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~ Charles Darwin (it's evolutionary baybeee!)

Sunday, December 26, 2010

Gastric Bypass Surgery & Diabetes

If you've read at all on the LC web you'll see that there's an almost grudging hatred (well that might be too strong a word, but ...) towards those who take "the easy way out" getting gastric bypass surgery.  If not aimed at the person who has undergone surgery, a palpable feeling of animosity towards the WLS "industry" and the "pusher" doctors is in the air.  At some point someone will chime in to remind everyone that "you know what kind of diet they eat don't you?", because it is low carb.  The implications of which are that the weight loss is due to going LC so why not forego the surgery.  

I tend to agree with this sentiment, somewhat, especially since most WLS candidates must follow a diet and lose a bit of weight before the surgery.  Which begs the question of if one can do this before the surgery, why can't they just keep it going and lose weight w/o the surgery?  It's a fair enough question, but one with no easy answer.  But leaving aside this issue, the LC community seems to jump quickly to attribute the improvements in diabetes markers seen with GBP to the diet.  Seems like a reasonable assumption, but wait .....

I came across this paper looking into the whole gut flora obesity thing which led me to GLP-1 and eventually to this paper popped up in a search.


Bariatric surgery is the most effective available treatment for obesity. The most frequently performed operation, Roux-en-Y gastric bypass (RYGB), causes profound weight loss and ameliorates obesity-related comorbid conditions, especially type 2 diabetes mellitus (T2DM). Approximately 84% of diabetic patients experience complete remission of T2DM after undergoing RYGB, often before significantweight reduction. The rapid time course and disproportional degree of T2DM improvement after RYGB compared with equivalent weight loss from other interventions suggest surgery-specific, weight-independent effects on glucose homeostasis.  Potential mechanisms underlying the direct antidiabetic impact of RYGB include enhanced nutrient stimulation of lower intestinal hormones (e.g. glucagon-like peptide-1), altered physiology from excluding ingested nutrients from the upper intestine, compromised ghrelin secretion, modulations of intestinal nutrient sensing and regulation of insulin sensitivity, and other changes yet to be fully characterized. Research aimed at determining the relative importance of these effects and identifying additional mechanisms promises not only to improve surgical design but also to identify novel targets for diabetes medications. 




What is GLP-1?  It stands for glucagon-like protein 1 and is secreted by distal (end of small intestine) intestinal cells in response to fats and carbs.  Incretins stimulate insulin secretion and may be improve insulin sensitivity although I'm seeing some conflicting reports on the latter.   Diabetes drugs like Byetta are GLP-1 analogs (mimic GLP-1) and there are more in the works.  Something about GLP-1 seems to be involved in satiety.


The Swedish Obese Subjects study, a prospective, contemporaneously matched, multicenter trial of bariatric surgery vs. medical care for obesity, reported outcomes after 2 yr in4047 patients and 10 yr in 1703 patients (2). At 2 yr, no postsurgical patients had developed T2DM, whereas 5% of the medical group had. This protection persisted to 10 yr, at which time the risk of developing T2DM was more than three times lower for surgically treated patients, whereas recovery from T2DM was more than three times as common. In these studies, the few RYGB patients who remained diabetic after surgery had longer duration of disease, suggesting that they lacked sufficient residual β-cell mass to recover normal glucose regulation (17). Nevertheless, the vast majority of these patients enjoyed improvements in their glycemic control and reduced medication dependence. At least seven published reports show significantly decreased overall mortality after RYGB, most notably two large, multicenter studies recently published in the New England Journal of Medicine (20, 21). One described a remarkable 92% decrease in diabetes-related deaths after RYGB (21).
Although bariatric procedures have traditionally been reserved for patients with body mass index (BMI) higher than 40 kg/m2, or higher than 35 kg/m2 with significant comorbidities, the remarkable impact of these operations on diabetes raises the possibility of surgical therapy for less obese patients with T2DM. Trials of RYGB in people with BMI lower than 35 kg/m2 have reported similar or even higher diabetes remission rates than those conducted in severely obese patients (2223). Given that leaner individuals lose less total and percent body weightafter RYGB than do more obese persons, the similarity in T2DM response hints that the operation might exert antidiabetic effects unrelated to weight loss. Consistent with this concept, experimental studies indicate that variations of RYGB improve T2DM in both obese and nonobese diabetic animals (24252627).  Although there is growing interest in using RYGB specifically to target T2DM, the mechanisms mediating metabolic effects of this procedure remain poorly understood. The evidence that gastrointestinal (GI) surgery eliminates T2DM more effectively than do existing nonsurgical therapies and the rapidly increasing number of bariatric operations performed worldwide (28) mandate that elucidating the physiological mechanisms underlying these procedures be an important research priority. Such insights could provide guidance in proper patient selection for future diabetes surgery and, importantly, might lead to new pharmaceuticals that would obviate the need for surgery.
I think this is definitely a reason for obese diabetics and perhaps even some not quite so obese ones to consider surgical intervention, particularly if they are unable to manage their blood sugars through diet and weight loss.  And the sooner the better for curing diabetes!   (No I'm not arguing pro or con on the surgery, just that there's far more than weight loss benefits of this surgery).   The role of GLP-1 is interesting, and all of this happening days after surgery.  It might also be reason to consider pharmaceutical intervention with drugs like Byetta as an alternative to surgery.

