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.)

Blood Flow To The Pancreas

Analogy: Consider the case of a poor gold processing plant (the pancreas). It has tremendous capacity, works perfectly, and at a magically high rate of speed. In fact, the plant has multiple crushers and smelters (B Cells) inside it. The gold processing plant is fed by trucks bearing ore (glucogan in the blood). The trucks run on an 6-lane one-way highway (artery). Sometimes there are only a few trucks on the road, sometimes hundreds.

One day, a landslide (partial arterial blockage due to arterial twist perhaps) shuts down 5 lanes on the highway. Now, despite the ability of the gold processing plant to refine gold at a high rate of speed, its output is severely limited because it can only refine at the rate the gold ore comes in. At times of the day when traffic is light, the gold processing plant kicks out gold at the same rate as before. When there are a lot of trucks on the road, production only increases a little bit because the amount of ore coming in is limited by the bottleneck in the road.

The B cells in the Islets of Langerhans in the Pancreas make insulin from nutrients in the blood. I'd like to say, "from glucogan" but I've lost the quote. All I can find now is that they make insulin from pro-insulin, and pro-insulin from pre-pro-insulin (his favorite protein). Pre-pro-insulin has the same elements in it as glucogan. But whatever, something traveling in the blood is used by the pancreas to make insulin. Note well: the B cells not only sense an increased level of glucogan in the blood and make insulin, which they would presumably do whether the blood supply was diminished or not, they make insulin from something in the blood. If there is less blood coming in, and hence less raw material available, less insulin can be made in a given time period. A strangled pancreas makes this likely.

(The pressure put on the pancreas need not be directly due to compression. It need not be that fat pushes on the duodenum and the duodenum crushes the pancreas. It may be more like one end of a string is tied to the stomach, the other end is tied to the ligament of treitz, and fat pushes the stomach over which tightens the loop. Perhaps the ligament of treitz plays no roll.  Perhaps the fact the duodenum is attached to the right abdominal wall and the stomach attached to the left abdominal wall is what's doing it.  As the two stretch apart due to fat increasing the space (like an inflating balloon), the superior pancreaticoduodenal artery gets yanked and twisted near where the stomach intersects the duodenum.  See my "Anatomy of a Strangle" entry, above.)

Analogy

There is an organ in the body that can suffer from a degradation of function but still appear normal. I speak, of course, about the penis. If you have erectile dysfunctionality, this can be caused by a decreased blood flow into the penis, and an increased blood flow out of the penis. Drugs like Viagra act by dilating the blood vessels leading out of the penis, allowing the penis to stay erect even if there is a less than optimal blood flow going into it. The kinking or partial blockage of the artery that leads to the penis, causing the decreased blood flow into it, is thought to occur in the pelvic region somewhere quite far away from the penis. It's not the penis's fault. An examination of the penis itself could not tell you conclusively if its owner was erectiley dysfunctional. The penis appears to be healthy and performs one of its functions, urination, well enough; it just doesn't work optimally for sex.

My theory is quite simple: physical pressure on the pancreas, or on something that leads to or out of the pancreas (nerves, blood vessels), is causing the pancreas to malfunction, or to function slowly, without actually harming the pancreas. Should the circumstance that is preventing optimal pancreatic functioning be relieved, the pancreas will again function normally and Type 2 Diabetes will go away. That is my theory.