Abstract: Background With the increasing aging population，the prevalence of osteoporosis in patients with type 2diabetes mellitus（T2DM）is rising year by year. It has also been found that impaired sensitivity to thyroid hormone is associated with abnormal bone metabolism. However，there are few studies on the relationship between thyroid hormone sensitivity and the risk of osteoporosis in patients with T2DM. Objective To analyze the relationship between thyroid hormone sensitivity index and osteoporosis in T2DM patients with normal thyroid function. Methods This cross-sectional study included 723 T2DM patients with normal thyroid function admitted to the Department of Endocrinology of Nanjing University Affiliated Drum Tower Hospital from 2022 to 2023. Based on the results of bone mineral density（BMD）measurements，the patients were divided into three groups：normal bone mass group（n=362），osteopenia group（n=291），and osteoporosis group（n=70）. The thyroid feedback quotient index（TFQI），thyroid-stimulating hormone index（TSHI），thyroid-stimulating hormone resistance index（TT4RI），and the ratio of free triiodothyronine to free thyroxine（FT3/FT4）were measured and calculated in each patient to assess thyroid hormone sensitivity. One-way analysis of variance（ANOVA）and chi-square test were used for intergroup comparisons. Spearman's correlation analysis and logistic regression analysis were employed to explore the association between thyroid hormone sensitivity indices and the risk of osteoporosis in T2DM patients. Results The osteoporosis group had higher age，proportion of females，diabetes duration，systolic blood pressure，body mass index（BMI），2-hour postprandial glucose（2 hPG），alanine aminotransferase（ALT），high-density lipoprotein cholesterol（HDL-C），and TFQI compared with the normal bone mass group（P<0.05）. In contrast，diastolic blood pressure，creatinine，triglycerides，FT3，and FT3/FT4 were lower in the osteoporosis group than in the normal bone mass group（P<0.05）. The osteoporosis group also had higher age，proportion of females，diabetes duration，2 hPG，HDL-C，and TFQI compared with the osteopenia group（P<0.05），while ALT，triglycerides，FT3，and FT3/FT4 were lower（P<0.05）. Spearman rank correlation analysis showed that the occurrence of osteoporosis in T2DM patients was positively correlated with TFQI（rs=0.553，P<0.001）and negatively correlated with FT3 and FT3/FT4（rs=-0.098，P=0.009；rs=-0.080，P=0.031）. Multivariate logistic regression analysis revealed that，after adjusting for confounding factors，TFQI was positively associated with the risk of osteoporosis in T2DM patients（OR=6.612，95%CI=5.793-8.192）. The area under the receiver operating characteristic（ROC）curve（AUC）for predicting the risk of osteoporosis in T2DM patients using TFQI was 0.831（95%CI=0.794-0.867），with a best cutoff value of -0.029. The sensitivity and specificity were 100.0% and 55.4%，respectively. Conclusion Elevated levels of TFQI are associated with a higher risk of osteoporosis in T2DM patients with normal thyroid function，suggesting that reduced central sensitivity to thyroid hormone in this population is related to the development of osteoporosis.

Key words: Diabetes mellitus, type 2；Osteoporosis；Bone mineral density；Thyroid gland；Thyroid hormones；Forecasting

摘要： 背景 随着老龄化的加剧，2型糖尿病（T2DM）并发骨质疏松症患病率逐年上升，同时发现甲状腺激素敏感性受损与骨代谢异常发生相关，但目前关于 T2DM 患者甲状腺激素敏感性与骨质疏松症发生风险的相关研究较少。目的 分析甲状腺功能正常的 T2DM 患者甲状腺激素敏感性指数与骨质疏松症的关系。方法 本研究为横断面研究，选取 2022—2023 年南京大学医学院附属鼓楼医院内分泌科收治的的甲状腺功能正常的 T2DM 患者 723 例，并依据骨密度（BMD）测定结果将其分为三组：骨量正常组（n=362）、骨量减少组（n=291）以及骨质疏松症组（n=70）。分别测量并计算患者的甲状腺反馈分位指数（TFQI）、促甲状腺激素指数（TSHI）、促甲状腺素抵抗指数（TT4RI）和游离三碘甲状腺原氨酸与游离甲状腺素比值（FT3/FT4），以评估甲状腺激素敏感性。采用单因素方差分析、χ2 检验进行组间比较；Spearman 秩相关分析、多因素 Logistic 回归分析探究T2DM患者甲状腺激素敏感性指数与骨质疏松症发生风险的关联。结果 骨质疏松症组年龄、女性所占比例、糖尿病病程、收缩压、BMI、餐后 2 h血糖（2 hPG）、丙氨酸氨基转移酶（ALT）、高密度脂蛋白胆固醇（HDL-C）、TFQI 高于骨量正常组，舒张压、肌酐、三酰甘油、FT3、FT3/FT4 低于骨量正常组（P<0.05）；骨质疏松症组年龄、女性所占比例、糖尿病病程、2 hPG、HDL-C、TFQI 高于骨量减少组，ALT、三酰甘油、FT3 和 FT3/FT4 低于骨量减少组（P<0.05）。Spearmen 秩相关性分析结果显示，T2DM 患者发生骨质疏松症与 TFQI 呈正相关（rs=0.553，P<0.001），与 FT3 和 FT3/FT4 呈负相关（rs=-0.098，P=0.009；rs=-0.080，P=0.031）。多因素 Logistic 回归分析结果显示，经调整混杂因素后，TFQI 与 T2DM 患者并发骨质疏松症的风险呈正相关（OR=6.612，95%CI=5.793~8.192）。TFQI 预测 T2DM 患者并发骨质疏松症风险的 ROC 曲线下面积（AUC）为 0.831（95%CI=0.794~0.867），最佳截断值 -0.029，灵敏度、特异度分别为 100.0%、55.4%。结论 甲状腺功能正常 T2DM 患者 TFQI 水平的升高与更高的骨质疏松症发生风险相关，提示在该群体中降低的甲状腺激素中枢敏感性与骨质疏松症的发生有关。

关键词: 糖尿病, 2 型；骨质疏松；骨密度；甲状腺；甲状腺激素类；预测