C-peptide Emerging as Significant Factor in Nerve Recovery

| Jan 3, 2008

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.

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Categories: Blood Glucose, Blood Sugar, Diabetes, Diabetes, Eye Care (Retinopathy), Insulin, Insulin Pumps, Kidney Care (Nephropathy), Low Blood Sugar, Nerve Care (Neuropathy), Professional Issues, Type 1 Issues, Type 2 Issues

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Posted by Anonymous on 3 January 2008

Nice article, on the whole, but I strongly object to this characterization of people with diabetes (type 1 or 2) as unhealthy. I have had type 1 for 39 years now, and I am quite healthy.

"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."

I think it would be much more accurate and respectful to phrase it as, "In people without diabetes, this hyperglycemia would stimulate secretion of insulin molecules..."

Posted by Chrissie in Belgium on 4 January 2008

If a T1 diabetic wants to take c-peptides, does there exist a medication that can be taken? I know my c-peptide level is very low, less than 0.009µg/l! If such a medication does exist, do there exist any guidelines for how much one should take? Is it correct that animal insulins contain C-peptides? Can we then give ourselves c-peptides by using animal insulins rather than "human insulins"? PLEASE CONTINUE TO INFORM US OF ALL RESEARCH CONCERNING C-PEPTIDES! Thank you!

I would really appreciate answers to the questions in my above comment.

Posted by Anonymous on 4 January 2008

While the article is accurate about the levels of C-Peptide found in people with both types of diabetes, the author failed to mention that all insulins sold by Novo Nordisk, Eli Lilly & Co. and Sanofi-Aventis are completely stripped of C-peptide in the laboratory before they are even sold. E.coli or yeasts are injected with genetically modified insulin A and B peptide chains, but not the C peptide chain. This is one reason why the incidence of the incidence neuropathy in type 1 diabetes has risen steadily over the last 30 years in spite of better glycemic control overall. The drug companies are knowing making an incomplete product ... in fact, Eli Lilly has a strategy (see the company's quarterly earnings releases for details) to instead sell people with type 1 diabetes additional drugs to treat diabetes complications which might have been prevented if the insulin they sold was complete. Incidentally, prior to the 1982 introduction of synthetic "human" insulin, residual C-Peptides (albiet in miniscule quantities) were contained in the animal-sourced insulin sold to patients, although it is believed that the quantity was not sufficient to have any therapeutic impact.

Posted by Anonymous on 6 January 2008

Nowdays, most people with Type 1 diabetes ARE tested using C-peptide levels and antibody levels. Both are use to distinguish a diagnosis of Type 1 from Type 2 diabetes.

C-peptide should be mandatory for all Type 1 diabetics.

Posted by Anonymous on 7 January 2008

This is a very interesting article. Unfortunately, the information you give isn't enough for me to navigate to the original articles. Could you post citations, especially for the "three-month clinical trial involving patients with peripheral diabetic neuropathy"?

Posted by Anonymous on 15 January 2008

Where can I buy c-peptide ready for subcutaneous injection?

Posted by Anonymous on 19 January 2008

I've been following c-peptide research for several years. The research has looked very promising but the medical establishment has been largely ignoring it. Ever since insulin treatment was first introduced Drs. have been assuming that C-Peptide (created at the same time as insulin and as part of the insulin creation process) was just a "throw-away" substance. Surprise! The body doesn't make "throw-away" substances. When I ask researchers about it they say that it has to be proved that it's useful. I say, if it's part of what the body naturally produces in reaction to the presence of glucose, they should have to prove why it's NOT important. These are the same yahoos who said that formula was better than breast milk, that the appendix had no purpose (SURPRISE THEY JUST FOUND OUT IT DOES), and that margarine (jammed full of trans-fats) was healthier than butter. A properly functioning body generally doesn't make mistakes and we have to assume if it creates a substance it does so for a reason. I hope many of you will contact scientific journals, the Juvenile Diabetes Foundation, and anyone else you can think of to encourage them to fast-track research on supplementing with C-Peptide. The research to date shows it can have significant impact on preventing or reversing diabetic complications -- an absolutely critical issue for millions of Type 1 diabetics.

Posted by Limehouse on 20 January 2008

Why do they not develop C-peptide that can be either indegsted or injected by we Type 1's? Please post any available info on C-peptide or its development, we neuropathic Type 1.s do not have anything else to hope for.

Posted by Anonymous on 24 January 2008

Sweden based company creative peptide has started producing c peptide.Soon they are going to start to produce it at commercial scale.

Posted by Anonymous on 1 February 2008

Here's how to obtain c-peptide:
1. Find some people who have a compatible blood type.
2. Get a reliable mob surgeon.
3. Pay the people with compatible blood for a half a unit per week, and rotate each individual.
4. Have the mob surgeon put their blood into you.

America has the best health care system on earth!

Posted by Anonymous on 6 February 2008

For what its worth, the folks at Eli Lilly and Co. tested making rDNA proinsulin, which happens to include C-peptide. However, they pulled the plug on those studies in February 1988 when "the fact that unique efficacy in controlled multicenter studies was not demonstrated suggested that these pharmacological features were not translated into clinical benefit". They also claimed that there were 6 myocardial infarctions, including 2 deaths, although that was not proven to be caused by proinsulin per se, but being risk-averse, the company called it quits. Let the Swedes go with it, they'll make billions on something Lilly discarded a decade ago!

