Arteries

(This is a work in progress.  When I'm done, I'll remove this paragraph.)

My wife has asked some very interesting questions over time.  Think of the following topics as being preceded by "If the reduced blood flow theory is correct, that how do you account for..."

Growth
As a child grows to become an adult, he or she increases size.  His or her chest expands.  Why don't all children, then, get diabetes?  Wouldn't this normal expansion of the chest cause the same problem that visceral fat expanding the chest causes in the chest?  --  Well visceral fat may actually press on arteries as well, but if we just go with the stomach yanked to one side and duodenum yanked to the other, this is a valid question.  The answer, I propose, is that the arteries in children also grow, but that the adult body loses the ability to grow.  Therefore, an increase in chest diameter for an adult is a big problem, but it is not for a child.

• I'd like to propose a possible explanation for juvenile onset diabetes.  In rare cases, a child experiences a growth spurt and suddenly gets diabetes.  Perhaps the arteries of such children have been forced into adult, non-growing mode before the rest of their bodies are forced into that mode, and they suffer reduced blood flow to the pancreas as a result.  (It could also have something to do with congenitally short ligament of treitz.)  -- This is just a theory, folks.  

How Does Blood Get To Fat Cells?

Turns out that stem cells still exist in the body and that new miniature arteries needed to feed fat cells can grow even in adults.  It's just the larger, preexisting arteries that can no longer grow.

How Can Arteries Work After Being Nearly Collapsed?

If you tie a string to a small tree's top, and pull the string over to the side, the tree will bend.  If you leave the tree like that for long enough, when you remove the string, the tree will stay bent.  This is one of the techniques of bonsai.  So why don't arteries stay tweaked if they are being pulled on, even if the pressure is released?  There are two answers:  First, those arteries don't grow into position.  They're done growing.

So why don't arteries just stay collapsed, as a pipe stays collapsed if you dent it?  Arteries have muscle cell walls.  That's why you get a pulse, because the muscle cells fire off and help the blood flow.  These muscle cells are resilient.  There is something called the "elastic limit."  If you do not force a piece of metal to its elastic limit, you can bend it many times and it will spring back to where it was.  Metal that is used in such a manner is, in fact, called a spring.  There are leaf springs and coiled springs.  I propose that the arteries leading to the B cells in the pancreas are forced out of shape, but they are not stressed to their elastic limits, and therefore they spring back to where they need to be when the pressure is released.

Two Plausible Theories

I'm going to cobble these thoughts together over the course of days.  When I'm done, I'll remove this paragraph.  Please bear with me.

Gestational Diabetes

I read an article that said they had discovered the reason for gestational diabetes in mice.  If mommy mouse got sufficient serotonin during her first trimester, then she developed an increase in B cells.  If she did not, then when the baby mice got big during the third trimester, the extra demand for insulin forced her to develop gestational diabetes.  Once the babies were delivered, her need for insulin returned to normal and she no longer had diabetes.

The Role of Sugar

Mark Bittman wrote an editorial in the New York Times relating the work of a group of scientists who had done statistical research on sugar and diabetes.  They found a correlation between sugar-of-any-kind (corn syrup or just plain sugar) and diabetes.  The incidence of diabetes rose within a data group (country) in direct proportion to per capita sugar intake.  This was the same kind of correlation used by scientists to show the link between cigarette smoking and lung cancer.

Another article I found explains that sugar is processed slightly differently in the body than other carbohydrates.  It turns to the kind of fat that produces triglycerides.  The presence of triglycerides in the blood causes muscle cells to become more insulin resistant.

Correlating This Gestational Theory With This Sugar Theory

Clearly, these two theories don't correlate.  In fact, (and I have to look this up), doesn't eating sugar produce serotonin?  Doesn't it give you a serotonin high?  (I think that eating fat produces dopamine and sugar or carbs in general serotonin, but I have to reconfirm - post a reply if you have any thoughts).

Do the theories have to correlate?  Do Gestational Diabetes and regular Type 2 Diabetes have to be caused by the same thing in all cases?  No. It could be like "leg pain," which could be caused by sore muscles, a bullet, a nerve in the back being pinched, cancer, etc.  However, the Reduced Blood Flow Theory could be the holy grail of diabetes, something that isn't obvious that actually does explain both gestational and regular Type 2 Diabetes.

