HbA1c is widely used for diagnosis and management of diabetes and prediabetes, but HbA1c may be high or low relative to underlying glucose levels in different individuals-“mismatches.” We hypothesized that “high mismatches” could lead to overdiagnosis, and “low mismatches” to underdiagnosis of diabetes and prediabetes. We pooled 31generally healthy subjects without known diabetes from the Screening for Impaired Glucose Tolerance study (n=1571) and the VA Screening for Diabetes study (n=1535); each had a 75g OGTT and a 50g glucose challenge on separate days. Subjects were 66% male, 65% black, with mean age 52 year, BMI 30 kg/m2 and HbA1c 5.6%. By ADA OGTT criteria, 56% had normal glucose metabolism (NGM, FPG <100 and 2hPG <140), 37% had prediabetes (PreDM), and 7% had T2DM (FPG >125 or 2hPG >199). To approximate glucose levels during the day, we took the mean of each subject’s OGTT FPG and 2hPG, and 1 hPG after 50 g glucose. Linear regression was used to derive [predicted HbA1c = 0.0078*GLUC + 4.70], from which the HbA1c Glycation Index (HGI) for each subject was expressed as [observed-predicted HbA1c]. Subjects were divided into tertiles according to their HGI levels: “high mismatch” (high HGI), “no mismatch” (mod HGI), and “low mismatch” (low HGI). The “high mismatch” group was enriched in African-Americans (84%) and males (78%) but otherwise clinically comparable, all p<0.001. By ADA OGTT criteria, the distribution of NGM, PreDM, and T2DM (55%, 37%, 7%, resp) was comparable across HGI tertiles. However, by ADA HbA1c criteria, the “no mismatch” group had 67% NGM, 32% PreDM, and 1% T2DM, but “high mismatches” were 7% NGM, 80% PreDM, and 13% T2DM-mostly abnormal, and “low mismatches” were 96% NGM, 4% PreDM, and 0% T2DM-mostly normal.

Conclusion: “Mismatches” in HbA1c vs. glucose are common, and could lead to errors if the diagnosis is based only on HbA1c - overdiagnosis in “high mismatches”, and underdiagnosis in “low mismatches.” FPG and/or OGTT should be used to complement HbA1c in diagnosing diabetes and prediabetes.


A. Gonzalez: None. X. Cui: None. L.R. Staimez: None. C.N. Ford: None. F.N. Khan: None. P.W. Wilson: None. L.S. Phillips: Other Relationship; Self; DIASYST Inc.. Research Support; Self; Amylin Pharmaceuticals, Eli Lilly and Company, Novo Nordisk Inc., Sanofi-Aventis, PhaseBio Pharmaceuticals, Inc., Roche Diabetes Care Health and Digital Solutions, AbbVie Inc., Vascular Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., GlaxoSmithKline plc., Pfizer Inc.. Other Relationship; Self; Novartis Pharmaceuticals Corporation, Merck & Co., Inc.. M. Rhee: None.

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