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,
- the TEDDY, TRIGR,,
- Diabetes Prevention Trial-Type 1, and 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.
- Received January 17, 2012.
- Accepted April 10, 2012.
- © 2012 by the American Diabetes Association.
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