C-Peptide (Insulin, Proinsulin) and Interpretations
Sample for C-Peptide
- 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-hour sample is needed.
- Neutralize the urine to pH 7.0 to 7.5.
- It can be stored at -15 °C.
Precautions for C-Peptide
- As most 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 (Indications) C-Peptide test
- 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 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.
- It is helpful for patients with pancreatectomy, where it will be undetectable.
Precautions for C- peptide
- 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.
Definition of C-Peptide:
- Proinsulin is converted into insulin and C-Peptide.
- C-Peptide is released into the blood circulation.
- C-peptide serum level correlates with insulin in the blood except in islet cell tumors and possibly obese patients.
Pathophysiology of C-Peptide
- C-peptide is a connecting peptide for the β and α-chains 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-peptides are present in the circulation.
- It is cleaved into Insulin + C-peptide (biologically inactive).
- Proinsulin is synthesized in the pancreas and is 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 and is formed by the ribosomes in the rough endoplasmic reticulum of the pancreatic β-cells.
- Preproinsulin is not detected in blood circulation and is rapidly converted by cleaving enzymes into proinsulin.
- Proinsulin consists of α and β chains connected by an area called connecting peptide (C-Peptide).
- Proinsulin is cleaved by a proteolytic enzyme in the β-cells into equal amounts of insulin and C-peptide.
- C-Peptide connects the α and β-chains of the proinsulin.
- Its 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 of 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.
- C-peptide level and insulin level generally correlate with each other (except for obese patients and patients with insulinoma).
- The fasting C-peptide level is five 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. Type 1 diabetes mellitus will have a low level of C-peptide and insulin, while 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 are 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. There will be raised insulin levels, 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.
The advantages of C-peptide over Insulin are:
- C-peptide is a better indicator of β- cell functions due to its good concentration level in the blood than peripheral insulin concentration.
- It does not cross-react with the insulin antibody, interfering 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- cell’s function than the peripheral insulin.
- To evaluate insulin reserve or production in diabetics who are on insulin therapy.
- It is used to assess the pancreatectomy status.
- It is used to detect or prove false medication and insulin-induced hypoglycemia.
- C-peptide value in the following conditions:
- Insulin assay can not differentiate between exogenous insulin and that produced by insulinoma.
- The C-peptide level is estimated on the same specimen with elevated insulin levels.
- In hyperinsulinemia due to islet tumor, C-peptide levels are also elevated.
- In the case of exogenously administered insulin, the C-peptide level is low.
|Clinical condition||Glucose level||Insulin level||C-peptide|
|Factitious hypoglycemia||Decreased||Increased||Normal or decreased|
|Anti-insulin antibodies||Decreased||Increased||Normal or decreased|
- (values vary from lab to lab, best to establish your values)
The raised level of C-peptide is seen in the following:
- 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 the following:
- 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 its initial passage through the liver.
- Insulin will be metabolized in the liver; 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:
Questions and answers:
Question 1: What is the half-life of C-Peptide?
Half-life of C-Peptide is longer than insulin and is around 35 minutes.
Question 2: What is the level of glucose in insulinoma?
Glucose level in insulinoma is decreased, while insulin level is increased.