Evidence for C-Peptide as a Validated Surrogate to Predict Clinical Benefits in Trials of Disease-Modifying Therapies for Type 1 Diabetes.
Diabetes
; 73(6): 823-833, 2024 Jun 01.
Article
en En
| MEDLINE
| ID: mdl-38349844
ABSTRACT
Type 1 diabetes is a chronic autoimmune disease in which destruction of pancreatic ß-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 ß-cell function that is not cleared by the liver and can be measured in the peripheral blood. Studies of quantitative measures of ß-cell function have established a predictive relationship between stimulated C-peptide as a measure of ß-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 ß-cell function but also as a specific, sensitive, feasible, and clinically meaningful outcome defining ß-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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Péptido C
/
Biomarcadores
/
Diabetes Mellitus Tipo 1
/
Células Secretoras de Insulina
Tipo de estudio:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Diabetes
Año:
2024
Tipo del documento:
Article