Use of HbA1c for diagnoses of diabetes and prediabetes: comparison with diagnoses based on fasting and 2-hr glucose values and effects of gender, race, and age

Abstract

Background: Glycated hemoglobin (HbA1c) has been advocated for the diagnosis of diabetes and prediabetes. Its performance has been commonly assessed in corroboration with elevated fasting plasma glucose (FPG), but not the combination of FPG and 2-hr glucose values. This study assesses receiver operating characteristics (ROC) curves of HbA1c pertaining to the diagnoses of prediabetes and diabetes by FPG and/or 2-hr glucose, and the effects of age, gender, and race.

Methods: We assessed the utility of HbA1c for diagnosing diabetes and prediabetes among 5395 adults without known diabetes from the National Health and Nutrition Examination Survey (NHANES) 2005-2010.

Results: Current cutoffs of HbA1c for diabetes (6.5%) or prediabetes (5.7%) exhibited low sensitivity (0.249 and 0.354, respectively) and high specificity in identifying patients diagnosed using both FPG and 2-hr glucose, resulting in large false-negative rates (75.1% and 64.9%). Misdiagnosis rates increased with age and in non-Hispanic whites and Mexican Americans. When HbA1c was combined with FPG for diagnoses, the false-negative rate remained high for diabetes (45.7%), but was reduced for prediabetes (9.2%).

Conclusions: When assessed against diagnoses using both FPG and 2-hr glucose, HbA1c had low sensitivity and high specificity for identifying diabetes and prediabetes, which varied as a function of age and race. Regarding recently released American Diabetes Association (ADA) and joint European guidelines, it is important to consider that HbA1c values below 6.5% and 5.7% do not reliably exclude the presence of diabetes and prediabetes, respectively. Overall, the data argue for greater use of oral glucose tolerance tests (OGTTs) and both FPG and 2-hr glucose values for diagnosis of diabetes and prediabetes.

FIG. 1.

Fasting plasma glucose and 2-hr glucose with glycated hemoglobin (HbA1c) levels among US adults (≥20 years) in National Health and Nutrition Examination Survey (NHANES) 2005–2010. (A) Fasting plasma glucose and HbA1c. (B) 2-hr glucose and HbA1c.

FIG. 2.

Receiver operating characteristics (ROC) curves of glycated hemoglobin (HbA1c) for diagnosis of diabetes. (A) ROC curves of HbA1c for diagnosis of diabetes (fasting glucose •126 mg/dl). (B) ROC curves of HbA1c for diagnosis of diabetes (2-hr glucose •200 mg/dl and FPG <126 mg/dl). (C) ROC curves of HbA1c for diagnosis of diabetes (FPG •126 mg/dl and/or 2-hr glucose •200 mg/dl). (D) ROC curves of HbA1c for diagnosis of diabetes (FPG •126 mg/dl and 2-hr glucose •200 mg/dl). *Area under the ROC curve (standard error). (†) p value for comparison of AUC between groups. Women were compared with men, whereas Mexican American and non-Hispanic black with non-Hispanic white, and 60+years and 40–59 years with 20–39 years. ♦HbA1c 6.5%. FPG, fasting plasma glucose.

FIG. 2.

Receiver operating characteristics (ROC) curves of glycated hemoglobin (HbA1c) for diagnosis of diabetes. (A) ROC curves of HbA1c for diagnosis of diabetes (fasting glucose •126 mg/dl). (B) ROC curves of HbA1c for diagnosis of diabetes (2-hr glucose •200 mg/dl and FPG <126 mg/dl). (C) ROC curves of HbA1c for diagnosis of diabetes (FPG •126 mg/dl and/or 2-hr glucose •200 mg/dl). (D) ROC curves of HbA1c for diagnosis of diabetes (FPG •126 mg/dl and 2-hr glucose •200 mg/dl). *Area under the ROC curve (standard error). (†) p value for comparison of AUC between groups. Women were compared with men, whereas Mexican American and non-Hispanic black with non-Hispanic white, and 60+years and 40–59 years with 20–39 years. ♦HbA1c 6.5%. FPG, fasting plasma glucose.

FIG. 3.

Receiver operating characteristics (ROC) curves of glycated hemoglobin (HbA1c) for diagnosis of prediabetes. (A) ROC curves of HbA1c for diagnosis of IFG (100• fasting plasma glucose <126 mg/dl, and HbA1c <6.5%). (B) ROC curves of HbA1c for diagnosis of IGT (140• 2-hr glucose <200 mg/dl, fasting plasma glucose <100 mg/dl, and HbA1c <6.5%). (C) ROC curves of HbA1c for diagnosis of IFG and/or IGT (fasting plasma glucose •100 mg/dl or 2-hr glucose •140mg/dl) in participants (fasting plasma glucose <126 mg/dl, 2-hr glucose <200 mg/dl and HbA1c <6.5%). *Area under the ROC curve (standard error). (†) p value for comparison of area under the curve (AUC) between groups. Women were compared with men, whereas Mexican American and non-Hispanic black with non-Hispanic White, and 60+years and 40–59 years with 20–30 years. ♦HbA1c 5.7%.