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Monthly Archives: July 2013

Obesity, Diabetes and Gastric Bypass Surgery

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             Glucose

Several semesters ago, I was teaching a course called ‘Human Biology’ as an adjunct. As opposed to my normal class in General Biology, this one contained an anatomy and physiology component. My own history in the lab is one of a molecular and cellular biologist. The only system that I know reasonably well from personal experience is the immune system, so I was learning a lot by teaching this class and doing the reading to remind myself of what I learned many years ago.

I particularly enjoy making class a discussion about specific topics that my students are interested in (even if I cannot always answer such varied questions) and one day a student asked why it was that gastric bypass surgery immediately cured diabetes.  

As I said, I’m something of a novice in these areas of systems biology, and given what I knew I could not come up with a reasonable explanation. In fact, I doubted that this could happen and the weekend digging for any publications describing the effect. To my surprise, it was well known. Unfortunately, no one else had a very good explanation for it either. However, as asserted in the associated Perspective article, “gastric bypass surgery pImageatients can stop taking diabetes medications before substantial weight loss has occurred” –  a surprising feature of the intervention also seen by my student (who had this surgery himself). This suggests that the surgery itself must trigger a hormonal change in patients, rather that weight loss simply reversing the condition over time.

Happily, the most recent edition of Science caught my eye with an article titled, ‘Reprogramming of Intestinal Glucose Metabolism and Glycemic Control in Rats After Gastric Bypass,’ by Saeidi et al that examined the effect in a rodent model. As Hans-Rudolf Berthoud explains in his review of the work, 

“glucose preferably enters the pentose phosphate and other glycolytic pathways that provide substrates for nucleotide and protein synthesis, consistent with accelerated tissue growth. Most important, and as an “unintended” by-product of increased glucose uptake by the expanding gut tissue, systemic glucose concentrations are reduced and the diabetic state is reversed.”

As satisfying as this finding may be, it remains a mystery why this effect would persist long term after the new gut has completed its transformation. An alternate, or perhaps complementary explanation for this effect in humans may lie in the extreme calorie restriction patients are required to adopt post-surgery. “When control subjects were given the same low amounts of food eaten by surgical patients, the same rapid improvements in glycemic control were observed,” providing evidence for a non-surgical pathway to the same endpoint. 

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One last point…

This article immediately reminded me of work done by Craig Thompson and others on the relationship between obesity, diabetes and cancer, summarized in a review article in a 2009 issue of Science. This article described how it is that obese individuals suffer higher rates of cancer than non-obese persons. Among the links they described was how obesity leads to type 2 diabetes resulting in higher blood sugar concentrations, a condition favorable to oncogenesis.

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                    Explaining the Warburg Effect

The same article went on to add that cancer cells often use glucose in a way that that is surprisingly inefficient in terms of the energy it captures (known as the Warburg Effect). This paradox of rapidly dividing cells apparently underutilizing glucose was resolved once it was observed that cancer cells get not only energy from glucose metabolism, but building materials to keep up with the unusually high demand that rapid grown imposes.

Altogether, these articles do much to clarify how the body utilizes fuel, regulates blood glucose and the what the overall health affects of these regulations.

 
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Posted by on July 27, 2013 in Uncategorized

 

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“Greed is Good” -or it least it feels that way to some people

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Hey buddy, watch the paint!

An interesting article appeared in PNAS, the Proceedings of the National Academy of Science, last year: “Higher Social Class Predicts Increased Unethical Behavior.” Thank you to Xenophilius for posting a link to this. Basically, the paper reports the behavior of motorists based on the ‘status level’ of the car they drive. “[W]e used observers’ codes of vehicle status (make, age, and appearance) to index drivers’ social class.” Unfortunately, this is all that was said in the article and its supplementary material about how ‘vehicle status’ was calculated.

I can’t say that the results of this study are surprising, but it does provide some support for the feeling that people in ‘rich’ cars act more callously towards people than those who drive more common vehicles. The data presented here shows the likelihood of a car yielding to a pedestrian at a crosswalk (something mandated by California State Law.Image

 

I have always remained convinced that BMWs are the only cars on the road where blinkers come as optional equipment.

 

 
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Posted by on July 25, 2013 in Uncategorized

 

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All in a kerfuffle

I’m all bent out of sorts since I decided to write about the green coffee extract paper popularized by Dr. Oz. 

Here’s the problem: in my last post I attempted to unpack the data presented in the article describing a weight loss trial using this supplement. Yet, the closer I examined the data, the more clear it was to me that the data presented in that paper does not support any conclusions.

This does not mean that the supplement is effective or not. It doesn’t even mean that the group is lacking in data that would answer the question. It merely means that the numbers they present and the descriptions of their methods do not allow one to scrutinize the data in a way that supports or refutes their claims.

