C-Peptide, Insulin, Proinsulin

What sample is needed for C-Peptide?

1. Venous blood is collected to prepare the serum.
2. A fasting sample is needed.
3. Glucose samples should also be taken simultaneously.
4. Keep the blood at 4 °C.
5. Stable for 30 days when frozen.
6. A urine 24-hour sample is needed.
   1. Neutralize the urine to pH 7.0 to 7.5.
   2. It can be stored at -15 °C.

What are the precautions for C-Peptide?

1. As most of the C-peptide is degraded in the kidneys, renal failure will increase the level of C-peptide.
2. Take H/O drugs that may increase the level of hypoglycemic agents (sulfonylureas).
3. Oral hypoglycemic agents may increase the C-peptide level.

What are the Indications for the C-Peptide test?

1. This test is done to evaluate diabetic patients.
2. This test is the best tool for the diagnosis of hypoglycemia.
3. It provides a reliable indication of pancreatic secretory function and insulin secretion.
4. It is helpful to diagnose an Insulinoma (a Tumor of the islets of Langerhans).
   1. It is advised for the follow-up of a patient treated for insulinoma.
5. To find patients injecting exogenous insulin.
6. The C-peptide level can be used to diagnose insulin resistance syndrome.
7. It is helpful for patients with pancreatectomy, where it will be undetectable.

How will you define C-Peptide?

1. Proinsulin is converted into insulin and C-peptide.
2. C-peptide is released into the bloodstream.
3. C-peptide serum levels correlate with insulin levels in the blood, except in cases of islet cell tumors and possibly in obese patients.

How will you discuss the pathophysiology of C-peptide?

1. C-peptide is a connecting peptide for the β and α-chains of proinsulin.
2. C-peptide is formed during the conversion of proinsulin to Insulin.
   1. C-peptide is released into the portal vein in an equal amount.
   2. It has a longer half-life than insulin. So more C-peptides are present in the circulation.

What do you know about Proinsulin?

1. Proinsulin is cleaved into Insulin + C-peptide (biologically inactive).
2. Proinsulin is synthesized in the pancreas and is metabolically inactive.
3. It is larger and is also called big insulin.
4. It consists of 100 amino acids and has a molecular weight of 12,000 and is formed by the ribosomes in the rough endoplasmic reticulum of the pancreatic β-cells.
5. Preproinsulin is not detected in blood circulation and is rapidly converted by cleaving enzymes into proinsulin.
   1. Proinsulin consists of α and β chains connected by an area called the connecting peptide (C-Peptide).
6. Proinsulin is cleaved by a proteolytic enzyme in the β-cells into equal amounts of insulin and C-peptide.

The C-peptide:

How will you define C-Peptide?

1. C-Peptide connects the α and β-chains of the proinsulin.
2. Its assay provides the difference between endogenous and exogenous insulin.
3. C-peptide consists of 31 amino acids connecting peptides with a molecular weight of 3600.

What is the metabolism of C-Peptide?

1. Its half-life is 35 minutes, slightly longer than insulin.
2. The liver does not extract the C-peptide, which is removed from the circulation by the kidneys and degraded.
3. A small fraction of unchanged is excreted in the urine.
4. C-peptide levels correlate with insulin levels in the blood, except in cases of islet cell neoplasm and possibly in obese patients.
5. C-peptide level and insulin level generally correlate with each other (except for obese patients and patients with insulinoma).
6. The fasting C-peptide level is five to 10 times higher than the insulin due to a longer half-life.
7. The capacity of beta cells in the pancreas to produce insulin can be measured either by directly measuring insulin or C-peptide.
8. C-Peptide level estimation is helpful in the following conditions:
   1. Differentiate type 1 and type 2 diabetes mellitus. Type 1 diabetes mellitus typically has a low level of C-peptide and insulin, whereas type 2 diabetes mellitus usually has a normal or elevated level of C-peptide.
   2. In patients taking exogenous insulin, C-peptide is a more accurate measure of islet cell function. This will also help to see the endogenous production of insulin.
   3. DM patients are treated with insulin and have anti-insulin antibodies. These antibodies falsely increase the level of insulin.
   4. In people who produce hypoglycemia, by giving them insulin. There will be raised insulin levels, but the C-peptide level will be normal.
   5. Exogenous insulin suppresses the production of endogenous insulin and C-peptide.

9. A rise in the C-peptide level in a treated patient with insulinoma indicates recurrence.

What are the advantages of C-peptide over Insulin?

1. C-peptide is a better indicator of β-cell function due to its good concentration level in the blood than peripheral insulin concentration.
2. It does not cross-react with the insulin antibody, interfering with insulin immunoassay.
3. The C-peptide assay doesn’t measure the exogenous insulin.
4. C-peptide is not found in the commercial preparation of insulin.
5.  C-peptide has a longer half-life than insulin.
6. C-peptide is a better indicator of fasting hypoglycemia.
7. 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.
8. To evaluate insulin reserve or production in diabetics who are on insulin therapy.
9. It is used to assess the pancreatectomy status.
10. It is used to detect or prove false medication and insulin-induced hypoglycemia.

What will be the C-peptide value in the following conditions?

1. The insulin assay cannot differentiate between exogenous insulin and that produced by an insulinoma.
2. The C-peptide level is estimated on the same specimen as elevated insulin levels.
3. In hyperinsulinemia due to an islet tumor, C-peptide levels are also elevated.
4. In the case of exogenously administered insulin, the C-peptide level is low.

What is normal C-peptide?

Source 2

• • (values vary from lab to lab; it’s best to establish your values)

Source 1 Normal C-Peptide

What are the causes of a raised level of C-peptide?

1. Insulinoma.
2. Oral hypoglycemic drugs.
3. Islet cell tumor-producing insulin (Insulinomas).
4. Type 2 DM (non-insulin-dependent).
5. Renal failure.
6. Hyperthyroidism.
7. Cirrhosis.

What are the causes of decreased C-peptide levels?

1. Exogenous administration of insulin, e.g., Factitious hypoglycemia.
2. Type 1 diabetes mellitus.
3. Pancreatectomy.

How will you discuss the insulin/C-peptide ratio?

1. This insulin/C-peptide ratio is 1:5 to 1:15.
2. 50% of the insulin is removed from the blood during its initial passage through the liver.
3. Insulin is metabolized in the liver, with a half-life of 30 minutes, while the half-life of C-peptide is 35 minutes.
4. The normal molar fasting ratio of C-peptide: Insulin = 5.
   1. <1.0 ratio is seen in:
      1. Insulinoma.
      2. Sulfonylurea administration.
      3. Renal failure.
   2. >1.0 ratio is seen in:
      1. Exogenous insulin administration.
      2. Cirrhosis.

Questions and answers: