Relevance of quantitative measures of beta-cell function in clinical practice

BACKGROUND: Type 1 diabetes (T1D) is a chronic autoimmune disease that causes the progressive irreversible loss of pancreatic beta-cell function, leading to glycemic dysregulation. T1D progresses through stages, beginning with a presymptomatic phase marked by multiple islet autoantibodies (stage 1), dysglycemia (stage 2), and ultimately, clinical (stage 3) and established (stage 4) disease. Although stage 3 is characterized by significant loss of beta-cell function, the remaining reserve can be assessed by measuring markers of residual function, such as C-peptide. Residual C-peptide is associated with improved clinical outcomes, including reduced risk for severe hypoglycemia and long-term complications, improved glycemic control, and lower insulin requirements. SUMMARY: Understanding and monitoring the state of the functional residual beta-cell population may yield useful insights for clinical management of T1D throughout its course. Because early beta-cell dysfunction can already be detected with C-peptide‒based metrics in stage 1, in the future advanced C-peptide measures could aid in earlier identification of presymptomatic individuals to guide treatment management before irreversible beta-cell damage occurs. Currently, C-peptide measurement is most applicable in individuals with stage 3 and stage 4 T1D, where it serves as a surrogate measure of beta-cell function that can inform differential diagnosis, improve identification of those who may be eligible for disease-modifying therapy, and facilitate dynamic tracking of therapeutic responses. Despite these benefits, C peptide measurement is not yet a part of routine clinical care and is rarely performed after disease onset. C-peptide assessment continues to be complicated by logistical barriers, individual variance in pancreatic reserve, insulin sensitivity, and other patient-specific factors, along with a lack of standardized, age-specific normative values. KEY MESSAGES: In this review, we describe beta-cell function across T1D stages, testing strategies to quantify beta-cell health such as C-peptide, and potential benefits of beta-cell monitoring in clinical practice. When used in the correct context, C-peptide combined with other glycemic monitoring can give clinicians real-time insights into residual beta-cell function throughout T1D progression and therapeutic interventions.