Performance of HbA1c as an Early Diagnostic Indicator of Type 1 Diabetes in Children and Youth
- Kendra Vehik, PHD1⇓,
- David Cuthbertson, MS1,
- David Boulware, MS1,
- Craig A. Beam, PHD1,
- Henry Rodriguez, MD2,
- Laurent Legault, MD3,
- Mila Hyytinen, PHD4,
- Marian J. Rewers, MD, PHD5,
- Desmond A. Schatz, MD6,
- Jeffrey P. Krischer, PHD1 and
- the TEDDY, TRIGR, Diabetes Prevention Trial–Type 1, and Type 1 Diabetes TrialNet Natural History Study Groups
- 1Department of Pediatrics, Pediatrics Epidemiology Center, Morsani College of Medicine, University of South Florida, Tampa, Florida
- 2Morsani Diabetes Center, University of South Florida, Tampa, Florida
- 3McGill University Health Center, Montreal, Quebec, Canada
- 4Institute of Clinical Medicine, University of Helsinki, Helsinki, Finland
- 5Barbara Davis Center, University of Colorado, Aurora, Colorado
- 6Department of Pediatrics, College of Medicine, University of Florida, Gainesville, Florida
- Corresponding author: Kendra Vehik, .
OBJECTIVE The aim of this study was to evaluate HbA1c as an alternative criterion for impaired glucose tolerance (IGT) or type 1 diabetes (T1D) in high-risk subjects <21 years of age.
RESEARCH DESIGN AND METHODS Subjects <21 years of age who participated in the prospective DPT-1, TEDDY, TRIGR, and Type 1 Diabetes TrialNet Natural History (TrialNet) studies and had an HbA1c within 90 days of an OGTT with a 2-h plasma glucose (2-hPG) measure were included. An OGTT of 140–199 mg/dL defined IGT, and an OGTT with 2-hPG ≥200 mg/dL or fasting plasma glucose ≥126 mg/dL defined diabetes. HbA1c ≥5.7% defined IGT, and HbA1c ≥ 6.5% defined diabetes. Receiver-operating characteristic curve analysis was used to assess diagnostic accuracy of HbA1c compared with OGTT.
RESULTS There were 587 subjects from DPT-1, 884 from TrialNet, 91 from TEDDY, and 420 from TRIGR. As an indicator for IGT, HbA1c sensitivity was very low across the studies (8–42%), and specificity was variable (64–95%). With HbA1c ≥6.5% threshold used for T1D diagnosis, the sensitivity was very low and specificity was high (sensitivity and specificity: DPT-1 24 and 98%, TrialNet 28 and 99%, TEDDY 34 and 98%, and TRIGR 33 and 99%, respectively). The positive predictive value of HbA1c ≥6.5% for the development of T1D was variable (50–94%) across the four studies.
CONCLUSIONS HbA1c ≥6.5% is a specific but not sensitive early indicator for T1D in high-risk subjects <21 years of age diagnosed by OGTT or asymptomatic hyperglycemia. Redefining the HbA1c threshold is recommended if used as an alternative criterion in diagnosing T1D.
This article contains Supplementary Data online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc12-0111/-/DC1.
The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the NIH, JDRF, or ADA and does not reflect the views of the Commission of the European Communities or in any way anticipate the Commission’s future policy in this area.
- Received January 17, 2012.
- Accepted April 10, 2012.
- © 2012 by the American Diabetes Association.
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