What does an elevated C-peptide (connecting peptide) level indicate?

From the Guidelines

An elevated C-peptide level indicates increased insulin production by the pancreatic beta cells, which can be seen in conditions such as type 2 diabetes, obesity, metabolic syndrome, and insulinoma. C-peptide is produced in equal amounts to insulin when proinsulin is cleaved in the pancreas, making it a reliable marker of endogenous insulin secretion 1. High C-peptide levels commonly occur in conditions of insulin resistance, and unlike insulin levels, C-peptide specifically measures the body's own insulin production, which is particularly valuable when evaluating patients who are taking insulin medications, as injected insulin doesn't contain C-peptide 1.

Key Points to Consider

• The measurement of C-peptide helps differentiate between type 1 and type 2 diabetes, assess beta cell function, and identify causes of hypoglycemia 1.
• Normal C-peptide levels typically range from 0.5 to 2.0 ng/mL, but reference ranges may vary between laboratories 1.
• When interpreting elevated C-peptide results, they should always be considered alongside blood glucose levels, as high glucose with high C-peptide suggests insulin resistance, while high C-peptide with low glucose raises concern for inappropriate insulin secretion 1.
• C-peptide levels can also be used to diagnose and manage insulinomas, with elevated levels indicating increased insulin production by the tumor 1.

Clinical Implications

• Elevated C-peptide levels can be seen in various clinical conditions, including type 2 diabetes, obesity, and metabolic syndrome 1.
• The use of C-peptide measurement can aid in the diagnosis and management of these conditions, particularly in differentiating between type 1 and type 2 diabetes 1.
• It is essential to consider C-peptide levels in the context of blood glucose levels and other clinical factors to accurately interpret the results and make informed clinical decisions 1.

From the Research

Elevated C-Peptide Levels

Elevated C-peptide levels can indicate several conditions, including:

• Endogenous hyperinsulinism, a condition where the body produces too much insulin 2
• Beta-cell function, as C-peptide is a marker of endogenous insulin production and a reflection of beta-cell function 3
• Type 2 diabetes, where C-peptide levels can be used to inform clinical practice and guide treatment decisions 4

Diagnostic Criteria

Diagnostic criteria for endogenous hyperinsulinism include:

• A C-peptide level of 0.3 nmol/L concomitant with a hypoglycemia <2.3 mmol/L 2
• A C-peptide level of less than 0.2 nmol/L is associated with a diagnosis of type 1 diabetes mellitus (T1DM) 5

Clinical Utility

The clinical utility of C-peptide measurement includes:

• Guiding diabetes diagnosis and management 5
• Informing clinical practice and guiding treatment decisions in type 2 diabetes 4
• Predicting future outcomes in type 2 diabetes 6

Limitations

Limitations of C-peptide measurement include:

• Lack of robust evidence about the clinical utility of C-peptide measurement in type 2 diabetes 4
• Problems with standardization of the assay for C-peptide, raising concerns about comparability of measurements between different laboratories 4