Remember to take your Bile Acids before you go to bed, Dear.

From NPR.org

Bile Acids?

For Metabolic Diseases, like Diabetes?

Maybe this ad from the 1940's wasn't to far off - touting the health benefit of bile-like ingredients.

And maybe someday taking a bile acid pill will be a pleasant reality for those suffering from T2DM, thanks to a recent "breakthrough" finding from Sahlgrenska Academy in Sweden, and the University of Cincinnati.

As reported in the Journal Nature recently, in a study just concluded, found that metabolic surgery-induced (in this case Vertical Sleeve Gastrectomy) elevation in bile acids in the blood, was the principal effect that causes such a rapid improvement in obesity-related Diabetes.

Not only is this interesting and exciting news unto itself, but it may shed some new light on an area that could be developed in the future as a pharmacological intervention, without surgery, to positively effect Diabetes.

The research led to pinpoint a receptor, named FXR, that is directly involved in bile acid signaling.
The study showed that signaling through FXR is essential for the metabolic effects of surgery to be achieved.

This was demonstrated by performing the equivalent of a Vertical Sleeve Gastrectomy on two sets of mice: those with the FXR receptor, and those who genetically were altered to not have the receptor.  The researchers observed that the operation produced weight loss and improved glucose metabolism in the mice with the FXR receptor, yet no effect n the mice that lacked FXR.

The study also showed that VSG produced changes in gut microflora, and that may or may not be working in concert with the FXR receptor to drive the beneficial metabolic results.  More study is needed to investigate those relationships.

"Can't I Just Take A Pill For That?"

From surgerywithoutmedicalinsurance.com

Admittedly, it would be nice.  To have a Bariatric surgical  procedure, with the weight loss and the metabolic benefits of the procedure, without the hassle and potential risk of the surgery itself.  None of the associated surgical and anesthetic risks. Just the benefits. Like the frosting without the cake, right?

So, are we yet to the point yet that medical therapy, in today's advanced age of interventions, non-surgical treatments and pharmacotherapy, that we can duplicate the wide-ranging effects that Bariatric Surgery can provide?

I have spent some time reviewing an article in the International Journal of Obesity, from 2014, that sets out to illuminate us on such a question.

In "Can medical therapy mimic the clinical efficacy or physiological effects of bariatric surgery?" the authors from London, England make their case, and describe where we are as of now. 

Certainly we have come a long way in new medical (Non-surgical) interventions and pharmacotherapy, as we have also come a long way in our understanding of the significance of the benefit and some (but not all) of the physiologic mechanisms of how / why bariatric surgery works.

But, as the article concludes, we are not totally there yet.  Closer than we ever have been to purely medical treatments, yes, but not all there yet.

And, as I have said many times in this blog, surgery is not for everyone.  For most obese patients, with their obesity and their comorbidities, weight loss is weight loss, and in a perfect world if they can lose a substantial amount of weight, and keep it off, we are still talking apples and apples (or pears in the morbidly obese world).

But, in the real world, there aren't many that are very successful with non-surgical weight loss, especially in the context of keeping it off.

And there aren't many that see the long term benefit of weight loss, either to degree or duration, to make a longstanding difference in their comorbidites, their quality of life, or to their longevity of life.

However, that being said, as the article details, there have been many 'new' developments that help us to inch closer to mimicking what a Bypass, Band or Sleeve can do, for example. Here are a few of the developments.

* T2DM benefit after surgery seems to come from improved beta cell function and reduced insulin resistance, as well as a change in gut nutrient sensing.  As the search for how bariatric surgery seems to work physiologically, it has opened new potential metabolic targets for medical therapy to effect.  Both a change in diet amount / portion, calories, and makeup of the diet have been studied to carry about a similar effect.  New T2DM agents, such as GLP-1 agonists and DPP-4 inhibitors and SGLT-2 inhibitors have a new role in the step care approach to T2DM.

*Lifestyle modification for weight loss begins with caloric intake restriction. In a perfect world, it is certainly aided by appetite reduction, as occurs at least temporarily with bariatric surgical procedures, and is reinforced longer term by the restrictive element of the surgical 'tool' that is created through the patient's Sleeve, Bypass or Band.  Medically, newer agents such as Qsymia, in addition to conscious lifestyle modifications, may offer a somewhat similar effect. Further studied dietary makeup, both for calorie amount (?1000-1200) as well as composition (Low glycemic, high protein, high fiber) may offer additional benefit in conjunction with the above. 

