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“The Blasphemy of C-peptide Removal”
Allie Beatty, formerly of TheDiabetesBlog, has established a new multimedia site “Allies Voice” where she has launched a crusade. The issue at stake is a substance called C-peptide, which in a healthy body, is present in tandem with insulin, but is removed during the manufacturing process of human insulin analogs that we PWDs must inject. Allie and others believe that Big Pharma is doing Type 1 patients a grave disservice by removing this substance, and failing to make it available to us.
Why? There is some scientific evidence indicating that C-peptide can improve neuropathy, kidney function, and high blood pressure in Type 1 diabetics — and yet insulin manufacturers have done away with the C-peptide, some say, because they don’t find it profitable; Type 2 diabetics apparently produce plenty and don’t need any more of the stuff, therefore the vendors don’t bother adding it back into their products in order to make their insulins more marketable to a larger audience.
It’s important to note the phrase “adding it back in.” Because the process of creating injectable insulin is actually the act of breaking down a “prohormone” called proinsulin into insulin and C-peptide. The latter was traditionally considered nothing but a byproduct of the production process, until some researchers began investigating it not long ago. Most notably, Dr. J. Wahren of Karolinska Hospital in Stockholm, Sweden. He argues pro on the critical point: that C-peptide is indeed a biologically active molecule that can have proactive, positive effects on patients with diabetes. Obviously, he’s quite convinced that C-peptide can be used successfully to treat long-term complications of Type 1 diabetes, as he’s even co-founded a company around the concept.
“In contrast to his view, the general consensus has been that there is not much of a role of C-peptide per se,” said Dr. Jay Skyler, Associate Director of the Diabetes Research Institute (DRI) in Miami and Chairman of the national Type 1 Diabetes TrialNet study, in a written response to my email last week.
In fact, to get to the bottom of this issue, I was very busy emailing an array of experts late last week. Here’s a quick overview of what I learned:
* For a short time many years ago, Eli Lilly & Co. tested the use of proinsulin, the precursor molecule of insulin that still has the C-peptide component within it. Unfortunately the program was aborted after some of the studies suggested that proinsulin use was associated with an increased risk of heart attacks. (Dr. Steven Edelman of US San Diego and TCOYD can attest to this; his center was one of the research sites.) Millions of dollars were swallowed up in that research program.
* Even if there were compelling human studies confirming the benefits of C-peptide (which there current aren’t), bringing it to market would involve HUGE investment costs, by some estimates up to $300 M to go through the full FDA submission process. “Money IS finite and these decisions have to be made,” Dr. Nancy Bohannon of St.Luke’s Hospital in San Francisco reminds us.
* According to Dr. Camilo Ricordi, Director of the Miami DRI, it’s unlikely that manufacturers could even produce and mix these “already cleaved” products — insulin and C-peptide. This means C-peptide would likely need to be sold separately, so patients would be forced to take a separate injection, as is the current case with Symlin. “I believe c-peptide could be valuable and so far there is no data indicating that it would be harmful, so I would certainly support the concept of producing it and administering it with insulin,” Ricordi wrote me.
* Most of the experts queried (including some big names in diabetes research: Dr. Bruce Bode, Dr. David Klonoff, and Dr. Barry Ginsberg), agreed that A LOT more, far-reaching and very expensive research would be necessary to evaluate the true value of C-peptide. Since this money would be channeled away from other D-research pursuits, it’s a matter of opinion, I suppose, whether one thinks exploring the potential benefits of C-peptide is worth the ROI.
So does the Pharma companies’ failure to distribute C-peptide really constitute “blasphemy”? I know a lot of patients who believe in its value feel outraged, but in all honestly, my takeaway here is that this issue may not be worth all the gut-grinding. From the early research, it looks like the health risks could very well outweigh the benefits. If Dr. Wahren and others successfully manage to produce strong, unquestionable evidence that C-peptide is important, we may see a turn-around in our lifetimes. But for the moment, this looks like an uphill battle — and our advocacy energies are probably better spent elsewhere.
That being said, I think it’s important for the patient community to keep up the pressure on drug makers to keep their marketing practices clean and their motives and tactics transparent. Thank you, Allie, and thank you, Scott S, for your advocacy efforts along those lines!
Explore posts in the same categories: Diabetes Essentials, Diabetes Product Parade
Wow Amy, This is very good yo know, its very interesting. Thanks.
Posted by: Cesar | December 6th, 2007 at 6:48 amWow, what a toss up… Either use proinsulin (which has insulin and C-peptide) and risk heart attack or use just insulin and not C-peptide and increase chances for neuropathy and kidney function. Gee, what a toss up…
It sounds to me like most of the experts (all of whom I greatly respect) don’t see much need for C-peptide. And honestly, with so many people doing just fine on the insulin we have now, I don’t know why we would spend millions of dollars on possibly lowering risk for complications when that money could significantly progress CURE research.
