Williams MacKenzie D, Grace Catherine Ramsey, Posgai Amanda L, McGrail Kieran M, Brusko Maigan A, Haller Michael J, Jacobsen Laura, Schatz Desmond, Brusko Todd M, Atkinson Mark, Bacher Rhonda, Wasserfall Clive H
Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, Florida, USA.
Department of Pediatrics, University of Florida, Gainesville, Florida, USA.
BMJ Open Diabetes Res Care. 2025 Jan 4;13(1):e004655. doi: 10.1136/bmjdrc-2024-004655.
Altered serum levels of growth hormones, adipokines, and exocrine pancreas enzymes have been individually linked with type 1 diabetes (T1D). We collectively evaluated seven such biomarkers, combined with islet autoantibodies (AAb) and genetic risk score (GRS2), for their utility in predicting AAb/T1D status.
Cross-sectional serum samples (n=154 T1D, n=56 1AAb+, n=77 ≥2AAb+, n=256 AAb-) were assessed for IGF1, IGF2, adiponectin, leptin, amylase, lipase, and trypsinogen (n=543, age range 2.7-30.0 years) using random forest modeling.
GRS2, age, lipase, trypsinogen, and AAb against ZnT8, GAD65, and insulin were the most informative markers. Notably, these variables were differentially informative according to AAb/T1D status. Higher GRS2 (p<0.001) and lower lipase levels (p=0.002) favored ≥2AAb+ versus AAb- classification. AAb against ZnT8 (p<0.01), GAD65 (p=0.021), or insulin (p=0.01) each independently favored ≥2AAb+ versus 1AAb+ classification. Reduced trypsinogen (p<0.001) and increased lipase levels (p<0.001) favored recent-onset T1D versus ≥2AAb+ classification.
Among the serological markers tested, lipase and trypsinogen levels were the most informative for differentiating among clinical groups, with the utility of each enzyme varying according to GRS2 and AAb/T1D status. These data support exocrine pancreas enzymes as candidates for longitudinal follow-up.
生长激素、脂肪因子和外分泌胰腺酶的血清水平改变已分别与1型糖尿病（T1D）相关联。我们综合评估了七种此类生物标志物，并结合胰岛自身抗体（AAb）和遗传风险评分（GRS2），以评估它们在预测AAb/T1D状态方面的效用。
使用随机森林模型对横断面血清样本（n = 154例T1D患者，n = 56例1AAb+，n = 77例≥2AAb+，n = 256例AAb-）进行了IGF1、IGF2、脂联素、瘦素、淀粉酶、脂肪酶和胰蛋白酶原的评估（n = 543例，年龄范围2.7 - 30.0岁）。
GRS2、年龄、脂肪酶、胰蛋白酶原以及针对锌转运体8（ZnT8）、谷氨酸脱羧酶65（GAD65）和胰岛素的AAb是最具信息量的标志物。值得注意的是，根据AAb/T1D状态，这些变量提供的信息有所不同。较高的GRS2（p < 0.001）和较低的脂肪酶水平（p = 0.002）有利于将≥2AAb+与AAb-进行分类。针对ZnT8（p < 0.01）、GAD65（p = 0.021）或胰岛素（p = 0.01）的AAb各自独立地有利于将≥2AAb+与1AAb+进行分类。胰蛋白酶原降低（p < 0.001）和脂肪酶水平升高（p < 0.001）有利于将近期发病的T1D与≥2AAb+进行分类。
在所测试的血清学标志物中，脂肪酶和胰蛋白酶原水平在区分临床组方面最具信息量，每种酶的效用根据GRS2和AAb/T1D状态而有所不同。这些数据支持外分泌胰腺酶作为纵向随访的候选指标。
