From the Guidelines
C-peptide levels should be measured to distinguish between type 1 and type 2 diabetes in ambiguous cases, such as individuals with a type 2 phenotype who present in ketoacidosis, as recommended by the most recent guidelines 1.
Importance of C-peptide Measurement
C-peptide testing is a valuable tool for evaluating insulin production capacity and investigating suspected cases of insulinoma or factitious hypoglycemia.
- Normal fasting C-peptide levels typically range from 0.5 to 2.0 ng/mL (0.17-0.67 nmol/L), though reference ranges may vary slightly between laboratories.
- Low C-peptide levels indicate decreased insulin production, as seen in type 1 diabetes, while normal or elevated levels in the presence of hyperglycemia suggest insulin resistance typical of type 2 diabetes.
- The test is particularly valuable because C-peptide is produced in equimolar amounts to insulin but has a longer half-life and isn't affected by exogenous insulin administration.
Clinical Applications
C-peptide measurement provides objective data about a patient's endogenous insulin production, which helps guide appropriate diabetes treatment strategies.
- For accurate results, the test should be performed after an 8-12 hour fast, and patients should follow their healthcare provider's specific instructions regarding medication timing.
- According to the guidelines, 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 1.
- The guidelines also recommend that C-peptide must be measured prior to insulin discontinuation to exclude severe insulin deficiency, and it should not be tested within 2 weeks of a hyperglycemic emergency 1.
Recent Guidelines
The most recent guidelines from 2025 recommend using C-peptide measurements to help distinguish type 1 from type 2 diabetes in ambiguous cases, such as individuals who have a type 2 phenotype but present in ketoacidosis 1.
- The guidelines also provide a flowchart for the investigation of suspected type 1 diabetes in newly diagnosed adults, which includes C-peptide testing as a key component 1.
- Another study from 2023 also supports the use of C-peptide measurements in the diagnosis and management of diabetes mellitus, particularly in cases where the diagnosis is unclear 1.
From the Research
C-Peptide Levels
- C-peptide is produced in equal amounts to insulin and is the best measure of endogenous insulin secretion in patients with diabetes 2, 3, 4
- 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 can be used to assist in patient selection for islet cell transplantation and post-transplant monitoring 3
- A C-peptide level of less than 0.2 nmol/l is associated with a diagnosis of type 1 diabetes mellitus (T1DM) 4
- C-peptide level may correlate with microvascular and macrovascular complications and future use of insulin therapy, as well as likely response to other individual therapies 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
- Utility is greatest after 3-5 years from diagnosis when persistence of substantial insulin secretion suggests Type 2 or monogenic diabetes 2
- C-peptide measurement can be used to identify patients with latent autoimmune diabetes in adults (LADA) and maturity-onset diabetes of the young (MODY) 3
- High uncorrected fasting C-peptide in the presence of hyperglycemia may suggest insulin resistance 3