HbA_1c Measurements Do Not Improve the Detection of Type 2 Diabetes in a Randomly Selected Population

Perry et al. (1) compared the sensitivity of fasting plasma glucose (FPG) concentrations and HbA_1c levels to diagnose diabetes in high-risk subjects whose 2-h glucose concentrations on an oral glucose tolerance test (OGTT) exceeded 11.1 mmol/l (200 mg/dl) and therefore met the OGTT criterion for diabetes (2). A total of 950 subjects with the following high-risk parameters were recruited: 1) obesity (BMI ≥24 kg/m²), 2) a family history of diabetes, and 3) individuals who had been told that they had “a touch of sugar,” “borderline diabetes,” or “glucose intolerance.” Of these subjects, 244 had FPG concentrations between 5.5 and 8.0 mmol/l (99 and 144 mg/dl) and underwent an OGTT. Of the 121 subjects with OGTT-diagnosed diabetes, 101 had complete data that also included FPG and HbA_1c values; 45% had an FPG concentration of ≥7.0 mmol/l, whereas 62% had an HbA_1c level exceeding the upper limit of normal (ULN) for the assay used (6.1%). The authors concluded that in a high-risk population with FPG concentrations between 5.5 and 8.0 mmol/l (99 and 144 mg/dl), an elevated HbA_1c level was more sensitive in diagnosing diabetes than an FPG concentration ≥7.0 mmol/l (126 mg/dl), the FPG criterion for the diagnosis (2). They appropriately raised the question of whether this conclusion was justified in more general populations.

We have attempted to answer this question in the randomly selected population evaluated in the Third National Health and Nutrition Examination Survey (NHANES III). NHANES III is a national health survey that includes historical, physical, and laboratory examination of subjects selected through a stratified multistage probability-cluster sampling design. Minorities were oversampled, and the results were weighted to provide data representative of the U.S. population. Subjects in NHANES III who met the following criteria were identified using STATA 6.0 (STATA, College Station, TX), in accordance with the method described by Harris et al. (3): 1) between 40 and 74 years of age, 2) no known history of diabetes (other than gestational diabetes), and 3) fasting, 2-h 75-g postglucose load and HbA_1c measurements taken after an appropriate overnight fast.

Of the 2,836 subjects in NHANES III who met these criteria, 261 had a 2-h postglucose value ≥11.1 mmol/l (200 mg/dl), 51% had an FPG concentration ≥7.0 mmol/l (126 mg/dl; a very similar percentage to Perry’s high-risk group), and 49% had an HbA_1c level exceeding the ULN for the assay used (6.1%). We have previously shown in the NHANES III population that 70% of those with 2-h values between 11.1 and 13.3 mmol/l (200 and 239 mg/dl) had normal HbA_1c levels, whereas 60% with 2-h values ≥13.3 mmol/l (240 mg/dl) had elevated HbA_1c levels (4). Therefore, we tested the hypothesis that HbA_1c levels might be more sensitive than FPG concentrations in diagnosing diabetes in the 150 NHANES III subjects with 2-h postglucose values ≥13.3 mmol/l (240 mg/dl). As expected, the proportion with elevated FPG and HbA_1c values was higher in this group. However, the hypothesis was still not supported, because 74% had FPG concentrations ≥7.0 mmol/l (126 mg/dl) and only 59% had elevated HbA_1c levels.

Perhaps the difference in the sensitivities of the FPG and HbA_1c values in diagnosing diabetes in a high-risk population versus a randomly selected one is not surprising. In the high-risk group, 50% (121 of 244) had 2-h values on the OGTT that met the criterion for the diagnosis of diabetes (2), whereas only 9% (261 of 2,836) of the randomly selected NHANES III population had values in this range. Because postprandial (rather than fasting) hyperglycemia characterizes early diabetes, it is likely that members of the high-risk group who suspected that they may have had diabetes had higher postprandial glucose concentrations (and therefore higher HbA_1c levels) than people from the randomly selected population.