Diabetes Care. 1992 May; 15(5): 666-92

Posted by Anonymous on 15 February 2008

The C-peptide story is similar to the INGAP Peptide (Islet NeoGenesis Associated Protein, a peptide stimulating the genesis of Alfa & Beta cells from Stem cells alive but sleeping in pancreatic Islets).
Lilly in 2002, abandoned the level1 human trial on INGAP when they understud that the end of the BIG business of antidiabetic substances was coming. Procter&Gamble too decided to ends the level2 human trial on INGAP using the same words than Lilly on 2006 and now a new "noprofit" (kinexum.com) after less than 12 month says: "we will do INGAP on 2009" !!!! I'm not optimistic, do you think that THEY simply stay watching the end of the big business?

Posted by dorisjdickson on 21 August 2008

This article says they strip C-peptide from injectable insulin. Why don't they just leave it in?

Posted by Anonymous on 30 August 2008

Two years ago I wrote to the Juvenile Diabetes Foundation to ask what they were doing to fund the promising area of using C-Peptide to treat and delay complications in Type 1 diabetics. I got a very generic form letter back (from Jullian Lubarsky, Coordinator Public Information, JDRF) stating "JDRF is familiar with the origin of C-peptide and its use in humans with type 1 diabetes to determine its effect. JDRF has followed reports of the early-stage human studies taking place in Europe that are asking whether the administration of C-peptide might prove beneficial in reducing or eliminating the signs of nephropathy and neuropathy complications. We’re cautious about the interpretation of these studies and will seek the guidance of our scientific and lay committees to determine the timing and specifics of a course of action. In the meantime the outcomes of these studies are of interest, and may at some future time be the subject of well-controlled safety and efficacy studies." Recently (two years later) I wrote to ask whether their position had changed based on the significant number of additional positive studies that have been completed demonstrating effectiveness of C-Peptide across a wide spectrum of critical Type-1 complications. Imagine my surprise and dismay to receive exactly the same form letter (this time from a new person in the position) ... word for word the same as the one from two years ago (with a little generic filler before and after). In other words, while the research has marched on and the need is never great, the JDRF hasn't even updated their boilerplate response to desparate diabetics looking for answers. I was beyond disappointed. Follow up e-mails to ask what the diabetic community can do to move this forward and why their statement does not reflect the changing world of C-Peptide research have gone unanswered. showing little interest in the subject: "JDRF is familiar with the origin of C-peptide and its use in humans with type 1 diabetes to determine its effect. JDRF has followed reports of the early-stage human studies taking place in Europe that are asking whether the administration of C-peptide might prove beneficial in reducing or eliminating the signs of nephropathy and neuropathy complications. We’re cautious about the interpretation of these studies and will seek the guidance of our scientific and lay committees to determine the timing and specifics of a course of action. In the meantime the outcomes of these studies are of interest, and may at some future time be the the subject of well-controlled safety and efficacy studies." I wasn't very satisfied at the time. Imagine how much LESS satisified I was when I wrote once again last month to ask what their current position is givent he significant amount of ad

Posted by Anonymous on 3 November 2008

Can we buy c-peptides anywhere?

Posted by Anonymous on 3 November 2008

Are there any clinical trials on C-peptides?

Posted by Anonymous on 20 November 2008

There have been dozens of trials on c-peptide but they've mostly been small scale trials, many in animals by researchers who care enough about discovering the truth to investigate something that doesn't promise them a big pay-day in terms of patents and is very hard to find outside funding for. The results to date are VERY promising. If this had a large potential financial upside for big pharma the research would be much farther along and we it would probably be FDA approved by now. But as long as big pharma drives most of the research in this country, critical research areas like this will move forward slowly if at all.

Posted by Anonymous on 21 February 2009

I have been an insulin dependent diabetic for 43 years. When I developed diabetes it was a condition not many people were aware of. Now it is a pandemic. Research has led us to believe we are moving forward with control and cures. When C-peptide was present in the insulins I had no side effects or secondary diseases. Once the C peptide was removed. I developed severe retinopathy, (blind in one eye), diabetic neuropathy, diabetic nephropathy, as well as heart problems.
C-peptide worked!!! I can not stress this enough!
Wikipedia: "Inspite of these physiological functions, C-Peptide is not present in pharmaceutical preparations of insulin sold by drug companies that are in wide-scale clinical usage today, a practice seen as unethical in light of more research suggesting the peptide's utility."
I suppose the idea is to keep the newbie diabetics from realizing there were better functioning insulins in the good old days, more efficient than what we see on the market today.
Then they will come up with C-Peptide as another new discovery and charge an arm and a leg to purchase it. Well you can have my arm and leg as they are useless to me these days.
I suppose the moderator of this site will edit this post, but it is time that the public stand up and shouts "This is a scam!", a conspiracy all led by Big Pharma playing around with our health.
A class action suit should be started against Eli Lilly and the like.
No one else can judge unless they have walked in a diabetic's shoes.

Posted by Anonymous on 13 May 2011

C-peptide... sure it works, but who will fund the research? It was discovered in 1967, so a company can not register it as their own, so not worth the research dollars. That is just how the world is, so don't get you hopes up. It is all about economics, the bottom line and shareholders.

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