How The REDUCED BLOOD FLOW THEORY Could Still Be True

Gestational:  Just because gestational diabetes can be caused in mice by messing with serotonin in the first trimester doesn't mean that that is actually what is causing it in mice or humans.  It could be that most mice and human mothers do increase their B cells during the first trimester, and a reduced blood flow during their third trimesters prevents an insulin surge.  It could be there is a combination of these factors.  The "you need an increase in B cells" theory does not explain why some women retain their diabetes after delivering the baby.  The Decreased Blood Flow Theory does explain it:  the arteries remain tweaked, most likely because of added visceral fat.

Sugar:  More than one factor is going on in diabetes.  Since the factors are related, it is an oversimplification to break the phenomenon down into distinct, separate factors.  However, for the sake of understanding, I am going to do just that for now.  In Type 2 Diabetes, there's what's happening up at the muscles, and there's what's happening down at the pancreas.  There's insulin resistance and there's insulin.  Clearly, all this information about how bad sugar is, and what triglycerides do, relates to why muscles become insulin resistant, but says nothing about pancreas.

Sugar(2):  It could well be that both sugar and reduced blood flow conspire to cause diabetes.  Sugar use makes you need more insulin in a timely manner, and reduced blood flow insures that you're not going to get it.  The sugar use theory does not explain why diabetics lack an insulin surge, except in the leprechaun sense.  You could say, "Somehow the triglycerides prevent an insulin surge as well.  We're still working on the how."  Also, the sugar use theory leaves unanswered why bypass surgeries relieve diabetes.  The Reduced Blood Flow Theory explains why bypass surgery relieves diabetes.

Sugar(3):  The Reduced Blood Flow Theory is a theory that entirely places the development of diabetes down at the pancreas.  It is my idea that any muscle cell in any body would develop insulin resistance given an environment of high blood sugar, or an environment of high triglycerides.  I propose that muscle cells would go back to normal if that environment was the only factor.  Unfortunately, people with diabetes can eat healthily for days, then eat normally and have high blood sugar/diabetes.  I propose that the reason they do not go back to truly normal is a reduced blood flow, not a continuation of triglyceride being released into the blood from their fat cells.  I propose that if triglyceride from the fat cells was causing diabetes, bypass patients would continue to have diabetes until they lost fat, not immediately after surgery.

Sugar(4):  Epedimiological (I have to look up this word) studies, such as the one that shows heart disease rises with smoking, are very useful.  Over time, however, a cause for the effect ought to become clear.  With smoking what we have learned is that smoke enters the blood stream, causes inflammation in the arterial walls, and the inflammation is fought off by the body in a way that produces swelling.  The swelling diminishes or shuts off blood flow and all kinds of problems ensue from that:  heart problems, strokes, legs not getting enough blood.  To date, the step by step link between sugar intake and diabetes has been hinted at on the insulin resistance end, but remains completely unproved on the insulin side of the equation.  Perhaps it will eventually come to light what the link is.  Perhaps the link doesn't exist.

Funny Explanation

This blog is getting unwieldy.  Please refer to my new blog for a coherent presentation.  I will keep this blog for interesting sideshows such as this one.

Overview of This Entry
I will present what somebody said about why duodenal switch resolves diabetes.  I will then mock that.  I will thereafter explain more academically why I think the explanation is either wrong or severely limited, and what it would take to prove it was right.

Someone Else's Explanation of Why Duodenal Switch Works

This article attempts to explain the diabetes reversal effect of duodenal bypass surgery in the following way.  Dr. John Husted is quoted.

(undigested food enters the non-bypassed part of the stomach and therefore) ...secretion of GLP-1 is enhanced. Enteroglucogan (GLP-1) has the effect of suppressing the secretion of insulin in response to a carbohydrate meal, resulting in a lesser amount of ingested carbohydrates being converted to body fat.

The portion of intestine that is bypassed holds an important role as well. Enterogastrone is a hormone that is secreted by the upstream small intestine when food passes through it. This hormone has the effect of converting food to fat. When the upstream portion of the intestine is bypassed - as is the case with Duodenal Switch - enterogastrone secretion is suppressed. The effect of this bypass is that the patient's body after Duodenal Switch has less of a tendency to convert food to fat. 

Not quoting Dr. Husted now, the article then states:  "The metabolic effect of Duodenal Switch surgery... explains why there is a 99% cure rate for type 2 diabetes following the Duodenal Switch procedure."

I Mock This Explanation

Are you telling me that an increase in something that suppresses the secretion of insulin can help cure diabetes?  What about the insulin spike needed to shut down the liver and get the whole business of muscles absorbing gluocogan going?  Did that just go out the window?  You're saying that what diabetics have needed all along was a way to suppress insulin release, not increase it?  Are you mad?

