Latent autoimmune diabetes in adults (LADA)
— Older studies in predominantly Scandinavian populations have suggested that as many as 7.5 to 10 percent of adults in populations with a high prevalence of type 1 diabetes and with apparent type 2 diabetes may have circulating autoantibodies directed against pancreatic beta-cell antigens (islet-cell antibodies [ICA] or glutamic acid decarboxylase [GAD65]) [2-4
]. The prevalence of LADA is almost certainly lower in the more diverse US population. These adults do not require insulin at diagnosis but progress to insulin dependence after several months to years. This entity is sometimes referred to as "latent autoimmune diabetes in adults" (LADA) and may account for a very small fraction of all cases of diabetes [5-7
In genotyping analyses, LADA shares genetic features of both type 1 and type 2 diabetes [8-10
]. As an example, in one analysis, patients with LADA shared an increased frequency of risk for an HLA-DQB1 genotype with patients with type 1 diabetes and for a variant in the transcription factor 7-like 2 (TCF7L2) gene with patients with type 2 diabetes [8
]. The variant in TCF7L2 has been shown to increase the risk for type 2 diabetes in several populations, and the effect size was similar for LADA and type 2 diabetes [9
]. Thus, LADA appears to be on the spectrum of insulin deficiency between type 1 and type 2 diabetes. (See "Pathogenesis of type 1 diabetes mellitus", section on 'Autoimmunity'
and "Pathogenesis of type 2 diabetes mellitus", section on 'Genetic susceptibility'
Patients with LADA are a heterogeneous group of patients with variable titers of antibodies, body mass index, and frequency of progression to insulin independence [11
]. Patients with high compared with low titers of GAD65 antibodies usually have a lower body mass index, less endogenous insulin secretion (as measured by stimulated serum C-peptide concentrations), and progress more quickly to insulin dependence [11,12
]. Thus, the presence and titers of anti-GAD antibodies (or ICA) can help to identify patients thought to have type 2 diabetes, who are likely to respond poorly to oral hypoglycemic drug therapy, require insulin, and to be at increased risk for developing ketoacidosis [4,5,11-13
]. Studies are underway to determine whether early treatment with insulin or use of immunomodulator therapy can prevent disease progression [6
]. (See 'Distinguishing type 1 from type 2 diabetes'