Abstract
Hemoglobin A1C (A1C) is used in various settings. Its performance has not been evaluated systemically. We compared A1C in diagnosis of diabetes with fasting plasma glucose (FPG) and 2-h postchallenged plasma glucose (2hPG) parameters in a cross-sectional cohort in the United Stated. Adult subjects (≥20 years) were identified from the National Health and Nutrition Examination Survey 2005–2016 without a history of diabetes who had BMI, A1C, FPG, and 2hPG (n = 10,416). For comparisons, we calculated the sample weighted prevalence, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) with subgroup analyses. For the retinopathy study, diabetic subjects with established diabetes who responded to the question of diabetic retinopathy were evaluated (n = 3907). Compared to the FPG/2hPG criteria, A1C ≥ 48 mmol/mol (6.5%) had a low sensitivity at 25.90%, with specificity 99.70%, PPV 84.70%, and NPV 95.70%. Subgroup analyses revealed a lower sensitivity in males (24.52%); the lowest in non-Hispanic White (21.35%), in the third decade (14.32%), and in the BMI < 22.50 kg/m2 group (7.21%). The prevalence of self-reported diabetic retinopathy increased drastically with an inflection point at A1C 48 mmol/mol (6.5%) from 11.52% to 18.32% (p < 0.0001). A1C ≥ 48 mmol/mol (6.5%) should be cautiously used to diagnose diabetes in certain subgroups due to very low sensitivity in certain groups. With the confirmation of the association of increasing self-reported diabetic retinopathy with A1C ≥ 48 mmol/mol (6.5%), the current A1C cutoff is an acceptable value with the understanding of especially low sensitivity in certain subgroups.
Highlights
Between 1999 and 2006, oversampling was performed for Mexican American and between 2007 and 2010, oversampling was performed for all Hispanic persons
We demonstrate that the current A1C cutoff has a significant tendency of underdiagnosing diabetes mellitus (DM) with an exceptionally low and significant variable sensitivity, such as the lowest sensitivity, 7.21% in subjects with body mass index (BMI) < 22.5 kg/m2 by BMI category, 14.32%
The current criterion of A1C ≥ 48 mmol/mol (≥6.5%) has an exceptionally low sensitivity in the diagnosis of DM by missing more than 50% of DM defined by the gold standard which is based on the fasting plasma glucose (FPG) and/or 2-h postchallenged plasma glucose (2hPG) criteria
Summary
The prevalence of diabetes mellitus (DM) has been steadily increasing since 1999 [1]. According to the National Diabetes Statistics Report 2020 from the Centers of Disease. Control and Prevention (CDC), the estimated prevalence of DM was 13.0% of the US adult population (34.1 million), of which 7.3 million people (21.4%) of people with DM were still undiagnosed [2]. The prevalence of total DM and diagnosed DM increased in parallel while the prevalence of undiagnosed DM decreased since 2010. No definite explanation for the decreasing prevalence of undiagnosed DM is available, the improvement in the diagnosis of DM could play a role. Diagnosis and intervention of diabetes is highly recommended since serious diabetic complications is preventable through early intervention [4,5]
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