Interestingly enough, some long term patients end up hypoglycemic because their pancreas' have apparently lost something in the signalling and still pump out too much insulin.

As profit-driven as the WLS industry is, I do believe this article gives reason to reconsider views on this procedure given the myriad complications and health risks of T2.


26 comments:

Melchior Meijer said...

This conundrum has been fascinating for some time too. Bypass the upper part of the small intestine and glucose tolerance is restored immediately. My gut feeling ;-) says this could be neurological. I smell a parallel with this weird Canadian finding where they reversed type 1 diabetes overnight (in rodents), just by partly paralizing pancreatic nerves (injecting capsaicine). Complete beta cell regeneration by tinkering with a part of the nervous system.

Have you read the series of articles on gastric bypass by Sandy Szwarc? The side effects may be more crippling and more common than the big trials suggest...

Sanjeev said...

Any inkling that this could be how bromocriptine works? Bromo somehow helps control insulin, and appetite suppression is a common effect (along with nausea from the dopamine stimulation outside the CNS)

Todd Becker claims he "learned to control" his insulin using Seth Roberts' techniques, among others. Todd attributes most of the benefit directly to insulin, and "detraining" the cephalic insulin response.

Now, if I were talking about _learning_ and habits and related stuff, first I would think of dopamine, and acetylcholine, and so on - with effects on insulin coming way down the line ;

"hear hoofbeats, think of moose (horses to my American friends[0])" kind of thing

but the world seems a different place when one's been indoctrinated into the Taubesian faith, to wit:
"hear hoofbeats, think platypus"



> Have you read the series of articles on gastric bypass by Sandy Szwarc?
yeah, too bad she's on hiatus. I hope she's OK.

[0] castanets to my Spanish friends, coconut halves to fans of "Monty Python's Search for the Holy Grail"

Sanjeev said...

mea culpa ... that short-hand or substitution is just too habitual

> Bromo somehow helps control insulin

What I meant: helps control blood glucose in diabetics

Melchior Meijer said...

Thanks for mentioning bromocriptine, Sanjeev! I had never heard of it before, so I haven't the foggiest... Very interesting, though.

I too hope Sandy is okay.

Nigel Kinbrum said...

Lyle McDonald has written a book about Bromocriptine and its effects on dieting. See Google search for Bromocriptine on Lyle's forum.

CarbSane said...

Never heard of the stuff. Thanks for mentioning it, I'll have a look!

dietconcepts said...

Yeah, but as with every mildly effective drug, it's either banned or on prescription. :(

Sanjeev said...

Cincotta and Meier wrote the paper that got Lyle interested.

An interview with Cincotta


a list of papers:



a diabetes trial

Sanjeev said...

I came across this first during the whole deprenyl (the parkinson's drug) story

> mildly effective drug

for most people, yes -

and isolated reports put it WAY beyond mildly effective; some people have to force themselves to eat even a small amount of food.

Forget about the skinny people who can't gain weight, these reports have people having to force themselves to eat so they don't lose too much weight.

Again, these reports are rare - it's much milder for most people.

Nigel Kinbrum said...

On your side of the pond, you can get the dopamine agonist Bupropion prescribed as an anti-obesity aid.

On my side of the pond, it's only prescribed as an anti-smoking aid.

Jin said...

