Li Xia, Campbell-Thompson Martha, Wasserfall Clive H, McGrail Kieran, Posgai Amanda, Schultz Andrew R, Brusko Todd M, Shuster Jonathan, Liang Faming, Muir Andrew, Schatz Desmond, Haller Michael J, Atkinson Mark A
Institute of Metabolism and Endocrinology, The Second Xiangya Hospital and the Diabetes Center, Metabolic Syndrome Research Center, Central South University, National Clinical Research Center for Metabolic Diseases, Changsha, China.
Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL.
Diabetes Care. 2017 Apr;40(4):577-582. doi: 10.2337/dc16-1774. Epub 2017 Jan 23.
The pancreas in type 1 diabetes exhibits decreased size (weight/volume) and abnormal exocrine morphology. Serum trypsinogen levels are an established marker of pancreatic exocrine function. As such, we hypothesized that trypsinogen levels may be reduced in patients with pre-type 1 diabetes and type 1 diabetes compared with healthy control subjects.
Serum trypsinogen levels were determined in 100 persons with type 1 diabetes (72 new-onset, 28 established), 99 autoantibody-positive (AAb) subjects at varying levels of risk for developing this disease, 87 AAb-negative (AAb) control subjects, 91 AAb relatives with type 1 diabetes, and 18 patients with type 2 diabetes.
Trypsinogen levels increased significantly with age in control subjects ( = 0.71; < 0.0001) and were significantly lower in patients with new-onset (mean ± SD 14.5 ± 6.1 ng/mL; < 0.0001) and established type 1 diabetes (16.7 ± 6.9 ng/mL; < 0.05) versus AAb control subjects (25.3 ± 11.2 ng/mL), AAb relatives (29.3 ± 15.0 ng/mL), AAb subjects (26.5 ± 12.1 ng/mL), and patients with type 2 diabetes (31.5 ± 17.3 ng/mL). Multivariate analysis revealed reduced trypsinogen in multiple-AAb subjects ( < 0.05) and patients with type 1 diabetes ( < 0.0001) compared with AAb subjects (control subjects and relatives combined) and single-AAb ( < 0.01) subjects when considering age and BMI.
These findings further support the interplay between pancreatic endocrine and exocrine dysfunction. Longitudinal studies are warranted to validate trypsinogen as a predictive biomarker of type 1 diabetes progression.
1型糖尿病患者的胰腺表现出体积减小(重量/容积)和外分泌形态异常。血清胰蛋白酶原水平是胰腺外分泌功能的既定标志物。因此,我们推测与健康对照者相比,1型糖尿病前期患者和1型糖尿病患者的胰蛋白酶原水平可能降低。
测定了100例1型糖尿病患者(72例新发病例,28例病程较长者)、99例处于不同发病风险水平的自身抗体阳性(AAb)受试者、87例自身抗体阴性(AAb)对照受试者、91例1型糖尿病患者的AAb亲属以及18例2型糖尿病患者的血清胰蛋白酶原水平。
对照者的胰蛋白酶原水平随年龄显著升高(r = 0.71;P < 0.0001),与AAb对照受试者(25.3±11.2 ng/mL)、AAb亲属(29.3±15.0 ng/mL)、AAb受试者(26.5±12.1 ng/mL)和2型糖尿病患者(31.5±17.3 ng/mL)相比,新发病例(平均±标准差14.5±6.1 ng/mL;P < 0.0001)和病程较长的1型糖尿病患者(16.7±6.9 ng/mL;P < 0.05)的胰蛋白酶原水平显著降低。多因素分析显示,在考虑年龄和体重指数时,与AAb受试者(对照受试者和亲属合并)和单AAb(P < 0.01)受试者相比,多AAb受试者(P < 0.05)和1型糖尿病患者(P < 0.0001)的胰蛋白酶原水平降低。
这些发现进一步支持了胰腺内分泌和外分泌功能障碍之间的相互作用。有必要进行纵向研究以验证胰蛋白酶原作为1型糖尿病进展的预测生物标志物的作用。