Glycated haemoglobin (HbA_1c) and fasting plasma glucose relationships in sea-level and high-altitude settings

Aim: Higher haemoglobin levels and differences in glucose metabolism have been reported among high-altitude residents, which may influence the diagnostic performance of HbA_1c. This study explores the relationship between HbA_1c and fasting plasma glucose (FPG) in populations living at sea level and at an altitude of > 3000 m. Methods: Data from 3613 Peruvian adults without a known diagnosis of diabetes from sea-level and high-altitude settings were evaluated. Linear, quadratic and cubic regression models were performed adjusting for potential confounders. Receiver operating characteristic (ROC) curves were constructed and concordance between HbA_1c and FPG was assessed using a Kappa index. Results: At sea level and high altitude, means were 13.5 and 16.7 g/dl (P > 0.05) for haemoglobin level; 41 and 40 mmol/mol (5.9% and 5.8%; P < 0.01) for HbA_1c; and 5.8 and 5.1 mmol/l (105 and 91.3 mg/dl; P < 0.001) for FPG, respectively. The adjusted relationship between HbA_1c and FPG was quadratic at sea level and linear at high altitude. Adjusted models showed that, to predict an HbA_1c value of 48 mmol/mol (6.5%), the corresponding mean FPG values at sea level and high altitude were 6.6 and 14.8 mmol/l (120 and 266 mg/dl), respectively. An HbA_1c cut-off of 48 mmol/mol (6.5%) had a sensitivity for high FPG of 87.3% (95% confidence interval (95% CI) 76.5 to 94.4) at sea level and 40.9% (95% CI 20.7 to 63.6) at high altitude. Conclusion: The relationship between HbA_1c and FPG is less clear at high altitude than at sea level. Caution is warranted when using HbA_1c to diagnose diabetes mellitus in this setting.