated antigen-2A (IA-2A) and managed as if they had Type 2 diabetes according to the UKPDS protocol. Here, we compare data from UKPDS LADA patients with that from other cohorts. In common with other groups, UKPDS LADA patients required insulin therapy earlier post-diagnosis than non-LADA patients. Reduction of islet function was similar in UKPDS LADA groups randomised to oral glucose-lowering agents or insulin replacement therapy, contesting the current hypothesis of reduced decline of insulin secretion in LADA by immediate insulin therapy. Disease progression was not predicted by post-diagnosis GADA levels or epitope specificities as has been suggested. Slowly progressing insulitis and pancreatic beta-cell loss at post-mortem are consistent with sustained retention of residual C-peptide secretion in LADA. Genetic association patterns at the human leucocyte antigen (HLA) and insulin gene (INS) regions are similar in UKPDS LADA patients and individuals with adult and childhood-onset Type 1 diabetes. The combined evidence suggests that LADA is an adult-onset form of Type 1 diabetes, rather than a separate condition or an intermediate state in a continuum of phenotype from Type 1 to Type 2 diabetes.