Diabetes cured... through surgery?

[jryan]

I have several friends and family members who have diabetes. Because of this I end up getting tipped on meidcal news regarding disease quite frequently.

 

Lately everyone is abuzz about this new medical procedure that is apparently curing diabetes in the majority of patients... as well as high blood preasure, and obesity.

 

It soulnds too good to be true, and I am working my way through the journal articles, but I felt that it is intriguing enough that I would clue folks in here in case they suffer from diabetes and haven't heard of it yet.

 

http://www.sciencedaily.com/releases/2008/03/080305113659.htm

Edited June 30, 2008 by jryan

[Mr Skeptic]

Seems plausible. We'll find out for sure soon enough.

[blike]

It's basically a duodenaljejunal bypass (form of gastric bypass). They haven't completely worked out the mechanism of action, but it's hypothesized that it may have to do with glucagon-like peptide or glucose-dependent insulinotropic peptide (both are incretins). Below is a paper published on the animal model, but there's actually a clinical trial going on now at SUNY. They've enrolled about fifty non-obese type-2 diabetics to do duodenojejunal bypasses. In the animal model the control of type-2 diabetes doesn't appear to be a secondary outcome of treating the obesity, but instead appears to be a primary effect of the bypass itself.

 

Looks interesting, and may hold some promise, but there's a lot of hurdles to overcome before this surgery would ever become mainstream.

 

Effect of Duodenal-Jejunal Exclusion in a Non-Obese Animal Model of Type 2 Diabetes: A New Perspective for an Old Disease

The demonstration that surgery can directly influence T2D as opposed to being a secondary effect of the treatment of obesity is not a mere intellectual exercise; it has, instead, important implications. One is that it implies the new concept of "diabetes surgery" as an independent new surgical discipline for which surgeons need to develop specific knowledge and competence. Indeed, clinical studies with diabetes-specific endpoints are now justified to define whether or not surgical treatment of type 2 diabetes should be extended also to moderately obese or overweight patients as well as which surgical technique has the best risk/benefit ratio and whether there are specific indications and contraindications for surgical treatment of type 2 diabetes.

[cellbioS]

One of the nightly news shows did a story on this a while back; I didn't watch it but saw the preview. I just hope that people don't see this as a first alternative before trying less invasive actions (diet, exercise) that don't have the surgery complications. Many family memebers have type 2 diabetes that is controllable through diet and exercise; some have improved and some are refusing to change their behaviour before trying more complicated treatments that require less dedication.

[iNow]

To be clear, it's only Type II diabetes. I first heard about it on 60 Minutes:

 

http://www.cbsnews.com/stories/2008/04/17/60minutes/main4023451.shtml

 

It's pretty well known to doctors that the most successful treatment for obesity is surgery, especially the gastric bypass operation. But here's something the medical world is just realizing: that the gastric bypass operation has other even more dramatic effects. It can force type 2 diabetes into almost instant remission and it appears to reduce the risk of cancer.

 

 

VIDEO:

http://www.cbsnews.com/sections/i_video/main500251.shtml?id=4029652n

 

http://www.cbsnews.com/sections/i_video/main500251.shtml?id=4029656n

[arnoldschwartz]

I agree this does seem to be plausible ive studies diabetes and think replacement of beta cells through surgery can have a theraputic effect

[iNow]

Does replacing beta cells work for type II diabetes, or only type I?

[ecoli]

type-1 only. In type II diabetes, beta cells are intact, but become unresponsive to insulin or the body stops producing insulin. Type-1 diabetes mellitus is an auto immune disorder in which beta cells are actively destroyed.

[iNow]

That's precisely what I thought. Thanks for the confirmation, ecoli.

[lucaspa]

I have several friends and family members who have diabetes. Because of this I end up getting tipped on meidcal news regarding disease quite frequently.

 

Lately everyone is abuzz about this new medical procedure that is apparently curing diabetes in the majority of patients... as well as high blood preasure, and obesity.

 

As Ecoli pointed out, remember, this is type 2 diabetes. Not type 1. Type 1 is an autoimmune disease and this surgery won't touch it. Since the insulin-producing cells have been destroyed, there needs to be some way to replace them.

