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Increasing ICA512 autoantibody titers predict development of abnormal oral glucose tolerance tests
Author(s) -
Sanda Srinath
Publication year - 2018
Publication title -
pediatric diabetes
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.678
H-Index - 75
eISSN - 1399-5448
pISSN - 1399-543X
DOI - 10.1111/pedi.12542
Subject(s) - autoantibody , titer , medicine , diabetes mellitus , type 1 diabetes , endocrinology , odds ratio , glucose tolerance test , immunology , antibody , insulin resistance
Objective Determine if autoantibody titer magnitude and variability predict glucose abnormalities in subjects at risk for type 1 diabetes. Research Designs and Methods Demographic information, longitudinal autoantibody titers, and oral glucose tolerance test ( OGTT ) data were obtained from the TrialNet Pathway to Prevention study. Subjects (first and second degree relatives of individuals with type 1 diabetes) with at least 2 diabetes autoantibodies were selected for analysis. Autoantibody titer means were calculated for each subject for the duration of study participation and the relationship between titer tertiles and glucose value tertiles from OGTTs (normal, impaired, and diabetes) was assessed with a proportional odds ordinal regression model. A matched pairs analysis was used to examine the relationship between changes in individual autoantibody titers and 120‐minute glucose values. Titer variability was quantified using cumulative titer standard deviations. Results We studied 778 subjects recruited in the TrialNet Pathway to Prevention study between 2006 and 2014. Increased cumulative mean titer values for both ICA512 and GAD65 (estimated increase in proportional odds = 1.61, 95% CI = 1.39, 1.87, P < 1 × 10 −9 and 1.17, 95% CI = 1.03, 1.32, P = .016, respectively) were associated with peak 120‐minute glucose values. While fluctuating titer levels were observed in some subjects, no significant relationship between titer standard deviation and glucose values was observed. Conclusion ICA512 autoantibody titers associate with progressive abnormalities in glucose metabolism in subjects at risk for type 1 diabetes. Fluctuations in autoantibody titers do not correlate with lower rates of progression to clinical disease.