Abstract 520 Pulmonary: Cystic Fibrosis Poster Symposium, Tuesday, 5/4

Background. Patients with cystic fibrosis (CF) have a high incidence of impaired glucose tolerance (IGT) and cystic fibrosis related diabetes (CFRD). A recent national survey documented that the most common test used to diagnose CFRD is hemoglobin A1c (HbA1c). Multiple publications have documented poor reliability of HbA1c as a diagnostic test for CFRD; including finding normal HbA1c results in patients with frank CFRD. The reason for the lack of reliability of this test has been poorly understood. Normal values for HbA1c were developed using the normal turnover time (t1/2) of the human red blood cell (RBC). Thus any condition which shortens the life-span of the RBC causes the HbA1c value to be lower than expected for the average blood glucose levels. Aim. We hypothesized that HbA1c levels are lower in CF because RBC turnover time is more rapid. We further hypothesized that RBC t1/2 correlates with pulmonary function and resting energy expenditure (REE). Subjects/Methods. We studied 9 CF adults (ages 22-32 yrs, 5 male). Two of the subjects were studied during acute exacerbation of pulmonary illness, the other subjects were studied when clinically well. All subjects had previously been diagnosed with impaired glucose tolerance (IGT) by a two-hour OGTT. HbA1c levels ranged from 5.1-6.1%. Pulmonary function (FEV1,FVC) ranged from 82-92% predicted (n=5; "good PFT"), or from 32-48% predicted (n=4; "poor PFT"). REE was measured in each subject using 30 minute hood indirect calorimetry. RBC t1/2 was measured by determination of the functional half-clearance time of 51Cr-labeled isologous red cells, using methodology standardized and validated for diagnostic use in the department of nuclear medicine at Hermann Hospital. Results from CF subjects were compared to published normal values. Results. When RBC t1/2 was meaned for the entire CF group, there was no significant difference from published normal values (t1/2,dys:CF=23.7±6.5, normal=28, range 25-35). However, when results from the "poor PFT" group were compared to normal values and to the "good PFT" group, RBC turnover was markedly more rapid (RBCt1/2, dys: "poor PFT"=17.7±4.0, "goodPFT"=28.3±4. The two patients studied during acute pulmonary exacerbation had the most rapid RBCt1/2. There was a strong positive correlation between RBCt1/2 and FEV1 (r=0.89, p=0.01). There was also correlation between FVC and RBCt1/2 (r=0.75,p=0.049). No correlation was found between REE and RBCt1/2. Summary. 1) RBCt1/2 can be normal or rapid in CF; 2) pulmonary function, especially FEV1, seems to have the most impact on RBC t1/2; 3) RBC t1/2 may also be shortened by acute illness, but this probably also related to pulmonary function; 4) REE does not appear to be related to RBC turnover. Conclusion. 1) Accelerated RBC turnover can cause artificially low HbA1c results in CF; 2) HbA1c should not be used as a diagnostic test for CFRD.