Influence of High-Altitude Residential History on Optimal HbA1c Cutoff for Detecting Abnormal Glucose Metabolism

Zengmei, Sun, Suyuan Wang, Hua He, Chenghui Zhang, Mingxia Li, Yan Ye, Huiqin Zhang, Xuanyu Yao, Shuyao Sun, Yuanze Du, Yang Zhong, and Yunhong Wu. Influence of high-altitude residential history on optimal HbA1c cutoff for detecting abnormal glucose metabolism. <i>High Alt Med Biol.</i> 26:45-54, 2025. <b><i>Aims:</i></b> To explore the influence of recent high-altitude residential history on the optimal cutoff of glycosylated hemoglobin (HbA1c) for detecting abnormal glucose metabolism. <b><i>Methods:</i></b> The study included 505 self-reported healthy Han participants of age 18-65 years, recruited in Chengdu and categorized based on recent (within 3 months) high-altitude (>2,500 m) residential history. The 1999 WHO criteria was used as the gold standard for defining prediabetes and diabetes. HbA1c test performance was assessed using receiver operating characteristic curve, with the optimal cutoff determined by Maximum Youden index. Propensity score matching with 0.02 calipers and nearest neighbor method was used to balance confounding factors between groups. <b><i>Results:</i></b> Of the participants, 238 (47.13%) were populations with recent high-altitude residential history (HA group), and 267 (52.87%) were low-altitude dwellers (LA group). The HA group had slightly higher HbA1c levels (<i>p</i> > 0.05) and higher erythrocyte and hemoglobin levels (<i>p</i> < 0.05), compared to the LA group. Weak correlations between prediabetes and HbA1c levels were observed in the HA group (<i>r</i>_s = 0.21, <i>p</i> < 0.05) and the LA group (<i>r</i>_s = 0.07, <i>p</i> = 0.25). The optimal cutoff for the detection of diabetes was 6.5% (area under the curve [AUC] 0.94) in the HA group and 5.9% (AUC 0.97) in the LA group, which remained unchanged after adjustment for confounders. <b><i>Conclusions:</i></b> The optimal cutoff of HbA1c for the detection of diabetes in populations with recent history of living at high altitude was higher than that in general populations living at low altitude, and the diagnostic value of HbA1c for prediabetes was also inadequate.