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

Abstract

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.

Metabolic Syndrome and Autoimmune Diabetes: Action LADA 3

“…Diabetes was designated according to standard criteria, and LADA was defined as patients aged 30 -70 years with GADAs who did not require insulin treatment for at least 6 months after diagnosis (7,8). Type 1 diabetic patients and normal subjects fulfilling the inclusion criteria were ascertained consecutively from three of these five European centers (London, Barcelona, and Rome).…”

“…Several groups, including the International Diabetes Federation (IDF) and the National Cholesterol Education Program (NCEP), with Adult Treatment Panel III (6), have proposed their own definitions for the metabolic syndrome. LADA is clearly distinct from type 2 diabetes, in that LADA is associated with histocompatability (HLA) genes, diabetes-associated autoantibodies, reduced insulin secretion, no need for insulin therapy initially after diagnosis, and less prevalence of metabolic syndrome (7)(8)(9). The key question is whether LADA is distinct from type 1 diabetes (1,10,11), that is, whether LADA is one end of a rainbow of pathophysiological variations encompassing autoimmune diabetes with a frequency of metabolic syndrome similar to that of childhood-onset type 1 diabetes or whether LADA is a distinct form of autoimmune diabetes that resembles type 2 diabetes, showing evidence of insulin resistance with a high frequency of metabolic syndrome (1).…”

Latent autoimmune diabetes in adults in a population-based cohort of Polish patients with newly diagnosed diabetes mellitus

“…Although a recent hypothesis proposed that LADA is a mixture of two major types of diabetes, comprising a heterogeneous population, it can be identified mainly based on the presence of auto-antibodies [1].…”

“…Anti-insulin antibody has now been demonstrated as an autoimmune marker for prediction and diagnosis of type 1 diabetes [12,13]. According to the Immunology of Diabetes Society, IAA can also be used to identify patients with LADA [1]. In a large Chinese population, IAA was found to be present (3.39%) in phenotypic type 2 diabetes patients and, in combination with GADA, significantly increased the number of patients diagnosed with LADA [14].…”

Glutamic Acid Decarboxylase Autoantibodies Role in Reclassifying Diabetes of Adulthood in Basrah

“…Diabetes was designated according to standard criteria, and LADA was defined as patients aged at time of diagnosis 30 years or more with GADA-positive who did not require insulin treatment for at least 6 months after diagnosis [16]. Participants were classified according to the following definitions: type 1 diabetes, insulin-dependent <6 months from diagnosis; LADA, GADApositive, age ≥ 30 years and insulin-independent ≥6 months from diagnosis; type 2 diabetes, GADA-negative and insulin-independent ≥6 months from diagnosis.…”