Titre and combination of ICA and autoantibodies to glutamic acid decarboxylase discriminate two clinically distinct types of latent autoimmune diabetes in adults (LADA)

Aims/hypothesis. This study aimed to define the immunological parameters which could be used to identify patients with the distinct metabolic features of adult latent autoimmune diabetes. Methods. Sera of 312 patients with short-term diabetes (duration < 5 years) over 35 years of age at diagnosis were screened for ICA, GAD- and IA2-Ab by antibody assays validated in workshops. The antibody status was correlated with age, BMI, residual beta-cell function, measured by fasting C-peptide, onset of diabetes-related complications and markers of the metabolic syndrome (hypertension and hyperlipidaemia). Results. A total of 51 antibody positive patients were identified. These patients had lower fasting C-peptide and less neuropathy and hypertension compared with matched antibody-negative patients. However, only patients with two or more antibodies had reduced residual beta-cell function compared with antibody-negative or single antibody-positive (ICA or GAD-Ab only) patients. Patients with two or more antibodies were also leaner and had diabetes-related complications or hypertension less frequently than single antibody-positive or antibody negative-patients. IA2 antibody status did not substantially contribute to the diagnosis or differentiation of LADA patients. Conclusion/interpretation. We concluded that the combination of ICA and GAD antibodies and high titre of GAD antibodies are characteristic of patients with insulin deficiency with the clinical features of Type I (insulin-dependent) diabetes mellitus (LADA-type 1). Single antibody positivity and low titre antibodies are markers for LADA-type 2 associated with the clinical and metabolic phenotype of Type II (non-insulin-dependent) diabetes patients.