C-peptide (connecting peptide) is a protein that connects the beta and alpha chains of proinsulin. In the beta cells of the islet of Langerhans of the pancreas, the chains of proinsulin are separated during the conversion of proinsulin to insulin and C-peptide. C-peptide is released into the portal vein in nearly equal amounts. Because it has a longer half-life than insulin, more C-peptide exists in the peripheral circulation.
In general, C-peptide levels correlate with insulin levels in the blood, except possibly in islet cell tumors and in obese patients. The capacity of the pancreatic beta cells to secrete insulin can be evaluated by directly measuring either insulin or C-peptide. In most cases, direct measurement of insulin is more accurate. However, in some instances, direct measurement of insulin does not accurately assess the patient’s insulin-generating capability. C-peptide levels more accurately reflect islet cell function in the following situations:
- Patients with diabetes who are treated with insulin and who have antiinsulin antibodies. This most often occurs in patients treated with old bovine or pork insulin. These antibodies falsely increase insulin levels.
- Patients who secretly administer insulin to themselves (factitious hypoglycemia). Insulin levels will be elevated. Direct insulin measurement in these patients tends to be high, because the insulin measured is self-administered exogenous insulin. But C-peptide levels in that same specimen will be low, because exogenously administered insulin suppresses endogenous insulin (and C-peptide) production.
- Diabetic patients who are taking insulin. The exogenously administered insulin suppresses endogenous insulin production. Insulin levels only measure the exogenously administered insulin and do not accurately reflect true islet cell function. C-peptide would be a more accurate test of islet cell function. This is performed to see if the diabetes is in remission and the patient may not need exogenous insulin.
- Distinguishing type 1 from type 2 diabetes. This is particularly helpful in newly diagnosed diabetics. A person whose pancreas does not make any insulin (type 1 diabetes) has a low level of insulin and C-peptide. A person with type 2 diabetes has a normal or high level of C-peptide.
The C-peptide test is indicated for the clinical situations described above. Further, C-peptide is used in evaluating patients who are suspected to have an insulinoma. It can differentiate patients with insulinoma from patients with factitious hypoglycemia. In the latter patients, C-peptide levels are suppressed by exogenous insulin challenge. In patients with an autonomous secreting insulinoma, C-peptide levels are not suppressed. Furthermore, C-peptide can be used to monitor treated patients with insulinoma. A rise in C-peptide levels indicates a recurrence or progression of the insulinoma. Likewise, some clinicians use C-peptide testing as an indicator of the adequacy of therapeutic surgical pancreatectomy in patients with pancreatic tumors. C-peptide can also be used to diagnose “insulin resistance” syndrome.
Before the test, the patient is required to fast for 8 to 10 hours. Only water is permitted.
Causes of C-Peptide Test False Results
- Because the majority of C-peptide is degraded in the kidney, renal failure can cause increased levels of C-peptide.
- Drugs that may cause increased levels of C-peptide include oral hypoglycemic agents (e.g., sulfonylureas).
Normal C-Peptide Levels
Fasting: 0.78 to 1.89 ng/mL (0.26 to 0.62) nmol/L
1 hour after glucose load: 5 to 12 ng/mL
Causes of High C-Peptide Levels
Insulinoma: Insulin and C-peptide are made concomitantly by the neoplastic cells.
Pancreas transplant: Excess C-peptide is produced by the transplanted islet cells.
Renal failure: C-peptide is removed from the blood by the kidneys. Diminished kidney function will lead to elevated levels.
Administration of oral hypoglycemic agents: Oral hypoglycemic agents stimulate insulin and C-peptide synthesis.
Causes of Low C-Peptide Levels
Diabetes mellitus: The self-administered insulin suppresses endogenous insulin and C-peptide production.
Total pancreatectomy: All islet cells have been surgically removed. C-peptide production ceases.