4th Thursday Update

September 24, 2015

Note: this post was revised a bit on Friday, because I didn't think I made my point clearly enough in the version I posted on Thursday.


Stockholm Syndrome?

I think most people are vaguely familiar with the term Stockholm Syndrome, as the name of a bizarre psychological phenomenon in which a hostage begins to identify with his or her captors. (It's also called capture-bonding, which is a straightforward term; the less-straightforward term Stockholm Syndrome refers to a 1973 bank robbery in that Swedish city, in which bank employees, after several days spent as hostages, sided with their captors against their rescuers.)

There is more speculation than knowledge about what causes Stockholm Syndrome, but it seems to be part of a larger pattern in the way the human mind adapts to intolerable trauma, and protects itself, by re-imagining the source of the trauma as appealing rather than menacing. (It might be part of the same mechanism which causes many people to be sexually aroused -- in fantasy -- by things which would frighten and disgust them in the real world.) The most popular evolutionary speculation about Stockholm syndrome is that, in pre-historic human societies, being captured by a rival tribe and forcibly incorporated into it was a common enough experience for human females that some kind of adaptation for it was needed. (Sounds like pure guesswork to me, but the bottom line seems to be: people sometimes deal with a situation that's forced on them by telling themselves they love it.)

Contrary to popular belief, Stockholm syndrome is not seen only in people kidnapped by criminals and terrorists. It is fairly common in people who are caught in abusive relationships. Perhaps some people find it more painful to wonder "why is he hitting me?" than to think "he's hitting me for my own good, and anyway I was kind of asking for it -- I shouldn't have given him that look". People who feel trapped in a situation sometimes fear they will go mad if they admit to themselves how bad the situation is -- so they don't admit to themselves how bad the situation is.

I tend to apply the term Stockholm Syndrome to any situation where someone seems to be a happy captive -- including those situations where being surrounded by members of an institution or an industry makes someone want to identify with that institution or industry, and see the world through its eyes. When we hear about government officials being "captured" by the industry which they are allegedly regulating, I think of that as a kind of Stockholm Syndrome. When the U.S. military "embeds" a journalist within a platoon, so that the journalist identifies with the platoon and therefore refrains from criticizing anything it does, I think of that as a kind of Stockholm Syndrome. When people within an industry only see reality through the filter of that industry's interests, I think of that as a kind of Stockholm Syndrome. When people in a profession don't look beyond their own professional concerns, I see that as a kind of Stockholm Syndrome. Our tendency to embrace, with apparent enthusiasm, whatever restrictive conditions we find ourselves in may be "natural", but it's a bit of a problem. It doesn't tend to promote a good objective understanding of the world.

No doubt I am sometimes unfair about this, suspecting more dishonesty or a delusion in a situation than is actually present, but I tend to think that suspicion is a pretty good starting point when you're evaluating health claims. (Why do they believe this, and why do they want me to believe it?)

I offer all this as an explanation of why I was so suspicious of the news coming out of -- wait for it! -- Stockholm this week. Here is Medscape explaining the aftermath of a presentation at a recent medical conference in that city: "Experts in diabetes and cardiology are both excited and admittedly somewhat perplexed by the results of the EMPA-REG OUTCOME study reported at the European Association for the Study of Diabetes (EASD) 2015 Meeting last week and published simultaneously in the New England Journal of Medicine. Hailed as historic, the findings were presented to a packed hall in Stockholm, where audible gasps and spontaneous applause erupted each time Silvio Inzucchi, MD, of Yale Diabetes Center, New Haven, Connecticut, showed a slide demonstrating how the survival curves for the high-risk type 2 diabetes patients taking empagliflozin (Jardiance, Lilly/Boehringer Ingelheim) diverged from those on placebo over the course of the 3-year trial, with the effect starting very early, at 3 months."

Audible gasps and spontaneous applause? We're talking about the Stockholm EASD meeting, right? Not Burning Man?


What caused the gasps was a set of graphs illustrating a comparison between the health outcomes of diabetes patients treated with an SGLT-2 inhibitor called empagliflozin and a placebo. (SGLT-2 inhibitors are those drugs which interfere with normal kidney function in such a way as to cause glucose in the bloodstream to leak out in the urine, thus reducing the concentration of it in the blood.) Consistently, the patients given empagliflozin fared better in terms of cardiovascular death, death in general, and heart failure than patients given a fake pill containing no medication:

The final graph combines all risks together; the divergence may be smaller overall than one might expect, but that is partly because a larger scale is used on the X-axis, compressing the range of variation:


The reason this consistent, though perhaps not terribly dramatic, difference between the tested diabetes drug and a placebo produced "audible gasps" is that other diabetes drugs usually produce no measurable divergence (in terms of cardiovascular risk) between people taking the drug and people not taking it.

