Year: 2007
Abstract Number: 0436-P
Authors: ROBERT M. COHEN, PETER CIRAOLO, MARY B. PALASCAK, CHRISTOPHER J. LINDSELL, PARAMJIT K. KHERA, ERIC P. SMITH, CLINTON H. JOINER, ROBERT S. FRANCO, Cincinnati, OH
Results: It is commonly stated that HbA1c represents glycemic control over the RBC lifespan of “90-120” days. Yet if in reality some lifespans were 90 and others 120 days, then this would be responsible for a variation of 25-30% in HbA1c which could be mistakenly attributed to differences in glycemic control. The glycation gap is a measure of discordance between HbA1c and serum fructosamine (FA), a measure of glycemic control independent of RBC lifespan. This gap, calculated as HbA1c(measured)-HbA1c(predicted from FA), is negative when HbA1c is lower than expected, zero when results are concordant, and positive when HbA1c is higher than expected. We selected 6 people with diabetes and a wide range of glycation gap and a non-DM control group (n=4) and determined RBC survival and in vivo HbA1c synthetic rate. RBC lifespan was measured using an ex vivo biotin label with fractional RBC survival determined by flow cytometric analysis of post-reinfusion blood samples using fluorochrome-conjugated streptavidin. RBC survival is curvilinear and we therefore calculated mean red cell age by curve fitting. From the post-reinfusion blood samples, biotin-labeled RBC were isolated with magnetic beads and assayed for HbA1c by HPLC to determine the synthetic rate of HbA1c as the labeled RBCs aged in the circulation. HbA1c in newly released reticulocytes was determined on transferrin receptor-expressing peripheral blood RBCs to assess changes during RBC maturation prior to release into the circulation. Mean circulating red cell ages ranged 40-52 and 38-49 days in DM and non-DM subjects, respectively. Expressed as RBC lifespan, the range was 77 to 104 days extrapolated from the linear portion of the curve. Mean red cell age was a major determinant of glycation gap, modified by diabetes status (multivariate r2=0.66). HbA1c synthesis was linear in each case from mean cell age until red cell disappearance.
In summary, there is sufficient variation in red cell lifespan among hematologically normal people with diabetes to contribute clinical-decision-altering differences to HbA1c. The glycation gap provides a useful means of screening for people in whom mean age of circulating RBCs may be a consideration in clinical interpretation of HbA1c. The distribution of glycation gap in the population raises the prospect that RBC survival variation is more commonly a factor than has been recognized.
Category: Clinical Therapeutics/New Technology - Glucose Monitoring and Sensing