C-peptide (connecting peptide) is part of the endocrine component of the pancreas and serves as an indicator of insulin production. It is widely used in the diagnosis of diabetes. During insulin biosynthesis, C-peptide is synthesized alongside insulin as a byproduct of the proteolytic cleavage of proinsulin. The precursor molecule, proinsulin, is located in the Golgi apparatus within the secretory granules of beta cells. Proinsulin itself is derived from preproinsulin, and the formation of C-peptide occurs as a molecule containing 31 amino acid residues. The peptide is cleaved from its main molecule by peptidase enzymes and enters the bloodstream alongside insulin.

C-peptide plays a crucial role in forming the two-chain structure of insulin (A- and B-chains) and in the creation of two disulfide bridges within the proinsulin molecule. Insulin and C-peptide are produced in equimolar quantities and enter the bloodstream through the portal vein. While half of the insulin is metabolized in the liver, C-peptide has a longer half-life (about 35 minutes), making its concentration in peripheral blood 5–10 times higher than insulin. Unlike insulin, C-peptide is not subject to "first-pass effect" in the liver, meaning its blood levels accurately reflect its secretion.

This stability makes C-peptide a reliable marker for assessing pancreatic insulin secretion, even under conditions that affect insulin levels, such as food intake, fasting, or diseases like diabetes.

Role in Diabetes:
In healthy individuals, insulin is secreted by pancreatic beta cells in response to rising blood glucose levels. Insulin facilitates glucose uptake into insulin-dependent tissues (e.g., liver, adipose, and muscle tissues). When insulin levels or function are impaired, glucose metabolism is disrupted, leading to hyperglycemia.

Diabetes is primarily classified into:

  • Type 1 Diabetes: Characterized by autoimmune destruction of pancreatic beta cells, often detected by the presence of autoantibodies and reduced insulin levels. It frequently manifests in individuals under 30 with pronounced hyperglycemia and symptoms like polydipsia, polyuria, weight loss, and, in severe cases, diabetic ketoacidosis. C-peptide measurement helps predict disease progression and assess residual beta-cell function.
  • Type 2 Diabetes: Characterized by insulin resistance and impaired insulin secretion. This form, accounting for 90–95% of diabetes cases, is often associated with obesity and has a slower onset. Hyperglycemia is less evident initially but may progress to complications such as cardiovascular disease, renal failure, and retinopathy.

Clinical Applications of C-Peptide Testing:

  • Differential Diagnosis: Helps distinguish between Type 1 and Type 2 diabetes and identify latent autoimmune diabetes in adults (LADA).
  • Prognosis: Predicts disease progression and assesses the success of therapies.
  • Monitoring Insulin Therapy: Reflects endogenous insulin production in patients receiving exogenous insulin.
  • Detection of Insulinomas: Identifies insulin-secreting tumors.
  • Hypoglycemia Assessment: Differentiates between natural and artificial causes of hypoglycemia.
  • Fetal Risk Assessment: Evaluates potential complications in pregnant women with diabetes.
  • Post-Pancreatic Surgery Monitoring: Tracks pancreatic function after surgical procedures.

 

  • Avoid alcohol for 24 hours prior to testing.
  • Do not eat for 8 hours before the test (water is allowed).
  • Avoid physical and emotional stress 30 minutes before the test.
  • Refrain from smoking 3 hours before the test.
  • Blood should be collected between 8:00 AM and 11:00 AM.
  • Sample Type: Venous blood.
  • Differential diagnosis of Type 1 and Type 2 diabetes.
  • Prognosis of diabetes progression.
  • Infertility and polycystic ovary syndrome (PCOS).
  • Diagnosis of hypoglycemic states.
  • Detection of artificial hypoglycemia.
  • Monitoring remission in juvenile diabetes.
  • Identification of insulinomas.
  • Assessing potential fetal pathology in pregnant women with diabetes.
  • Evaluating insulin secretion in liver diseases.
  • Post-surgical evaluation after pancreatic resection.
  • Increased C-Peptide Levels:

    • Increased beta-cell activity (e.g., insulinomas, renal failure, obesity).
    • Hyperlipoproteinemia and arterial hypertension.
  • Decreased C-Peptide Levels:

    • Fasting or artificial hypoglycemia.
    • Hypoinsulinism (Type 1 or advanced Type 2 diabetes).
    • Addison's disease.
    • After radical pancreatic surgery.

C-peptide testing is crucial for managing diabetes and preventing complications by guiding therapeutic interventions and assessing residual pancreatic function.