外周血CXC基序趋化因子配体10与CC基序趋化因子配体11预测2型糖尿病性骨质疏松症的价值: 一项前瞻性队列研究与预测模型构建

Value of CXC motif chemokine ligand 10 and CC motif chemokine ligand 11 in peripheral blood in predicting type 2 diabetic osteoporosis: a prospective cohort study and predictive model construction

  • 摘要:
    目的 探讨外周血CXC基序趋化因子配体10(CXCL10)和CC基序趋化因子配体11(CCL11)与2型糖尿病性骨质疏松症(T2DOP)的关系, 并构建预测模型。
    方法 前瞻性选取260例2型糖尿病(T2DM)患者为T2DM组,根据T2DOP发生情况分为T2DOP组(n=82)和非T2DOP组(n=178)。另选取68例健康体检者作为对照组。采用酶联免疫吸附法检测外周血CXCL10、CCL11和骨代谢指标β-Ⅰ型胶原交联C末端肽(β-CTX)、Ⅰ型前胶原N端前肽(PINP)水平。采用皮尔逊相关性分析探讨T2DM患者外周血CXCL10、CCL11与骨代谢指标水平的相关性; 采用多因素非条件Logistic回归分析探讨T2DOP的影响因素并构建预测模型,采用H-L检验拟合优度; 采用受试者工作特征(ROC)曲线分析各指标及预测模型对T2DOP的预测价值,采用决策曲线和Bootstrap自抽样进行内部验证。
    结果 与对照组比较, T2DM组外周血CXCL10、CCL11、β-CTX水平升高, PⅠNP水平降低,差异有统计学意义(P < 0.05)。皮尔逊相关性分析显示, T2DM患者外周血CXCL10、CCL11与β-CTX水平呈正相关(r=0.786、0.816, P < 0.001), 与PⅠNP水平呈负相关(r=-0.675、-0.716, P < 0.001)。与非T2DOP组比较, T2DOP组年龄增大和糖尿病肾病比率增高,糖尿病病程延长,体质量指数(BMI)和PⅠNP水平降低,空腹血糖、糖化血红蛋白(HbA1c)、β-CTX、CXCL10、CCL11水平升高,差异有统计学意义(P < 0.05)。非条件Logistic回归分析结果显示,年龄大、糖尿病病程长、HbA1c高、CXCL10高、CCL11高为T2DOP的独立危险因素(P < 0.05), BMI高为独立保护因素(P < 0.05)。ROC曲线显示,预测模型预测T2DOP的曲线下面积(AUC)为0.919, 大于年龄、糖尿病病程、BMI、HbA1c、CXCL10、CCL11单独预测的0.643、0.742、0.654、0.715、0.759、0.741(Z=7.468、5.400、7.415、6.365、5.242、5.800, P均 < 0.001)。经内部验证,预测模型的决策曲线高于2条极端曲线,经1 000次Bootstrap法自抽样内部验证,预测模型预测的一致性指数为0.919(95%CI: 0.914~0.923)。
    结论 外周血CXCL10、CCL11水平升高与T2DOP有关,基于此构建的预测模型预测T2DOP的价值较高。

     

    Abstract:
    Objective To investigate the relationships of CXC motif chemokine ligand 10 (CXCL10) and CC motif chemokine ligand 11 (CCL11) in the peripheral blood with type 2 diabetic osteoporosis (T2DOP), and to construct a predictive model.
    Methods A total of 260 patients with type 2 diabetes mellitus (T2DM) were prospectively selected as the T2DM group. They were divided into T2DOP group (n=82) and non-T2DOP group (n=178) according to the occurrence of T2DOP. Additionally, 68 healthy volunteers with physical examinations in the same period were selected as control group. Enzyme-linked immunosorbent assay was used to detect the levels of CXCL10 and CCL11 in the peripheral blood as well as bone metabolism indicatorsβ-C-terminal telopeptide of type Ⅰ collagen (β-CTX), N-terminal propeptide of type Ⅰ procollagen (PINP). Pearson correlation analysis was used to explore the correlation of CXCL10 and CCL11 in peripheral blood with bone metabolism indicator levels in patients with T2DM. Multifactor non-conditional Logistic regression analysis was used to explore the influencing factors of T2DOP and construct a predictive model. The Hosmer-Lemeshow (H-L) test was used to assess the goodness of fit. The receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive value of each indicator and the predictive model for T2DOP, and decision curve analysis and Bootstrap resampling were used for internal validation.
    Results Compared with the control group, the levels of CXCL10 and CCL11 in the peripheral blood as well as β-CTX in the T2DM group were significantly increased, while the level of PⅠNP was significantly decreased (P < 0.05). Pearson correlation analysis showed that CXCL10 and CCL11 in the peripheral blood in patients with T2DM were positively correlated with β-CTX level (r=0.786, 0.816, P < 0.001) and negatively correlated with PⅠNP level (r=-0.675, -0.716, P < 0.001). Compared with the non-T2DOP group, the T2DOP group had significantly increased age and the ratio of diabetic nephropathy, prolonged duration of diabetes, decreased body mass index (BMI) and PⅠNP levels, and increased fasting blood glucose, glycated hemoglobin (HbA1c), β-CTX, CXCL10, and CCL11 levels (P < 0.05). Non-conditional Logistic regression analysis showed that advanced age, long duration of diabetes, high HbA1c, high CXCL10, and high CCL11 were independent risk factors for T2DOP (P < 0.05), while high BMI was an independent protective factor (P < 0.05). The ROC curve showed that the area under the curve (AUC) of the predictive model for predicting T2DOP was 0.919, which was significantly greater than the AUCs of 0.643, 0.742, 0.654, 0.715, 0.759 and 0.741 respectively for age, duration of diabetes, BMI, HbA1c, CXCL10 and CCL11 alone (Z=7.468, 5.400, 7.415, 6.365, 5.242, 5.800, P < 0.001). After internal validation, the decision curve of the predictive model was higher than the two extreme curves. After 1, 000 times of Bootstrap resampling internal validations, the concordance index of the predictive model was 0.919(95%CI, 0.914 to 0.923).
    Conclusion Increased levels of CXCL10 and CCL11 in the peripheral blood are associated with T2DOP, and the predictive model constructed based on these factors has a high predictive value for T2DOP.

     

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