C-Peptide and Your Nerves

When a beta cell synthesizes insulin it creates a substance called "proinsulin" which splits into the actual insulin molecule and another substance--a chain of proteins called C-peptide. Details of this process are described in this Wikipedia article: http://en.wikipedia.org/wiki/Proinsulin

Most of us learn about C-peptide because testing its concentration in our blood is useful for determining if a person's beta cells are making insulin. This is especially true if a person is injecting insulin. That is because injected insulin only contains the actual insulin molecule not C-peptide. So the only way you get C-peptide in your blood is if your beta cells are making proinsulin, which then is presumed to turn into insulin.

For years C-peptide was considered to be inert, but it now turns out that C-peptide may play an important role in our body. There is some evidence that it is actively involved in the processes that fight oxidation in our blood vessels. This is important because damage to our blood vessels is what causes neuropathy. When tiny capillaries are damaged they do not supply blood to our nerves. Damage to blood vessels also leads to kidney damage.

A recently published study found one mechanism which may explain the effects of C-peptide on blood vessels. You can read the abstract HERE:

Human C-peptide antagonises high glucose-induced endothelial dysfunction through the nuclear factor-κB pathway .

How important this could be is suggested by a very small controlled study where for three months human C-peptide was injected in people with Type 1 diabetes who produce no C-peptide of their own. Improvements were seen in neuropathy and kidney function in the group who received the C-peptide.

Beneficial effects of C-peptide on incipient nephropathy and neuropathy in patients with Type 1 diabetes mellitus.

Another very similar study that lasted 6 months found a similar effect on nerves:

C-Peptide Replacement Therapy and Sensory Nerve Function in Type 1 Diabetic Neuropathy

It is important to understand that the process by which synthetic insulin is manufactured never produces C-peptide. There is a false belief floating around the internet that insulin manufacturers "throw out" the C-peptide. In fact, what they do is get genetically modified microbes to spit out copies of the final insulin molecule. Pro-insulin is never produced in the insulin manufacturing process. Pro-insulin was present in the old animal insulins but the process of purifying those animal insulins which was necessary to eliminate substances that caused serious allergic reactions in some people also eliminated the C-peptide, so you will not find C-peptide in any animal insulins sold today as they too contain only the actual insulin molecule.

The good news for those of us who are lacking C-peptide is that it appears that drug companies are working on producing synthetic C-peptide. If the initial, admittedly very small scale, research on the ability of C-peptide to prevent complications holds up, in a few years you might be able to inject synthetic C-peptide and lower your chances of developing microvascular complications.

But that said, it is very important to realize that there is just as much--if not more--research that suggests that you can also reverse and prevent microvascular complications by keeping your blood sugar within truly normal limits, and avoiding highs that go over 140 mg/dl for any significant amount of time. That level appears to be the level at which neuropathy first appears. You can read the research that shows this on this page:

Research Connecting Organ Damage with Blood Sugar Level.

One thing that makes me question whether C-peptide is a truly magical elixir is how many people with Type 2 who still produce insulin--often a lot of it--develop neuropathy and early kidney damage before they have blood sugars high enough to give them a diabetes diagnosis. Since these people are secreting proinsulin and often test with very high levels of C-peptide since they are primarily insulin resistant, not insulin deficient, one has to wonder how potent the effects of C-peptide really are. Clearly the presence of C-peptide in these people's blood streams does not prevent the microvascular complications.

Another question that rises in the minds of those of us who still can produce some insulin is whether we are suppressing our C-peptide secretion by injecting insulin and if we are, if this might make complications more rather than less likely.

The evidence, such as it is, suggests that injecting insulin early rather than late lowers the rate of microvascular complications--mostly because, as stated before, the benefits of lowering blood sugar to normal levels appear to outweigh any possibly helpful impact of C-peptide.

So if your own native--produced insulin is not able to keep your blood sugar in normal limits, any benefits you get from producing C-peptide are outweighed by the damage caused by the high blood sugars your inadequate insulin production creates. In any event, it appears that even when you inject insulin your body still produces some insulin. That is why doctors will give C-peptide tests to people with Type 2 who inject insulin and use the results to rule out Type 1 diabetes. Even when people with Type 2 diabetes are injecting large amounts of insulin, if some beta cells are still alive they will secrete detectable amounts of C-peptide.

Since there is clearly another big-selling diabetes product in the works here, if you start seeing a lot of studies promoting the value of C-peptide in the journals you should assume that some company is about to launch a blockbuster new, and of course expensive, synthetic C-peptide.

We won't know how effective it really is until we can see the results of some large trails with thousands rather than tens of subjects. My guess is that it will have some value, as does Symlin, another drug that replaces a hormone destroyed when the pancreas is the subject of immune attack. But is the case with Symlin, the value of an artificial C-peptide will be enormously enhanced if it is used in conjunction with a diet that cuts way, way down on the carbohydrates that raise blood sugar.

No magic bullet is going to prevent complications when your blood sugar is well over 200 mg/dl for hours at a time. And fortunately, we already know how to prevent that from happening. Cut back on the carbs!