Clinical, Genetic and Metabolic Characterisation of LADA (Latent Autoimmune Diabetes in Adults)

Abstract: Latent autoimmune diabetes in adults (LADA) comprises about 10% of patients initially diagnosed with type 2 diabetes but who are positive for pancreatic islet antibodies, especially to glutamic acid decarboxylase (GADabs). The present studies focused on clinical, genetic and metabolic characterisation of patients with LADA. In LADA, the frequency of the type 1 diabetes susceptibility genotype HLA-DQB1'0201/'0302 and genotypes including the 0302 allele was higher than in type 2 diabetes but lower than in type 1 diabetes. No difference was seen between LADA and type 2 diabetic or control subjects regarding the frequency of the insulin gene alleles associated with the risk of type 1 diabetes, whereas the frequency of these alleles was high in type 1 diabetic patients. In the LADA subjects, beta-cell function was significantly impaired at diagnosis compared with type 2 diabetic patients, but was markedly better preserved compared with age-matched adult type 1 diabetic patients. GADab positivity was linked with decreased insulin secretion in non-diabetic subjects, suggesting that GADabs are markers of beta-cell autoimmunity, although this does not always lead to overt diabetes. Features of the metabolic syndrome in LADA were fewer than in type 2 diabetes but more common than in type 1 diabetes. The results show that although LADA shares characteristics with both type 1 and type 2 diabetes it can be clinically, genetically, and metabolically distinguished from both types. The distinction is of clinical importance for identifying LADA and to achieve proper care of these patients.