Østergaard J A, Thiel S, Hoffmann-Petersen I T, Hovind P, Parving H-H, Tarnow L, Rossing P, Hansen T K
Department of Endocrinology and Internal Medicine, Aarhus University Hospital and Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark.
The Danish Diabetes Academy, Odense, Denmark.
Diabetes Metab Res Rev. 2017 Jul;33(5). doi: 10.1002/dmrr.2895. Epub 2017 Apr 11.
Evidence links the lectin pathway of complement activation to diabetic kidney disease. Upon carbohydrate-recognition by pattern-recognition molecules, eg, mannan-binding lectin (MBL), the MBL-associated serine protease (MASP-2) is activated and initiates the complement cascade. The MASP2 gene encodes MASP-2 and the alternative splice product MBL-associated protein 19 (MAp19). Both MAp19 and MASP-2 circulate in complex with MBL. We tested the hypothesis that MAp19 and MASP-2 concentrations predict the risk of incident microalbuminuria.
Baseline MAp19 and MASP-2 were measured in 270 persons with newly diagnosed type 1 diabetes tracked for incidence of persistent microalbuminuria in a prospective observational 18-year-follow-up study.
Seventy-five participants (28%) developed microalbuminuria during follow-up. MBL-associated protein 19 concentrations were higher in participants that later progressed to microalbuminuria as compared with those with persistent normoalbuminuria (268 ng/mL [95% CI, 243-293] vs 236 ng/mL [95% CI, 223-250], P = .02). Participants with MAp19 concentration within the highest quartile of the cohort had an increased risk of microalbuminuria as compared with participants with MAp19 concentration within the combined lower 3 quartiles in unadjusted Cox analysis, hazard ratio 1.86 ([95% CI, 1.17-2.96], P = .009). This remained significant in adjusted models, eg, adjusting for age, sex, HbA , systolic blood pressure, urinary albumin excretion, smoking, serum creatinine, and serum cholesterol. MBL-associated serine protease concentration was not associated with incidence of microalbuminuria.
In conclusion, the results show an association between baseline MAp19 concentration and the incidence of microalbuminuria in an 18-year-follow-up study on persons with newly diagnosed type 1 diabetes.
有证据表明补体激活的凝集素途径与糖尿病肾病相关。在模式识别分子（如甘露聚糖结合凝集素，MBL）识别碳水化合物后，MBL相关丝氨酸蛋白酶（MASP-2）被激活并启动补体级联反应。MASP2基因编码MASP-2和可变剪接产物MBL相关蛋白19（MAp19）。MAp19和MASP-2均与MBL形成复合物循环。我们检验了MAp19和MASP-2浓度可预测新发微量白蛋白尿风险的假设。
在一项前瞻性观察性18年随访研究中，对270例新诊断的1型糖尿病患者进行基线MAp19和MASP-2检测，追踪持续性微量白蛋白尿的发生率。
75名参与者（28%）在随访期间出现微量白蛋白尿。与持续正常白蛋白尿者相比，后来进展为微量白蛋白尿的参与者中MBL相关蛋白19浓度更高（268 ng/mL [95% CI，243 - 293] 对比236 ng/mL [95% CI，223 - 250]，P = 0.02）。在未调整的Cox分析中，与MAp19浓度处于队列中较低3个四分位数总和的参与者相比，MAp19浓度处于最高四分位数的参与者发生微量白蛋白尿的风险增加，风险比为1.86（[95% CI，1.17 - 2.96]，P = 0.009）。在调整模型中（如调整年龄、性别、糖化血红蛋白、收缩压、尿白蛋白排泄、吸烟、血清肌酐和血清胆固醇），这一结果仍然显著。MBL相关丝氨酸蛋白酶浓度与微量白蛋白尿的发生率无关。
总之，在一项针对新诊断的1型糖尿病患者的18年随访研究中，结果显示基线MAp19浓度与微量白蛋白尿的发生率之间存在关联。
