1. Prognostic Accuracy of Immunologic and Metabolic Markers for Type 1 Diabetes in a High-Risk Population: Receiver Operating Characteristic Analysis Featured Article: Ping Xu, M.P.H., Craig A. Beam, Ph.D., David Cuthbertson, M.S., Jay M. Sosenko, M.D., Jay S. Skyler, M.D., Jeffrey P. Krischer, Ph.D., The DPT-1 Study Group Diabetes Care Volume 35: 1975-1980 October, 2012

2. STUDY OBJECTIVE To establish and compare the prognostic accuracy of immunologic and metabolic markers in predicting onset of type 1 diabetes in high-risk individuals Xu P et al. Diabetes Care 2012;35:1975-1980

3. STUDY DESIGN AND METHODS 339 subjects from the Diabetes Prevention Trial–Type 1 (DPT-1) parenteral study followed until clinical diabetes onset or study end (5-year follow-up) Subjects were islet cell antibody (ICA)-positive, with low first- phase insulin response (FPIR) and/or abnormal glucose tolerance at baseline Prognostic performance of biomarkers estimated using receiver operating characteristic (ROC) curve analysis and compared with nonparametric testing of ROC curve areas Pearson correlation used to assess the relationship between the markers Xu P et al. Diabetes Care 2012;35:1975-1980

4. RESULTS Insulin autoantibody titer, ICA512A titer, peak C-peptide, 2-h glucose, FPIR, and FPIR/homeostasis model assessment of insulin resistance provided modest but significant prognostic values for 5-year risk, with a similar level of area under ROC curve between 0.61 and 0.67 Combining 2-h glucose, peak C-peptide, and area under the curve C-peptide improved the prognostic accuracy compared with any solitary index (P < 0.05), with an area under ROC curve of 0.76 (95% CI 0.70–0.81) Adding antibody titers and/or intravenous glucose tolerance test (IVGTT) markers did not increase the prognostic accuracy further (P = 0.46 and P = 0.66, respectively) Xu P et al. Diabetes Care 2012;35:1975-1980

8. CONCLUSIONS Combining metabolic markers derived from oral glucose tolerance test improved accuracy in predicting type 1 diabetes progression in a population with ICA positivity and abnormal metabolism Autoimmune activity may not alter the risk of type 1 diabetes after metabolic function has deteriorated Future consideration needed about eliminating IVGTT measurements as an effective cost-reduction strategy for prognostic purposes Xu P et al. Diabetes Care 2012;35:1975-1980