Performance of HbA1c as an early diagnostic indicator of type 1 diabetes in children and youth.
OBJECTIVE
The aim of this study was to evaluate HbA(1c) as an alternative criterion for impaired glucose tolerance (IGT) or type 1 diabetes (T1D) in high-risk subjects <21 years of age.


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 HbA(1c) 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. HbA(1c) ≥5.7% defined IGT, and HbA(1c) ≥ 6.5% defined diabetes. Receiver-operating characteristic curve analysis was used to assess diagnostic accuracy of HbA(1c) 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, HbA(1c) sensitivity was very low across the studies (8-42%), and specificity was variable (64-95%). With HbA(1c) ≥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 HbA(1c) ≥6.5% for the development of T1D was variable (50-94%) across the four studies.


CONCLUSIONS
HbA(1c) ≥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 HbA(1c) threshold is recommended if used as an alternative criterion in diagnosing T1D.
Department of Pediatrics, Morsani College of Medicine, Universityof South Florida, Tampa, FL, USA. kendra.vehik@epi.usf.edu
Kendra
K
Vehik
David
D
Cuthbertson
David
D
Boulware
Craig A
CA
Beam
Henry
H
Rodriguez
Laurent
L
Legault
Mila
M
Hyytinen
Marian J
MJ
Rewers
Desmond A
DA
Schatz
Jeffrey P
JP
Krischer
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis* / Q000378:metabolism*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D008297:Male; D055815:Young Adult
D006442:Glycated Hemoglobin