Monday, February 11, 2013

Poor man’s cure for diabetes II

Andre Willers

11 Feb 2013

Synopsis :

A pulsed cure is possible .

Discussion :

1.I was horrified to see the costs of gastric bypass (excuse me , bariatric surgery) as the good doctors get onto the bandwagon of curing something they long touted as incurable , but manageable .

2. See Appendix I on how it works .

3.Basically , the peristalsis of the descending duodenum has to be inhibited . But then you have to restart it .

4.We can inhibit that with Imodium or alcohol , or surgically bypassing the descending duodenum .

5.Why I could not try it : the restart is not that simple .

Until I found this :

"There is also evidence that 'sham (imitated) feeding', such as chewing gum, may stimulate gastrointestinal motility in the post-operative period.[9]"

6.This restarts the intestinal contraption .

7. The chewing gum should have some sugar , but the main action is the chewing . The mouth chewing sends peptide signals to the gastric muscle walls to get the lead out .

8. This begs the question whether the whole Imodium/alcohol block is necessary .

9 . A continuous stream of chewing and buccal sugar from the signals from the mouth would habituate descending duodenal systems into a stand-down mode . In other words , a cure for diabetes II . Easily tested .

10. If the chewing gum gets tasteless, just sprinkle it with your favourite flavoured sugar .(A big market) . The sugar and chewing is vital .

11. Santa Anna of Alamo fame also gets into it .

" Instead, Adams helped to found the chewing gum industry with a product that he called "Chiclets".[17]"

12. Can it be that simple ?

Try it and see .

Chewbacca would know .



Appendix I

A Cure for Diabetes

Andre Willers

31 May 2012

Synopsis :

The control-system short-circuit that causes diabetes can be interrupted in humans by a simple surgical procedure . This cures diabetes , insulin resistance and high blood pressure . We try to trace why .

Discussion :

1.Read Appendix I . This is a succinct summation of the state–of-play as at May 2012 .

2.Why should bypassing the duodenum have such drastic effects ?

Because the system outsmarted itself . Too many vital feedback loops are being controlled by the same chemicals . (A similar effect is observed in brain-stress and body-stress systems) . Inappropriate responses are triggered . The system is unstable .

2.1Peristaltic action in the duodenum is accompanied by vasoactive intestinal peptide (VIP) release, a marker for inhibitory neurotransmitter release . See Appendix III . (Note the effect on blood pressure )

But this and PHI release (see Appendix II) affect the Prolactin system ,(see ) which is tied to at least 300 other biochemical processes , as well as the prion system (see "Prions and the Amygdala" May 2012) .

This whole mess is an unstable system , that can and does go wrong in a large number of ways . And the original trigger can be impossible to trace .

2.2To add insult to injury , the original trigger can cause an amygdala reaction : ie a memory remains in the system , and there few , if any , "OFF" switches . Hence nasties like insulin resistance . There are doubtlessly many more . Amygdala's are notoriously stupid . It is the function of other systems to reprogram them .

See Appendix IV for the ratchet-effect on bloodpressure .

2.3Milk and milk-products can be identified as one of the factors that should cause the system to destabilise .Lactogen breakdown products interfere with some of the feedback loops in the energy metabolism . The result will be idiosyncratic according to individual metabolism , but insulin resistance will ratchet up . (A calf-protection system short-circuits)

What to do ?

Surgery seems a bit drastic . All we want to do is inhibit peristalsis in the duodenum . Food can be massaged through to the jejenum . I can't find a drug that does this selectively , but I am sure there are some .

But in the meantime we are stuck with something like Loperamide (Imodium) . It is like stopping an enormous factory to fix some small problem at the front-end of the production lines .

The following is not medical advice , and you proceed at your own peril .

Use the pulse principle .

1.Fast until the duodenum is empty , (+-6 hours) . No water .

2.Take Loperimide (Imodium) .. This stops peristalsis and release of neuro-markers .

3.Exercise (walking , jogging – this moves food without peristalsis ) . I have no idea what effect this will have on digestion . But no lying in bed allowed .

4.Then eat and drink mildly on low-carb foods . Appetite will be sharply decreased as alternate demand pathways kick in (Cf Atkins , etc) . Drink when thirsty (cf Noakes) . No milk products of any kind .Verboten

5. How often ? I noticed when writing this that this regimen is remarkably similar to religious regimens like Ramadan , Jewish , Christian , Hindu and Buddhist fasts . Two weeks to a month per year seems adequate . This should reprogram some of the systems to at least a modicum of initial states .

6.Monitor blood glucose about 2 hours after eating .

