New possible trigger for beta cell destruction in T1D

New research published today in Nature Medicine suggests that certain types of stress (like ER stress) cause beta cells to mistranslate insulin mRNA, which leads to the production of immunogenic polypeptides and subsequent destruction of beta cells.

http://www.nature.com/nm/journal/vaop/ncurrent/full/nm.4289.html

Here is some more information about this research:

I think we’ve known for a long time that both T1 and T2 diabetes seem to have a relation to high lipid numbers.

I first came to this realization when I visited my state’s research hospital 35 years ago to see about possibly getting involved with the DCCT and the intake was being managed at the Lipid Research Clinic. I asked the researchers and they told me they thought there was a very real correlation.

Many here and elsewhere have assumed that the lipid numbers are a result of high bg but I’ve always had the hunch it was not so simple, that it seemed more likely they were both caused by the same factors or even the other way around.

The DCCT results very clearly point to a strong relation between high average bg and microvascular complications like kidney disease, retinopathy, neuropathy. But the relation between high average bg and macrovascular complications has always, to me, been much less convincing, such that it looked to me like macrovascular complications are related but not in a simple “caused by high bg” way. It always looked to me like they both had the same root cause.

On the relation between autoimmune diseases and cancer research, that is very interesting. My wife has Rheumatoid Arthritis and takes Methotraxate, which was first used as an anti-cancer drug. http://www.arthritis.org/living-with-arthritis/treatments/medication/drug-types/disease-modifying-drugs/understanding-methotrexate.php

The association between lipids and diabetes is well established, but as of today that’s all it is, an association. The question of which is the chicken and which is the egg is hotly debated and the definitive research to settle the question has never been done.

See Gary Taubes’s new book, _The Case Against Suga_r. He discusses the subject at length, with a great many references.

I saw this research, think it’s interesting but also the way they were overhyping it in some press releases was a little bit unethical. The press release made it sound like autoimmunity was not really important; but clearly most of the genes associated with T1D play a role in immune response, so there has to be something beyond this initial trigger.

Still, seems like it could help those who develop diabetes after a specific trigger, like immunotherapy for cancer treatment. An earlier study in Cell Press also identified decorations on the packages which carry insulin from the beta cells as sending out a distress signal that lured in immune cells. So i think this story (i.e. ER stress --> autoimmunity) has been building for quite some time along several lines of research.

But since the number of factors that can cause such stress (infection, poor diet, inflammation, etc. etc. etc.) is so wide, I’m not sure it gets us further in preventing the disease.

@Tim12, yes this is what always worries me when I look through the data. Seems like you are doing a great thing to keep BG numbers in check for all those microvascular complications, but it’s not clear that you’re cutting the risks of the biggest complications in significant ways.

I’m the only one in my family with T1 diabetes. But There is a deep history of heart disease in males in my family history. I am doing everything I can to stay healthy on the macrovascular side too. I have very tight goals for blood pressure and cholesterol, I have been taking statins for over a decade now, and Just in the past year (since I am almost 50) I am going to a cardiologist every year for testing in hope of catching anything as early as possible.

Hi @Tim12, sorry I wasn’t clear, when I said “you,” I meant the universal “you” of people with diabetes. Not meaning to comment on your personal health regime or your risk of CV disease :slight_smile:

David, I think the DCCT produced some very clear-cut results and some not-so-clear results. But the not-so-clear results have implications too.

It is super duper clear from the DCCT that complications like neuropathy, retinopathy, and kidney disease - microvascular complications - are strongly tied to average blood sugar and that by working on our bg control that we can do a lot to delay or prevent these complications. The standards of care for diabetes (both T1 and T2) have advanced incredibly quickly and powerfully as a result of this clear result.

The not-so-clear results have value too. The relation between diabetes and lipids and macrovascular complications, are not so strongly tied through average blood sugars. How I personally take this, is that I have to not just work on my bg control, but I also have to work on cardiovascular health in other ways too. There have been advances in the standards of cardiovascular care for both T1’s and T2’s but they are not as quick or as powerful as the advances related to bg control.

Uhh . . . I’m not sure what you were responding too. I’ve never criticized the DCCT or its conclusions, here or anywhere else.

???