Should anti-glutamic acid decarboxylase antibody levels be determined in new-onset diabetes?

Abstract

By measuring C-peptide levels in patients with a clinical diagnosis of type 2 diabetes (based on information such as age at onset, presence of symptoms at onset, body weight, and family history), the diagnosis of type 2 diabetes can be confirmed in most cases, and treatment decisions can be based on the C-peptide level (1). When insulin reserve is quantified, however, the C-peptide level cannot be used as a predictor for later development of insulin insufficiency. Screening for glutamic acid decarboxylase (GAD) antibodies has revealed a surprisingly high number of patients with latent autoimmune diabetes in adults (LADA) who were previously assumed to have type 2 diabetes. In addition, we are now aware that at least 10% of cases of diabetes manifesting in children and adolescents are type 2 diabetes and are associated with insulin resistance. Finding negative results of an anti-GAD antibody determination in conjunction with a high-normal or high C-peptide level is supportive of the clinical diagnosis of type 2 diabetes in this group (2). Stratifying patients as having type 1 or type 2 diabetes is of more than academic interest because it will determine the appropriate therapy for these patients. Because better glycemic control and, therefore, fewer long-term complications are achieved in patients with type 2 diabetes by using an insulin sensitizer with or without insulin secretagogues or insulin, an insulin sensitizer is the choice for initial monotherapy. Alternatively, patients with type 1 diabetes are best treated by using insulin as a preventive agent from the onset. By taking over the function of the insulin-producing islet cells, insulin release declines or ceases from these cells; because the destructive autoimmune process attacks only insulin-producing cells, these cells may be protected from further damage. Preservation of endogenous insulin production will lead to less brittle diabetes (which is easier to control), and the better glycemic control obtained will result in fewer long-term complications of diabetes. Therefore, measuring anti-GAD antibodies and C-peptide levels is important to avoid misdiagnosing LADA or maturity-onset diabetes of youth . LADA AND ANTI-GAD ANTIBODIES Characteristically, the clinical onset of autoimmune diabetes occurs suddenly in childhood or adolescence and is associated with insulin deficiency. In contrast, patients with LADA have a much slower and more insidious onset of the disease and do not become insulin dependent for several years (2,3). Inasmuch as at least 60% of cases of