JDRF, New York, NY.
Benaroya Research Institute at Virginia Mason, Seattle, WA.
Diabetes. 2024 Jun 1;73(6):823-833. doi: 10.2337/dbi23-0012.
Type 1 diabetes is a chronic autoimmune disease in which destruction of pancreatic β-cells causes life-threatening metabolic dysregulation. Numerous approaches are envisioned for new therapies, but limitations of current clinical outcome measures are significant disincentives to development efforts. C-peptide, a direct byproduct of proinsulin processing, is a quantitative biomarker of β-cell function that is not cleared by the liver and can be measured in the peripheral blood. Studies of quantitative measures of β-cell function have established a predictive relationship between stimulated C-peptide as a measure of β-cell function and clinical benefits. C-peptide levels at diagnosis are often high enough to afford glycemic control benefits associated with protection from end-organ complications of diabetes, and even lower levels offer protection from severe hypoglycemia in type 1 diabetes, as observed in large prospective cohort studies and interventional trials of islet transplantation. These observations support consideration of C-peptide not just as a biomarker of β-cell function but also as a specific, sensitive, feasible, and clinically meaningful outcome defining β-cell preservation or restoration for clinical trials of disease-modifying therapies. Regulatory acceptance of C-peptide as a validated surrogate for demonstration of efficacy would greatly facilitate development of disease-modifying therapies for type 1 diabetes.
1 型糖尿病是一种慢性自身免疫性疾病，其中胰腺β细胞的破坏导致危及生命的代谢失调。人们设想了许多新疗法，但当前临床结果测量的局限性严重阻碍了开发工作。C 肽是胰岛素原加工的直接副产物，是β细胞功能的定量生物标志物，不会被肝脏清除，并且可以在外周血液中测量。对β细胞功能的定量测量研究已经建立了刺激 C 肽作为β细胞功能的测量与临床益处之间的预测关系。诊断时的 C 肽水平通常足够高，可以提供与糖尿病终末器官并发症保护相关的血糖控制益处，即使较低的水平也可以预防 1 型糖尿病的严重低血糖，这在大型前瞻性队列研究和胰岛移植的干预试验中得到了观察。这些观察结果支持不仅将 C 肽视为β细胞功能的生物标志物，而且还将其视为定义临床试验中β细胞保存或恢复的具体、敏感、可行和临床有意义的结果，用于疾病修饰疗法。监管机构接受 C 肽作为疗效验证的替代指标，将极大地促进 1 型糖尿病疾病修饰疗法的开发。