ImageFor anyone interested in a fun discussion of statistics and what they mean, I strongly recommend the classic text, How to Lie with Statistics, by Darrell Huff.It’s a bit out of date, but still a lot of fun to read and educational for those who have not spent much time analyzing figures.

One thing the Mr. Huff’s book does well is brings the reader into the discussion of data and how to present it. A lot of his focus is on how advertisers manipulate their graphs and language in order to obfuscate the truth.

I don’t think this coffee extract paper is intentionally obfuscating the truth, rather, I think the confusion comes from an inability of the authors to present their data clearly (even to themselves perhaps). I’ve worked in a number of labs with a number of scientists in my life and I can say with conviction that not all scientists ability to analyze their data is the equal. In fact, I have seen a number of presentations where the presenter clearly did not understand the results of their own experiments. I can say that sometimes I have not understood my own data until presenting it before others allowed us to analyze it together (i.e. I am not exempt from this error).

I would love to have the opportunity to examine the raw data from these experiments to determine if they really do address the question – and whether, once addressed, the question is answered. I’m going to appeal to both the journal and the authors for more clarification on this and will report my findings here. 

 

 
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Posted by on July 23, 2013 in Uncategorized

 

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Because it was on Dr. Oz, I’m more likely to think it’s a scam

doctor-ozI got something interesting in my inbox the other day. Something that I assume was a  friend’s email address getting hacked – although it’s the least offensive (apparent) hack I’ve ever seen (he says as the viruses circulate around his computer’s RAM).

It was a nearly blank email with a link to a Dr. Oz clip about the weight-loss promoting effects of green coffee extract, which contains high concentrations of chlorogenic acids. These molecules are said to promote weight loss through increasing metabolism.

Being a scientist means being a skeptic. In this case, because I already feel like it must be BS due to its connection with Dr. Oz (an Oprah-elevated proponent of many untested, ‘alternative’ therapies), the challenge for me is to admit the possibility that this stuff may work. So, rather than looking through the data to see if there’s anything to deny the claim, I’m really trying hard to look at the data to see any glimmer  of possibility.

Here’s a link to the Dr. Oz article online. The article was published in the January 2012  Diabetes, Metabolic Syndrome and Obesity, and happily the entire article is available free of charge. So let’s look at the data…

The article examines a “22-week crossover study was conducted to examine the efficacy and safety of a commercial green coffee extract product GCA™ at reducing weight and body mass in 16 overweight adults.” Half of the participants were male and half female – a typical study setup (although I do worry about how data is handled when looking at both sexes together, so let’s pay attention to that.)

Dr. Oz’s website indicates that “The subjects (taking the supplement) lost an average of almost 18 pounds – this was 10% of their overall body weight and 4.4% of their overall body fat.” These are pretty hefty claims, but I could use losing 18lbs, so let’s see where this goes.

The study followed those eight men and eight women for 22 weeks. At the beginning of the study, the average body mass index (BMI) at the start of the study was 28.22 ±  0.91 kg/m2 . Determine your own BMI here.

Note that BMI < 18.5 is underweight

18.5  –  25     healthy weight

25   –   30      overweight

30+               obese

This puts the study participants at the high end of overweight, but ‘preobese’.

Dosages of the green coffee extract and placebo were as follows:

“This study utilized two dosage levels of GCA, as well as a placebo. The high-dose condition was 350 mg of GCA taken orally three times daily. The low-dose condition was 350 mg of GCA taken orally twice daily. The placebo condition consisted of a 350 mg inert capsule of an inactive substance taken orally three times daily.”

I don’t think I’m the first one to point out that it’s hard to have a double blind trial when the dosages are distinguishable (two times vs three times daily). At least the placebo should be indistinguishable from the high dose.

One early eye-catching piece of data is from Table I, that summarizes the data of all precipitants as

BMI (kg/m2) pre study:28.22 ± 0.91        post study:25.25 ± 1.19     change-2.92 ± 0.85**, -10.3%

On average, all subjects lost weight during the study. But this really tells us nothing because we could see a 10% drop in BMI if the test arm lost 20% and then placebo arm stayed the same, or we could see the same thing if the weight loss occurred during ALL arms of the study.

Perhaps this reporting of data is justified by the next statement that participants all rotated through being on high dose, lose dose or placebo with intervening washout periods. Presumably, this makes the most of a small sampling of people, but I do find it harder to be confident about the data. Then again, I have never been involved in any human trial of this kind.

here’s the data:

High Dose arm:

start    BMI (kg/m2) 26.78 ± 1.55  –>    end 26.03 ± 1.36

Low Dose arm:

start    BMI (kg/m2) 26.25 ± 1.37  –>    end 25.66 ± 1.20

placebo arm:

start    BMI (kg/m2) 25.66 ± 1.20  –>  and 26.67 ± 1.72

At first glance this might appear to be pretty good. But let’s graph it out:

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the data continue to look great.

Now, with error bars:

ImageHuh. Not so hot anymore.