It might sound as if I'm making this up --it makes no sense, after all -- but cardiovascular disease is the most significant and dangerous "complication" of diabetes, and yet most diabetes drugs don't seem to do anything to protect us from it. Apparently empagliflozin does do something to protect us from it. It doesn't eliminate cardiovascular events, but it reduces the risk of them, and no other diabetes drug has done even that much. (Some diabetes drugs even seem to make the cardiovascular risk worse.)

But now doctors have to start asking some challenging questions:

Whether any of this is truly gasp-worthy is hard to say. I would like to see a head-to-head competition between empagliflozin and exercise, to see which one of the two has a greater impact on glycemic control, blood pressure, and cardiovascular risk. I'm inclined to think that exercise has done more for me, in those regards, than empagliflozin would have done -- and so far exercise has not given me a urinary tract infection. (I've never had one of those, but the reports I hear about them don't make me want to expand my personal knowledge of that problem.)

The gasping physicians in Stockholm were probably impressed to such a remarkable degree because they were encountering something unfamiliar: encouraging data about a diabetes therapy which actually made patients less likely to die. They were used to seeing data which showed that a diabetes therapy had the effect of making the patient's final lab report before dying look better than it would otherwise have done. A diabetes therapy that went beyond improving the posthumous lab report, and actually made people live longer, seemed almost like a miracle to them. However, might it have seemed less miraculous to them, if they had ever looked at anything other than studies comparing one drug to another (or to nothing?) The narrowness of their focus on pharmaceuticals has made it hard for them to consider other possibilities.

To call their bedazzlement by the new data 'Stockholm Syndrome' is probably going too far. Still, I can't help feel that empagliflozin is exciting doctors and researchers in a way which it wouldn't if they'd had a chance to compare it with running or cycling.

However, if this drug is destined to become the standard drug therapy for diabetes, I'm glad to hear that it looks like an improvement on the other available drugs. Whether it's an improvement on exercise is a question for another day.


3rd Thursday Update

September 17, 2015


Diabetes, hemoglobin A1c, and risk

A lot of people hate quantitative thinking, and this is especially true when health and safety are under discussion. They don't want to hear any numbers. They don't want to be told about proportions or probabilities or "risk factors". They don't want to hear about what the odds favor or don't favor. They just want to be told, in absolute terms, whether a particular mode of travel is "safe" or "unsafe", and whether a particular food is "good for you" or "bad for you", and whether having a particular fasting blood glucose result means you're "fine" or "about to die".

There are two big problems with this way of looking at things. First, we live in a universe governed by the laws of physics, and that means everything that happens to us is all about proportions and probabilities rather than absolutes. If you try to leave numbers out of it, you will misunderstand pretty much every phenomenon of the real world that is ever going to have an impact on you.

The second problem is that trying to leave numbers out of your understanding of the world sets you up to be taken advantage of by advertisers and crooks (we will assume those are separate categories) who know how easy it is to put one over on non-quantitative thinkers. Countless diabetes patients, having heard that whole-wheat bread has more fiber than white bread, and therefore has less glycemic impact, jump to the conclusion that the difference is large (it's not!) and that they don't have to worry about the glycemic impact of bread in a meal so long as it's whole-wheat bread (utterly untrue!).

In addition to making you a sucker for misleading health claims, non-quantitative thinking also sets you up for needless health scares: plenty of people with diabetes get terribly depressed about health problems they assume they will suffer (and cannot prevent) because they haven't taken a realistic look at the probabilities.

Lately I have been seeing scary-looking health headlines about diabetes patients having high rates of dementia. I haven't been inclined to read these things, because I didn't think they would be a source of good cheer, and because I'm already used to be being told that virtually everything that can go wrong with a human body is more likely to happen if you have diabetes, and finally because I feel that I'm already doing whatever can be done to address the issue. But I suspect a lot of diabetes patients who've heard about this issue react by getting depressed, because they think it means everyone who has diabetes will also develop dementia, and there's nothing we can do about it.

Curiosity finally got the better of me when I heard that a large Swedish study uncovered some hopeful indications that the dementia problem among diabetes patients might be preventable.

