Prognostic Accuracy of Immunologic and Metabolic Markers for Type 1 Diabetes in a High-Risk Population: Receiver Operating

Characteristic Analysis

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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

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

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

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

Xu P et al. Diabetes Care 2012;35:1975-1980

Xu P et al. Diabetes Care 2012;35:1975-1980

Xu P et al. Diabetes Care 2012;35:1975-1980

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