Saturday, July 4, 2015

News from ADA 2015

The American Diabetes Association's annual conference is the largest scientific gathering covering diabetes in the United States.  Even though most of the conference is aimed at type-2 diabetes, the part covering type-1 diabetes is still overwhelming.  About 18,500 people attended this year.

I was not able to go this year (it was in Boston), so I tried an experiment.  I closely followed tweets and news coverage of the convention.  I thought of myself as a wire service and the tweeters/bloggers/reporters at the conference as my freelancers.  I was reading about 1000 tweets a day from the following sources: #2015ADA, #ADA2015, @diaTribeNews, @DiabetesMine, @sarhoward, @AmyDBMine, and @kellyclose.

I'm going to summarize these in two postings.  This posting has four sections: an overview, research in people aimed at a cure, research which has cured mice, and non-cure related research. The next posting will cover artificial pancreas research. There was a lot.

ADA includes a sea of expert opinions, but also the results of many experiments.  So it is especially important to remember these words by Robert H. Mathies  (Often incorrectly attributed to von Braun):

"One experiment is worth a thousand expert opinions"


You can read the abstract to every poster session at the link below, and most of them have a PDF of the poster itself:
Although the posters are easy to search, I cannot set up a link to one once I find it.  So I have put in the poster number (like 1234-P  or 42-LB).  Go to the link above and search for the number to find the abstract and the poster itself, when it's on line.

The following search page can get you to abstracts for many presentations, but I found it very hard to use:!/3699

The link below is a summary of the conference by Insulin Nation.  Some of it is reporter-insider snark, but other points are quite good.  The useful and the useless are mixed together:
P.S. The answer to 41 is "brown fat".

The link below is someone else's summary of the conference.  I completely disagree with the headline, but the section on type-1 research is a good summary.  You'll notice that only one of the possible cures they mention are in human trials now.  (Unless you consider AP or transplantation to be cures.)

Below is a link to Sarah Howard's summary.  She follows possible environmental causes for both types of diabetes, so she focuses on different parts of the conference than I would:

A big theme of the conference seemed to be treating patients rather than numbers, and generally emphasizing holistic care, and looking at more complex (and realistic) measures of health, than single numbers.  For me, this was typified by the following tweet which I saw repeated several times:  "A three-month average cannot tell the full story."  I think the tweet originated with @kellyclose (diaTribe), but I'm not sure.

Research On Potential Cures In Human Trials

I expect to blog on each of these trials in the coming months.

Fastuman Starts a Phase-II Trial Off BCG
Here's the press release:

Obviously, this is big news, and I'll blog about it in the next few months. But in the meantime, you can read my last blog on her BCG research:
The new news is that the trial is actually recruiting patients now.  Any updated details will be in my new blog.

ViaCyte's Phase-I Trial is 1/10th Enrolled
JDRF sent out this update on ViaCyte's Phase-I clinical trial:
There are as many as 4 people in SoCal currently testing @ViaCyte's experimental devices. That's progress.
The trial plans to enroll 40 people, so it sounds like they are 1/10th of the way there (depending on exactly what "as many as" really means).

1102-P: Immune Modulation of Stem Cell Educator Therapy in Caucasian Type 1 Diabetic Subjects
This poster contained information from the Phase-II trial of the Stem Cell Educator currently running in Spain.  I will blog more on this later, but for me, this poster had a "split personality".  On the one hand it was reporting on good changes to the immune system in people who got the treatment.  More good immune cells; less bad ones.  It looks like good news: the Educator is changing the immune system for the better.   On the other hand, there is none of the patient-focused data that would show progress to curing type-1 diabetes.  No data on C-peptide production; no improvements to A1c; no changes reported in insulin use.  (And the phase-I trial did have this kind of data.  So I'm not sure if this poster just focused on the immunology details, and a future paper will include C-peptide data, or if the C-peptide data in this second trial was not worth reporting.)

1099-P and 102-LB: Effect of Cell-Free Mesenchymal Stem Cells Microvesicles (MVs) and Exosomes Therapy on ß-Cell Mass in Type 1 Diabetes Mellitus (T1DM)
As far as I can tell, these two posters were identical, except that the LB poster only listed one author, and included the clinical trial registration number.
Patients were given stem cells (source not described), and compared to a control group.  Results were good:  HbA1c (6.67 ± 0.321 at 12 weeks vs. 8.245 ± 0.72 at baseline), fasting C-peptide levels (1.095 ± 0.215 at 12 weeks vs. 0.245 ± 0.069 at baseline) and C-peptide response following a 75-g oral glucose tolerance test (1.817 ± 0.27 at 12 weeks vs. 0.504 ± 0.065 at baseline).   To me, this looks like it is well worth a follow up.

Transplantation Work
So far with Edmonton protocol of islet Tx, 58% insulin free (need immunosupression), 92% have C-peptide after 7 years.  But those people will need to take immunosuppressives for the rest of their life.

Cured in Mice

Random quote from Richard Asher: "despair is best treated with hope not dope"

Poster 1812-P:
A new peptide (small protein like chemical), called KGYY15 is a honeymoon cure of type-1 diabetes in NOD mice.

Poster 1804-P:
Amylin Induces CD4+CD25+Foxp3+ Regulatory T Cells
Amalyin is a hormone given to type-2 diabetics, but there is some research to show that it would also help type-1 diabetics maintain better BG and A1C numbers.  This poster reports that it also increases the number of a specific type of helpful T cell.  This work is related to human trials, because at least two groups are "growing out" CD4+CD25+ T cells in the hopes that they will be a honeymoon cure to type-1 diabetes. Obviously, if Amylin has the same effect in people as these researchers found in mice, and if the researchers "growing out" these cells in people get a good result, that's good all around.

