2 However, the invariance of synthetic rate between persons in the face of potential modifiers has largely been assumed 3 and becomes an issue as ever greater precision in glycemic control and the identification of more precise targets for complication prevention are explored.

1 The relationship of synthetic rate to blood glucose and the agreement of the single subject in vivo kinetics to in vitro kinetics were established very shortly thereafter. Its linearity with time is largely based on a seminal observation with one normal subject and one subject recovering from erythrocyte aplasia in whom the appearance of 59Fe in the HbA1c fraction was found to lag behind the appearance in the HbA fraction and the time course of the specific activity of 59Fe in the HbA1c fraction was linear. The synthetic rate of HbA1c as RBCs age in the circulation is the variable that should be most directly related to blood glucose over a defined time period. The value of HbA1c in transferrin receptor-positive (TfR(+)) cells, which are essentially reticulocytes, most probably depends on the glucose milieu in the marrow a few days preceding release and could potentially reflect a different rate of glycation compared with mature RBCs resulting from variations in environment and glucose transport.

Blood HbA1c is a mean for RBCs with values that range from very low for reticulocytes to approximately twice the mean for the oldest RBCs. The hemoglobin A1c (HbA1c) determination used clinically to evaluate glycemic control depends on 3 factors: (1) the HbA1c in reticulocytes when they are released from the bone marrow (2) the synthetic rate of HbA1c (or Hb glycation rate) as red blood cells (RBCs) become older, a function of glucose concentration to which Hb is exposed and (3) the mean age of RBCs in the circulation. The observed variation in RBC survival was large enough to cause clinically important differences in HbA1c for a given mean blood glucose. HbA1c synthesis was linear and correlated with mean whole blood HbA1c (R 2 = 0.91). The mean age of circulating RBCs ranged from 39 to 56 days in diabetic subjects and 38 to 60 days in nondiabetic controls. In addition, HbA1c in magnetically isolated labeled RBCs and in isolated transferrin receptor-positivereticulocytes was used to determine the in vivo synthetic rate of HbA1c. Mean RBC age was calculated from the RBC survival curve for all circulating RBCs and for labeled RBCs at multiple time points as they aged. To explore the hypothesis that variation in RBC life span could alter measured HbA1c sufficiently to explain some of this discordance, we determined RBC life span using a biotin label in 6 people with diabetes and 6 nondiabetic controls. However, an unexplained discordance between HbA1c and other measures of glycemic control can be observed that could be, in part, the result of differences in RBC life span. Although red blood cell (RBC) life span is a known determinant of percentage hemoglobin A1c (HbA1c), its variation has been considered insufficient to affect clinical decisions in hematologically normal persons.

Normal hgb a1c normal range