Friday, April 2, 2010

Hypoglycemia and AutoImmunity?

High Blood Sugar's Impact On Immune System Holds Clues To Improving Islet Cell Transplants

A biological tit for tat may hold clues to improving the success of islet cell transplants intended to cure type 1 diabetes, according to a Medical College of Georgia scientist.
In type 1, the immune system attacks insulin-producing cells causing high blood glucose levels that may temporarily reduce the attack, said Dr. Rafal Pacholczyk, an immunologist in the MCG Center for Biotechnology and Genomic Medicine.

High blood glucose, or hyperglycemia, causes all sorts of dysregulation throughout the body. "It throws off metabolism, hormonal interplay and increases the risk of severe infections," Dr. Pacholczyk said. A shot of insulin or an islet cell transplant normalizes blood glucose levels, enabling, among other things, restoration of the usual balance between effector T cells which mount an immune or autoimmune response and regulatory T cells which suppress attacks.

The suggestion here seems to be that the autoimmune attack on beta cells occurs during hypo- or normal glycemia, rather than hyperglycemia. Maybe this is the major difference between the development of diabetes type I and II. Type II diabetics usually have large amounts of free fatty acids in the blood, insulin resistance comes before the development of full-blown diabetes. Dr Harris recently wrote in a comment that type I diabetics seem to be able to maintain lower blood sugars on a ketogenic diet than people without diabetes. This might not be a good thing. Maybe type II and insulin resistance is preserved in the genome because of the obvious dangers of type I?

The idea that the beta cells are protected from autoimmune attacks during hyperglycemia --when they are most needed, and prone to attack during hypoglycemia --when they are [I]least[/I] needed, makes me wonder if autoimmune is the right word, here. Pathological re-modeling?

Dr Bernstein writes about the impossibility of maintaining perfect blood sugar levels when there is an infection.

Tumour necrosis factor is a part of the inflammatory response; tumour necrosis factor promotes insulin resistance, and mice that don't express tumour necrosis factor heal poorly. I made a bit too much of this in a recent post about TNF, wound healing, and heart disease. But that insulin resistance has a legitimate role during some part of the healing process makes sense.

So; you are wounded. The wound becomes inflamed. Your fasting blood glucose goes up. What's going on? Is the increase in blood sugar just pathological, or is it a consequence of increased lipolysis-induced physiological insulin resistance? Is extra glucose needed in the high-energy healing process? Does the increase in blood glucose have the (sometimes beneficial) effect of decreasing the immune response?

I banged up my shoulder a few years back. Fish oil worked for a while, vitamin d helps. The one fail-safe is nicotinic acid (niacin). The only way I know that the niacin is working is that when I stop taking it, the pain eventually comes back.

Niacin temporarily prevents lipolysis. But an hour or so after taking it, there is a rebound effect and lipolysis is elevated. Niacin has been shown to increase fasting blood glucose; higher free fatty acids could explain this. I prefer the idea that the thing with my shoulder improving on niacin is caused by a less interrupted flow of energy (free fatty acids, etc, not mystic stuff), less "hypoglycemia." What we call hypoglycemia isn't a lack of glucose, it's a lack of glucose and those things that spare glucose, fat, ketones.

But what if it's an immune thing, higher fasting glucose lowering the immune response? Or a remodeling thing, when energy is low, some tissue is taken apart to improve the energy status of other tissue? Unwelcome bacteria being taken apart, damaged cells being taken apart --these are similar jobs. That the immune system is involved in both of these processes is uncontroversial.

Collagenous joints are sort of at the end of the supply line, as far as blood supply goes, they could be particularly susceptible to this sort of thing.

When a wound is healing, there is a rapid local proliferation of cells. Is there an increased risk of an autoimmune response against new tissue? (Or an increase in the breakdown vs buildup portion of remodeling?)

I may be making too much from too little. That seems to be what I do.

Thursday, April 1, 2010

March Madness

In March, I learned that supplementing with Creatine and Glutamine can give some people manic episodes. Careful.

I'm some people. I took the blog down for a while. While my thoughts were racing, I had a tendency to jump to conclusions way too quickly. I don't like the idea of spreading misinformation.

I plan to go through some of my March posts, and try to weed out some of the noise, but for now, I'm going to just put it back out there. I'm having a little trouble telling the baby from the bathwater, now that I'm back at normal speed.