Glycated hemoglobin for the diagnosis of diabetes and prediabetes: Diagnostic impact on obese and lean subjects, and phenotypic characterization

Aims/Introduction: Measurement of glycated hemoglobin (HbA1c) has been recommended for the diagnosis of diabetes and prediabetes. However, epidemiological studies have shown significant discordance between HbA1c and glucose-based tests. Of the factors that could influence agreement between HbA1c and the oral glucose tolerance test (OGTT), bodyweight has not been fully evaluated. The aims of the present study were to evaluate the impact of HbA1c criteria to diagnose diabetes and prediabetes compared with OGTT, and to examine HbA1c in relation to body mass index. Materials and Methods: Two cohorts were studied, one from an obesity clinic (n = 592) and one from subjects undergoing screening for diabetes (n = 462). All underwent OGTT and HbA1c measurement. Results: In the obese cohort, HbA1c ≥6.5% (≥48 mmol/mol) showed a sensitivity of 69.3% for diabetes, whereas HbA1c 5.7-6.4% (39-46 mmol/mol) did not identify prediabetes well (sensitivity 39.1%). In the diabetes screening cohort, HbA1c had low sensitivities for both diabetes (39.2%) and prediabetes (53.3%). When participants were stratified according to body mass index class I-III, HbA1c agreement with the OGTT for diabetes was much higher (80%, P < 0.005) in class I obesity compared with class II-III obesity; whereas for prediabetes, HbA1c had a low sensitivity in all obesity classes. Conclusions: The agreement between HbA1c, fasting plasma glucose and 2-h glucose post-OGTT for the diagnosis of prediabetes was poor in our Italian population; whereas HbA1c ≥6.5% showed a relatively good agreement with OGTT for the diagnosis of diabetes. For the first time, we have shown that obesity class influences the diagnostic performance of HbA1c.