C-Peptide (Insulin, Proinsulin) and Interpretations
- Venous blood is collected to prepare the serum.
- A fasting sample is needed.
- Glucose samples should also be taken at the same time.
- Keep the blood at 4 °C.
- Stable for 30 days when it is freezed.
- A urine 24 hours sample is needed.
- Neutralize the urine to pH 7.0 to 7.5.
- Can store at -15 °C.
- As the majority of the C-peptide is degraded in the kidneys, renal failure will increase the level.
- Take H/O drugs that may increase the level of hypoglycemic agents (sulfonylureas).
Purpose of the test (Indications)
- This test is done to evaluate diabetic patients.
- This test is the best tool for the diagnosis of hypoglycemia.
- It provides a reliable indication of the pancreatic secretory function and insulin secretion.
- It is helpful to diagnose Insulinoma (Tumor of islets of Langerhans).
- It is advised for the follow-up of a patient treated for insulinoma.
- To find patients injecting exogenous insulin.
- The C-peptide level can be advised to diagnose insulin resistance syndrome.
- Helpful in the case of patients with pancreatectomy where it will be undetectable.
- Patients with renal failure may have a high level of C-peptide because it is mostly degraded in the kidney.
- Oral hypoglycemic agents may increase the C-peptide level.
- C-peptide is a connecting peptide for the β and α chain of proinsulin.
- C-peptide is formed during the conversion of proinsulin to Insulin.
- C-peptide is released into a portal vein in an equal amount.
- It has a longer half-life than insulin. So more C-peptide is present in the circulation.
- Proinsulin is cleaved into Insulin + C-peptide (inactive biologically).
- Proinsulin is synthesized in the pancreas and metabolically inactive.
- It is larger in size and is also called big insulin.
- It consists of 100 amino acids and mol. Weight is 12,000, is formed by the ribosomes in the rough endoplasmic reticulum of the pancreatic β-cells.
- Preproinsulin is not detected in the blood circulation, is rapidly converted by cleaving enzyme into proinsulin.
- Proinsulin by proteolytic cleavage gives rise to insulin and C-peptide.
- The C-peptide assay provides the difference between endogenous and exogenous insulin.
- C-peptide is 31 amino acids connecting peptides with a molecular weight of 3600.
- Its half-life is 35 minutes, slightly longer than insulin.
- The liver does not extract the C-peptide, which is removed from the circulation by the kidneys and degraded.
- A small fraction unchanged is excreted in the urine.
- C-peptide level correlates with insulin level in the blood except in islet cell neoplasm and possibly in obese patients.
- In general C-peptide level and insulin level correlates with each other (except obese patient and patient with insulinoma).
- The fasting C-peptide level is 5 times to 10 times higher than the insulin due to a longer half-life.
- The capacity of beta cells of the pancreas to produce insulin can be measured either by measuring C-peptide or insulin directly.
- C-peptide level estimation is helpful in the following conditions:
- Differentiate type 1 and type 2 diabetes mellitus. In type 1 diabetes mellitus, there will low level of C-peptide and insulin, while in type 2 diabetes mellitus will have a normal or high level of C-peptide.
- In patients who are taking exogenous insulin, C-peptide is a more accurate test of islet cell function. This will also help to see the endogenous production of insulin.
- DM patients treated with insulin and have anti-insulin antibodies. These antibodies falsely increase the level of insulin.
- In people who produce hypoglycemia by giving them insulin. Where there will be raised levels of insulin, but the C-peptide level will be normal. Exogenous given insulin suppresses endogenous insulin and C-peptide production.
- A rise in the C-peptide level in a treated patient with insulinoma indicates recurrence.
- Advantages of C-peptide over Insulin are:
- C-peptide is a better indicator of β- cells functions due to its good concentration level in the blood than peripheral insulin concentration.
- It does not cross-react with the insulin antibody, which interferes with insulin immunoassay.
- The C-peptide assay doesn’t measure the exogenous insulin.
- C-peptide is not found in the commercial preparation of insulin.
- C-peptide has a longer half-life than insulin.
- C-peptide is a better indicator of fasting hypoglycemia.
- C-peptide has negligible metabolism in the liver, so its concentration is a better indicator of the β- cells function than the peripheral insulin.
|Fasting level||0.78 to 1.89 ng/mL (0.26 to 0.62 nmol/L)|
|One hour after glucose load (or glucagon)||2.7 to 5.64 ng/mL (0.9 to 1.87 nmol/L).|
|Urinary C-peptide||74 t± 26 µg/L (25 ±8.8 µmol/L)|
- (values varies from lab to lab, best to establish your own values)
|Serum (fasting)||0.78 to 1.89||0.26 to 0.63|
|24 hours||64 ± 20.5||21.5 ± 6.8|
The raised level of C-peptide seen in:
- Oral hypoglycemic drugs.
- Islet cell tumor producing insulin (Insulinomas).
- Type 2 DM (non-insulin dependant).
- Renal failure.
The decreased C-peptide level is seen in:
- Exogenous administration of the insulin, e.g., Factitious hypoglycemia.
- Type 1 diabetes mellitus.
- This insulin/C-peptide ratio is 1:5 to 1:15.
- 50% of the insulin is removed from the blood during initial passage through the liver.
- Insulin will be metabolized in the liver, and its half-life is 30 minutes, while the half-life of C-peptide is 35 minutes.
- The normal molar fasting ratio of C-peptide: Insulin = 5.
- <1.0 ratio is seen in:
- Sulfonylurea administration.
- Renal failure.
- >1.0 ratio is seen in:
- Exogenous insulin administration.
- <1.0 ratio is seen in: