use of C-peptide in diagnosis of diabetes

Last reviewed 07/2021

C-peptide is a peptide composed of 31 amino acids

• released from the pancreatic beta-cells during cleavage of insulin from proinsulin
  • preproinsulin, is produced in pancreatic beta-cells and is later cleaved to proinsulin and transported to the Golgi apparatus, where is packed into secretory granules
    • during maturation of this granules, proinsulin is cleaved into 3 peptide chains - insulin (2 chains, A and B) and C-peptide
  
  
• C-peptide mainly excreted by the kidney
  
  
• half-life of C-peptide is 3-4 times longer than that of insulin
  
  
• amount of C-peptide in the blood can indicate the production or absence of endogenous insulin production
  • abnormally low amounts of C-peptide in the blood suggest the insulin production is too low (or absent) because of type I diabetes
    • C-peptide testing can help differentiate between factitious hypoglycemia due to exogenous insulin use (low C-peptide level, high insulin level)
  • abnormally high amounts of C-peptide if hypoglycaemia warn of the possible presence of an insulinoma
    • C-peptide measurement can be used to differentiate between insulin-dependent hypoglycemia (high C-peptide levels) versus insulin-independent hypoglycemia (low C-peptide levels)
      
      
• in a person with diabetes, a normal level of C-peptide indicates the body is making plenty of insulin but the body is just not responding properly to it - hallmark of type 2 diabetes (adult insulin-resistant diabetes)
  • C-peptide can help differentiate between type 2 diabetes mellitus (normal C-peptide levels) and latent autoimmune diabetes of adults (LADA) (low C-peptide levels)

Use of C-peptide in diagnosis of diabetes (1)

• do not measure C-peptide and/or diabetes-specific autoantibody titres routinely to confirm type 1 diabetes in adults
  
  
• consider further investigation in adults that involves measurement of C-peptide and/or diabetes-specific autoantibody titres if:
  
  
  • type 1 diabetes is suspected but the clinical presentation includes some atypical features (for example, age 50 years or above, BMI of 25 kg/m2 or above, slow evolution of hyperglycaemia or long prodrome) or
    
    
  • type 1 diabetes has been diagnosed and treatment started but there is a clinical suspicion that the person may have a monogenic form of diabetes, and C-peptide and/ or autoantibody testing may guide the use of genetic testing or
    
    
  • classification is uncertain, and confirming type 1 diabetes would have implications for availability of therapy (for example, continuous subcutaneous insulin infusion [CSII or 'insulin pump'] therapy)
    
    
• When measuring C-peptide and/or diabetes-specific autoantibody titres, take into account that:
  
  
  • autoantibody tests have their lowest false negative rate at the time of diagnosis, and that the false negative rate rises thereafter
  • C-peptide has better discriminative value the longer the test is done after diagnosis
  • with autoantibody testing, carrying out tests for 2 different diabetes-specific autoantibodies, with at least 1 being positive, reduces the false negative rate

Reference:

• NICE (August 2015). Type 1 diabetes in adults: diagnosis and management