Wednesday, October 16, 2013

The Value of a few Beta Cells

This blog post is about type-1 diabetes research, but not research aimed at a cure.

The Value of a few Beta Cells

A recently published study, which you can read about here:
found that type-1 diabetics who were long out of the honeymoon phase and generated their own insulin had fewer long term side effects than those who did not.  This was true even if the amount of generated insulin was tiny.  I had always assumed this was true, so it is not a surprising finding.  However it is important, because in the past studies have shown that people over a certain level (0.2 nmol/l) benefited, but only about 10% of type-1 diabetics generated that much insulin.  What was found in this study, was that even people who generated 0.15 nmol/l were better off than people who generated 0.10 nmol/l, and so on.

Specifically, they found the effect was "linear" down to even the smallest amount of insulin they could measure.  This is very good.  It means that no matter how little insulin you generate, if you generate a little more, it is better for you.  The example in the abstract was that going from 0.10 to 0.15 nmol/l, resulted in an 8.2% drop in serious low blood sugar events, and a 25% drop in serious eye-sight issues.  Obviously, more type-1 diabetics have these lower insulin levels, so this study covers more real people.

Why Does This Matter?

Over the last few years there have been several trials, which have raised the amount of insulin a person generates by similar amounts, which have been measured for months or years:

0.15 nmol/l    Zhao's Stem Cell Educator
0.16 nmol/l    Marek-Trzonkowska's Polyclonal Tregs
0.60 nmol/l    Herold's Teplizumab
(Numbers are measured under different circumstances, so should not be compared directly.  But you get the idea.  There are several different treatments which are all giving these kinds of results.)

This study shows the benefit of these treatments as they exist right now.  This can serve four important purposes:

First, it gives these clinical trials a benefit to the people participating, which makes it easier to recruit.  Right now, a researcher can say, we hope that your insulin dose might go down 2%.  And the patient (or their parents) say "who cares".  But if the researcher can say, "if successful you might have a 25% lower chance of blindness, or an 8% lower chance of serious low blood sugar, or something similar for kidney failure" (or all of these things).  That's a clear benefit.

Second, it gives insurance companies a reason to pay for these treatments (if/when the FDA approves them).  Insurance companies know how expensive blindness is, and the same for kidney failure, and trips to the hospital for low blood sugar.  They can do the math for every treatment, and this will encourage them to pay for the treatments.

Third, it gives a quicker, shorter path to a benefit.  Although a cure remains the same distance that it always was, this study suggests intermediate benefits might be seen much earlier in the process.

Fourth, it suggests that curing type-1 diabetes might be a little easier than our worst case worries. The worst case for curing type-1 is that we will need to stop the autoimmune attack and then regenerate all the beta cells that have been lost.  This research suggests that once the autoimmune attack is stopped, that maybe the body's own beta cells will regrow, or maybe they will only need a little prodding to regrow.  (This study does not provide any direct evidence that beta cells will regrow without help, but it does provide a little hope in that area.)

Related News

This study is not the only recent study showing that even long term type-1 diabetics generate some of their own insulin.  The link below is to a different study, which also found some natural production of insulin in established type-1s.  I think the link above is more interesting, because it went a step farther: it connected the small amounts of insulin to fewer long term complications, and fewer low blood sugar episodes.  But the one below also adds support to the idea that tiny amounts of insulin are produced in many type-1 diabetics: is a

(If you are reading this on Brave Buddies, you notice this is the study that Lynn asked about a few days ago.)

A Quick History of Measuring Insulin Production

In order to measure insulin production, researchers actually measure C-peptide, because it is made when your body makes insulin, but is not part of injected insulin, so you can tell the difference between generated insulin and injected insulin, by measuring C-peptide.  In the past, about 10 years ago, the smallest amount of C-peptide that could be measured was 0.2 nmol/l.  Many studies found that about 10% of type-1s generated that much insulin, or slightly more, and 90% did not.  The tests reported no C-peptide, but everyone knew that it meant less than 0.2.

Meanwhile, pathologists looking at the pancreases of long term diabetics who had died, often found tiny, tiny numbers of beta-cells.  So they suggested that even long term diabetics generated a tiny, tiny amount of insulin.  But there was argument about this, and no way to know.  (Many researchers felt that the high BG numbers of a type-1 would prevent those beta cells from working, even if they did exist, for example.)

However several years ago, some researchers (in Europe, I think) created a lab test that could measure C-peptide amounts as low as 0.003 nmol/l.  As is the nature of these things, when it first came out, very few people knew about it, I suspect it was expensive, and no one was sure it actually worked.  (How do you test a test that is so much more sensitive than other common tests?) Anyway, over time the test became more widely known, I suspect it became cheaper, and researchers became more confident that it was actually as sensitive as claimed.

So now, we are starting to see papers that use this much more sensitive test to look at long term type-1 diabetics.  It is becoming pretty clear, by multiple studies, that if you look carefully enough, many more type-1 diabetics are generating a very little of their own insulin.

And now for something completely different.....My Involvement With Tidepool

Tidepool is a non-profit which is developing open source software to help use, manage, store, analyze, and communicate blood glucose data. This would be especially useful between different devices, over wireless networks, and on the web.  You can read more about it here:
Howard Look is the prime mover behind it, and Dr. Adi (of UCSF) is also involved.  For those familiar with venture capital,  Bryan Roberts, who is a partner at Venrock is on the board of directors.

It is my hope that Tidepool will do two things:
1. Make it easier for companies (especially start ups and hobbyists) to create useful BG tools for type-1 diabetics.  I hope this will lead to more and different types of tools; things we can not even imagine now.
2. Make it easier for researchers to run experiments on new hardware and software.  Right now, in many cases, before you even start such an experiment, you need to duct tape cell phones to CGM devices, yourself, and write special purpose software, and so on.  I'm hoping the free software that Tidepool produces will help these researchers focus on their research, and not cobbling together software.

So in my professional capacity as a software engineer, I will be doing volunteer work for them.  It is certainly possible that in the future I will report on artificial pancreas clinical trails that use Tidepool software.  At least I hope that I do.

Joshua Levy --
publicjoshualevy at gmail dot com 
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF, JDCA, or Tidepool news, views, policies or opinions. My daughter has type-1 diabetes and participates in clinical trials, which might be discussed here. My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog.


Kathy said...

I can attest to the help of a lower level of beta cells. My islet cell transplant is five years old now and is weakening. Watching my C-peptide decrease over time is heartbreaking, but I have been very surprised at how much they still help with my blood sugars compared to how I was pre-transplant. I'm presently at 0.4 C-peptide, but use less insulin than pre-transplant.

ANY help with glucose management is beneficial. If I could get back to a C-peptide of about 1.0, I think that I would feel almost normal. Hopefully, someday.....

Joshua Levy said...

Charles Weber has a theory that Capsaicin (the "hot" in hot peppers) is a cause of diabetes and it's effect is increased by copper deficiency. I have never seen any research testing this theory in people, so I am deleting his comment above.