Interesting Asides :

1.Excessive alcohol intake paralyses the pylorus valve between the stomach and the duodenum . The same effect as fasting , in that food does not enter the duodenum to trigger peristalsis . Typically bloated feeling , with big "beer bellies" . Since alcohol is a product of carbohydrates , this is a fascinating adaptation to high carbohydrate intake .

To put it another way , agricultural farming only took off because periodic alcoholic binges enabled re-normalization of glycemic systems . As this dwindled , so diabetes increased .

2.Milk and Cheese : as use of these increased , systems increasingly crashed in the Prolactin areas . Energy metabolisms became unstable , and auto-immune diseases increased .And you can't reinstate the original system simply by stopping milk products : amygdala's have to be reprogrammed .

These are but the a sketch of the bare bones of complex mechanism . But at least some indication of where to go or where not to go .

But I refuse to countenance a system that does not allow toasted cheese sandwiches .

There must be a better way .

Andre .


Appendix I

Cristina Iaboni had the dubious distinction of being not quite obese enough. For all the pounds on her 5'5" frame, she did not meet the criteria for bariatric surgery to help control her type 2 diabetes.

Yet six years of medications and attempts at healthy living had failed to rein in her blood glucose, leaving Iaboni terrified that she was on course to have her kidneys fail "and my feet cut off" -- common consequences of uncontrolled diabetes.

Then the 45-year-old Connecticut wife, mother of two and head of human resources for a Fortune 500 company, lucked out. In 2009 she met with Dr Francisco Rubino of Weill Cornell Medical Center in New York. He had just received approval to study experimental surgery on diabetics with a relatively lean weight-to-height ratio, or body-mass index (BMI). Iaboni was among his first subjects.

Three years on, she has dropped 50 pounds to reach a healthy 145 and has normal blood pressure without medication. That isn't too surprising: Weight loss is the purpose of bariatric surgery and often reduces blood pressure. More remarkable, Iaboni no longer has diabetes.

She is not the first patient with diabetes, which can be triggered by obesity, to be cured by weight-loss surgery. But she is a rarity for having it with a BMI well below 35 and over. That's the level at which the American Diabetes Association says surgery "may be considered" and that Medicare and some private insurers cover. And Iaboni's diabetes disappeared months before she shed much weight.

Her experience has raised an intriguing possibility: that some forms of bariatric surgery treat diabetes not by making patients shed pounds. Instead, by rerouting part of the digestive system, they change what signals the gut sends to the brain and the brain sends to the liver, altering the underlying causes of diabetes.

If proven, bariatric surgery may help people with type 2 diabetes who are less obese, overweight or even of healthy weight. And it might be effective against the currently incurable type 1, or "juvenile," diabetes, too.

"Every textbook says that diabetes is chronic, irreversible, and progressive," said Rubino. "But we have thousands of patients who once had diabetes and now do not."


Bariatric surgeons have long been prone to declaring victory against diabetes way too soon, before large-scale, long-term data proved their case. "The evidence for the success of bariatric surgery in patients with a BMI below 35 is not very strong," said Leonid Poretsky, director of the Friedman Diabetes Institute at Beth Israel Medical Center in New York City. "Most of the studies have been very small and not well controlled."

The American Diabetes Association rates the evidence that bariatric surgery can cure diabetes as "E," the lowest of four grades. It calls data on patients with a BMI below 35 "insufficient," and says the procedure cannot be recommended except as part of research.

The immediate risks of bariatric surgery are small -- a 0.3 per cent chance of dying within 30 days of the procedure. But a small fraction of patients develop infections, leaking from the stomach into the abdominal cavity, or gallstones, and it can cause nutritional deficiencies: There is less intestine to absorb vitamins and minerals, raising the possibility of osteoporosis and anemia.

Despite these red flags, the surgical option is attracting intense interest because the quest to cure diabetes has become almost desperate. In type-1 diabetes, the pancreas does not produce enough insulin, a hormone that moves the glucose in food into cells. In type 2 diabetes, cells become resistant to insulin. In either case, glucose remains in the blood, damaging cells and blood vessels, sometimes severely enough to cause blindness, kidney failure, or gangrene requiring foot or limb amputations.

In 2010, 8.3 per cent of adults worldwide had type 2 diabetes (11.3 per cent did in the United States), resulting in direct medical costs of $376 billion ($116 billion in the United States). By 2030, the global incidence is projected to rise to 9.9 per cent, partly because of the rising obesity rate, with costs reaching $490 billion.

The possibility that bariatric surgery could cure diabetes emerged about a decade ago. A long-term study of thousands of patients in Sweden reported in 2004 that both gastric bypass and banding improved diabetes in many subjects. A 2008 study of 55 obese patients found that 73 per cent of those who underwent gastric banding saw their diabetes disappear after two years, compared to 13 per cent undergoing standard medical treatment such as medication, diet and exercise.

