Cycling of hemoglobin A1c associated with hemoglobin cycling in diabetic patients under hemodialysis and its theoretical simulation

Levels of hemoglobin A1c (HbA1c) in patients under hemodialysis (HD) show lower values than expected based on plasma glucose levels, and they fluctuate according to changes in the weekly dosage of erythropoiesis-stimulating agent (ESA) administered for the treatment of renal anemia. We should therefore consider how these factors affect the levels of HbA1c when HbA1c is used as a marker of glycemic control in HD diabetic patients. To clarify the relationship between the weekly ESA dosage and HbA1c levels, we examined whether HbA1c levels show cyclic changes associated with hemoglobin (Hb) cycling in HD diabetic patients. In 3 of the 39 HD diabetic patients studied, the weekly ESA dosage was frequently changed and Hb levels showed Hb cycling. The HbA1c levels in these three patients also showed cyclic changes that synchronized Hb cycling. To quantitatively analyze the relationship between ESA and HbA1c, we established a mathematical model of Hb glycation in HD diabetic patients. The simulation results using this model agreed well with the observed data. The present model is considered to provide a new method for the analysis of HbA1c levels in HD diabetic patients.