C-Peptide replacement therapy

Most here know that the Beta cells secret proinsulin which is cleaved into insulin and C-Peptide. For a long time it was thought that the only use for C-Peptide was to measure secreted insulin since it has a longer half-life than insulin and is a fairly cheap way to measure endogenous insulin.

There is research that show promising benefits to C-Peptide- nerve and blood vessels health.

The lack o C-Peptide is a T1 given, but late stage T2s like myself have low or zero C-Peptide.

Has anyone here know of anybody receiving C-Peptide replacement?

https://academic.oup.com/cardiovascres/article/104/2/234/2931071

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Google ā€œC-peptide injectionsā€; you will get what might be the latest research (well, I get those results). You are quoting a 2014 paper.

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It’s the most recent I found. The first was 2007. I think it’s something of interest. If there’s more current papers I would be interested in reading them.

The other hormone secreted by the Beta cells, amylin has mixed results hypoglycemia for one, having to inject it and insulin as separate injections for another, and gastric distress.

I suppose C-Peptide will likely have pros and cons.

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I’ve done a quick literature search from 2015 onward. What I’ve found has not impressed me about the potential for C-peptide replacement. (The usual qualifications: I don’t specialize in this, and scholars outside their own fields often look like idiots.)

Briefly, C-peptide has been linked in early studies with reducing retinal, kidney, and nerve damage in T1D (e.g., this paper reviewing its potential as a therapy for kidney disease). These studies are at least based on reasonable guesses given our mechanistic understanding of what C-peptide does, molecularly.

The situation with respect to T2D is far less clear and I would not assume based on what I have read that it works the same as in T1D–see here for the role of C-peptide in T2 as well as the abstract of this paper.

As for therapies, there seems to be good reason why research into them has dropped off. This, from 2017, is the best review of the then-current literature and it offers what I think are plausible reasons why it stalled out. Two of them are methodological, having to do with the variable purity and formulation of the C-peptide used in replacement studies. This is a huge problem in molecular biomedicine. The third is a fundamental problem I’ve mentioned before, namely whether the standard animal model of T1 is a good analogue of what happens in human diabetics, especially those who have had the disease for a long time. An example of the kind of inconsistencies they found:

ā€œC-peptide proved to be effective in improving motor nerve conduction velocity (MNCV), a common metric of nerve damage in diabetes, in both the STZ and BB/Wor rat. However, in a study titled ā€˜ā€˜Amelioration of Sensory Nerve Dysfunction by C-Peptide in Patients With Type 1 Diabetes’’ the authors report no improvement in MNCV in humans following 12 weeks of C-peptide treatment. Similarly, in 2015 it was published that a PEGylated C-peptide analogue (Peg-C-peptide) was able to significantly prevent losses in sensory nerve conduction velocity, paw thermal response latency, and other indices of peripheral neuropathy in STZ mice. However, in 2016 it was published that a large-scale 12 month human trial of Peg-C-peptide showed no improvement in sural sensory nerve conduction velocity in Type 1 Diabetic patients when compared to placebo.ā€

It’s hard to disagree with the conclusion the authors draw: ā€œClearly, there are stark inconstancies between the diabetic-animal model and the diabetic human, and these inconsistencies have repeatedly caused misperceptions in the efficacy of diabetic treatments.ā€

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Thanks @needlesandmath As to my clan, T2, in the early stages we will have abnormally high C-Peptide levels. Over time this will decrease as the Beta cells die from over work. You might say we have a very long honeymoon.

The use of synthetic C-Peptide needs to be taken into consideration. Just lik the insulin we use is different from endogenous insulin, modified to have various half-lives and preservatives.

There is nothing simple in life and especially in biomedical research.:face_with_monocle::rofl:&:sob:

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There’s one in 2021 specifically for T1DM. Comes up first for me on Google after I’ve scrolled through the AI (normally I also have to scroll down 10 pages of ads too, so I guess this isn’t a corporate favourite topic!)

T2 queries get foxed by the fact that C-peptide is a measure of endogenous T2 insulin production and that is a pretty much dominant factor. Adding C-peptide just messes up the docs diagnostics for T2. This is not true for T1 - we have no C-peptide so measuring it is not helpful! From that paper, emphasis added by me:

T1DM patients do not produce C-peptide, a cleavage product from insulin processing. C-peptide has potential therapeutic effects in vitro and in vivo on many complications of T1DM, such as peripheral neuropathy, atherosclerosis, and inflammation.

It’s not a research paper; it’s a second source, so is valuable here. Table 1 is the place to look. There are no long term studies (so far as I could see), it’s clear that C-peptide does something although the table at least does not document the amounts used. However the things it is doing are not things that other chemicals can’t do.

In other words C-peptide itself is a chemical that, in some concentrations, causes changes in our (and rats) cardiovascular systems that may help with diabetic complications.

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Yeah. It seems to be an on-again, off-again thing which started maybe before the 2014 paper. A cure looking for a condition. The 2021 paper considers six separate T1DM studies, so slightly up from four, The papers consider an number of different things. I get the feeling, ā€œWill it help with this?ā€, ā€œWill it help with that?ā€

I’ll read it later. My wife is in hospital with a stroke, our non- local sons are badgering for information that’s just not available to me now. One wants me to insist that we have the results of a MRI and EEG done this afternoon NoW. It’s not like I am already stressed.

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Oh jeez, @CarlosLuis, so sorry to hear that! Hoping that she’s ok. Best to you and the family.

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I hope she makes a complete recovery. Please keep us posted.

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@needlesandmath and @CatLady even though the hospital is overcrowded she’s getting very good care. We will have to wait an see. Today is a good day, she’s speaking more and alert. I’m having difficulty understanding and she stuck her tongue out at me😁

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Oh my goodness, CL. Sending all my best thoughts your way and a big, gentle hug to both you and your wife. Please do keep us posted xoxoxoxo

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Sorry to hear this, @CarlosLuis, but am certainly glad she seems to be getting better and has her wits (and humor) about her! Praying for your wife to make a full recovery! :folded_hands:

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We appreciate your prayers and support. It means a lot. We are Catholic and the priest chaplain is an old friend. He comes to visit every day and she lights up.

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I’m sorry to hear this. I know it is hard. I’ll keep your wife and you in my prayers.

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Thoughts and best wishes go out to you CL and your wife. Although I am agnostic, I believe that knowing others keep you in their thoughts (prayer or best wishes) helps with healing.

C-peptide having a therapeutic effect is nothing new. The issue has always been having some way of measuring any biological effect in a human, and that does not require a long term study. Given the diversity of T!D population recruited for such studies, it becomes an issue of studying a large number of people, across a very diverse genetic background. Think predisposition to complications. The only easy endpoint one could imagine is improved glycemic control, and with the improvements in technology toward euglycemia - it can be difficult to measure.

I am not an MD, but a Ph.D., who has worked in academia and in a pharmaceutical company (now retired over 10 years). So I could be wrong…

Mike

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Thanks, Mike, for your kind words and expertise. I am retired 10 years as well. I haven’t a clue of the technological changes in my former work.

In 1970 I was trained In avionics. Most of the devices are obsolete as well as the systems. Those that I know are still in use, INS, radar, IFF transponders and ILS devices must be radically different.

Towards the latter years of my Telephony career, we were no longer able to repair units. We just isolated to a pwc card and shipped it to a repair center.

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