CONCLUSIONS

Our findings suggest that assessing multiple clinical features of presentation enables adults with diabetes to be triaged into two groups: lower risk for LADA (LADA clinical risk score ≤1) and higher-risk for LADA (LADA clinical risk score ≥2). The benefits of this screening tool approach for LADA are several. First, it assists in identification and management of patients with LADA. Physicians dealing with a patient who has a higher risk for LADA and who has suboptimal glycemic control should have an increased level of suspicion that the lack of control may be due to insulin deficiency secondary to autoimmune β-cell pathologic changes. With such a patient, it would be logical to perform islet antibody testing to exclude autoimmune diabetes. Our experience is that suboptimal glycemia in such patients is frequently prolonged because it is not attributed to autoimmune diabetes and insulin deficiency. Second, this simple clinical screening tool is practical and cost-effective. LADA can be excluded in a majority of adults with diabetes, e.g., approximately two-thirds (84 of 120) in the prospective study, on the basis of a clinical risk score ≤1. Finally, this screening tool could be used to identify subjects with LADA for inclusion in intervention trials. LADA populations are attractive candidates for autoimmune diabetes intervention trials because they have slowly progressive loss of β-cell function and therefore potentially a wider therapeutic window than in classic type 1 diabetes.

We have pragmatically adopted the five-point LADA clinical risk score over the multivariate scoring method to determine which patients should be tested for GADAs because it is simple to use and has better specificity in the prospective study. The use of the tool in clinical practice will depend on the reliability of the patient’s history, which can be influenced by language and culture, inaccurate reporting of acute symptoms, and lack of awareness of the family medical history. Diabetes in relatives of patients with LADA may also be misclassified, i.e., relatives with LADA may be diagnosed as having type 2 diabetes. Misclassification of diabetes in relatives could only be excluded by testing for islet antibodies. The ability of the LADA clinical risk score to predict LADA in the prospective study, a homogeneous source of diabetic patients, confirms the utility of the clinical screening tool. The applicability of our findings to LADA cohorts from other nations and ethnicities will be important to establish. Finally, testing for other islet antibodies in patients with high-risk LADA clinical risk scores ≥2 could potentially enhance our prediction of autoimmune diabetes, as some of these patients may be GADA− but IA-2A+ and/or IAA+.

In summary, a majority of patients with LADA have at least two of five distinguishing clinical features (age of onset <50 years, acute symptoms before diagnosis, BMI <25 kg/m2, personal history of autoimmune disease, or family history of autoimmune disease) at diagnosis of diabetes. The presence of at least two of these clinical features (LADA clinical risk score ≥2) in adults with diabetes justifies GADA testing. This clinical screening tool should increase the identification of autoimmune diabetes in adults and hopefully improve clinical management of their disease.