In 2009, surgeons at the University of Minnesota analyzed 621 mostly small studies of bariatric surgery in obese, diabetic patients. Their conclusion, reported in the American Journal of Medicine: 78 per cent no longer needed medication to control their blood sugar. They'd been cured. Lap banding had the worst results, worsening diabetes in some patients.

But most patients in these studies were obese, many morbidly so. (The average BMI was 48.) The improvement in glucose control could therefore be credited to the patients' weight loss, which averaged 85 pounds.


Rubino had a hunch that something else was at work. As a research fellow in diabetes at Mount Sinai Hospital in New York in 1999, he was reviewing the medical literature one day for guidance on how to best perform bariatric surgery on a man with a BMI of 80. He found papers from the 1950s and earlier reporting that surgery for peptic ulcers had cured diabetes.

Ulcer surgery removes a portion of the stomach and reconstructs a connection to the intestine, much as gastric bypass does. Few diabetes experts had noticed the old papers; they were published in surgery journals, which endocrinologists seldom read.

His serendipitous find led Rubino to other papers describing operations on the digestive tract that cured diabetes, something that, according to medical textbooks, was unthinkable.

"Within two weeks of surgery and sometimes sooner, these patients were off their insulin, off their diabetes drugs, and with normal blood glucose levels," said Rubino. "That was too fast to explain by weight loss."

Yet that's how experts explained bariatric surgery's effect on diabetes, especially as the procedure took hold in the 1990s. Few surgeons focused on how quickly the condition disappeared, said Rubino, "or they speculated that patients weren't eating much after the surgery, and that's what cured their diabetes."

He began pursuing the idea that surgery might improve diabetes directly, rather than through weight loss. "I was ignorant of diabetes, so I wasn't burdened by too much knowledge," Rubino said. "Something that might have seemed heretical didn't seem impossible to me."

Rubino modified the popular gastric bypass surgery, called Roux-en-Y, to test his idea on diabetic lab rodents. In the classic operation, the stomach is pinched off so it can hold less food. Surgical cuts keep the rest of the stomach and the top of the small intestine, called the duodenum, from receiving any food. Instead, the stomach empties directly into the bottom of the small intestine, the jejunum. In Rubino's variation, called duodenal-jejunal bypass (DJB), the stomach is untouched, but the rest of the procedure is the same.

The rats that Rubino operated on beginning in 2000 were cured of diabetes much more quickly than their weight fell. It was the first rigorous evidence, from a well-controlled study, that gut surgery has an anti-diabetes effect.

In 2006, Rubino was ready to move from rats to people. Two patients, with BMIs of 29 and 30, underwent his procedure. Their blood sugar levels returned to normal within days, though they lost no weight. In his most recent trial, reported in March in the New England Journal of Medicine, Rubino and colleagues at Catholic University in Rome performed standard gastric bypass surgery or a procedure similar to DJB on people with type 2 diabetes. After two years, 15 of 20 bypass patients and 19 of 20 DJB patients no longer had diabetes.

Curiously, although patients shed pounds, there was no correlation between weight loss and blood glucose, the key marker of diabetes. "Bariatric surgery is more effective on diabetes than obesity," said Rubino. "Patients don't become lean, but they do not have diabetes anymore."


Research from the University of Toronto, reported online this month in Nature Medicine, may finally explain why. It examined the effects of bypass surgery on rats with type-1 diabetes, which is considered even harder to treat than type 2. Normally the jejunum receives only digested mush, as nutrients have already been absorbed in the duodenum, explained lead researcher Tony Lam.

Bypassing the duodenum allows the jejunum to receive an influx of nutrients for the first time, said Lam. Sensing them, the jejunum sends a "got glucose!" signal to the brain. The brain interprets that as a sign of glucose overabundance and orders the liver to decrease glucose production. Result: The rats no longer have diabetes.

"I believe that similar mechanisms are taking place in surgery for type 2 diabetes," said Lam. "It strengthens the case for the surgery treating diabetes independent of weight loss."

His rat study shows why lap banding and stomach stapling are less effective against diabetes than gastric bypass. Banding causes diabetes to go into remission in about 50 per cent of patients, probably due to weight loss, said endocrinologist Dr Allison Goldfine of the Joslin Diabetes Center in Boston.

In contrast, the diabetes-remission rate after Roux-en-Y is 80 to 85 per cent. "The improvements in blood glucose with Roux-en-Y appear to occur very early, by day three after surgery, so patients are being discharged with no medication," she said. Something other than weight loss "must be going on."

Goldfine has launched a study of diabetics with BMIs of 30 to 42 to compare outcomes after lap band surgery, Roux-en-Y, and intense medical management.

