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



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.



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).



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.
1 Division of Endocrinology, University of Miami , Miller School of Medicine, Miami, Florida.
Jay M
JM
Sosenko
2 Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine , Aurora, Colorado.
Liping
L
Yu
1 Division of Endocrinology, University of Miami , Miller School of Medicine, Miami, Florida.
Jay S
JS
Skyler
3 Division of Informatics and Biostatistics, University of South Florida , Tampa, Florida.
Jeffrey P
JP
Krischer
2 Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine , Aurora, Colorado.
Peter A
PA
Gottlieb
3 Division of Informatics and Biostatistics, University of South Florida , Tampa, Florida.
David
D
Boulware
2 Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine , Aurora, Colorado.
Dongmei
D
Miao
4 VA Puget Sound Health Care System, Division of Endocrinology, Metabolism, and Nutrition, University of Washington , Seattle, Washington.
Jerry P
JP
Palmer
2 Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine , Aurora, Colorado.
Andrea K
AK
Steck
D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D001786:Blood Glucose / Q000032:analysis*; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000276:immunology*; D018450:Disease Progression; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology; D006801:Humans; D007330:Insulin Antibodies / Q000097:blood* / Q000276:immunology; D008163:Luminescent Measurements; D008297:Male; D055815:Young Adult
D001323:Autoantibodies; D001786:Blood Glucose; D007330:Insulin Antibodies; D005968:Glutamate Decarboxylase
Autoantibodies; Hyperglycemia; Pediatrics; Type 1 diabetes