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C-peptide levels in differentiation of type 1 and type 2 diabetes

Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

Authoring team

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


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