Monday, July 14, 2014

ADA 2014: Type-1 Diabetes Cure Research, Immunology

This posting discusses two treatments which have the potential to cure type-1 diabetes, which have been tested on people, and which were reported on at the ADA's 2014 Scientific Sessions.  They were both tested in honeymoon diabetics (as I define "honeymoon").

The soundtrack for this posting (in honor of the Ramones,  RIP):!/s/What+A+Wonderful+World/1XjvmQ?src=5

Expanded Polyclonal Tregs

There was a presentation of results from a clinical trial on Expanded Polyclonal Tregs, which I've blogged about before:
Remember that this line of research is being pursued by two teams: the UCSF team (led by Dr. Gitelman) which is reported on here, and a team at Medical University of Gdańsk lead by Dr. Trzonkowski.

A quick summary of this treatment is as follows: remove one specific type of T regulator cell (called "CD4(+)CD25(+)CD127(lo)") from a person with type-1 diabetes.   Grow them out so you have about 500 times more, and then put them back in the body.  Since regulatory T cells naturally regulate the body's immune system, the hope is that they will prevent the autoimmune attack which causes type-1 diabetes.

The UCSF team ran a phase-I clinical trial with 14 people.  There was no placebo group and the patients had type-1 for between 3 and 24 months.  The basic results were that after two years, these patients continued to generate C-peptide at the same rate as when they started the trial.  There was no drop off in C-peptide production.  That means there was no drop off in insulin production.  Since all these people were already diagnosed with type-1 diabetes, they were not generating much insulin, however people with type-1 generally generate less and less insulin over time.  So these patients did better than would be expected of an untreated group.   (Although as a pilot study, there was not an untreated group here.)

Source: ADA 2014 Presentation 174-OR.


There was presentation of results from a clinical trial on Antithymocyte Globulin (also called Thymoglobulin or ATG) and Granulocyte Colony Stimulating Factor (GCSF).  I've blogged on this trial before:

The basic idea behind this research is that ATG modulates the body's immune system, while GCSG causes the body to generate more T-cells directly from it's own bone marrow.  So this therapy is a combo therapy with one treatment to stop the autoimmune attack, and another to restore beta cells.

This study had 17 patients who got the treatment, and a placebo group of 8 who did not.  People had type-1 diabetes for 4-24 months when they received the treatment.  Basically, the 8 untreated people lost C-peptide production (which means they lost insulin production), just as you would expect.  The 17 treated patients ended up, after one year, at about the same C-peptide level from where they started. So they did significantly better than the untreated group.

This news article covers this research as well:
But note that this story has some phrases like this "there was an increase in the insulin-producing beta cells in the pancreas" which is overselling, in my opinion.  This treatment preserved beta cell levels; I don't see evidence that it increased them.

The most interesting quote in this story is the following forward-looking view from the researcher:
[Dr.] Haller said the eventual goal, years down the road, is developing a therapy that first uses an IV infusion of Thymoglobulin and then a Neulasta [trade name of GCSF] treatment once every two weeks for three months to greatly reduce or eliminate the need for some Type 1 diabetes patients to take insulin injections.
Another interesting point, is that both ATG and GCSF are already FDA approved for other uses.  This makes them easier to use in clinical trials, and means they could be used "off label" for type-1 diabetes, if prescribed by a physician.

Source ADA 2014 Presentation 173-OR.


First, these two studies highlight the lack of standardization in terminology used to describe "honeymoon" type-1 diabetes.  The first study enrolled people 3-24 months after diagnosis, and used the term "recent onset" (which I interpret as a more scientific way of saying "honeymoon").  The second study enrolled people 4-24 months after diagnosis, and used the term "established" (which I interpret to mean "non-honeymoon").

For my part, I'm considering both of these clinical trials to be "honeymoon" tests, because they included people who had been diagnosed for less than a year.  That's the dividing line I've used informally in the past, and I'm going to continue to use it, until I see a better definition.

Second, I view both of these results as honeymoon style results.  If they gave these treatments to people with long established type-1 diabetes, one would expect no improvement because the group would start out with no C-peptide production. On the other hand, these treatments have real benefits to recently diagnosed type-1s (who still have some insulin production), and could be even more beneficial to people who are losing insulin production, but have not yet been diagnosed. This is the hallmark of a honeymoon style result to me: it is highly dependant on how long a person has had type-1 diabetes.

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.


Mike Kleinhenz said...

I wish they would include truly "established" diabetics in these honeymoon trials. Having had Type 1 for almost 12 years now, I find that my insulin requirements can vary considerably (i.e. half again as much or half again as little)over both shorter and longer periods, with absolutely no external changes to my regimen. (Believe me, it is impossible to overestimate the constancy of my diet and routine.) Much more to the point, when my insulin use drops into the lower range, the dosages are essentially identical to what they were at onset, 12 years ago. Barring other explanation, the evidence suggests to me that the immune attack on my beta cells (following its first huge, alas misguided, "success") now goes on in fits and starts, reacting to some threshold level of beta cells that the pancreas continues to produce ever so quietly--or perhaps in blazing streaks--between times. It would be interesting to know the result of a C-peptide lab done during one of these honeymoon-like periods; but, of course, no doctor would authorize such a "pointless" test.

Erin Shapiro said...

Hi, my son is 2 years and 4 months old. he was diagonalized when he was 12 month old. (so he is still in a honeymoon stage). i have managed to keep his insulin intake to only one doze in the am. is he too young to participate in any trials like the one you mentioned last week?

Joshua Levy said...

Here is my previous post on how to find a clinical trial:
take a look at it, and also talk to your doctor.


TVital1 said...

Interesting, Mike. I hear people ask that question often. Too bad there wasn't a way for people to check their c-peptide levels during periods of differing insulin needs. Other factors I'd love to know would be to see the amounts of other gut hormones and inflammatory factors during different phases of insulin needs.