C-peptide Emerging as Significant Factor in Nerve Recovery

Because scientists often tend to dismiss what they don’t fully understand, many of them used to think that C-peptide had no physiological function. But while it’s true that C-peptide does nothing to lower blood sugar, recent research is finding that it might have a role in preventing diabetes complications.

C-peptide binds to cell surfaces and activates cell-signaling pathways, stimulating enzymes that usually have reduced activity in people with type 1.

Pancreas transplants promote reversal of diabetic neuropathy and stabilization of diabetic retinopathy, and both pancreas and islet transplants lead to reversal of diabetic nephropathy (kidney dysfunction). The assumption now is that the production of C-peptide associated with these procedures is behind the improvements.

C-peptide administration is also accompanied by increased blood flow in skeletal muscle, heart, and skin reduced glomerular hyperfiltration and urinary albumin secretion, and improved nerve function. This effect occurs in patients with type 1 diabetes, but not in healthy people.

In one study, nerve conduction speeds were measured in diabetic and healthy rats that were treated with either C-peptide or a placebo. The progressive decline in nerve conduction speed seen in placebo-treated rats was arrested when C-peptide treatment was started one week after onset of diabetes. The nerve conduction velocity also increased significantly when C-peptide was administered at five months after onset of diabetes.

In a three-month clinical trial involving patients with peripheral diabetic neuropathy, sensibility impairment improved after C-peptide treatment but then returned three months after treatment stopped. In another trial, sensibility impairment improved after three months of replacement C-peptide treatment.

Where C-peptide Comes From and What It Does

Discovered in 1967, C-peptide is a byproduct of insulin production that starts out as part of the proinsulin molecule. Proinsulin is the raw material for finished insulin. Made up of 86 amino acids, it’s produced in the endoplasmic reticulum, deep within the beta cells of the pancreas. During the manufacturing process, the proinsulin molecule is folded into a tidy shape that can be neatly severed by enzymes into three parts: the A chain of the insulin molecule, the C-peptide molecule, and the B chain of the insulin molecule.

C-peptide, so named because it connects the A chain and B chain of insulin within the proinsulin molecule, is snipped out from the center of the proinsulin. C-peptide ends up with 31 amino acids, and four amino acids are removed altogether. The two ends of the proinsulin (the B chain, made up of 30 amino acids) and the A chain (made up of 21 amino acids) are connected to each other by two disulfide bonds, forming the finished insulin molecule of 51 amino acids.

For each insulin molecule produced, obviously, one C-peptide molecule is also produced. Measuring C-peptide, therefore, is a handy way to measure naturally produced insulin and to distinguish it from injected insulin, which has no C-peptide. (The C-peptide is removed when insulin is manufactured synthetically.)

What’s Normal in People With Diabetes

In non-diabetics, a normal concentration of C-peptide is about 0.5 to 3.0 ng/ml. Even though C-peptide and insulin are produced at the same rate, the body’s levels of the two are not identical because they leave the body at different speeds. Insulin is processed and eliminated mostly by the liver and has a half-life of about five minutes. C-peptide is removed by the kidneys and has a half-life of about thirty minutes. As a result, there is usually about five times as much C-peptide in the blood as insulin.

Because type 1 diabetes is caused by autoimmune destruction of beta cells, it is characterized by reduced levels of both insulin and C-peptide. Type 2 diabetes, in contrast, which begins with resistance to insulin, is initially associated with normal or even increased insulin and C-peptide levels. That’s why a C-peptide test is often used to help distinguish between type 1 and type 2 diabetes. In a basic C-peptide test, fasting C-peptide levels are measured. Blood glucose levels are measured at the same time, and the two are correlated.

How a C-peptide Stimulation Test Works

In a C-peptide stimulation test, which is far less common than the fasting test, glucagon is administered to stimulate high blood sugar. In healthy people, this hyperglycemia would stimulate secretion of insulin molecules, each one associated with a C-peptide molecule. With type 1 diabetes, however, the pancreas is on the fritz. As a result, little insulin and C-peptide is secreted.

Conversely, C-peptide levels are increased in early type 2 diabetes because the pancreas is still going strong but the body’s cells aren’t able to use the insulin it produces. In people with type 2, C-peptide levels may also be monitored to determine whether the pancreas is burning out and insulin production is dropping, resulting in a need for insulin supplementation.

C-peptide and Medicare/Medicaid’s Insulin Pump Policies

Medicare and Medicaid regulations require C-peptide testing as part of the qualification process for an insulin pump. C-peptide testing is also used to differentiate among different causes of low blood sugar, such as an insulin-producing pancreatic tumor called an insulinoma, which leads to excessive production of insulin and associated C-peptide.

The test can also identify an accidental or deliberate over-administration of insulin; because synthetic insulin does not contain C-peptide, C-peptide is low in persons with hypoglycemia due to overdose of insulin. C-peptide levels are also used to monitor beta cell function following surgical removal of all or part of the pancreas. Additionally, they are used to find out whether transplanted islet cells are producing insulin.