Using Th17 to prevent type-1 diabetes in mice:

Poster 1818-P: Local Expression of CCL21 in Pancreatic Islets Prevents Autoimmune Diabetes in Mice and Is Associated with Beta Cell Antigen-Expressing Lymphoid Stromal Cells
The poster was not on line, but the abstract was.  CCL21 (another small protein) prevented type-1 diabetes in NOD mice.

Poster 1826-P:
Prevention or Early Cure of Type 1 Diabetes by Intranasal Administration of Gliadin in NOD Mice
The poster was not on line, but the abstract was.

Poster 218-LB:
Nasal Administration of Novel Insulin Degrading Enzyme Inhibitor Ameliorates Autoimmunity in [NOD mice]
The poster was not on line, but the abstract was.

For those keeping track, that is six mouse cures presented at one scientific meeting.  For me, the interesting point will be: how many eventually get into human trials.  One?  None?  Only time will tell.

Non-Cure Research, But Interesting To Me

FDA Bullshit
This tweet really angered me:
Stayce Beck of @US_FDA calls out companies for not including kids in pediatric studies, says it's opposite of what agency wants.
This is completely two-faced, as far as I'm concerned.  Every researcher I interact with wants to have more kids involved in their studies.  Especially for honeymoon research, there are just so many more kids around.  But they can't because the FDA has specific regulations which prevent it!  It's the FDA who is creating and enforcing unreasonable limitations, and to turn around and "blame the victim" is scummy.  And the FDA's policies on kids in research does victimize researchers (as well as children) because it really slows down research and at the same time limits approved options for treating kids.

(I don't think I've ever sworn on this blog before, but this quote -- if true, and if really said by an FDA employee -- really deserves it.   I'm proud to say:  I call bullshit on that!)

Type-1 vs. LADA
There were several posters and papers which reported on differences between people diagnosed with type-1 as kids, and those diagnosed with it as adults.  Some researchers consider these to be the same disease with slightly different natural histories (sort of like chickenpox vs. shingles) while others consider these two to be two different diseases (with different causes or "etiologies"). All of the following posters described differences in early onset type-1 diabetes and late onset type-1 diabetes:
Poster 1801-P: Heterogeneity in Type 1 Diabetics Is Defined by Contrasting C-Peptide Declines, Autoreactive T Cell Burdens, and Metabolomic Differences
Poster 1819-P: IGRP-specific CD4+ T Cell Response Is Distinct between Adult-Onset and Juvenile-Onset Type 1 Diabetes Patients
Poster 212-LB: Anti-paralemmin 2 Antibody as a Novel Antibody for Latent Autoimmune Diabetes in Adults
Poster 1723-P: Determinants and Prognosis of Early- vs. Late-Onset Islet Autoimmunity

Poster 1737-P:
Ecological Study between the Incidence of Type 1 Diabetes and Geochemical Data in Sardinia: Negative Correlation with Zinc and Copper
Sardina has a high rate of type-1 diabetes, and the rate is not the same throughout the island, so these researchers tried to correlate various heavy metals in the environment to the higher type-1 rates in the same areas.  Higher levels of Zinc and Copper were found to protect people from type-1 (ie. higher levels of these metals correlated with lower levels of type-1), and no correlation was found for the rest of the metals they researched.  Here are the metals they checked: As, Be, Cd, Co, Cr, Cu, Mn, Ni, Pb, Sb, Se, Sn, Th, Tl, U, V, Zn.

Unexpected Stability of Type 1 Diabetes Incidence in a U.S. Cohort, 1994-2010
Basically, they found a type-1 rate of about 1 in a 1000 (lower than expected) and found that this number was going up before 2002, but going down after that.  That's not the common wisdom.  Most researchers think the type-1 rate is steadily going up.

For the opposite viewpoint: 1735-P:
The Incidence of Type 1 Diabetes Mellitus in Romanian Children Aged 0-14 Years Increased Constantly
(No poster, but a very nice graph in the abstract.)  This is the opposite finding as the previous poster, but this is the conventional wisdom about what is happening.  The two posters covered different geographical areas.

Dance-501 Inhaled Human Insulin
Research results from another inhaled insulin.  Phase-I trial, 24 people, type-2 diabetics.  Affrezza might have competition someday, and that can only be good, in terms of more choices for type-1s.

Big claim by Dr. Dandona: “Predict w/ this 3x therapy (insulin, GLP-1, SGLT-2) we can get at least 50% of #T1D patients [below] 6% A1c"
If he is right (and that is a big "if"!) this will be a big change in the treatment of type-1 patients. Right now, insulin-only treatment is normal, and A1Cs are rarely this low.  GLP-1 is widely used in type-2, but not widely used in type-1.  In my opinion, the results of the GLP-1 in type-1 studies that we do have, show some improvement, but not a lot. SGLT-2 is even farther away from type-1 use, as there is even less research.  But again, in my opinion, the improvements that have been seen are real (in early testing) but not dramatic.  However, this doctor thinks that by combining these two treatments, we can lower A1c between 1 and 2 points;  that would be great, if it were true, and if type-1s were willing and it was safe to take both drugs for the rest of their lives.

In large Dexcom-funded analysis, CGM users had a 42% lower hospital admission rate and 17% lower ER ad. rate over non-CGM users.

“Preprandial Oral Insulin (ORMD-0801) Reduces Rapid-Acting Insulin Requirements and Fasting Glucose Levels in T1DM Patients”

Some things are more scary than others:
Studies of diabetes blogs don't show discussion of complications but more near term issues like nighttime hypoglycemia

If you got all the way down here, you deserve a laugh:
which came from this tweet:

Joshua Levy
publicjoshualevy at gmail dot com
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF or JDCA 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.


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