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Does C-Peptide have a role in preventing diabetes-related complications?
Section:  Nursing

The December 2011 issue of insulin Dependent Diabetes Trust (IDDT) Newsletter had some interesting thoughts about C-Peptide.

It is important first of all, to know that human and analogue insulins do not contain C-Peptide because they are made by genetic modification in a lab. C-Peptide is release from the pancreas when insulin is released.. People with type 1 Diabetes are deficient in C-Peptide as well as insulin. C-peptide blood testing is being used to determine how much, if any, insulin is being produced by an individual’s pancreas.

It had been assumed that “C-Peptide had no function, but in recent years it has been discovered that C-Peptide binds to the surface of certain cells and activates their signaling mechanism in different ways.” Some studies suggest that C-Peptide may protect the kidney from diabetes-related kidney disease. Diabetes UK is funding C-Peptide research at Leicester University that will “look more closely at the functions of C-Peptide and see if this produces any new approaches to protect against diabetes-related complications. This might lead to adding C-Peptide to insulin treatments.” Although people with type 2 diabetes may have C-Peptide, it is possible that they may be resistant to its actions.

Here are some excerpts from a study published in 2008 in Science/Technology

You can read the whole article at: http://pubs.acs.org/cen/science/86/8602sci1.html"Called C-peptide, this 31-amino-acid peptide is cleaved from the insulin precursor during synthesis of insulin, a peptide hormone that helps cells absorb glucose from the bloodstream. For a long time, researchers thought C-peptide had minimal biological activity, and they dismissed it as a by-product of insulin production. Because C-peptide is secreted at the same concentration as insulin, it has been used as a marker for endogenous insulin secretion and the health of insulin-producing pancreatic beta cells."

"But C-peptide may play a larger role than as just an insulin marker. In recent years, scientists have shown that C-peptide has beneficial effects in patients with type 1 diabetes, including improved kidney function, nerve function, and blood flow. Researchers hope that administration of C-peptide might help alleviate some complications of type 1 diabetes."

SOME PEOPLE have been skeptical about a beneficial role for C-peptide because many patients with early-stage type 2 diabetes have elevated levels of C-peptide. Dana A Spence, Chemistry Professor at Michigan State University thinks that is because the red blood cells of diabetic patients are stiffened. "We have data showing that when the cells get stiff, the C-peptide doesn't work. If the C-peptide doesn't work and it's not facilitating glucose transport into the red cells where it is consumed through glycolysis, one may become hyperglycemic," he says. "You always hear people talking about insulin resistance, but I also think people may be C-peptide resistant."

The study is "a significant contribution to our understanding of C-peptide biology," says Anders Sima, a professor of pathology and neurology at Wayne State University, in Detroit, who studies C-peptide. The findings "may have an impact on future development of C-peptide formulations for pharmaceutical purposes."

"Scientists don't know how C-peptide exerts its beneficial effects. Spence and colleagues at Michigan State University have found a clue to help solve that mystery. In assays where they combine C-peptide with isolated red blood cells from diabetic patients, they find that C-peptide facilitates glucose clearance and causes red blood cells to release adenosine triphosphate (ATP), a known stimulus for the blood vessel dilator nitric oxide (Diabetologia 2008, 51, 175). C-peptide causes these effects by activating the GLUT1 transporter, a protein that shuttles glucose across cell membranes."


Re: Does C-Peptide have a role in preventing diabetes-related complications?

That article is a little unusual as it talks as if C-peptide is an entirely different hormone/molecule than insulin, when indeed it is actually part of the insulin molecule itself, as I'm sure we all know.  It is the last peptide broken off to form insulin, so for every molecule of insulin there is one molecule of c-peptide, against which, as far as we know, we do not form antibodies. 

I really don't want them to add c-peptide into the insulin. I find c-peptide a very helpful measurement for me.  Not all T1DM are completely deficient in c-peptide, especially early on, and some, doing a radical dietary treatment--see  www.healthesolutions.com, which whom I am peripherally associated--have actually had their c-peptide increase as their need for injected insulin significantly decreased.  I also use the lab in T2DM to see if they have a chance of getting off their insulin (as some can if the c-peptide is normal) if they embrace my protocol whole-heartedly, or if they need to go on full insulin, too. 

If they put it in the insulin, the lab value would be meaningless, as is measuring insulin levels in anyone injecting insulin. 

Interesting to see what happens in the future.

Re: Does C-Peptide have a role in preventing diabetes-related complications?

Great observation...we surely are using the C-peptide test, and it is a great help in assessing a person's insulin production

Re: Does C-Peptide have a role in preventing diabetes-related complications?

There is certainly a bunch of work which suggests that c-peptide replacement may help treat diabetic neuropathy in T1.  But there is also some research suggesting that c-peptide may have a role in vascular damage and thickening in the arterial walls.  In particular, it may not be good in patients with insulin resistance and that c-peptide may have a role in formation of vascular lesions.  Other articles on this controversy are here and here.

Given the current situation, there is clearly a lot more work to do before we are going to see the FDA approve this type of c-peptide replacement therapy.  Despite my unwavering optimism on the subject, there is already a company named Cebix pursuing c-peptide replacement.

Re: Does C-Peptide have a role in preventing diabetes-related complications?

Thanks again, Brian, for your update on this topic. It is surely someting to be watched

Re: Does C-Peptide have a role in preventing diabetes-related complications?

Thank you all for a very intersting and stimulating discussion.  I have read some of this research, but there is obviously more work being done in this area than I way aware of and now, thanks to Brian, I know about Cebix.  To address your concern, Mona, on the use of C-Peptide assays if C-Peptide were actually to be added to insulin, there may very well be a way to differentiate the C-Peptide, or C-Peptide like, protein added to insulin from that which is naturally secrected by people with type 2 diabetes and C-Peptide function.

I plan to try to follow this research, as I do think it holds real promise from what I've read for those with significant neuropathy.

Re: Does C-Peptide have a role in preventing diabetes-related complications?

Mona: tell me more about the theory of pH and diabetes?