From the Guidelines
Fasting C-peptide is a crucial blood test for assessing pancreatic beta cell function and insulin production, particularly in distinguishing between type 1 and type 2 diabetes, with normal levels typically ranging from 0.5 to 2.0 ng/mL 1.
Importance of Fasting C-Peptide
The test is essential in evaluating hypoglycemia, monitoring pancreatic transplants, and assessing insulin resistance.
- C-peptide provides a more accurate assessment of the body's insulin production because it has a longer half-life than insulin and is not affected by insulin medications.
- Patients should fast for 8-12 hours before the test for accurate results.
Clinical Application
- A C-peptide test is only indicated in people receiving insulin treatment 1, and a random sample (with concurrent glucose) within 5 h of eating can replace a formal C-peptide stimulation test in the context of classification.
- If the result is >600 pmol/L (>1.8 ng/mL), the circumstances of testing do not matter, but if the result is <600 pmol/L (<1.8 ng/mL) and the concurrent glucose is <4 mmol/L (<70 mg/dL) or the person may have been fasting, consider repeating the test.
Interpretation of Results
- Results showing very low levels (e.g., <80 pmol/L [<0.24 ng/mL]) do not need to be repeated.
- C-peptide values 200–600 pmol/L (0.6–1.8 ng/mL) are usually consistent with type 1 diabetes or maturity-onset diabetes of the young but may occur in insulin-treated type 2 diabetes, particularly in people with normal or low BMI or after long duration 1.
Guidelines and Recommendations
- The American Diabetes Association recommends that C-peptide measurements may 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.
- Insulin and C-peptide assays should be standardized to facilitate measures of insulin secretion and sensitivity that will be comparable across research studies 1.
From the Research
Fasting C-Peptide Levels
- Fasting C-peptide levels can be used to assess residual β-cell function in patients with type 2 diabetes 2
- A study found that the average fasting C-peptide level was 1.81 ± 0.15 ng/mL in patients with type 2 diabetes, and its levels showed a significant inverse correlation with the duration of diabetes (r = -0.24, p = 0.03) 2
- Fasting C-peptide levels can also be used to differentiate type 1 from type 2 diabetes, but there is a range of C-peptide concentrations that does not help discriminate 3
- Low C-peptide concentrations are associated with a high odds ratio for type 1 diabetes and vice versa (p<0.0001) 3
Relationship with Insulin Treatment
- Fasting C-peptide levels can predict the adoption of a basal-bolus treatment in patients with type 2 diabetes, with concentrations below 1.09 ng/mL predicting the adoption of a basal-bolus treatment (Area 0.64,95%CI:0.521-0.759, p = 0.038, sensitivity 45% and specificity 81%) 2
- Reduced glycemic response to GLP-1 receptor agonist therapy is associated with lower fasting C-peptide levels, and participants with severe insulin deficiency (fasting C-peptide ≤0.25 nmol/L) had markedly reduced glycemic response to GLP-1RA therapy (mean HbA1c change -2.1 vs. -15.3 mmol/mol [-0.2 vs. -1.4%], P = 0.002) 4
Measurement and Diagnostic Value
- A quantitative point-of-care C-peptide test can measure C-peptide levels as low as 0.2 ng/ml, and the test was accurate over a range of 0.17 to 12.0 ng/ml 5
- The test exhibited a correlation of r = 0.98 with a high-sensitivity commercial ELISA assay and a correlation of r = 0.90 between matched serum and fingerstick samples 5
- Fasting C-peptide and derived parameters can help to differentiate type 1 from type 2 diabetes, but relating C-peptide to glucose did not improve diagnostic accuracy 3