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A Clinical Screening Tool Identifies Autoimmune Diabetes in Adults

¹ Autoimmunity and Transplantation Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
² Department of Diabetes and Endocrinology, The Royal Melbourne Hospital, Parkville, Victoria, Australia
³ Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia

Address correspondence and reprint requests to Peter G. Colman. Department of Diabetes and Endocrinology, The Royal Melbourne Hospital, Parkville 3050, Victoria, Australia. E-mail: peter.colman{at}mh.org.au

OBJECTIVE—Latent autoimmune diabetes in adults (LADA) is defined as adult-onset diabetes with circulating islet antibodies but not requiring insulin therapy initially. Diagnosing LADA has treatment implications because of the high risk of progression to insulin dependency. Currently, there are no recommendations for islet antibody testing in adult-onset diabetes. In this study, we aimed to develop a clinical screening tool to identify adults at high risk of LADA who require islet antibody testing.

RESEARCH DESIGN AND METHODS—Subjects with LADA (n = 102, GAD antibody [GADA]+) and type 2 diabetes (n = 111, GADA–) (aged 30–75 years) were interviewed retrospectively. The clinical features documented were age of onset, acute symptoms of hyperglycemia, BMI, and personal and family history of autoimmune disease. Any clinical feature that was significantly more frequent in LADA was designated as a distinguishing clinical feature. In each subject, a "LADA clinical risk score," based on the total number of distinguishing features, was calculated. A prospective study of adults with newly diagnosed diabetes (n = 130) was used to determine whether the LADA clinical risk score could identify LADA.

RESULTS—In the retrospective study, five clinical features were more frequent in LADA compared with type 2 diabetes at diagnosis: 1) age of onset <50 years (P < 0.0001), 2) acute symptoms (P < 0.0001), 3) BMI <25 kg/m² (P = 0.0004), 4) personal history of autoimmune disease (P = 0.011), and 5) family history of autoimmune disease (P = 0.024). In the prospective study, the presence of at least two of these distinguishing clinical features (LADA clinical risk score 2) had a 90% sensitivity and 71% specificity for identifying LADA and a negative predictive value for a LADA clinical risk score 1 of 99%.

CONCLUSIONS—At least two distinguishing clinical features are found in a majority of patients with LADA at diagnosis and can be used to identify adults with diabetes at higher risk for LADA.

Abbreviations: AUC, area under the curve • GADA, GAD antibody • IA-2A, tyrosine phosphatase–like insulinoma antigen 2 • IAA, insulin autoantibody • LADA, latent autoimmune diabetes in adults • ROC, relative operating characteristic • UKPDS, U.K. Prospective Diabetes Study

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