Hmm, possibly lower risk for complications or A CURE? Not much of a toss up there.
Posted by: Allison Blass | December 6th, 2007 at 7:03 amAllison is right, what a toss up.
-Cesar-
Posted by: Cesar | December 6th, 2007 at 7:06 amI agree with others. If the choice is between spending money on curing type 1 or figuring out whether we would be better off with C peptide, my vote is for the former.
Posted by: Anne | December 6th, 2007 at 7:50 amI would rather see some advocacy energy being spent on giving companies the right to produce generic insulin.
Scott has written about this at length and he’s exposed the political lobbying that has kept insulin unaffordable for so many people around the world. Preventing companies from entering the generic insulin market and bringing down the cost of insulin seems to me to verge on the criminal.
With Novo Nordisk going out of the R insulin business, the price of regular human insulin–the cheapest form available–will skyrocket. People will die because of this.
Posted by: Jenny | December 6th, 2007 at 7:56 amHmmm. Didn’t know about this. I am ready to go and get pork insulin from Canada now! Won’t my endo love it when I tell him that. I have been complaining about the new insulin for some time now. I was one the of the last to switch ot the “new” insulin. (analogues). Perhaps this is why the symptoms of a low are COMPLETELY different on the new insulin vs. animal source? Seems that now even though my A1c is good (6.8) my eyes are getting WORSE not better, but hanksfully a few laser zaps have helped a bit.
Posted by: Jim | December 6th, 2007 at 9:27 amThe studies conducted by Lilly with proinsulin were destined to fail to prove a point. Proinsulin is not the appropriate way to administer C-peptide. The advantage of C-peptide comes after blood sugar has been lowered. The half-life of C-peptide is twice as long as insulin. The half-life count begins once insulin has attached to glucose and C-peptide has cleaved from the insulin.
Often times I feel like I’m smarter than Lilly — until I realize how cunning they are with their research. They know exactly what they want to prove before they even get to the lab. If the Zyprexa pharmaceutical rep training wasn’t proof enough for you – I don’t know what It’ll take.
Recombining insulin and C-peptide, after it has been cleaved, is the physiologically appropriate way to administer it. Lilly knew that!! These guys are not stupid. They’re very crafty and spending money on things that will ensure the designer pharmaceutical business of diabetes is first and foremost.
Like a bad marriage – Big Pharma has been cheating on our captive loyalty for Type 1 diabetes treatment for decades. But without proof — is it really cheating? Exactly!
Posted by: Allie Beatty | December 6th, 2007 at 9:51 amI should note something about your reference to Eli Lilly & Co.’s investigation of proinsulin. Those studies, which incidentally were jointly funded by the NIDDK (Lilly didn’t loose too much of its own money) were arguably skewed because they only tested replacing the amount of C-Peptide that normally accompanies insulin secretion. Although that sounds rational, in fact, when a patient has been without insulin (and C-Peptide) for many years, many argued that merely replacing the lost peptide was insufficient to see any results, and subsequent animal research done by Washington University at St. Louis suggested that was indeed a correct assumption. Nevertheless, Lilly abandoned the research (around 1997) because they were instead investing in Zyprexa and felt that with Humalog recently approved, they no longer needed to invest in it. I would hardly call that a black hole of research dollars, especially when many of the dollars spent weren’t their own.
Posted by: Scott | December 6th, 2007 at 10:08 amI’d rather have a cure than something to prevent complications, but if they can’t find a cure, why not make our lives healthier?
I look at my swelled up ankles, think of my too-quickly-beating heart, and I can’t help but wonder what could have been if we all had C-Peptide in some form all along.
I think what hurts those of us with diabetes the most is the COST involved in researching helpful things and ways to cure us. If research wasn’t so expensive, we all might be a little better off because it would be easier for scientists to make progress.
Posted by: Hannah | December 6th, 2007 at 11:46 amAmy
Thanks for opening this discussion up to a wider audience.
Clearly there’s no simple answer here. Big pharma won’t make a change unless they’re convinced that they can make a profit. And that makes some sense.
I’d rather have a cure. But I realize that may not happen in my lifetime. So I’d like something, anything, to help me maybe last until a cure is available.
What would it take to get someone interested in producing C-Peptide? Are there companies in Europe who are investigating this?
