Association between Hemoglobin and Hemoglobin A(1c): A Data-Driven Analysis of Health Checkup Data in Japan

Background: Interpretation of hemoglobin A(1c) (HbA(1c)) levels may be confounded by spurious results in anemic persons, but its degree is not well-established. Methods: We used an employer-based health insurance database, containing health checkup data and medical claims data; both were linked via a unique identifier of each beneficiary. This study included persons aged 18–75 years who participated in health checkups, with a confirmed or suspected diagnosis of diabetes. The relationship between hemoglobin (Hb) and HbA(1c) is shown in a spline curve using a machine learning technique accounting for patient factors and within-person correlations. Spline curves were also shown in several sub-populations. Results: Overall, a decreased Hb value was associated with a lower HbA(1c) value, but the extent differed among populations. In the whole cohort of the type-2 diabetes group (55,420 persons), the curve was generally a plateau in the persons with a Hb value <120–130 g/L. Among the 18,478 persons with HbA(1c) around 48 mmol/mol, we observed a liner trend. Among the current glucose-lowering medication users (6253 persons), we found a right upward curve. Conclusions: The relationship between Hb and HbA(1c) may not be straightforward, varying among populations of different clinical interest. Our results indicate that a simple formulation between the Hb and HbA(1c) values is unlikely.