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. 2017 Mar;19(3):183-187.
doi: 10.1089/dia.2016.0243. Epub 2017 Feb 8.

The Use of Electrochemiluminescence Assays to Predict Autoantibody and Glycemic Progression Toward Type 1 Diabetes in Individuals with Single Autoantibodies

Jay M Sosenko  1 , Liping Yu  2 , Jay S Skyler  1 , Jeffrey P Krischer  3 , Peter A Gottlieb  2 , David Boulware  3 , Dongmei Miao  2 , Jerry P Palmer  4 , Andrea K Steck  2
Affiliations

The Use of Electrochemiluminescence Assays to Predict Autoantibody and Glycemic Progression Toward Type 1 Diabetes in Individuals with Single Autoantibodies

Jay M Sosenko et al. Diabetes Technol Ther. 2017 Mar.

Abstract

Background: Electrochemiluminescence (ECL) assays have shown promise for enhancing the prediction of type 1 diabetes (T1D) with autoantibodies. We thus studied relatives of T1D patients to determine whether ECL assays can be used to refine risk assessments for T1D among individuals either positive for single GADA or single mIAA autoantibodies.

Subjects and methods: TrialNet Pathway to Prevention (PTP) study participants with either GADA or mIAA single autoantibodies were tested for ECL positivity during their participation in the TrialNet PTP study. Those ECL positive (ECL+) were compared with those ECL negative (ECL-) for conversion to multiple autoantibodies, 6-month glycemic progression (PS6M), and the progression to T1D.

Results: The progression to multiple autoantibodies was significantly higher for those GADA/ECL+ (n = 107) than those GADA/ECL- (n = 78) (P = 0.001) and for those mIAA/ECL+ (n = 24) than those mIAA/ECL- (n = 63) (P < 0.001). The hazard ratios with 95% confidence intervals were 3.42 (1.58-7.39; P < 0.01) for GADA and 8.15 (3.02-22.00; P < 0.001) for mIAA. GADA/ECL+ and mIAA/ECL+ participants had significantly higher PS6M values than their ECL- counterparts (P = 0.001 for GADA and P = 0.009 for mIAA). Of those GADA/ECL+, 14% progressed to T1D; of those mIAA/ECL+, 17% progressed to T1D. Only 1 individual (positive for GADA) of the 141 who was ECL- progressed to T1D (median follow-up: 5 years).

Conclusion: ECL measurements appear to have utility for natural history studies and prevention trials of individuals with single autoantibodies. Those ECL+ are at appreciable risk for developing multiple autoantibodies and for glycemic progression toward T1D, whereas those ECL- are at very low risk.

Keywords: Autoantibodies; Hyperglycemia; Pediatrics; Type 1 diabetes.

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Conflict of interest statement

No competing financial interests exist with regard to this article for any of the authors. J.M.S. analyzed data and wrote the manuscript. L.Y. performed the assays and reviewed the manuscript. J.S.S. conducted the study and reviewed the manuscript. J.P.K. conducted the study and reviewed the manuscript. P.A.G. conducted the study and reviewed the manuscript. D.B. performed programming and provided statistical support. D.M. performed the assays and reviewed the manuscript. J.P.P. conducted the study and reviewed the manuscript. A.K.S. conducted the study, reviewed the manuscript, and assisted in writing the manuscript.

Figures

<b>FIG. 1.</b>
FIG. 1.
Shown are cumulative incidence curves according to ECL status for progression to multiple autoantibodies among Pathway to Prevention participants with single GADA autoantibodies (A) or with single mIAA autoantibodies (B). The progression was substantially higher among those ECL+ for both GADA and mIAA. Proportions of those who developed multiple autoantibodies are indicated in parentheses. ECL, electrochemiluminescence.
See this image and copyright information in PMC

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