I have read that one of the horrible realities of diabetes is that muscle requires insulin to absorb glucogan, but fat doesn't.  Therefore, when there is insulin resistance in the muscle cells, fat cells just gobble up a lot of the glucogan - they 'convert food to fat.'  Now you're telling me that that isn't exactly true, that fat cells need insulin to ingest glucogan just as muscle cells do.  Ok, fine, whatever.  So now, you're telling me that duodenal switch surgery decreases insulin (thus stopping fat cells from absorbing glucogan as quickly as they would) and it also decreases the fat cells' ability to absorb food by suppressing enterogastrone secretion.  By two ways fat cells just aren't going to take as much of the glucogan that is out there as they would otherwise.  Fine.  How exactly does that help the muscle cells?  Wouldn't that mean that there'd be even more glucose in the blood even longer, because fat cells weren't absorbing glucogan, and because there'd be less insulin for the muscle cells?  Wouldn't that, in the short term, create even greater hyperglycemia, and all the damage resulting therefrom?

Keep in mind that duodenal switch surgery resolves diabetes nearly immediately - before fat is lost.  The longterm goal of fat reduction, albeit noble, ought not to come into consideration when trying to understand why duodenal switch bypass resolves diabetes in the near term.  Dr. Husted's explanation might help explain longterm fat decrease, but what's happening in the blood, in the muscle and fat, before fat is lost is the more relevant concern.  So, really, after all the jargon slinging, absolutely nothing is proposed to explain the diabetes reversal.  Some explanation!

A Slightly More Academic Response

O.k, o.k., I'll try to be calm.  Clearly what we are presented with is a great, mysterious truth:  duodenal switch surgery resolves diabetes.  It is wonderful.  But why?  Well, let's look at what the bypassed parts do.  That's a good place to start.  Bypassed Part #1 absorbs proteins and sugars.  Bypassed Part #2 makes enterogastrone.  So, maybe the presence of more proteins and sugars, and less enterogastrone, explains diabetes reversal.  But does it?  Where are the follow-up experiments that prove it?  Let's say you bypass part of the stomach in a diabetic rat without bypassing the duodenum - just the stomach.  Does that resolve diabetes?  

I think that the part of the "upstream small intestine" that releases enterogastrone is not the duodenum, but the jejunum.  Let's say you bypass part of the jejunum after the duodenum, without bypassing either the stomach or duodenum.  Does that resolve diabetes?  Show me!

Perhaps I am wrong.  Perhaps enhanced enteroglucogan (GLP-1) and decreased enterogastrone, through a series of as-yet unexplained steps, resolve diabetes.  Until that is conclusively shown, however, I'm sticking with the Reduced Blood Flow Theory.

Aloha

I am Matthew Kenney. My theory is that pressure from fat or baby causes the pancreas to malfunction and diabetes.

Please forward this blog. Eventually a researcher will be moved by it to do experiments that test the theory.

Read this blog top to bottom by clicking on "Blog Archive" headings on the left, or by clicking on "older posts" at the bottom.

Challenge: Prove me wrong (and post it as a comment on this blog)! Also, just "comment" to say hello.  It's good to know somebody's interested.

Anatomy of a Strangle

Pressure Drill Down

I have been challenged. A friendly acquaintance told me he doubted that the pancreas would be pressured by fat because the skin is so malleable. He was apparently unaware that visceral fat is not between muscle and skin, but rather between internal organs and abdominal muscles. He was talking about guys who had to be moved on pallets, though, so he was talking about visceral fat. His point would have been that abdominal muscles are malleable, too.

I was thinking that abdominal muscles may expand, but they do provide more inward pressure than skin. Secondly, the rib cage is bone and cartilage. It surely has an expansionary limit. So my first drill down was to locate the duodenum / pancreas vis a vis the rib cage. Check out this absolutely gorgeous graphic of the stomach and duodenum in a chest. The stomach is mostly in the rib cage. The duodenum is right where the rib cage ends. It seems that the pressure theory is still on.

Next I went looking for what affect a fetus has on the internal organs, whether it puts pressure on them. All I could find was a doctor saying that it's like putting a meatball in spaghetti; the spaghetti just slithers out of the way. I was thinking that this only applied if there was room in the pot for the meatball. What if the pot was full and you put in a huge meatball, then shoved the lid back on? Wouldn't that lid put pressure on the whole works? ... But if we just go with the meatball analogy, the pressure theory looks less likely. (Although, wait a minute, it says here the internal organs are under pressure in pregnancy.)