Also, I’m not how sure this was done, but they get p values for HD p = 0.002, LD p = 0.003, placebo p = 0.384. These stats mean that the HD and LD groups are showing very significant differences, while the placebo group is not. You should be able to see this in the graph with error bars (as an approximation of significance). Unfortunately, I see a whole lot of no nothing. But, perhaps BMI is not the appropriate way to observe weight change (we are, after all not seeing specific weight changes, but changes within a group, i.e. diversity)

Another way to try to see what’s going on is to take a look at the weight data:

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The data were presented in a number of other ways, but each of these was confusing and didn’t illustrate any clear conclusion (my interpretation).If the individuals’ data were visualized as a scatter plot, this might show us something – or data for each individuals change while in each group… As it is, we see unclear data with spectacular statistics, but we don’t get to see enough to be convinced of the changes.

Rather than go on and get more and more skeptical, let’s say, although we don’t see a lot here, the data,as reported, would make us want to see a larger study with some revisions for control of diet, exercise monitoring and a change in the way osage is administered so as to maintain the ‘blindness’ of the study.

 
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Posted by on July 22, 2013 in Uncategorized

 

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V GER

ImageLast week’s Science magazine had a pair of articles about Voyager 1’s arrival at the heliopause and the fluctuations of particles it has encountered. For about a year astronomers have been talking about the limits of the solar system.  An idea that I admit I had never entertained in any absolute way. Instead, my image of the extent of the solar system is mostly shaped by the most distant planets’ orbital paths. Sometime in the past decade or two, I became aware of plutoid objects, among which Pluto is one and that there is an Oort Cloud beyond that. I’ve always been a bit hazy about the details of what comprises the Oort cloud and how this differs from the plutoid objects.

Sometime during the conversation ignited by Pluto’s demotion to a dwarf planet, I head a good description of the solar system that described it as: four small, rocky planets close to the sun, then a belt of asteroids, followed by four large, gas planets, then another ring of small objects.

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The edge of the solar system

I really am looking for someone to explain this in terms that a reasonably intelligent person without much astronomy background can comprehend. That is, I don’t want too much left out, but I’m not necessarily ready for an overly technical explanation.

With respect to local suns, what is the position of our solar system? What forces interact between the suns? What do we know of the space between solar systems (or between galaxies?)

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A simplistic view of nine balls circling a star

That’s a pretty tidy description, but I think it leaves out a lot.

The interest now is in defining the edges, the limitation of the sun’s influence on space in favor of extra-solar forces. From what I gather, this is referring to both ‘solar wind’ and magnetic field.

I can understand this from the inside (although I need correcting here too) ,  but what I don’t fully grasp are what the forces are outside of the solar system. What dominates those forces? One thing I notice in the illustrations I’ve seen is a teardrop shape to the system resulting from a unidirectional current. What is this current? Is it emanating from other solar systems? Some local influence of nearby stars? Or a galactic force?

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Heliosphere warping under external pressure

I hope someone out there can help me understand this better.

 
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Posted by on July 20, 2013 in Uncategorized

 

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Limited Time Promotion – 100% off

Until Sunday, my iBooks, The Thirteenth Labor of Heracles, In Parts and The Curse of Sisyphus are free in the iTunes Store. Click the titles for more information.

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Can I hez Brainz?!!!

 
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Posted by on July 19, 2013 in Uncategorized

 

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Dry County – prayers for rain

ImageLast Year I wrote extensively about the drought conditions here in Kansas.

Luckily, we had a very wet winter and spring this year, catching us up on our annual precipitation data, but since the beginning of June, the rain has stopped (maybe even longer, I’m just relying on memory, not real data here).

As much as I dislike hot weather, I dislike drought even more. I feel as though I, as well as my plants and yard, get my energy from the rain. And this year is shaping up a lot like last year.

More than just feeling better when it rains, I was really hoping for a wetter year this year to help replace some of the trees that died in our yard from last summer’s conditions. Despite my efforts in setting up automatic watering systems and taking garbage barrels of water to our parched trees, I simply couldn’t keep up.

This year, my strategy was to get cheap, small trees from Walmart and Home Depot to at least lower the financial risk (we spent about $1k last year and lost every one of the trees we planted in addition to others throughout the yard). This year, our investment is only around $150 and we have about twice as many new trees as last year.

Anyway, here’s some actual data from NOAA that illustrates our wet spring + dry summer:

Current Condition: Abnormally Dry

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Year to date: KC at ~100% or better precipitation

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Spring Data (April 1 – May31): Already Drying up (~60%)

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(I guess the rain stopped earlier than I remembered)

Although there is no data available for the current period, I don’t think we’ve had so much as a shower since May 31.

 

 

ps- just to clarify, I don’t live in a dry county – that would be intolerable.

 

 
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Posted by on July 17, 2013 in Uncategorized

 

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