Yu D D, Zhou X L, Niu D J, Wang S H
Department of Endocrinology, Zhongda Hospital Southeast University, Nanjing 210000, China.
Zhonghua Yi Xue Za Zhi. 2024 Oct 15;104(38):3593-3599. doi: 10.3760/cma.j.cn112137-20240505-01041.
To analyze the influencing factors of type 2 diabetes mellitus (T2DM) patients with mild cognitive impairment (MCI), and to explore the association between plasma osteopontin (OPN) levels and MCI. A retrospective analysis was conducted on the clinical data of 254 patients with T2DM admitted to Zhongda Hospital Affiliated to Southeast University from October 2021 to May 2023. The patients were divided into MCI group (=106) and normal cognitive function control group (=148) according to whether they had MCI. Clinical data were collected, cognitive function was assessed using neurological scales and plasma OPN levels were measured by enzyme linked immunosorbent assay. A multivariate logistic regression model was applied to analyze the influencing factors of MCI in T2DM patients. Interaction terms between gender, age, body mass index (BMI), and OPN were established to verify their significance levels. Receiver operating characteristic (ROC) curves were plotted to evaluate the predictive value of OPN for MCI in T2DM patients. The mediation model of OPN-FPG-montreal cognitive assessment(MoCA) was constructed with fasting plasma glucose (FPG) as the mediating variable to test the mediating effect, and the mediating effect percentage was calculated. A total of 254 patients were included, including 162 males and 92 females, with an average age of (61.5±7.5) years old. Compared with the control group, the patients in MCI group were older[63.0(59.0, 69.0) years vs 60.0(54.2, 66.8) years], had a greater proportion of females [(43.4%(46/106) vs 31.1%(46/148)], shorter years of education[12(9, 12) years vs 12(9,15) years], longer duration of diabetes[15.0(8.0, 20.0) years vs 10.0(5.0, 15.0) years], and higher levels of FPG[7.78(6.07, 10.23) mmol/L vs 6.86(5.36, 8.59) mmol/L], insulin resistance index[2.93(2.47, 3.98) vs 2.79(2.27, 3.25)], glycated hemoglobin (HbA1c) [9.24%(7.89%, 10.96%) vs 7.97%(7.00%, 9.45%)], total cholesterol(TC)[(4.51±1.17) mmol/L vs (4.19±0.99) mmol/L], and OPN [11.30(8.68, 12.84) ng/ml vs 9.69(7.82, 11.74) ng/ml] (all <0.05). The scores of various neuropsychological tests in MCI patients were lower than those in control group with normal cognitive function (all <0.05). Spearman correlation analysis showed that age(=-0.212), duration of diabetes mellitus(=-0.156), duration of hypertension(=-0.132), FPG(-0.207), insulin resistance index(=-0.171), HbA1c(=-0.271), OPN(=-0.238), and total cholesterol (=-0.125) were negatively correlated with MoCA scores, whereas years of education(=0.285) were positively correlated with MoCA scores(all <0.05). Multifactorial logistic regression analysis showed that age, years of education, duration of diabetes mellitus, HbA1c, TC and OPN levels were the influencing factors of T2DM patients with MCI, and the risk of MCI increased by 15% for every 1 ng/ml increase in OPN (=1.15, 95%: 1.021-1.295, =0.021), and the relationship was not affected by age, gender and BMI(The interaction effects are all >0.05). The area under the curve (AUC) of the working curve of subjects with OPN predicting combined MCI in patients with T2DM was 0.612 (95%: 0.541-0.682), and the AUC was 0.702 (95%: 0.638-0.767) after the combination of HbA1c and OPN. The results of the mediated effect model showed that FPG partially mediated the correlation between OPN and MoCA in T2DM patients, and the mediated effect accounted for 11.34% of the total effect. Plasma OPN level is associated with MCI in patients with T2DM,and the higher the OPN level, the higher the risk of T2DM patients developing MCI.
分析2型糖尿病(T2DM)合并轻度认知障碍(MCI)患者的影响因素,探讨血浆骨桥蛋白(OPN)水平与MCI之间的关联。对2021年10月至2023年5月在东南大学附属中大医院住院的254例T2DM患者的临床资料进行回顾性分析。根据是否患有MCI将患者分为MCI组(n = 106)和正常认知功能对照组(n = 148)。收集临床资料,采用神经量表评估认知功能,酶联免疫吸附测定法检测血浆OPN水平。应用多因素logistic回归模型分析T2DM患者发生MCI的影响因素。建立性别、年龄、体重指数(BMI)和OPN之间的交互项,以验证其显著性水平。绘制受试者工作特征(ROC)曲线,评估OPN对T2DM患者MCI的预测价值。以空腹血糖(FPG)为中介变量构建OPN-FPG-蒙特利尔认知评估(MoCA)中介模型,检验中介效应,并计算中介效应百分比。共纳入254例患者,其中男性162例,女性92例,平均年龄(61.5±7.5)岁。与对照组相比,MCI组患者年龄更大[63.0(59.0,69.0)岁 vs 60.0(54.2,66.8)岁],女性比例更高[43.4%(46/106) vs 31.1%(46/148)],受教育年限更短[12(9,12)年 vs 12(9,15)年],糖尿病病程更长[15.0(8.0,20.0)年 vs 10.0(5.0,15.0)年],FPG水平更高[7.78(6.07,10.23)mmol/L vs 6.86(5.36,8.59)mmol/L],胰岛素抵抗指数更高[2.93(2.47,3.98) vs 2.79(2.27,3.25)],糖化血红蛋白(HbA1c)更高[9.24%(7.89%,10.96%) vs 7.97%(7.00%,9.45%)],总胆固醇(TC)更高[(4.51±1.17)mmol/L vs (4.19±0.99)mmol/L],OPN更高[11.30(8.68,12.84)ng/ml vs 9.69(7.82,11.74)ng/ml](均P < 0.05)。MCI患者各项神经心理学测试得分均低于认知功能正常的对照组(均P < 0.05)。Spearman相关性分析显示,年龄(r = -0.212)、糖尿病病程(r = -0.156)、高血压病程(r = -0.132)、FPG(r = -0.207)、胰岛素抵抗指数(r = -0.171)、HbA1c(r = -0.271)、OPN(r = -0.238)和总胆固醇(r = -0.125)与MoCA评分呈负相关,而受教育年限(r = 0.285)与MoCA评分呈正相关(均P < 0.05)。多因素logistic回归分析显示,年龄、受教育年限、糖尿病病程、HbA1c、TC和OPN水平是T2DM合并MCI患者的影响因素,OPN每升高1 ng/ml,MCI风险增加15%(OR = 1.15,95%CI:1.021 - 1.295,P = 0.021),且该关系不受年龄、性别和BMI影响(交互作用均P > 0.05)。OPN预测T2DM患者合并MCI的受试者工作曲线下面积(AUC)为0.612(95%CI:0.541 - 0.682),HbA1c与OPN联合后AUC为0.702(95%CI:0.638 - 0.767)。中介效应模型结果显示,FPG在T2DM患者中部分介导了OPN与MoCA之间的相关性,中介效应占总效应的11.34%。血浆OPN水平与T2DM患者的MCI相关,OPN水平越高,T2DM患者发生MCI的风险越高。