C‐peptide determination in the diagnosis of type of diabetes and its management: A clinical perspective

Abstract

Impaired beta-cell function is a recognized cornerstone of diabetes pathophysiology. Estimates of insulin secretory capacity are useful to inform clinical practice, helping to classify types of diabetes, complication risk stratification and to guide treatment decisions.Because C-peptide secretion mirrors beta-cell function, it has emerged as a valuable clinical biomarker, mainly in autoimmune diabetes and especially in adult-onset diabetes.Nonetheless, the lack of robust evidence about the clinical utility of C-peptide measurement in type 2 diabetes, where insulin resistance is a major confounder, limits its use in such cases. Furthermore, problems remain in the standardization of the assay for C-peptide, raising concerns about comparability of measurements between different laboratories. To approach the heterogeneity and complexity of diabetes, reliable, simple and inexpensive clinical markers are required that can inform clinicians about probable pathophysiology and disease progression, and so enable personalization of management and therapy. This review summarizes the current evidence base about the potential value of C-peptide in the management of the two most prevalent forms of diabetes (type 2 diabetes and autoimmune diabetes) to address how its measurement may assist daily clinical practice and to highlight current limitations and areas of uncertainties to be covered by future research.

Prolonged diabetic ketoacidosis due to SGLT2 inhibitor use and low‐carbohydrate diet

“…19 It will also stratify the intensity of insulin regimen required. 20 For example, in patients with type 2 diabetes, a fasting C-peptide below 360pmol/L was more likely to indicate a requirement for basal-bolus regimen than a basalonly insulin regimen. 21 While it may be impractical to measure paired serum glucose and C-peptide on every patient starting on an SGLT2 inhibitor, it may be more pragmatic to consider this test in patients who have additional risk factors for developing DKA.…”

“…It would be important to repeat his C‐peptide levels after recovery of his illness as C‐peptide may recover in patients following ketoacidosis 19 . It will also stratify the intensity of insulin regimen required 20 . For example, in patients with type 2 diabetes, a fasting C‐peptide below 360pmol/L was more likely to indicate a requirement for basal‐bolus regimen than a basal‐only insulin regimen 21 …”

High levels of serum C-peptide are associated with a decreased risk for incident renal progression in patients with type 2 diabetes: a retrospective cohort study

“…Overall, measurement of C-peptide is of a certain value in clinical practice, such as recognizing T1DM when autoantibodies present as a false negative, predicting the response to insulin treatment and assisting with complication risk stratification in T2DM. 33 RCS curves showed the cut-off values of 2hPCP, ΔCP, and PCGR (2.92 ng/mL, 1.86 ng/mL, and 1.11, respectively), meaning that kidney function progression would accelerate if the level of C-peptide were lower than the above threshold values. Data from a T1DM study have shown that a random C-peptide concentration of ≥0.20 nmol/L, compared with a random C-peptide concentration of <0.005 nmol/L, was associated with a 50% decreased risk for retinopathy, 34 but there has been little research on the relationship between C-peptide values and nephropathy risk in T2DM.…”

“…Overall, measurement of C-peptide is of a certain value in clinical practice, such as recognizing T1DM when autoantibodies present as a false negative, predicting the response to insulin treatment and assisting with complication risk stratification in T2DM 33. RCS curves showed the cut-off values of 2hPCP, ΔCP, and PCGR (2.92 ng/mL, 1.86 ng/mL, and 1.11, respectively), meaning that kidney function progression would accelerate if the level of C-peptide were lower than the above threshold values.…”

Comparability of C-Peptide Measurements – Current Status and Clinical Relevance

“…In contrast to insulin, C-peptide exhibits a prolonged biological halflife; therefore, its plasma concentrations are higher compared to insulin [1]. In clinical routine, C-peptide measurements are used to assess endogenous insulin secretion, to distinguish between type 1, type 2, and other specific types of diabetes, and for differential diagnosis of fasting hypoglycemia [1][2][3][4]. C-peptide is also used for the calculation of HOMA (homeostatic model assessment) indices (e. g., HOMA-2B or HOMA-IR), i. e., for estimating insulin secretion and insulin resistance, especially in patients on insulin therapy.…”