Then I found this quote regarding visceral fat and its effects on internal organs, "Many organs, including the stomach are forced into abnormal positions and sizes." Pressure is put on the lungs as well. I was back in the game. (Although I am not proposing that the stomach is extremely out of whack in diabetics, the stomach can and does go far out of position.)

Along the way, I decided to research just how it is the duodenum is attached to the greater structure of the body. I hit pay dirt. The duodenum is attached to the posterior abdominal wall in 3 places. It is also attached via a suspensory ligament, the ligament of treitz, near where it attaches to the jejunem. I infer that every place the duodenum changes angles, it is attached somewhere. The duodenum is commonly referred to as having a "C" shape. I propose that because of this suspensory ligament, it has a "G" shape.

What this means to the pressure theory is that the pressure does not work via compression, but rather via strangulation. The stomach is shoved over, the suspensory ligament stays put, the noose tightens. Because most of the duodenum is attached to the posterior abdominal wall, and the ligament of treitz is not, I propose that the duodenum twists as well as cinches. I bet you the arteries between the duodenum and pancreas love that.

The abdominal attachments of the duodenum explain explain the "sproing" that occurs when the duodenum is cut free from the stomach. It also provides somewhat of a dilemma if the pressure theory is correct and diabetes can be resolved by inserting a section of pipe right at the stomach/duodenum juncture, after the valve, of course. What happens if the patient, free now (we hope) from diabetes, loses weight? The stomach is going to want to move back over to its previous position near the pancreas. What problems will arise from that? Will the artificial section of duodenum kink and lodge food? The researchers will have to keep a close eye on that.

The GUTS Of The Pressure Theory

Here's the gist of it. After a person who does not have diabetes eats, he or she experiences a surge of insulin. That insulin stops the liver from releasing glucogen and turns it into create-glycogen-mode. The insulin turns on muscle cells to accept glucogen. If a person has diabetes, there is no surge. Some insulin comes out, but not enough to handle the bounty of glucogen coming from the food, and not enough to turn the liver off. The glucogen that the liver continues to produce compounds matters. Soon there is more glucogen in the system than the system can handle, even though insulin continues to be produced, slowly, by the pancreas. So the problem is, according to my theory, that the diabetic lacks an insulin surge.

The most likely culprit for the lack of insulin surge is a decreased blood flow to the pancreas. It just so happens that the same arteries that feed the first part of the small intestine (the duodenum) also feed the pancreas. They are "co" arteries: the superior and inferior pancreaticoduodenal arteries. It is my theory that branches of these arteries become pinched when fat or baby push on the stomach, yanking and torquing the duodenum. If that pressure is relieved by losing weight and keeping it off, by delivering the baby, or by surgery (Dr. Roubino showed that surgery resolves diabetes, though he does not propose pressure as culprit), then blood flows again, the insulin surge resumes, and diabetes is relieved.

If you read the entire essay, you will see references to articles and websites, references to illustrations. I propose experiments that will confirm or deny the theory. I also defend the theory against other theories.

Who Stops Having Diabetes - Common Denominator

• (A) Women with fat hips tend not to get diabetes. Women with fat bellies do. Men with fat bellies do (few men gain weight on the hips).

• (B) People with stomach bypass surgery (Roux en Y, RYGB), which bypasses both most of the stomach and the first part of the small intestine, who had diabetes, lose their diabetes within a week or two after surgery - before they lose significant weight. (As reported by Leslie Stahl on 60 Minutes)

• (C) People with bariatric banding (putting a band around the stomach) get diabetes reversal after they lose weight. (Large article in NY Times said this. Also here.)

• (D) Mice with diabetes lose their diabetes when the first part of the small intestine alone is bypassed (bilio pancreatic diversion – BPD). Their stomachs are still in the food path. (60 Minutes)

• (E) Pregnant women sometimes get diabetes. After they deliver the baby, these diabetic pregnant women oftentimes revert to not having diabetes. (Wikipedia)

...

The common denominator is when there is pressure on the first part of the small intestine, and hence the pancreas, due to abdominal fat or baby, diabetes comes about. Fat all by itself (A) does not cause diabetes. If the pressure is removed surgically (B, D), by losing weight (C), or by delivering the baby (E), then diabetes is reversed.  (Note:  this pressure from fat or fat plus baby need not be applied directly.  The fat might move the stomach, which would cause the duodenum to tighten near the ligament of treitz, which would pull and twist the arteries, and thus strangle the blood flow to the pancreas.  See my "Anatomy of a Strangle" post.)