A Practical Review of C-Peptide Testing in Diabetes

C-Peptide Review

The C-peptide is a by-product of insulin formation. The pancreas produces proinsulin, a precursor hormone that is broken down into the active, blood-sugar-lowering hormone insulin and the C-peptide. Find out here how much the C-peptide value is normally and what changed measured values mean

What is the C-peptide?

The C-peptide is produced in the pancreas during the formation of insulin: the so-called beta cells produce the inactive precursor proinsulin. To activate it, it is split into the blood-sugar-lowering hormone insulin and the C-peptide. The term stands for Connecting Peptide because it connects the building blocks of proinsulin with one another.

In contrast to insulin, C-peptide is broken down much more slowly, which makes it an ideal measurement value for the functionality of the pancreas and its insulin production.

When is the C-peptide determined?

In the laboratory, the C-peptide value is mainly determined to assess the performance of the beta cells of the pancreas. If the beta cells are able to produce insulin, C-peptide can also be detected. An assessment of the pancreas performance is also important for planning therapy in diabetes - i.e. when deciding whether a diabetic needs to inject insulin or not.

Sometimes it is necessary to measure both C-peptide and insulin and blood sugar levels. If the doctor suspects a proinsulin-producing tumor (insulinoma), blood samples are taken at regular intervals from the patient while he is starving. If high C-peptide values ​​and insulin values ​​are detected in the blood, although there is too little glucose in the blood (hypoglycemia), this is considered to be clear evidence of an insulinoma. Possible signs of this mostly benign pancreatic tumor include confusion, weakness and seizures, dizziness, weight gain, and cravings.

Very rarely, so-called hypoglycemia factitia can be diagnosed with hypoglycemia. This is a mental illness in which patients intentionally use insulin to lower blood sugar levels. In this way, those affected usually want to gain increased attention and attention from doctors, hospitals, or relatives. In this particular case, the C-peptide level is normal, while the insulin is too high and the blood sugar is too low. If the patient uses sulfonylureas to lower blood sugar, the C-peptide and insulin are increased.

Glucose or glucagon stimulation is done to assess whether a diabetic patient needs to inject insulin. To do this, the patient is given glucose or glucagon before the C-peptide level is measured.

When is the C-peptide decreased?

The C-peptide is naturally low when the pancreas does not have to produce any insulin, i.e. the blood sugar level is low and you have not eaten anything.

Due to illness, the laboratory value is too low if insulin production is restricted - i.e. in diabetes mellitus. In type 1 diabetes mellitus, which mainly occurs at a young age, autoantibodies attack the beta cells and destroy them so that they can no longer produce proinsulin. In type 2 diabetes mellitus, the C-peptide value is only lowered in the late stage, when the pancreas fails to produce insulin.

Other possible causes of a lowered C-peptide are Addison's disease and the administration of certain medications (alpha-sympathomimetics). 

When is the C-peptide elevated?

In the case of foods rich in carbohydrates or high in sugar, the pancreas releases insulin and C-peptide at the same time in order to encourage the body cells to absorb blood sugar. The laboratory value is then naturally increased.

In the early stages of type 2 diabetes mellitus, the C-peptide is also increased. This is due to the fact that the body cells of those affected are increasingly resistant to insulin, i.e. hardly or not at all to its signal for blood sugar uptake. In response, the beta cells produce more and more insulin and C-peptide until they are finally exhausted and production ceases.

Insulinomas are much more rarely the cause of a C-peptide increase. Other possible causes are kidney failure, metabolic syndrome, and treatment with corticosteroids.

What to do if the C-peptide is increased or decreased?

The treatment depends on the cause of the changed laboratory values. Your doctor will discuss the measurement results and further therapy with you.

For example, patients with type 1 and sometimes type 2 diabetes mellitus receive synthetic insulin preparations. Oral antidiabetic drugs such as metformin are also used in diabetes.

If an insulinoma causes increased C-peptide levels, this is surgically removed if possible.