Wen Zhangxin, Liu Xinpeng, Jin Wanlin, Sheng Zhi-Feng, Liu Hong
Department of Metabolic Endocrinology, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Zhuzhou, China.
National Clinical Research Center for Metabolic Diseases; Health Management Center and Department of Metabolic Endocrinology, Xiangya Second Hospital, Central South University, Hunan Key Laboratory of Metabolic Bone Diseases, Changsha, China.
Front Endocrinol (Lausanne). 2025 Jun 24;16:1574064. doi: 10.3389/fendo.2025.1574064. eCollection 2025.
Osteoporosis, marked by decreased bone density and heightened fracture risk, is prevalent in aging individuals with type 2 diabetes mellitus (T2DM). The hemoglobin glycation index (HGI), a novel biomarker for glycation status, reflects advanced glycation end products (AGEs) accumulation. However, its role in bone metabolism and osteoporosis development remains poorly understood.
We enrolled 412 hospitalized T2DM patients to investigate the relationship between HGI and vertebral bone mineral density (BMD). BMD was measured by dual-energy X-ray absorptiometry (DXA), and bone turnover markers (PINP, β-CTX, OC) were evaluated. Correlation analyses were conducted to explore the associations between HGI, BMD, and bone cell activity markers. Mediation analysis was performed to determine whether osteoclast activity mediated the relationship between HGI and vertebral BMD.
Patients with vertebral fractures exhibited significantly higher HGI levels compared to those without fractures (0.8 ± 2.1 vs. 0.3 ± 2.1, respectively). A negative correlation was observed between HGI and vertebral BMD (r = -0.140, p = 0.005), while HGI showed a positive correlation with CTX (r = 0.15, p = 0.03). No significant association was found between HGI and P1NP (r = 0.022, p = 0.755). Mediation analysis revealed that osteoclast activity accounted for 28.88% of the relationship between HGI and vertebral BMD. Further subgroup analysis by age (<65 and ≥65 years) indicated that the association between HGI and vertebral BMD was stronger in patients aged ≥65 years, suggesting age-related differences in the HGI-osteoporosis relationship.
This study demonstrates that HGI contributes to bone loss and reduced vertebral BMD by enhancing osteoclast activity. While the impact of HGI on osteoblast function remains unclear, its significant influence on bone resorption highlights its potential role in the pathogenesis of osteoporosis in T2DM patients. These findings offer novel insights into the relationship between diabetes and osteoporosis and suggest that managing HGI levels may provide a therapeutic target for preventing osteoporosis and fractures in T2DM patients.
骨质疏松症以骨密度降低和骨折风险增加为特征，在老年2型糖尿病（T2DM）患者中普遍存在。血红蛋白糖化指数（HGI）是一种用于评估糖化状态的新型生物标志物，反映了晚期糖基化终产物（AGEs）的积累。然而，其在骨代谢和骨质疏松症发展中的作用仍知之甚少。
我们纳入了412名住院的T2DM患者，以研究HGI与椎体骨密度（BMD）之间的关系。采用双能X线吸收法（DXA）测量BMD，并评估骨转换标志物（PINP、β-CTX、OC）。进行相关性分析以探讨HGI、BMD和骨细胞活性标志物之间的关联。进行中介分析以确定破骨细胞活性是否介导了HGI与椎体BMD之间的关系。
与未发生骨折的患者相比，椎体骨折患者的HGI水平显著更高（分别为0.8±2.1和0.3±2.1）。观察到HGI与椎体BMD之间呈负相关（r = -0.140，p = 0.005），而HGI与CTX呈正相关（r = 0.15，p = 0.03）。未发现HGI与P1NP之间存在显著关联（r = 0.022，p = 0.755）。中介分析显示，破骨细胞活性占HGI与椎体BMD之间关系的28.88%。按年龄（<65岁和≥65岁）进行的进一步亚组分析表明，HGI与椎体BMD之间的关联在≥65岁的患者中更强，提示HGI与骨质疏松症关系存在年龄相关差异。
本研究表明，HGI通过增强破骨细胞活性导致骨质流失和椎体BMD降低。虽然HGI对成骨细胞功能的影响尚不清楚，但其对骨吸收的显著影响突出了其在T2DM患者骨质疏松症发病机制中的潜在作用。这些发现为糖尿病与骨质疏松症之间的关系提供了新的见解，并表明控制HGI水平可能为预防T2DM患者的骨质疏松症和骨折提供一个治疗靶点。
