B R I E F R E P O R T
Time to Insulin Initiation Cannot Be Used in Deﬁning Latent Autoimmune Diabetes in Adults
SINEAD BROPHY, PHD1 KNUD YDERSTRÆDE, PHD2 DIDAC MAURICIO, PHD3 STEPHEN HUNTER, PHD4 MOHAMMED HAWA, PHD5 PAOLO POZZILLI, PHD6 GUNTRAM SCHERNTHANER, PHD7 NANETTE SCHOOT, PHD8 RAFFAELLA BUZZETTI, PHD9 HELEN DAVIES, PHD1 DAVIDLESLIE, PHD5 RHYS WILLIAMS, PHD1 ON BEHALF OF THE ACTION LADA GROUP* in the London Hospital using a Diabetes Antibody Standardization Programme (DASP) validated assay (in the 2005 DASP antibody workshop, the assay had a sensitivity 72% and speciﬁcity 95%). Values 70 World Health Organization units were regarded as positive. All patients were assayed in duplicate and included an in-house positive andnegative control subject. Clinicians in all nine centers completed a questionnaire reporting the criteria for initiating insulin in their center. One questionnaire per center reported the consensus opinion of the clinicians in that center. Center size varied between two and seven clinicians. The medical notes of the GAD-positive patients (522 of 5,812) were analyzed to examine time to insulin.Three centers were excluded from the analysis because these data were not in a format that could be analyzed. Cox regression/Kaplan-Meier analysis were used to examine survival in terms of time to insulin in GAD-positive patients in centers performing routine GADA testing compared with those not testing for GADA. RESULTS — The criteria for initiating insulin varied between centers. All used A1C andweight loss, eight of nine considered ketones, seven of nine considered complications, six of nine considered patient preference and/or other treatments, and ﬁve of nine used age and/or Cpeptide. All the centers except two in the U.K. used GADA testing. In centers where GADA testing was performed, the median time to insulin treatment for those testing GADA positive in the central laboratory wasearlier compared with that for centers with no GAD testing (Fig. 1). For GAD testing centers (Odense, n 32; Barcelona, n 67; Vienna, n 35; and Lyon, n 68), the median time was 4.8 (interquartile range 0 –12.8), 9.4 (1.1–17.8), 31 (3.5–59), and 29.4 (17.6 – 41) months, respectively, compared with that of non–GADA testing areas (Belfast, n 66; London, n 50) where median time (months) to insulintreatment was 38.1 (20.5–55.6) and 47 (29.5– 64.8) months (P
OBJECTIVE — Latent autoimmune diabetes in adults is type 1 diabetes presenting as non– insulin dependent diabetes. One feature of the selection criteria is time independent of insulin treatment. We examine the validity of this criterion. RESEARCH DESIGN AND METHODS — Patients were recruited in nine European centers, and cliniciansreported on criteria for initiating insulin. All patients were tested for GAD antibodies (GADAs) in a central laboratory. We examined time to insulin treatment for GADApositive patients in six participating centers. RESULTS — There was intercenter variation in the criteria used to initiate insulin. Median time to insulin was 16.15 months (interqartile range 6.7–25.5) in centers with GADA testingcompared with 45.6 months (29.5– 61.8) in centers without routine GADA testing (P 0.002). CONCLUSION — Time to insulin should not be used to deﬁne patients with LADA because it is dependent on local clinical judgment and the use of laboratory tests for GADA. Diabetes Care 31:439–441, 2008
atent autoimmune diabetes in adults (LADA) is a term applied to patients with apparent type 2 diabetes butwho have pancreatic islet cell autoantibodies. LADA patients have features of type 1 diabetes, including genetic risk markers and reduced rates of the metabolic syndrome (1–3). However, the selection criteria used in LADA research varies greatly (4 –13). While time from diagnosis to insulin treatment is not included in some deﬁnitions, others require
freedom from insulin treatment for a...