Impact of Altitude on the Accuracy of HbA1c in Reflecting Glycemic Status in Patients with Type 2 Diabetes: A Cross-Sectional Study in China

Objective To investigate the response of glycated hemoglobin (HbA1c) to fasting plasma glucose (FPG) under different altitude conditions, and to evaluate its applicability in the diagnosis of type 2 diabetes mellitus (T2DM). Methods A cross-sectional study was conducted involving 410 patients with T2DM from Shanghai (0 m) and Xining (2261 m) in China between 2022 and 2024. Biochemical indices including FPG, HbA1c, and hemoglobin (Hb) were collected to analyze the impact of altitude on HbA1c values and their correlation with FPG. Statistical methods included Mann–Whitney U test, Pearson correlation analysis, analysis of covariance (ANCOVA), and effect size evaluation (Cohen's d, r). Results Patients in the high-altitude group had significantly higher levels of FPG (10.32 ± 3.82 mmol/L vs. 7.25 ± 1.74 mmol/L) and HbA1c (9.21 ± 2.71% vs. 8.06 ± 1.73%) (both p < 0.001), while the HbA1c-to-FPG ratio was significantly lower (0.961 vs. 1.148, p < 0.001), suggesting that under equivalent glycemic levels, HbA1c may underestimate true glycemic burden at high altitudes. Correlation analysis showed a moderate correlation between HbA1c and FPG in both groups (r = 0.532), although FPG variability was higher in the high-altitude group. ANCOVA revealed a significant effect of FPG stratification on HbA1c (p < 0.001) and a marginal interaction between altitude and FPG (p = 0.066). Additionally, patients with high Hb levels (> 160 g/L) had significantly lower HbA1c levels compared to those with lower Hb (6.3% vs. 7.0%, p < 0.001). Conclusion High-altitude environments may interfere with the accuracy of HbA1c by increasing hemoglobin levels, potentially leading to an underestimation of true glycemia. It is recommended that diabetes monitoring in plateau regions incorporate direct glycemic indicators such as FPG or CGM to optimize clinical decision-making and risk management.