Erythrocytosis and Performance of HbA1c in Detecting Diabetes on an Oxygen-Deficient Plateau: A Population-based Study

Context The hemoglobin A1c (HbA1c) test is a standard test for diabetes screening and diagnosis. Objective To evaluate A1c performance for diabetes screening in high-altitude polycythemia compared to a population with a high proportion of people living in an oxygen-deficient environment. Design A population-based epidemiological survey was conducted. Setting The cities Lhasa and Shigatse were selected. Volunteers were recruited through educational advertisements about diabetes. Participants A total of 1401 Tibetan adults without known diabetes. Interventions Oral glucose tolerance test (OGTT), HbA1c, and complete blood cell count were performed. Hemoglobin A1c was evaluated using high-performance liquid chromatography, and serum glucose level, using the hexokinase method. Main Outcome Measures World Health Organization criteria were used to define diabetes and prediabetes. Hemoglobin A1c test performance was evaluated using receiver operating characteristic analysis. Results The participants’ mean age was 44.3 ± 15.0 years; 33.3% of the participants were men and 38.6% lived in urban areas. The prediabetes and diabetes prevalence rates were 7.5% and 3.6%, respectively. The optimal HbA1c cutoff for detecting diabetes was 46 mmol/mol (6.4%), with a sensitivity and specificity of 60.8% and 93.6%, respectively. The cutoff for detecting diabetes was 6.7% (50 mmol/mol) in subjects with high-altitude polycythemia (HAPC). The relationship between red blood cell (RBC) counts and HbA1c was significant (P < 0.001), while there was no correlation between hemoglobin (Hb) and HbA1c (P = 0.085). Multiple linear regression analysis showed that after adjusting for age and fasting serum glucose or 2-hour OGTT (OGTT2h) serum glucose, RBC count and not Hb level was an independent risk factor for HbA1c (β = 0.140, P < 0.001). Conclusions The optimal HbA1c cutoff for detecting diabetes was 46 mmol/mol (6.4%) in Tibet. Red blood cell count was an independent risk factor for elevated HbA1c, and HAPC may affect the predictive ability of HbA1c.