C-Peptide (Insulin C-Peptide, Proinsulin C-Peptide)

Sample
- 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.
Precaution
- 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 patient 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.
Precaution
- Patients with renal failure may have a high level of C-peptide because mostly it is degraded in the kidney.
- Oral hypoglycemic agents may increase the C-peptide level.
Pathophysiology
- 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).
- The C-peptide assay provides the difference between the endogenous and exogenous insulin.
- In general C-peptide level and insulin level correlates with each other (except obese patient and patient with insulinoma).
- 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 DM there will low level of C-peptide and insulin, while in type 2 DM 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.

C-Peptide functions
- A rise in the C-peptide level in a treated patient of insulinoma indicates recurrence.
- Advantages of C-peptide over Insulin are:
- C-peptide is a better indicator of β- cells functions due to its good level of concentration in the blood than is 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 the fasting hypoglycemia.
Normal C-peptide
Source 2
Fasting level | 0.78 to 1.89 ng/mL |
One hour after glucose load | 5 to 12 ng/mL |
Urinary C-peptide | 74 t± 26 µg/L |
- Fasting level = 0.78 to 1.89 ng/mL (0.26 to 0.62 nmol/L
- One hour after glucose load = 5 to 12 ng/mL.
- Urinary C-peptide = 74 ± 26 µg/L.
- (values varies with lab to lab)
Source 1
Normal C-Peptide
Sample | ng/mL | nmol/L |
Serum (fasting) | 0.78 to 1.89 | 0.26 to 0.63 |
Urine | µg/dL | |
24 hours | 64 ± 20.5 | 21.5 ± 6.8 |
The raised level of C-peptide seen in:
- Insulinoma.
- Oral hypoglycemic drugs.
- Islet cell tumor producing insulin (Insulinomas).
- Type 2 DM (non-insulin dependant).
- Renal failure.
- Hyperthyroidism.
- Cirrhosis.
The decreased C-peptide level is seen in:
- Factitious hypoglycemia.
- Type 1 diabetes mellitus.
- Pancreatectomy.