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)

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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.)

Foregut Hypothesis

Theory (Not Mine):

Bypassing the Duodenum Disallows Anti-incretins Into The System. Without Those Nasty Anti-incretins, Insulin Goes Back To Normal, Health Is Restored, And Cinderella Lived Happily Ever After (From the 2004 article in The Endocrine Society's Journal of Clinical Endocrinology & Metabolism, "Gastric Bypass for Obesity: Mechanisms of Weight Loss and Diabetes Resolution: http://jcem.endojournals.org/cgi/content/full/89/6/2608):

"The GJB (gastric jejunal bypass) resulted in better glycemic control than did either rosiglitazone therapy or substantial weight loss from food restriction. The implication of these findings is that bypss of the intestinal foregut (e.g. as accomplished by RYGB and BPD) can ameliorate type 2 DM independently of weight loss, through mechanisms that remain unclear. The authors hypothesize alternation in gut hormones, but candidate molecules are not obvious."

Oh Yeah?

Savor the beauty of this: "mechanisms that remain unclear…candidate molecules are not obvious." Give them credit for humility, honesty. Actually this is a wonderful thing… But look at the mountain they have to climb here. They have to find a molecule or two that they did not know about before, after studying the endocrine system for decades, and these molecules have to be so powerful that they cause diabetes. They have to show not only what the molecule(s) are but what they do – to the liver, the pancreas, the muscle cells.

We know that the duodenum only releases these putative mysterious chemicals when food is present, because the duodenum/bile duct/pancreatic duct, although cut off from food (chyme), is allowed to drain further down into the small intestine in these bypass operations. And the duodenum is healthy, so far as we know, so it's improbable that it's doing something that it wasn't designed to do. It almost defies nature. Why would the mammals evolve in such a way that, in the course of its natural functioning, a part of every mammal's intestines could cause diabetes? Perhaps there is a positive effect from these chemicals. Look at ghrelin. It impedes the action of insulin, but it has a positive effect: it makes you hungry. They've already ruled out ghrelin, though. So, what positive effect could these awful unknown molecules have that would allow the process of natural selection to retain them? (And if you don't believe in evolution, it's even worse. What was God thinking?) Why is food processed satisfactorily when the duodenum is bypassed, if there is a positive effect to these unknown hormones? … Or, perhaps these putative chemicals don't exist and something else is causing diabetes?

Actually, the theory of the mysterious anti-incretins is the only one that, like my theory of pressure, goes across all Type 2 diabetic categories. That is, although I have not seen wherein the proponents of the anti-incretins out of the duodenum theory say so, this theory could apply to all diabetic categories. It can only apply to them, though, if you factor in pressure. Pressure causes the duodenum to spectacularly malfunction and release an unknown hormone that in some mysterious way causes diabetes. The theory would be that once either the duodenum is bypassed or pressure is released by weight loss or delivering the baby, the duodenum no longer produces such hormones, at least not in sufficient quantity, and everything goes back to swank.