*Furthermore, Devices that are now available are also in play.  An endoscopically-placed duodenal-jejunal bypass liner, is a potentially less invasive treatment that aims to recreate the 'bypass' of the duodenal-jejunal region as occcurs in the Gastric Bypass surgically.  Studies have shown that this is a powerful part of the rerouting of the ingested nutrients that changes how the body, and the GI tract specifically, handles the ingested nutrients, and seems to greatly benefit how blood sugar is regulated. The experience with this approach is very early, and has had some complications, in so far as the need for explantation by 6-12 mos, some reports of bleeding, obstruction, abdominal pain, vomiting, etc. Gastric stimulators and intragastric balloons are other devices also in trials at a very early stage in their usage. Results remain to be seen.

So, yes, we have come a long way in our understanding of how and why surgery works so well for obesity and especially it's associated metabolic disease.  We are closer now than we have ever been to maximizing those medical therapeutics and procedures that may avoid surgery, but retain some of the benefits that surgery has shown to exact.

But, in summary, we are still a very long way away, I think, from being able to believably say that a pill, or a device, or a lifestyle change (or a combination of all of these) can mimic the established effects that bariatric surgery can produce for obesity and it's attendant comorbid disease states.

And so my job at this time is still somewhat secure, at least from the fate that has take the cardiac surgery subspecialty by storm over the past 10+ years. In somewhat of a similar phenomenon of scale that is potentially prposed here, with the advent of endovascular techniques (PCI - Percutaneous Coronary Interventions), the rate of CABG  for CAD decreased per hospital caseload by 28% from 2001-2008 in one study, whereby the rates of PCI stayed about the same over that time.

I guess in the area of medicine, and surgery specifically, the more things change, the more they stay the same...

What Happened?

From maniacworld.com

Into every life a little rain must fall.

Frequent music lyrics from a number of artists.  And, apropos for a patient who came in for a post op visit last week.

In the course of an unusually predictable day, I had a patient that I had seen a number of times in the past, and was in the office for her post op Sleeve Gastrectomy visit, closing in on 1 year post surgery.

She had a pre op history of HTN, OSA, Asthma, T2DM, and Depression.  Her start weight was 249 with a BMI of 45.5.

One of her ongoing issues from previous visits was the scarcity of her weight loss, and resultantly, the lack of significant positive change in her comorbidities .  At her visit last week, she had lost only a few pounds more than previous visits, had a history of a few pounds up and down in past visits, and her weight loss total, (including her 15# loss preoperatively) stood at a net of 0. 

That is, she was back to her pre operative weight.


How can that happen?


This issue, and this patient example, fortunately is not a common finding.  It is actually quite rare for a patient within their first year to lose very little, or actually start to gain at some time, already working against their expected mounting weight loss after their surgery.

As you can imagine, is is usually a neon red flag that something is up.

We had interactive, ongoing discussions from her previous visits, and the lack of her post op weight loss did have a cause.  She was going through some very rough times psychologically, with depression and having binge eating issues in response.  Some of the stress was likely brought on by her surgery, at least indirectly, but she also had new and significant stressors at home to deal with.

She fully admitted her issues, and her awareness about it's impact on the lack of success thus far from her surgery.  She was embarrassed and saddened about it, but was actively engaged in counseling and was slowly on the road to getting better in the mental health area.

A few key points.

Interesting, how most patients have a degree of "automatic" weight loss after surgery, most seeing the expected 60-80% loss of excess weight loss within that first year, but on occasion they do not.  Of those that do not, there are some practical prognostic signs can give us a tip off that something is up.

The amount of weight loss at post op visits varies widely, patient to patient.  There is no 'normal' so to speak, but lack of meaningful weight loss at earlier visits post op (1 mos, 3 mos, 6 mos), or weight gain often requires us to delve more into the history to see if there is a behavioral or dietary issue.

Specific and detailed questioning about portion sizes, junk food / empty calories, lack of protein, snacking, etc. may yield some clues.  A thorough exercise / activity review also is needed.

This being said, I also have a low threshold to call a patient out on a self-reported glowing history of bariatric lifestyle adherence, when it's in the face of fair to poor weight loss.

In the case of this patient, fairly superficial questioning allowed her to explain her psych issues, diet issues, and her understanding about the interaction between those factors and her lack of weight loss. Somewhat refreshing, actually, as I have had patients in the past with admittedly less obvious lack of weight loss, who have a hard time admitting to any correlative behavioral issues that may be at cause.

I did bring back this patient more frequently than our usual Q3 mos visits, in an effort to try and stay in touch with her, offer encouragement, and review proper lifestyle changes that were needed for better weight loss.

Sometimes you can only do what you can do.

We will continue to work with her, and support her as we can, and hopefully get her on track to realize some of the benefits she anticipated from her referral to us in the first place. Both for the weight and comorbidity benefit.

The honeymoon phase of 12 mos after the surgery is now nearly gone, but there still is hope if she can start to consistently use her 'tool' of her Sleeve the proper way long term.