Relationship Between GHb Concentration and Erythrocyte Survival Determined From Breath Carbon Monoxide Concentration

Abstract

OBJECTIVE -Subjects with decreased erythrocyte survival have an unusually low GHb percentage. The goal of this study was to determine whether hyperglycemia, as reflected by GHb percentage, is associated with decreased erythrocyte survival.RESEARCH DESIGN AND METHODS -Erythrocyte survival was quantitated in 23 subjects with type 2 diabetes, and these values were correlated with the subjects' GHb percentage. Erythrocyte survival was determined from the difference between the subjects' alveolar carbon monoxide (CO) concentration and atmospheric CO concentration. Reticulocyte counts were obtained in 16 subjects.RESULTS -Although the vast majority of the subjects had erythrocyte life spans that fell within the normal range (123 Ϯ 23 days), there was a highly significant inverse correlation (r ϭ Ϫ0.66, P Ͻ 0.01) between life span and GHb percentage, with an average decline in life span of 6.9 days for each 1% rise in GHb. The reticulocyte count inversely correlated with erythrocyte life span (r ϭ Ϫ0.77, P Ͻ 0.01).CONCLUSIONS -Hyperglycemia, as evidenced by high GHb percentage, is associated with an appreciable decrease in erythrocyte life span. Because GHb appears to be formed over the lifetime of the erythrocyte, this decreased erythrocyte survival suggests that high GHb percentages may systematically underestimate the true degree of hyperglycemia.

Glycated Albumin is a Better Indicator for Glucose Excursion than Glycated Hemoglobin in Type 1 and Type 2 Diabetes

“…In addition, hyperglycemia is known to reduce the survival of hemoglobin [6,7], thus a higher glucose fluctuation in type 1 diabetes may decrease HbA1c and increase the ratio of GA levels to HbA1c levels.…”

“…For example, lower HbA1c levels are observed in subjects with shortened erythrocyte survival or decreased mean erythrocyte age. Hyperglycemia is also known to reduce the survival of erythrocytes and to underestimate HbA1c levels in diabetic patients under poor glycemic control [6,7].…”

Red cell life span heterogeneity in hematologically normal people is sufficient to alter HbA1c

“…4,5 However, normal RBC life span has been reported to have a wide range of values regardless of the method used, [6][7][8] and there are also studies suggesting that RBC life span may depend on glycemic control, although evidence for this is conflicting. [9][10][11][12][13] It is also possible that heterogeneity in other features of red cell physiology, such as membrane glucose transport 14 and loss of Hb from older RBCs, 15 may influence the relationship between blood glucose and HbA1c.…”

“…Given the discordance between HbA1c and other measures of glycemic control observed in some subjects [31][32][33][34] and the evidence for a range of RBC survival in previous studies, 9,10,12,35 we sought to determine whether there is sufficient interindividual variation in RBC mean age to have an important effect on HbA1c. To maximize the probability of observing a wide range of life spans in a small number of subjects, patients with diabetes mellitus (DM) with discordance between HbA1c and serum fructosamine (FA) were selected.…”

The proposed terminology ‘A1c-derived average glucose’ is inherently imprecise and should not be adopted

“…Further studies are in progress of interrelationships between A 1c and erythrocyte survival, and between A 1c and the presence of renal and hepatic disease [22]. Interestingly, there is some evidence that high A 1c may itself be associated with reduced erythrocyte survival, so that A 1c might at high levels particularly underestimate the true degree of hyperglycaemia [23], further implying need to closely examine factors affecting A 1c rather than assuming that it directly represents average glucose concentrations [24].…”