From the Guidelines
C-peptide testing is a crucial tool for assessing insulin production and differentiating between type 1 and type 2 diabetes, with levels <200 pmol/L indicating type 1 diabetes or advanced type 2 diabetes with beta cell failure, and levels >600 pmol/L suggesting type 2 diabetes or insulin resistance, as per the most recent guidelines 1.
C-peptide Interpretation
When interpreting C-peptide results, it is essential to consider the patient's blood glucose levels, as C-peptide should be evaluated in relation to concurrent glucose measurements.
- Normal C-peptide levels typically range from 0.5-2.0 ng/mL (0.17-0.66 nmol/L) when fasting, with higher levels after meals.
- Low C-peptide levels (<0.2 ng/mL) suggest type 1 diabetes or advanced type 2 diabetes with beta cell failure, indicating a need for insulin therapy.
- High levels (>4.0 ng/mL) typically indicate insulin resistance as seen in early type 2 diabetes, obesity, or conditions like Cushing's syndrome.
Clinical Considerations
For accurate interpretation, the test should be performed after an overnight fast or as part of a stimulation test.
- C-peptide is preferred over direct insulin measurement because it has a longer half-life, isn't affected by insulin antibodies, and isn't cleared by the liver, making it a more reliable marker of endogenous insulin production.
- The presence or absence of measurable C-peptide levels does not correlate with response to intensive insulin therapy, as noted in studies 1.
Recent Guidelines
The most recent guidelines from 2025 1 emphasize the importance of C-peptide testing in the diagnosis and classification of diabetes, particularly in differentiating between type 1 and type 2 diabetes.
- A C-peptide test is only indicated in people receiving insulin treatment, and a random sample (with concurrent glucose) within 5 hours of eating can replace a formal C-peptide stimulation test in the context of classification.
- Results showing very low levels (e.g., <80 pmol/L) do not need to be repeated, but if the result is <600 pmol/L and the concurrent glucose is <4 mmol/L or the person may have been fasting, consider repeating the test.
From the Research
C-Peptide Interpretation
- C-peptide is produced in equal amounts to insulin and is the best measure of endogenous insulin secretion in patients with diabetes 2.
- Measurement of insulin secretion using C-peptide can be helpful in clinical practice, particularly in distinguishing between Type 1 and Type 2 diabetes 2, 3.
- A C-peptide level of less than 0.2 nmol/l is associated with a diagnosis of Type 1 diabetes mellitus (T1DM) 3.
- C-peptide levels can also be used to guide diabetes diagnosis and management, and may correlate with microvascular and macrovascular complications and future use of insulin therapy 3, 4.
Clinical Utility of C-Peptide Measurement
- The key current clinical role of C-peptide is to assist classification and management of insulin-treated patients 2.
- C-peptide measurement can be used to identify individuals at risk for or with Type 1 diabetes with residual β-cell function, and can aid in distinguishing Type 2 diabetes from Latent Autoimmune Diabetes in Adults and late-onset Type 1 diabetes 4.
- Advances in assays have made C-peptide measurement both more reliable and inexpensive, and recent work has demonstrated that C-peptide is more stable in blood than previously suggested or can be reliably measured on a spot urine sample 2.
C-Peptide Testing Methods
- Methods of estimation include urinary and unstimulated and stimulated serum sampling 3.
- Modern assays detect levels of C-peptide which can be used to guide diabetes diagnosis and management 3.
- A quantitative point-of-care C-peptide test has been developed, which can measure C-peptide levels as low as 0.2 ng/ml in a fingerstick sample 4.