Bruggeman Brittany Sorensen, Gornisiewicz Savanna, Bacher Rhonda, McGrail Kieran, Campbell-Thompson Martha, Wasserfall Clive, Jacobsen Laura M, Atkinson Mark, Haller Michael J, Schatz Desmond A
Division of Endocrinology, Department of Pediatrics, University of Florida, Gainesville, FL, United States.
College of Medicine, University of Florida, Gainesville, FL, United States.
Front Endocrinol (Lausanne). 2024 Nov 29;15:1497373. doi: 10.3389/fendo.2024.1497373. eCollection 2024.
The immune-mediated destruction of insulin-producing β-cells characterizes type 1 diabetes. Nevertheless, exocrine pancreatic enzymes, including amylase, lipase, and trypsin, are also significantly reduced in type 1 diabetes. With an immunotherapy now approved to treat early-stage type 1 diabetes, biomarkers to delineate response to treatment are needed. No study has yet evaluated whether serum exocrine pancreatic enzymes could delineate immunotherapy responders and non-responders.
In this novel study, we sought to identify longitudinal trends in the most commonly measured circulating exocrine enzymes before and after treatment with anti-thymocyte globulin (ATG) and pegylated granulocyte colony-stimulating factor (GCSF) in individuals with new-onset type 1 diabetes (n=34). We defined response to immunotherapy as participants with at least 60% of baseline area under the curve (AUC) C-peptide levels after a 2-hour mixed meal tolerance test (MMTT) at two years post-treatment. In the overall study (n=89), 42% of treated and 17% of placebo participants met this definition. Due to constraints of sample availability, we compared longitudinal serum amylase, lipase, and trypsin levels in a subset of responders to therapy (n=4-6), placebo "responders" (n=2), treated non-responders (n=16), and placebo non-responders (n=10).
There were no differences in amylase levels between groups at baseline or six months post-treatment. Baseline levels of lipase and trypsin tended to be lower in responders; however, these variations were not significant in this small study sample. Lipase and trypsin improved to 115% of baseline in responders to immunotherapy six months after treatment and declined to 80-90% of baseline in non-responders and placebo participants (p=0.03). This difference was not present before the six-month time point.
Our findings provide preliminary evidence that the exocrine pancreatic enzymes lipase and trypsin may be useful biomarkers of response to immunotherapy in type 1 diabetes. Further studies with larger numbers of participants are warranted.
胰岛素生成β细胞的免疫介导性破坏是1型糖尿病的特征。然而，1型糖尿病患者的外分泌胰腺酶，包括淀粉酶、脂肪酶和胰蛋白酶，也会显著减少。随着一种免疫疗法现已获批用于治疗早期1型糖尿病，需要有生物标志物来描述治疗反应。尚无研究评估血清外分泌胰腺酶是否能区分免疫治疗的反应者和无反应者。
在这项新研究中，我们试图确定新发病1型糖尿病患者（n = 34）在接受抗胸腺细胞球蛋白（ATG）和聚乙二醇化粒细胞集落刺激因子（GCSF）治疗前后，最常检测的循环外分泌酶的纵向变化趋势。我们将免疫治疗反应定义为治疗两年后，在2小时混合餐耐量试验（MMTT）后，曲线下面积（AUC）C肽水平至少达到基线60%的参与者。在整个研究（n = 89）中，42%的治疗参与者和17%的安慰剂参与者符合这一定义。由于样本可用性的限制，我们比较了治疗反应者子集（n = 4 - 6）、安慰剂“反应者”（n = 2）、治疗无反应者（n = 16）和安慰剂无反应者（n = 10）中血清淀粉酶、脂肪酶和胰蛋白酶的纵向水平。
治疗前基线或治疗后六个月，各组间淀粉酶水平无差异。反应者的脂肪酶和胰蛋白酶基线水平往往较低；然而，在这个小样本研究中，这些差异并不显著。免疫治疗反应者在治疗六个月后，脂肪酶和胰蛋白酶水平提高到基线的115%，而无反应者和安慰剂参与者则下降到基线的80 - 90%（p = 0.03）。在六个月时间点之前不存在这种差异。
我们的研究结果提供了初步证据，表明外分泌胰腺酶脂肪酶和胰蛋白酶可能是1型糖尿病免疫治疗反应的有用生物标志物。有必要进行更多参与者的进一步研究。
