Diabetes classification: grey zones, sound and smoke: Action LADA 1

Diabetes Metab Res Rev. 2008 Oct;24(7):511-9. doi: 10.1002/dmrr.877.


Diseases gain identity from clinical phenotype as well as genetic and environmental aetiology. The definition of type 1 diabetes is clinically exclusive, comprising patients who are considered insulin dependent at diagnosis, whilst the definition of type 2 diabetes is inclusive, only excluding those who are initially insulin dependent. Ketosis-prone diabetes (KPD) and latent autoimmune diabetes in adults (LADA) are each exclusive forms of diabetes which are, at least initially, clinically distinct from type 2 diabetes and type 1 diabetes, and each have a different natural history from these major types of diabetes.KPD can be diagnosed unequivocally as diabetes presenting with the categorical clinical feature, ketoacidosis. In contrast, LADA can be diagnosed by the co-occurrence of three traits, not one of which is categorical or exclusive to the condition: adult-onset non-insulin-requiring diabetes, an islet autoantibody such as glutamic acid decarboxylase autoantibodies (GADA) or cytoplasmic islet cell autoantibodies (ICA), and no need for insulin treatment for several months post-diagnosis. But while some would split diabetes into distinct subtypes, there is a strong case that these subtypes form a continuum of varying severity of immune and metabolic dysfunction modified by genetic and non-genetic factors. This article discusses the nature of disease classification in general, and KPD and LADA in particular, emphasizing the potential value and pitfalls in classifying diabetes and suggesting a need for more research in this area.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adult
  • Autoantibodies / analysis
  • Autoimmune Diseases / classification*
  • Autoimmune Diseases / genetics
  • Diabetes Mellitus, Type 1 / classification*
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 2 / classification*
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetic Ketoacidosis / classification
  • Diabetic Ketoacidosis / genetics
  • Genetic Predisposition to Disease
  • Glutamate Decarboxylase / immunology
  • Humans
  • Insulin / metabolism
  • Insulin Resistance / genetics
  • Insulin Secretion
  • Islets of Langerhans / immunology


  • Autoantibodies
  • Insulin
  • Glutamate Decarboxylase