 

For type 2, we'll have to wait and see. Maybe. The news report was very vague on mechanisms -- not surprising for surgeons. Based on what Blike said and the physiology, I would hypothesize that this particular area of the duodenum produces some type of inhibitor of insulin. Bypass the area and you reduce the inhibitor, allowing the normal insulin to work again.

[iNow]

Hey. I pointed that out!

 

 

Also, with Type II, there is more than one factor to consider. In Type I, it's clear (as lucaspa pointed out ) that the insulin-producing cells have been destroyed, and are not naturally replace. In Type II, it could be that they just don't produce enough insulin to cope with lifestyle. It could also be that they are just not sensitive enough to the insulin which is being produced by their body.

 

Since Type II generally indicates that the body "just can't keep up" with the food being ingested, this suggests why gastric bypass helps. There's less incoming food for the body to break down, convert to usable energy, aka... for the body to keep up with (whether their diabetes be due to a lack of sensitivity or lack of enough production).

[lucaspa]

Hey. I pointed that out!

 

My apologies.

 

Since Type II generally indicates that the body "just can't keep up" with the food being ingested, this suggests why gastric bypass helps. There's less incoming food for the body to break down, convert to usable energy, aka... for the body to keep up with (whether their diabetes be due to a lack of sensitivity or lack of enough production).

 

As I read the article, that is not the case. The bypass is in the duodenum and doesn't inhibit the amount of food. If they had done a stomach banding, yes, that would limit the amount of food the person would eat. But this doesn't do that. It simply bypasses a small part of the beginning of the small intestine. The amount of incoming food is the same.

[iNow]

That's an interesting clarification. If the change occurs in the duodenum, then I suppose it limits the amount of tract/time though/by which the sugars can be absorbed.

[lucaspa]

That's an interesting clarification. If the change occurs in the duodenum, then I suppose it limits the amount of tract/time though/by which the sugars can be absorbed.

 

Sugars are absorbed in the jujenum. The later part of the duodenum is where the pancreatic juices and bile duct products are secreted into the intestine. The sugery only bypasses the first part of the duodenum, leaving the secretion part intact.

[karim]

Hi, i was just wondering if any one has had the diabetes surgery. My mother is type 2 and not overweight. her BMI is 30. She will be the 11th person to have the surgery at this medical center. They have just completed the trial test. I've read that trials at the NY Presbyterian hospital will begin in late Sept '08, but being that my mother is already 61 and has been insilun dependent for over 15yrs she can't afford to wait a few more years. Please let me know if anyone out there has had the surgery. thansk

[jdurg]

As a Type I Diabetic for 26 years now, I am never even intrigued by announcements of new "treatments" unless it is for Type I diabetics. Sadly, there is little to no desire to work on Type I research since it isn't really an "epidemic" like Type II has become. There's no point in the eyes of researchers to spend so much time, money and effort on something that will help out an insignificant number of people compared to Type II which is much easier to treat.

 

In addition, the treatments for Type I Diabetes are deemed "good enough". The science community generally feels that there's no need to mess with what is already working.

 

At this point, I think the best line of action would be to develop a compound that will absorb extra insulin when the blood sugar is too low, yet not absorb it when the blood sugar is too high. This way, the number one danger of current treatments would be completely eliminated. Type I Diabetics could inject more insulin than they believe they need and not worry about going into a diabetic "blackout".

 

I myself have had a HORRIFIC time keeping my blood sugars in check. My A1c is averagin around an 8% which is HORRIBLE. The thing is, when my blood sugar level is between 200 and about 330 it seems to be quite stable. It takes a good deal of insulin to drop it down, and when I ingest carbohydrates it doesn't make it rise a great deal. If I get down into the "normal range" of 75-125, the slightest bit of food makes it skyrocket, and the slightest bit of insulin makes it plummet where my body starts having severe reactions. I completely totalled my car a few months back because my blood sugar was 90, I ate a breakfast bar for breakfast and gave two units of insulin to cover the breakfast bar. TWO FREAKING UNITS! I was driving into work when suddenly my blood sugar dropped and I lost all control of my body, and hence my car. THANK GOD nobody got hurt and the only damage was to the car. Still, my blood sugar was only 68 when the medics measured it and with what I ate and what I injected no reaction should have EVER happened.

