NK细胞数量在2型糖尿病患者外周血中的变化及临床意义

Changes of the number of NK cells in peripheral blood of patients with type 2 diabetes mellitus and its clinical significance

目的观察2型糖尿病(T2DM)患者不同情况下外周血中自然杀伤细胞(NK细胞)及自然杀伤T细胞(NKT细胞)的数量变化,分析其与T2DM心血管并发症的关系。方法纳入2015年6月—2016年2月于天津医科大学代谢病医院住院治疗的T2DM患者124例(T2DM组)和年龄、性别相匹配的天津医科大学总医院空港医院的健康体检者50名(NC组),于清晨空腹抽取外周静脉血,流式细胞仪检测T2DM组及NC组外周血中NK细胞数量和NKT细胞数量,并按照病程长短及是否合并心血管并发症分亚组,分别观察NK细胞数量和NKT细胞数量在T2DM不同病程、有无心血管并发症存在时的变化。结果T2DM组NK细胞数量及NKT细胞数量较NC组明显下降(t=4.63、5.38,P均<0.01)。T2DM患者外周血中NK细胞数量与年龄和病程呈负相关(r=-0.36、-0.38,P均<0.05),病程>8年组NK细胞数量较病程≤8年组明显降低(F=20.15,P<0.01)。NKT细胞数量与年龄、稳态模型评估-胰岛素抵抗指数、甘油三酯、极低密度脂蛋白-胆固醇呈负相关(r=-0.20、-0.49、-0.29、-0.28,P均<0.05),与高密度脂蛋白-胆固醇、估算的肾小球滤过率呈正相关(r=0.18、0.22,P均<0.05)。T2DM伴冠心病组NKT细胞数量较T2DM不伴冠心病组有下降趋势(F=20.37,P<0.05),而NK细胞数量较T2DM不伴冠心病组明显下降(F=33.90,P<0.01)。NK细胞监测T2DM伴冠心病患者的受试者工作特征(ROC)曲线下面积为0.92,95%CI为0.84~0.99,敏感性90.9%,特异性80.5%。结论T2DM患者外周血中NK细胞及NKT细胞数量下降,NK细胞数量对T2DM心血管并发症有监测价值。

Objective To investigate the changes of the number of natural killer cells(NK cells) and natural killer T cells(NKT cells) in peripheral blood in patients with type 2 diabetes mellitus (T2DM) under different conditions, and to analyze their relationship with cardiovascular complications of T2DM. Methods From June 2015 to February 2016, 124 T2DM patients(T2DM group)who were hospitalized in the Metabolic Diseases Hospital of Tianjin Medical University were included and 50 healthy subjects (NC group)matching with age and gender in the Airport Hospital of Tianjin Medical University General Hospital were included. Fasting peripheral venous blood was extracted. The number of NK cells and NKT cells in peripheral blood of T2DM group and NC group were detected by flow cytometry. All patients were then further divided into subgroups according to their diabetic duration and with or without cardiovascular diseases. The changes in the number of NK cells and NKT cells in T2DM with different disease course and with or without cardiovascular complications were observed. Results The number of NK cells and NKT cells in T2DM group were decreased significantly compared with NC group (t=4.63, 5.38, all P<0.01). The number of NK cells in peripheral blood of T2DM patients was negatively correlated with age and disease course (r=-0.36,-0.38, all P<0.05). The number of NK cells in the group with a disease course greater than 8 years was significantly lower than that in the group with a disease course less than or equal to 8 years (F=20.15, P<0.01). The number of NKT cells was negatively correlated with age, homeostasis model assessment of insulin resistance, triglyceride and very low density lipoprotein cholesterol level (r=-0.20,-0.49,-0.29,-0.28, all P<0.05), and positively correlated with the level of high density lipoprotein cholesterol and estimated glomerular filtration rate (r=0.18, 0.22, all P<0.05). In T2DM with coronary heart disease(CHD) group, the number of NKT cells was lower than that in T2DM without CHD group (F=20.37, P<0.05), while the number of NK cells was significantly lower than that in T2DM without CHD group(F=33.90, P<0.01). The area under the receiver operating characteristics (ROC) curve of NK cells predicting T2DM patients with CHD was 0.92 (95%CI: 0.84-0.99) with 90.9% sensitivity and 80.5% specificity. Conclusion The number of NK cells and NKT cells in peripheral blood in patients with T2DM are decreased, and the number of NK cells is of monitoring value for cardiovascular complications of T2DM.