Yep, a friend of mine had lap band surgery for obesity & T2D. She is no longer diabetic.

I wish I understood it better!

CarbSane said...

Welcome Jin! I think that even if someone is "against" surgical intervention, there is a LOT to be learned by the results. Did your friend lose a lot of weight and/or was the diabetes reversed early on or only with the weight loss?

There are a lot of hypotheses discussed in that paper that I think I'll do a follow-up post on sometime. Reading through this one I think I accidentally deleted a chunk of it prior to publishing but don't have the attention span at the moment to fix it.

Jin said...

She said her T2D was reversed very soon after surgery. She said she left the hospital not needing insulin or diabetes drugs.

It's so interesting, isn't it?

CarbSane said...

Very interesting indeed. Before finding this article I was not aware of the weight-loss independent quick reversal of T2. Getting such results with Lap band would seem to support the ghrelin hypothesis in this article over the GLP-1, although I suppose with a small "pouch" the food gets to the intestine faster anyway.

Hopefully the scientists are looking at these sorts of observations for strategies to treat T2 diabetes specifically and that may mean early aggressive pharmaceutical intervention to ameliorate the symptoms with the intent to wean the person from them as diet and weight loss reduce the cause.

Whatever the surgeries do, the effect seems to be to improve insulin sensitivity, because as I stated before, if it was just increasing insulin production it wouldn't work so suddenly.

Thanks for sharing!

scall0way said...

Hmm, just discovered your blog today from a mention elsewhere, and I'm still in perusal mode, though lots of great stuff so far! But as for the reversal of T2 from WLS, what do you feel about the information here:
http://diabetesupdate.blogspot.com/2010/01/reckless-recommendation-for-wls-by.html

CarbSane said...

I have a lot of respect for Jenny although have some disagreements with her assessments of science research. Not related to this post, but an example would be her out-of-hand dismissal of any and all rodent research. Clearly we are not mice or rats, but that doesn't mean all animal work is irrelevant ... indeed if it weren't for this work we wouldn't have anywhere near the understanding of metabolism and diseases as we do now. For example, we're not about to experiment with "knockout" humans but we can learn a lot from these genetically manipulated rodents. But I digress ...

Jenny certainly raises key issues with respect to the risk-benefit of WLS for diabetes. She focuses on the risk w/o giving due reference to the benefits on this issue IMO. Rather than focusing on the 17% who weren't "cured", I do find the 80+ percent almost instantaneous "cure" rate compelling. It is at least worth considering. I'm with Jenny that the risks need to be better communicated and assessed, but the flip side is that for the 80+ % of folk who are now suddenly normoglycemic and therefore at lower risk for complications of hyperglycemia we would have to factor those benefits in the balance ... no?

I would like to see the treatment of diabetes to where insulin delivery could be as "normalized" as possible rather than avoided to the greatest possible degree. I say this because of the various posts I've made on studies looking at insulin's protective roles in our physiology aside from just to move glucose into cells.

It seems to me that the 17% were those with sufficient permanent damage to their beta cells. Presumably there should be a way to assess this function and that may be something that should be considered as well should one consider WLS. It seems that normal function is restored rather quickly for the vast majority. I would be one that would prefer research into mimicking pharmaceutically what WLS does physically. It is just NOT possible to achieve certain of these effects through diet. If it is GLP-1, and that is impaired in diabetics, what would be so wrong about GLP-1 injections?

I'm somewhat befuddled by the aversion to insulin in LC circles wrt treatment of diabetes. It's NORMAL to secrete it. Why try to mimic a diabetic state?

I have lingering concerns over the focus on just the glucose levels as well. One of my "pet" issues is elevated free fatty acids (NEFA/FFA) and their deleterious effects. Unfortunately we don't have NEFA meters to "eat to".

ProudDaddy said...

I couldn't find any mention of PYY on your site, so I'm posting here. I'm having difficulty understanding how something such as PYY that is produced by the ileum in response to feeding can be increased by shortening the length of intestine that the food moves through. While some of the early studies of PYY in rodents were not replicated, I believe it is generally recognized that PYY increases markedly after GBS and may be one of the main reasons for the immediate reduction in appetite.

Like GLP-1 wrt diabetes, it would seem to be useful to find pharmacological mimics of the mechanisms of GBS wrt appetite, but I haven't found much about PYY in this regard. The enthusiasm for this "appetite suppressant" seems to be waning. What's the scoop?