A year ago, Rubino began the first large study for type 2 diabetes patients with a BMI as low as 26, where "overweight" begins. The cost of the bypass surgery is covered by a grant from Covidien Plc, which makes laparoscopic instruments and surgical staplers. He aims to enroll at least 50 patients, following them for five years; he has operated on 20 so far.

© Copyright (c) Reuters


Appendix II

Peptide PHI (or peptide histidine isoleucine) is a peptide which functions as a hormone.
It plays a role in the regulation of prolactin in humans.[1]

1.  peptide phi
A 27-amino acid peptide with histidine at the N-terminal and isoleucine amide at the C-terminal. The exactamino acid composition of the peptide is species dependent. The peptide is secreted in the intestine, but is foundin the nervous system, many organs, and in the majority of peripheral tissues. It has a wide range of biological actions, affecting the cardiovascular, gastrointestinal, respiratory, and central nervous systems.


Appendix III

Neurotransmitters Mediating the Intestinal Peristaltic Reflex in the Mouse
+Author Affiliations
  1. Address correspondence to:
    Dr. J. R. Grider, Department of Physiology, P.O. Box 980551, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298. E-mail:

The motor, modulatory, and sensory neurotransmitters that mediate the peristaltic reflex in the mouse colon were identified by direct measurement, and their involvement in various pathways was determined by selective receptor antagonists. Mucosal stimulation in the central compartment of a three-compartment flat sheet preparation of mouse colon elicited ascending contraction and descending relaxation in the orad and caudad compartments, respectively. Ascending contraction was accompanied by substance P release, a marker for excitatory neurotransmitter release, into the orad compartment and was partly inhibited by atropine and spantide, and abolished by a combination of the two antagonists.
Descending relaxation was accompanied by vasoactive intestinal peptide (VIP) release, a marker for inhibitory neurotransmitter release, into the caudad compartment,
and was partly inhibited by VIP10-28 and NG-nitro-L-arginine, and abolished by a combination of the two agents. Somatostatin release increased during descending relaxation: immunoneutralization of somatostatin or blockade of its effect with a selective somatostatin type 2 receptor antagonist inhibited descending relaxation. The δ-opioid receptor antagonist naltrindole augmented descending relaxation and ascending contraction. Calcitonin gene-related peptide (CGRP) release increased in the central compartment and was mediated by concurrent release of 5-hydroxytryptamine (5-HT) because its release was blocked by a 5-HT4 receptor antagonist. Both the latter and the CGRP antagonist CGRP8-37, inhibited ascending contraction and descending relaxation. Thus, the reflex in mouse like that in rat and human intestine is initiated by mucosal release of 5-HT and activation of 5-HT4 receptors on CGRP sensory neurons and is relayed via somatostatin and opioid interneurons to VIP/nitric-oxide synthase inhibitory motor neurons and via cholinergic interneurons to acetylcholine/tachykinin excitatory motor neurons.


Appendix IV

Peptides. 1984 May-Jun;5(3):593-606.
Co-existence of peptide HI (PHI) and VIP in nerves regulating blood flow and bronchial smooth muscle tone in various mammals including man.
Lundberg JMFahrenkrug JHökfelt TMartling CRLarsson OTatemoto KAnggård A.
By immunohistochemistry it was found that PHI- and VIP-like immunoreactivity (-IR) occurred in the same autonomic neurons in the upper respiratory tract, tongue and salivary glands with associated ganglia in rat, guinea-pig, cat, pig and man. VIP- and PHI-like immunoreactivity was also found in similar locations in the human heart. The N-terminally directed, but not the C-terminally directed, PHI antiserum or the VIP antiserum stained endocrine cells in the pig duodenum. This suggests the existence of an additional PHI-like peptide. Ligation of nerves acutely caused marked overlapping axonal accumulations of PHI- and VIP-IR central to the lesion. Two weeks after transection of the nerves, both types of immunoreactivities were still observed in accumulations both in the axons as well as in the corresponding cell bodies. The levels of PHI- and VIP-IR in normal tissues from the cat were around 10-50 pmol/g with a molar ratio of about 1 to 2. Systemic administrations of PHI and VIP induced hypotension, probably due to peripheral vasodilation in both guinea-pig and cat. Furthermore, both PHI and VIP caused an inhibition of the vagally induced increase in respiratory insufflation pressure in guinea-pig. PHI and VIP relaxed the guinea-pig trachea in vitro, suggesting a direct action on tracheobronchial smooth muscle. VIP was about 5-10 times more potent than PHI with regard to hypotensive effects and 2-3-fold, considering respiratory smooth muscle-relaxant effects in the guinea-pig. PHI was about 50-fold less potent to induce hypotension in the cat than in the guinea-pig. Although species differences seem to exist as regards biological potency, PHI should also be considered when examining the role of VIP as an autonomic neurotransmitter.


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