A Clinical Screening Tool Identifies Autoimmune Diabetes in Adults: Part 2

Latent autoimmune diabetes in adults (LADA) is a form of type 1 diabetes characterized by adult-onset diabetes (usually age >30 years), circulating islet antibodies, most commonly to GAD, and, initially, lack of requirement for insulin treatment. Based on findings in the U.K. Prospective Diabetes Study (UKPDS), ∼10% of adults with diabetes have LADA. LADA is believed to be a slowly progressive form of autoimmune β-cell destruction, given that people with LADA have evidence of islet autoimmunity, namely circulating islet antibodies and type 1 diabetes susceptibility HLA class II alleles DQ2 and/or DQ8. Tissue immunofluorescence islet cell antibodies and GAD antibodies (GADAs) are common in LADA, whereas antibodies to tyrosine phosphatase–like insulinoma antigen 2 (IA-2A) and insulin (IAAs) are not common. Patients with LADA typically present with more preserved β-cell function than those with classic type 1 diabetes but usually experience marked loss of β-cell function within 3 years of diagnosis, which eventually results in insulin dependence.

Detection of islet autoimmunity in adult-onset diabetes has prognostic and treatment implications. In the UKPDS, a majority of adults with diabetes, who had detectable GADAs, required insulin treatment within 6 years of diagnosis. We believe that physicians need to be aware that patients with LADA are prone to insulin deficiency and often require rapid escalation of oral hypoglycemic treatment or commencement of insulin earlier than islet antibody–negative patients.

Despite the frequency of LADA, there are no universal recommendations regarding testing for islet antibodies in adult-onset diabetes. Currently, many physicians test for islet antibodies only if they suspect LADA, generally on the basis of body weight. Overweight adults with diabetes are presumed to have type 2 diabetes and are not tested, whereas normal-weight adults are considered to potentially have LADA and may be tested. However, this approach neglects the many studies in which LADA has been documented with mean BMI in the overweight or even obese category. Moreover, with increasing obesity in adults worldwide, it will become even more difficult to distinguish LADA from type 2 diabetes based on BMI. A reliable clinical strategy is required to identify which adults with diabetes have a high likelihood of LADA and need testing for islet antibodies. Thus, we aimed to identify clinical features that distinguished LADA in adults presenting with diabetes and to establish a clinical screening tool that would improve the detection of LADA and ultimately the management of patients with LADA.