 

Sadly, because of that incident I've been running my blood sugar higher than I should in fear of having that happen again. Do I have any hope for a new treatment or a cure? Nope. The only thing I have to look forward to is decreased blood circulation, loss of nerve sensations, eyesight loss, kidney failure, and eventully death. I'm not even 30 and I've already lived well more than half of my life.

[Mr Skeptic]

You do know that keeping your blood sugar too high is also dangerous, right? A high level of glucose will result in your proteins getting glycosylated at a higher rate than normal, which will eventually take its toll on your organs and body in general.

 

Perhaps you could carry some candy and some insulin. If you can feel your blood sugar drop too low, eat some candy, and if too high, take the insulin. You'd probably only notice when it got to dangerously high or low levels though.

[iNow]

Have you considered going on the pump, jdurg? Once your body has spent some regular amounts of time in the normal zone, your hypoglycemic symptoms would likely become more related to a sub-80 or sub-70 meter reading.

 

 

 

 

You do know that keeping your blood sugar too high is also dangerous, right? A high level of glucose will result in your proteins getting glycosylated at a higher rate than normal, which will eventually take its toll on your organs and body in general.

 

He definitely showed his awareness of these issues in his closing.

Edited August 30, 2008 by iNow
multiple post merged

[jdurg]

You do know that keeping your blood sugar too high is also dangerous, right? A high level of glucose will result in your proteins getting glycosylated at a higher rate than normal, which will eventually take its toll on your organs and body in general.

 

Perhaps you could carry some candy and some insulin. If you can feel your blood sugar drop too low, eat some candy, and if too high, take the insulin. You'd probably only notice when it got to dangerously high or low levels though.

 

Oh yes, I am quite aware of that and do have insulin and glucose on me constantly. Symptoms of high blood glucose don't really kick in until blood sugar is too high anyway, and symptoms of low blood glucose can really be mistaken for may other things as well. Plus, the transition from "able to function" to "uh-oh" is VERY quick.

 

As a diabetic, you have to take the lesser of two evils:

 

1) Keep a lower blood sugar and deal with the side effects of hypoglycemia which can be broken bones due to falls caused by loss of muscle control, unconciousness, immediate death.

 

2) Keep a higher blood sugar. No short term issues, but over the long term it totally destroys your body.

[iNow]

It's all about balance. Hard to maintain, very much a moving target, and not something which easily accompanies an active life. It is, however, made easier with certain technologies.

 

 

 

 

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On another note, I just learned of an article being published in Nature about researches who have re-engineered exocrine cells via a small subset of transcription factors into beta-cells. How freakin' cool is that!?!

 

 

Here's a link the article:

 

http://www.nature.com/nature/journal/vaop/ncurrent/full/nature07314.html

In vivo reprogramming of adult pancreatic exocrine cells to -cells

 

One goal of regenerative medicine is to instructively convert adult cells into other cell types for tissue repair and regeneration. Although isolated examples of adult cell reprogramming are known, there is no general understanding of how to turn one cell type into another in a controlled manner. Here, using a strategy of re-expressing key developmental regulators in vivo, we identify a specific combination of three transcription factors (Ngn3 (also known as Neurog3) Pdx1 and Mafa) that reprograms differentiated pancreatic exocrine cells in adult mice into cells that closely resemble -cells. The induced -cells are indistinguishable from endogenous islet -cells in size, shape and ultrastructure. They express genes essential for -cell function and can ameliorate hyperglycaemia by remodelling local vasculature and secreting insulin. This study provides an example of cellular reprogramming using defined factors in an adult organ and suggests a general paradigm for directing cell reprogramming without reversion to a pluripotent stem cell state.

 

 

 

Also, PZMeyers breaks it down into understandable chunks for the non-expert over at Pharyngula:

 

http://scienceblogs.com/pharyngula/2008/08/reprogramming_the_pancreas.php

 

Wow…so have you heard about this result?

<...>

This is a big deal, I think, so allow me to translate.

 

First, a little... <

more at link

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Edited August 30, 2008 by iNow
multiple post merged

[jdurg]

The big advance in curing Type I Diabetes will be when they detemine exactly what it is that causes the body's own immune system to flag the islet cells as "foreign" and kill them, and not any other cells. Until they can figure that out, it's going to be a losing battle trying to reproduce islet cells or transplant them since the faulty immune system will promptly kill them.

