C-Peptide (Connecting peptide) is the binding peptide cleaved in proinsulin insulin processing. Responsive immunoassays in blood and urine can easily detect it. Serum C-peptide is a particularly useful marker of endogenous insulin secretion (a synthetic insulin that does not contain C-peptide). A patient is being diagnosed with exogenous (injected) insulin at the same time, while insulin assays can only recognise the insulin injected. Serum C-Peptide may help to explain the differential diagnosis of diabetes, as it is typically feeble in long-term type 1 diabetes and very strong in extreme insulin resistance. It also helps treat sporadic hypoglycaemia.

C‐peptide is formed in the pancreatic beta cells during the conversion of proinsulin into insulin. This is secreted with insulin in almost equivalent amounts in the bloodstream. Usually, there is a strong correlation between insulin and C-peptide levels, except for possibly obese subjects and islet cell tumors.

Measurement of C-peptide volume provides a clear indicator of beta and secretory activity and insulin secretions. This approach has the most valuable use in the estimation of endogenous insulin secretion where the involvement of circulatory insulin antibodies interferes with direct insulin assay. This situation most likely occurs in people with diabetes who have been treated with insulin from bovine pork. Moreover, screening for cancer removal after pancreatectomy may offer a way to identify the presence of residual tissue.

Testing C-peptide has a range of benefits relative to testing insulin. Since hepatic metabolism is marginal, concentrations of C-peptides are more reliable measures of beta-cell activity than levels of peripheral insulins. C-peptide assays do not test exogenous insulin, and do not cross-react with insulin antibodies that interact with the immunoassay of insulin.

The proposed structure of the insulin precursor molecule, proinsulin. Before secretion, the C-peptide fragment connecting the A and B peptide chains of the insulin molecule is enzymatically cleaved to yield insulin. Note the two disulphide bridges connecting the peptide chains and the third intrachain link within the A chain.

Fasting Hypoglycemia:The primary reason for measuring C-Peptide is to assess fasting hypoglycemia. Some patients with insulin-producing Beta cell tumors may have elevated C-peptide levels with normal insulin levels, particularly if hyperinsulism is intermittent. Since C-peptide is not present in commercial insulin preparations and exogenous insulin suppresses beta cell activity, when hypoglycemia is triggered by reptitious insulin injection, insulin concentrations will be high but C-peptide levels will be low.

Insulin Secretion: Basal or stimulated concentrations of C-peptides (by glucagon or glucose) can provide an estimate of the secretory capacity and rate of insulin for a patient. Of example, diabetic patients with concentrations of C-peptide greater than 1.8 μL after glucagon stimulation clinically behave like patients with type 2 diabetes, and patients with small peak C-peptide levels (less than 0.5 μg / L) behave like patients with type 1 diabetes. This strategy may be helpful in rare cases before the insulin treatment is discontinued. In differentiating patients with type 1 diabetes from those with type 2 diabetes, urinary and fasting serum concentrations of C-peptides also appear to be of some value. Furthermore, patients with type 1 diabetes but without C-peptide response are usually more labile than patients with some residual beta-cell function. Given these findings, assessment of the C-peptide has a marginal role in the daily treatment of diabetes patients.

Clinical Importance:

Symptomatic hypoglycemia treatment:

  • Diagnosis of  hypoglycemia owing to subreptitious insulin administration
  • Assessing possible insulinoma
  • Surrogate indicator of the absence or involvement of systemic repression of endogenous insulin secretion during hypoglycemia treated with insulin (C-peptide repression test)

Assessment of insulin secretory reserves in selected patients with diabetes (as listed below) who either have insulin autoantibodies or receive insulin treatment:

  • Assessment of endogenous latent, clandestine insulin stocks.
  • Monitoring of the function of pancreatic and islet transplants.
  • Monitoring of immunomodulatory therapy to slow down the progression of type 1 diabetes mellitus preclinical, or very early stage.

Reference Values

1.1-4.4 ng/mL


Factitious hypoglycemia caused by subreptious insulin administration results in elevated serum insulin and poor to undetectable C-peptide levels, with a simple reversal of a ratio of insulins to C-peptide (or = 1) physiological insulin and a ratio of more than C-peptide insulin. However, the level of insulin and the degree of C-peptis are both high in insulinome and 1 or lower in insulin to C-peptide molar. Sulfonylurea consumption is associated with the survival of insulin to C-peptide molar ratios of 1 or less.

Because of the long half-life of autoantibody-linked insulin, the insulin-C-peptide ratio can be reversed to greater than one in insulin autoantibodies.

In the case of hypoglycemic function, more advanced tests could be required; the C-peptide suppression test is more commonly used. C-peptide levels are measured after hypoglycemia has been treated with insulin administered exogenously. The research is focused on a presentation within 2 hours of insulin-induced hypoglycemia in patients with insulinoma who have loss of serum C-peptide levels.


  • The artifactual lower C-peptides are caused by significant hemolysis, and these specimens are generally rejected. Even mild bleeding, however, may cause smaller decreases in the value of C-peptide.
  • Cross-reactivity between C-peptide and proinsulin is significant (> 20%). No high cross-reactivity with specific peptides or neuroendocrine pancreatic islet cells.
  • The artifactually low measurements (hook effect) may occur at high concentrations (> 180 ng / mL) in C-peptides. Such concentrations are very unlikely in patients, but if people are suspected that there are serum concentrations above 180 ng / ml, a laboratory should be warned that the specimen can be diluted in advance.
  • In the study 2 monoclonal antibodies originating from the mouse are used, and heterofilm antimouse (HAMA) can also be susceptible to intervention. To allow the use of heterophile antibody block tubes for these specimens, the laboratory should be alerted to suspected or confirmed HAMA-positive specimens.
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