Posted by: Bernard Farrell | December 6th, 2007 at 1:45 pmHi Allie,
the physiological half-life of C-peptide is actually five or six times that of insulin, a large part of the reason being that just about all of the C-peptide is excreted unchanged through the kidneys, while insulin get destroyed in the liver (fisrt pass) and at the sites of use. Also, the half-life starts not when insulin attaches to a glucose molecule (the GLUT3 pathway doesn’t quite work this way). The half-life starts when the vacuoles which store the “ready-reserve” of insulin disgorge their contents. (The splitting off of the C-chain happens right after secretion, before insulin and C-peptide are stored in granules.)
With those minor items out of the way, the single biggest improvement I can think of short of a complete cure is an insulin infusion pump that delivers insulin directly into the bloodstream, where there is none of the delay to take effect or the nasty tail. Of course, that requires glucagon, extremely reliable and accurate sensors (ideally not just for BG but also for current insulin, glucagon, and activity levels), and dosing increments that are beyond current technology.
Cheers,
Posted by: Felix Kasza | December 6th, 2007 at 6:42 pmFelix.
Thanks for reporting this fact. All new news is old news happening to people that chose not to read history. Question? why would the body produce this product during insulin production and than “just throw the product away” with no use for the body. Could it be that this is the product that prevents a non-diabetic person from going into insulin shock.
Posted by: d2 | December 6th, 2007 at 8:32 pmMaybe there’s a reason not to want the c-peptide back?:
http://health.usnews.com/usnews/health/healthday/071207/obesity-diabetes-linked-to-cancers.htm
Posted by: Kathy | December 7th, 2007 at 10:32 amInteresting Articles for Week Ending Dec 7
The first week of the last month of the year is over and of course there was a ton of interesting stories thatPharmaGazette just didnt get the chance to cover. So, as usual, Ill list the top 10 or so…
Posted by: PharmaGazette | December 7th, 2007 at 1:45 pmExcellent article; both pro and con. I am always a sceptic on pharma motives. On the other hand, new methodologies and new information in general warrants a new look at old opinions so lets get on with the testing.
Posted by: camille johnson | December 7th, 2007 at 5:39 pmI’m a bit late commenting on this, but I come down squarely on the side of adding C peptide to insulin. There is an association between type 1 and small blood vessel damage, independent of glycemia. I think the missing part of the puzzle is C peptide. In animal models, C peptide replacement has been shown to be protective against neuropathy, for example. C peptide may act to increase endothelial blood flow, which helps keep vessels nourished and healthy. The cellular sodium-potassium pump, which is vital to the proper function of nerves and filtering cells within the kidney, is also assisted by C peptide. C peptide is not biologically inert. My guess is that the body puts its naturally produced C peptide to good use.
Longtime diabetics have trouble with nerves, blood vessels, and kidneys — three parts of the body on which C peptide exerts an effect. I think this is more than coincidence.
I recommend reading journal articles through PubMed for more information on C peptide. I’m still trying to wade through the volume of information available. I have a feeling that by the time I’m done with medical school, I will be a C peptide crusader. I’m fast approaching that point.
Posted by: Lauren | December 14th, 2007 at 2:09 amHas anyone heard of type 11’s(non-ketone producers with no history of coma or very high blood sugars-more in the 200-260 range with no treatment) using insulin intermittently to touch up out of control blood sugars for a few days, then stop and use diet, mild fasting, to keep from gaining weight for a few days and just accept an average of the two? The goal being to limit or lose weight with an overall lower insulin load. The two benifits would be to prevent hyperinsulinemia and its growth hormone-like effect on generating atherosclerosis and coronary disease and stroke, as well as weight gain which just increases insulin resistance. On the down side, higher blood sugars are associated with small blood vessel arteriosclerosis, such as affects the eyes, kidneys, nerves, and fine areas of the brain(pre-alzheimers). I would assume the person would still be taking metformin, possibly actos and prandin(short acting before meals), a statin, aspirin, and maintaining a lower than average blood pressure(120/70 range for middle aged) as well as exercising. I think most doctors would disagree or say everything is about controlling the sugars, but a researcher who specializes in diabetes with a lot of type 11’s might be more interested in thinking about it. Any thoughts on this?
Posted by: Brian | December 22nd, 2007 at 6:36 pmIt doesn’t make sense that proinsulin would cause heart attacks. Diabetics who make NO proinsulin are more likely to get heart attacks than people who produce their own internally.
I think it is more likely that their their test subjects were diabetics, and therefore more likely to get heart attacks anyway. Or maybe the sudden administration of normal levels of proinsulin after its long absence causes heart attacks. Maybe starting c-peptide administration slowly, and increasing to normal levels, is the right way to do it.
In any case, I would like to have normal circulating levels of c-peptide again, because I’ve read the research about what it prevents and fixes, and I don’t want vascular and neurological disease to overtake my body.
I hope Creative Peptides gets approval for a commercial version of c-peptide before I get to that point.
Posted by: Type 1 | February 6th, 2008 at 10:34 am