Objective: To investigate the changes of circulating proteinase 3 (PR3) in latent autoimmune diabetes mellitus in adults (LADA) patients, type 2 diabetes mellitus (T2DM) patients, obese patients without diabetes and healthy controls, and explore the value of serum PR3 in differentiating LADA and T2DM. Methods: Forty LADA patients, 29 T2DM patients, 26 obesity patients without diabetes, and 76 healthy controls were enrolled in Department of Metabolism & Endocrinology, the Second Xiangya Hospital, Central South University. Serum PR3 was detected by enzyme-linked immunosorbent assay (ELISA). The differences of serum PR3 among the four groups were compared. The correlation between serum PR3 and other metabolic indexes was analyzed. The value of serum PR3 in the differential diagnosis between LADA and T2DM was evaluated. Results: There was no significant difference in age among LADA patients, T2DM patients, obesity patients without diabetes and healthy controls [(50±13) years, (49±6) years, (49±6) years vs (47±7) years, P=0.254], while there was significant difference in gender among the four groups (χ(2)=18.28, P<0.001). Serum PR3 was significantly increased in LADA patients compared to the other three groups [195.4 (127.6, 288.1) μg/L vs 43.4 (30.9, 53.7) μg/L, 36.0 (29.2, 46.4) μg/L, 41.2 (30.2, 52.8) μg/L, all P<0.01], whereas there was no significant differences among the other three groups. After adjustment for age, gender and body mass index (BMI), serum PR3 remained higher in LADA patients compared to the other three groups. Correlation analysis indicated that PR3 correlated positively with fasting and 2-hour postprandial blood glucose (r=0.346, r=0.357, both P<0.001). Receiver operating characteristic (ROC) curve showed that the cut-off value of PR3 (71.7 μg/L) for differentiating LADA and T2DM had a sensitivity of 97.5% and specificity of 89.7% and rendered an area under the curve of 0.955 (95%CI: 0.894~1.000, compared to 0.5, P<0.01). Conclusion: Serum PR3 significantly elevated in LADA patients, and may serve as a biomarker for differentiating LADA and T2DM patients.
目的： 研究血清蛋白酶3（PR3）在成人隐匿性自身免疫糖尿病（LADA）、2型糖尿病（T2DM）、肥胖不合并糖尿病患者及健康对照者中的变化，并探讨血清PR3在鉴别LADA与T2DM中的价值。 方法： 纳入中南大学湘雅二医院代谢内分泌科2012年1月至2013年5月40例LADA患者，选择2007年6月至2008年5月全国糖尿病流行病学调查的湖南人群中年龄匹配的29例T2DM患者，26例肥胖不合并糖尿病患者（肥胖组）及76例健康对照者（健康对照组）。用酶联免疫吸附法（ELISA）检测血清PR3，比较四组间血清PR3的差别，分析其与其他代谢指标的相关性及在鉴别LADA与T2DM中的价值。 结果： LADA、T2DM、肥胖组、健康对照组四组患者的年龄差异无统计学意义[（50±13）岁、（49±6）岁、（49±6）岁比（47±7）岁，P=0.254]，组间性别差异有统计学意义（χ(2)=18.28，P<0.001）。LADA、T2DM、肥胖组、健康对照组组间血清PR3比较结果显示，LADA患者血清PR3水平明显高于其他三组[195.4（127.6，288.1）μg/L比43.4（30.9，53.7）μg/L、36.0（29.2，46.4）μg/L、41.2（30.2，52.8）μg/L，均P<0.01]，其他三组间比较差异均无统计学意义（均P>0.05）。校正年龄、性别、体质指数（BMI）之后，LADA患者血清PR3仍高于其他三组（均P<0.01）。相关性分析提示血清PR3与空腹血糖及餐后2 h血糖呈正相关（r=0.346、0.357，均P<0.001）。受试者工作特征曲线（ROC）显示PR3诊断界值为71.7 μg/L，区分LADA及T2DM的灵敏度和特异度分别为97.5%和89.7%，ROC曲线下面积为0.955（95%CI：0.894~1.000，与0.5相比，P<0.01）。 结论： 血清PR3在LADA患者中明显升高，可能成为鉴别LADA和T2DM的血清生物标志物。.
Keywords: Biomarker; Latent autoimmune diabetes in adults; Neutrophil; Proteinase 3.