Evelyn aka CarbSane said...

Haven't looked much into PYY. I believe the change is in dose/rapidity with which stimulating nutrients reach the cells that secrete them. The thing that I'd like to see more of is ... since the ability to make GLP-1 for example ... remains intact and can be "woken up" so quickly, how do we wake it up naturally rather than replace it or use surgery. Crash diets seem pretty useful in this regard. Which brings us to whether PYY and such are similarly effected. Seems not ...

ProudDaddy said...

So, if stomach banding reduced the size of the "buffering" volume of the stomach to that of bypass, we could expect to see similar increases in PYY? Further, the AUC of serum PYY would be good to know to determine whether it is the max post-prandial concentration or the total amount secreted that's causing the reduction in hunger, like a light switch vs a rheostat? Or, is the dose/response linear? (I have the same linearity question concerning adipocyte hormone production vs cell size, something one would think would be in the textbooks by now!)

ProudDaddy said...

Kokkinos, 2010, seems pretty certain that a SLOWLY eaten meal produces an INCREASE in PYY secretion. I have another reference indicating that resectioning of the ileum alone increases PYY. Perhaps I misunderstood your dose/rapidity theory?

Here are some conclusions from other studies:

1. Although the obese have lower fasting PYY, they are not "PYY resistant" (unlike leptin).

2. Infusion of PYY significantly reduces hunger and ad libitum food consumption.

3. PYY concentrations are highest in the terminal ileum.

So, since most of this info on PYY has been around since the 80s, why aren't researchers more excited about it? If it's because it is injectable-only, that didn't stop the hoopla over leptin. If it's because it's not patentable, same leptin comment.

Where's the PYY Reset Protocol bestseller?!?

ProudDaddy said...

I had a long comment get lost after hitting the publish button, so here's the short version. PYY secretions INCREASE when meals are eaten more slowly and also after ileum resectioning alone. Maybe I misunderstood your dose/rapidity theory.

Unlike leptin, PYY levels are reduced in the obese but they are not resistant to its actions. Infusion reduces hunger and ad libitum food intake in humans.

Where's the PYY Reset bestseller?

Evelyn aka CarbSane said...
This comment has been removed by the author.
Evelyn aka CarbSane said...

Sorry 'bout that PDaddy, it got dumped in my spam folder. Sigh ... I try to read comments at least once every couple days so I don't forget about that spam folder, but the new blogger interface is toying with me. I don't like it!

(I deleted last comment to fix this last part that made no sense to me when I reread it)

Like I said, I haven't looked much into PYY. I'm not sure why, if indeed PYY infusions reduce hunger, that it hasn't been developed. Insulin is marketed in like a zillion forms after all. Or PYY stimulants?

Lest it be said I never post anything pro LCHF, this study shows that LCHF stimulates PYY. Maybe this is why many seem to do well with a high protein/fat breakfast and then eating carbs at night (then to bed with you!). http://jcem.endojournals.org/content/92/10/4052.full.pdf

ProudDaddy said...

Probably shouldn't have bothered you, but thought you might be interested. Further Googling answered most questions. PYY half life is eight minutes, hense infusion. Problems of nausea. Same problems as GLP-1, so researchers are following the path that developed liguratide from Byetta. Most promising seems to be a combination of lower doses of PYY and GLP-1 which solves the nausea problem. A pill is a long way away, but the dramatic effectiveness of Byetta has finally got a lot of labs interested. Probably subcutaneous first. There's hope, and since we are looking at the body's natural hunger mechanism, it should prove safer than targeting neurotransmitters.

Evelyn aka CarbSane said...

That's interesting, but endogenous insulin has halflife about that more or less so they should be able to do injectable. Nausea is another issue. I agree, should be safer than targeting the receptors.

Tsimblist said...

@Evelyn "Maybe this is why many seem to do well with a high protein/fat breakfast and then eating carbs at night"

Just ran across this today and was reminded of your comment:

http://www.ncbi.nlm.nih.gov/pubmed?term=Meal%20timing%20and%20composition%20influence%20ghrelin%20levels
"CONCLUSION: A high carbohydrate and protein breakfast may prevent weight regain by reducing diet-induced compensatory changes in hunger, cravings and ghrelin suppression."

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