From the Guidelines
C-peptide testing is essential in distinguishing between type 1 and type 2 diabetes, particularly in ambiguous cases, and should be measured in people receiving insulin treatment, with a random sample replacing a formal C-peptide stimulation test in the context of classification, as stated in the 2025 standards of care in diabetes 1.
Key Points
- C-peptide is a protein fragment produced during insulin synthesis in the pancreas, released in equal amounts to insulin, and measures the body's natural insulin production.
- C-peptide testing is useful in distinguishing between type 1 and type 2 diabetes, with low levels indicating decreased insulin production and normal or high levels suggesting insulin resistance.
- The test is valuable for assessing residual beta cell function, determining if someone with diabetes still produces some insulin, and investigating causes of hypoglycemia.
- C-peptide has a longer half-life than insulin, providing a more stable measurement of insulin secretion, with normal fasting levels typically ranging from 0.5 to 2.0 ng/mL, but reference ranges may vary between laboratories.
- The presence or absence of measurable C-peptide levels does not correlate with response to intensive insulin therapy, as noted in the 2021 standards of medical care in diabetes 1.
Clinical Application
- C-peptide testing can help clinicians make appropriate treatment decisions, such as determining if a patient needs insulin therapy or might benefit from other diabetes medications.
- The test is particularly useful in cases where the diagnosis of type 1 or type 2 diabetes is uncertain, and can help guide treatment decisions, as recommended in the 2023 guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus 1.
- C-peptide measurement can also be used to assess the effectiveness of insulin therapy and to monitor changes in insulin production over time, as discussed in the 2025 standards of care in diabetes 1.
From the Research
C-Peptide Measurement
- 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 differentiating between Type 1 and Type 2 diabetes 2, 3.
- C-peptide levels are associated with diabetes type and duration of disease, with a level of less than 0.2 nmol/l indicating a diagnosis of Type 1 diabetes mellitus (T1DM) 3.
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 help guide diabetes diagnosis and management, including the choice of treatment and the prediction of microvascular and macrovascular complications 3, 4.
- C-peptide levels may correlate with the likelihood of response to other individual therapies, such as insulin therapy 3.
Methods of C-Peptide Measurement
- 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.
- The glucagon stimulation C-peptide test is recommended due to its balance of sensitivity and practicality 3.
C-Peptide in Type 1 and Type 2 Diabetes
- In Type 1 diabetes, C-peptide levels decline rapidly after diagnosis, followed by a slower rate of change 5.
- In Type 2 diabetes, C-peptide measurement may be useful in assessing beta-cell function and guiding treatment decisions, although the lack of robust evidence limits its use in such cases 4, 6.
- Early basal insulin treatment with glargine in Type 2 diabetes patients may provide better control of fasting plasma glucose, overall glucose load, and biomarkers of beta-cell function compared to metformin treatment 6.