Wednesday, November 28, 2007

Getting fat is bad when you stop

There comes a point beyond which getting fat becomes counter productive. This happens when you are too fat. What do I mean by too fat? Being fat is supposed to have survival benefits... I was thinking along the lines of type 2 diabetes, an enormously complex disease.

This problem is obviously "associated" with obesity, yet most obese people do NOT develop diabetes. Plus many thin people can and do develop type 2 diabetes.

From my perspective I think that type 2 diabetes occurs when people loose the ability to put on any more fat. This can happen at assorted body sizes, not just the seriously obese. In fact a huge person who is still gaining weight may well be safe.

We know that obesity requires just a small excess of fat per day to be locked in to adipose tissue by the insulin produced in response to dietary carbohydrate.

That's fine for a few tens of years. But there are limits on both the number of fat cells and the size to which they can be pumped. Eventually they get so full that they just say NO to any more fat. Bearing in mind that it is insulin which puts the fat in to fat cells, the easiest way to say NO is to refuse to put out any insulin receptors, the phenomenon of insulin resistance.

What happens when a fat cell refuses to listen to insulin's storage message? Well, it allows hormone-sensitive lipase freedom from insulin's restraint. This results in an outpouring of the energy set aside, over many years, for a rainy day which never came. Non esterified fatty acids (NEFA) in the plasma increase rapidly. NEFA are the high energy rival to glucose for cell power supply. The control of NEFA flow is at their release point (fat cells), not their uptake point. When the adipocytes thumb their nose at insulin, they release a flood of inappropriate energy which is taken up by just about every cell that can remotely use NEFA for fuel.

Packing NEFA in to cells beyond their wildest possible needs means that they have no logical use for glucose. Muscle tissue is the primary "sink" for glucose. Muscles love NEFA. Once they are packed with NEFA why should they accept glucose? They just say NO by becoming insulin resistant too. If there is no where for glucose to go, it builds up in the bloodstream (especially if you live on bagels and waffles) and you get the label of type 2 diabetes.

Much of this I worked out by slogging sentence by sentence through Dr Raz's article here. He gets hopelessly lost in ideas on treatment. His basic idea is that because the problem is one of excessive fat storage (it is) and the stored fat is from dietary fat (it is) then the correct approach is to reduce dietary fat (WRONG). The correct approach is to reduce the hormone which is causing the excess storage. That is insulin. The spectacular success of low carbohydrate diets for management of type 2 diabetes clearly show this is the way to go.

As soon as you drop insulin levels the fat cells, no longer over bombarded with the message to hyper-inflate themselves, start to listen to the voice of reason. Basal insulin can inhibit lipolysis to levels appropriate for energy needs of the body. Blood glucose normalises because the bagels are in the bin, not your bloodstream. Lipolysis without carbohydrate overload allows ketosis which controls appetite.

I also had some fun with this paper, which gets the prize for worst title ever on a diabetes paper.

Please Pass the Chips: Genomic Insights into Obesity and Diabetes

I guess that the chips are bits of information. I couldn't find anything in the paper about what I would call chips. It is an American paper so I guess they would have used the term French Fries if they had really meant chips... Still, an appalling suggestion for a diabetic diet.

Anyway. The paper has some interesting points. Ignore all the garbage about micro arrays and gene switching etc etc. Throwing money at a problem does not always mean that you understand it.

No, they discuss the lipodystrophies, spontaneous in humans and engineered in lab animals. The basic message is:

Total absence of fat cells equals severe type 2 diabetes, in an organism without any fat at all.

No fat cells means nothing to listen to insulin, so nowhere to store energy. The lack of adipocytes is the equivalent of being born with 100% ineffective adipocytes. If you have no storage space you have to shove your dietary fat in to whatever tissue will take it. Once the tissue, particularly muscle, has a generous supply of fat it will, as above, say no to glucose.

So, as I see it, type 2 diabetes is a condition where adipose tissue cannot accept energy, either through years of hyperinsulinaemia or because it never actually formed. The end result in both cases is muscle fatty acid build up to a level which causes glucose refusal.

You then pee the glucose down the loo. Or eat LC and fix your problem. If you have a lipodystrophy I'm not sure how effective LC eating would be, but it certainly works for standard type 2s.



Wifezilla said...

Great post!

You took a very complex issue and distilled it down quite nicely :D

Peter said...

Thanks wifezilla,

I still feel there is a lot more to it than this. What programs fat cells to give up growing, and why simple with loss, shrinking the fat cells, doesn't actually CURE T2 diabetes? It means that there probably really is gene switching happening, which is not easy or quick to reverse... Probably some of it may be prenatal or neonatal. But I hope the basic idea here could be useful to help someone avoid "breaking" their fat cells while they have the chance to control their blood insulin levels with a LC diet.


trinkwasser said...

They should study one side of my family. Really. We are plagued with metabolic syndrome and Type 2 but the symptoms are worse in skinny people. My overweight aunt had the blood pressure of a thirty year old in her eighties while I was the exact opposite.

Somehow we seem to turn the excess carbs into lipids, then fail to stash them in fat cells so they continue to rattle around in the blood. Not eating the carbs seems to work pretty well at forestalling the process. I wish they'd told me that 50 years ago.

Peter said...

They knew 50 years ago!

Kenneth said...

Hi Peter,

I am an admirer of Gary Taubes and his work, and he seems to be an admirer of you and yours.

He penned a fairly recent (17 July, 2009) in Science Magazine entitled "Prosperity's Plague". The subject of the article is essentially the same as that of your post, focusing on insulin resistance and the associated lipid metabolism (i.e. tissue lipotoxicity and inflammation). He interviewed and quoted many, and probably most, of the major figures in the associated research.

If you (and other readers) haven't already read this article you may be quite interested. I have an electronic copy from the library, but I can't (legally) supply the text unfortunately.

I recently found that I was borderline pre-diabetic, with isolated fasting hyperglycemia, and I have adhered to a pretty strict low-carb diet for the last 16 months or so. My interest in the low-carb diet preceded my awareness of the hyperglycemia by a year or so.

Holger Behrens said...

Hi Peter, 

I was lucky. Yours was one of the first material websites I found in my feverish research for my freshly diagnosed diabetes T2. ( FBG of 7.2, high triglycerides, high cholesterol ... Metabolic syndrome.)

Spending hours of researching, analyzing, hypothesizing, etc. I also concluded the same as your post. I also believe that high BG manifests when the body does not want to/ cannot store this energy as fat in adipose tissue. This could be due to many different reasons for people due to genetic and other variations. 

As we all know; that is not the conclusive answer. This is a complex syndrome... My quest continues...:).