[lucaspa]

The big advance in curing Type I Diabetes will be when they detemine exactly what it is that causes the body's own immune system to flag the islet cells as "foreign" and kill them, and not any other cells. Until they can figure that out, it's going to be a losing battle trying to reproduce islet cells or transplant them since the faulty immune system will promptly kill them.

 

I agree that finding the cause of the autoimmune destruction of the islet cells is going to be important. However, even when that is known, it may not be possible to prevent it. And yes, if the system is not shut down any transplanted cells will simply succumb to the same process.

 

But there are possible ways to avoid the process. One way is to hide the transplanted cells from the immune system. This can be done by placing the islet cells in a cylinder composed of material with a pore size that only allows molecules of < 50,000 MW to pass thru the membrane. This means that nutrients can enter the cylinder and insulin can leave the cylinder, but neither immune cells nor antibodies can get into the cylinder. Thus, no possible destruction of the islet cells.

 

The problem then becomes getting enough islet cells for every type I diabetic. Some companies are looking into using xenogenic islet cells (such as bovine) while others are looking at means of differentiating either ES cells or adult stem cells into islet cells. There are several papers claiming that various adult stem cells are capable of differentiating into islet cells. However, no one has found a way to do this efficiently. Once that is found, then the treatment is to isolate adult stem cells from an individual (not necessarily the patient), grow them in cuture, differentiate them, place them in the cylinder, and then place the cylinder in the abdominal cavity (in the omentum probably). Voila! Instant insulin producing organ. There are, of course, several engineering hurdles to pass, but several biotech companies have appropriate membranes.

 

On another note, I just learned of an article being published in Nature about researches who have re-engineered exocrine cells via a small subset of transcription factors into beta-cells. How freakin' cool is that!?!

 

It's cool. The problem here is how you have to get the transciption factors into the cells. You do that by transduction with a retrovirus and the danger is that the retrovirus will kick the cells into being cancer cells. FDA is not going to approve a treatment unless a safer method is devised to get the genes into the cell.

 

What is needed is the exogenous signal that tells exocrine cells during development to differentiate into islet cells. These are the genes that are turned on as a result of that signal. We need the original signal, but right now the molecular biology community is tunnel-visioned on transducing genes.

[iNow]

It's cool. The problem here is how you have to get the transciption factors into the cells. You do that by transduction with a retrovirus and the danger is that the retrovirus will kick the cells into being cancer cells. FDA is not going to approve a treatment unless a safer method is devised to get the genes into the cell.

An interesting point. I read that that there was little or no impact to other cells, or muscle tissue, but was not aware of the potential of becoming cancerous (despite the fact that this makes a lot of sense and seems abundantly obvious now that it's been pointed out to me).

 

 

What is needed is the exogenous signal that tells exocrine cells during development to differentiate into islet cells. These are the genes that are turned on as a result of that signal. We need the original signal, but right now the molecular biology community is tunnel-visioned on transducing genes.

 

I have a feeling that those students who have been focussing on epigenetics during the past decade may have some insights in this matter. We'll see. Thanks for taking the time to share some of your detailed knowledge with me and the others here. While I tend to do pretty well with high level understandings, once it gets down into the detail on subjects like this it's quickly beyond my existing education.

[lucaspa]

Sadly, there is little to no desire to work on Type I research since it isn't really an "epidemic" like Type II has become.

 

That's not what I get in reading the scientific literature. I see most of the work being done for Type I. This is first I've ever seen people seriously proposing a treatment for Type II.

[jdurg]

The literature I've seen regarding Type I is new methods of treatment and not really ways to cure it.

 

One thing that could be researched and might be the best option is to find a way to monitor blood glucose levels without the need for actual blood. With the advent of insulin pumps, the treatment options for Type I diabetics has gotten much better. Also, insurance companies are now starting to pay for them since the cost to the company is a lot less than the cost of ER visits and later complication treatment.

 

So if they can find a way to accurately, and continuously, monitor blood glucose levels they could tie that in to a pump and have the pump dispense the proper amount of insulin based upon the patient's current blood sugar. In a sense, they'd make a robotic pancreas. That's something that I think the medical/scientific community is getting closer to doing.