The researchers looked at a large number (nearly 400,000) of patients with Type 2 diabetes who were in the Swedish National Diabetes Registry, and sorted them into categories to see which factors caused a large increase in their risk of developing dementia.

The various categorizations were each analyzed to find the dementia "hazard ratio" for being in that category. The hazard ratio is a multiplier which increases or decreases the usual average risk of developing dementia. A hazard ratio of "1" means normal risk. A hazard ratio of "2" would mean twice the normal risk (that is, the risk went up by 100%). A hazard ration of "1.5" would mean the risk went up 50%. A hazard ratio of "0.5" would mean the risk was 50% below normal risk.

All sorts of random variations can seem to show a small difference in risk in a comparative study of this kind. However a large difference is a lot more likely to be significant. I would be concerned about any factor which seemed to show more than a 25% increase in risk -- that is, a hazard ratio of 1.25.

In this study, only a few factors showed a that large an increase in risk. I've highlighted those factors here:

The worst risk factor (not too surprisingly) was having had a stroke in the past; the hazard ratio there was a whopping 7.69, meaning that a patient who'd had at least one stroke was 7.69 times as likely as the average patient to develop dementia. The other significant factors increasing dementia risk were macroalbuminuria (leakage of protein into the urine -- an indicator of kidney disease) and elevated hemoglobin A1c results.

But wait a minute! The hazard ratio associated with elevated A1c depended very heavily on how elevated the patient's A1c result was. Let's take a closeup view of the A1c categories:

Patients with an A1c of 10.5% or higher had a risk factor of 2.36 (more than double the normal risk of dementia), but the risk factor was only 1.20 for patients with an A1c of 7.5 to 8.5%, and for patients with an A1c below 7.5% there was no increase in dementia risk (there was even a tiny decrease in it, though that is probably just meaningless random variation in the stats).

So, diabetes can set you up for dementia, but only if it's very poorly controlled. Well-controlled diabetes doesn't seem to have any significant impact on your dementia risk.

If you shun quantitative thinking, you might make the depressing assumption that merely being diabetic means you have dementia in your future. If you embrace quantitative thinking, you may be able to take some comfort in looking at the probabilities and finding that, for you, the risk is low. Or, if you find that the risk for you is high, you at least know what needs to happen to make the risk low. Bring your A1c down and you bring the risk down with it. Dementia may be unusually common among diabetes patients, but it's a preventable problem, not an inescapable fate.


Health headlines to ponder

And it's about time, too!

I'm willing to bet it has turned up in odder places than a French lab.

Who saw that coming? But, now that that's settled, maybe the researchers should see if they can find any link between wife-beating and wife-beater undershirts! (And they just might be able find out by interviewing the same set of people.)


2nd Thursday Update

September 10, 2015


Heat wave!

Most Americans think of the Labor Day holiday (which we celebrated on Monday) as marking the end of summer. Maybe so, but here in California we're having a heat wave, with triple-digit temperatures all week (that means 38 degrees and up, for those of you living in nations which the march of science has reached). The local soil is being baked into terra-cotta.

Exercising outdoors is a bit of a challenge under the circumstances, especially as my main opportunity to do it these days is at lunchtime. I ran today -- on the shadiest route available to me -- and afterwards I just lived with the fact that, even following a cold shower, I was sweating heavily for half an hour after I got dressed. (I had a meeting this afternoon with my boss's boss, and I made sure to schedule the encounter late enough that I would be dry by the time I had to go into his office.)

I live in a woodsy neighborhood, with a lot of shade, so most of the year I have absolutely no need for air-conditioning. Which is good, because I don't have air-conditioning. Usually there are no more than two weeks in a year when I'm wishing I did have some equipment to chill the air for me -- but this is one of those weeks.

It's funny how a heat wave can affect your mental attitude toward everything. "No, no, no -- it's too hot for that!" becomes your reaction to a particular food, drink, color of shirt, or type of music. (I'm currently listening to Ravel's piano music -- which I have regarded for many years as cooling music for reasons I cannot begin to explain.)

Another thing the heat can affect is concentration. I don't think I have enough attention span to write one of my lengthy essays tonight. So, I'll just write some short commentaries on whatever health news relevant to diabetes has come my way lately. With any luck, I'll remain conscious long enough to finish this and upload it, even though I am wilting and shriveling pretty fast.


Gestational diabetes affects fathers?

Bear with me, this is a little weird. It is well known that women who develop "gestational diabetes" (a temporary diabetic condition occurring during pregnancy and ending after delivery) have a very high risk of developing ordinary Type 2 diabetes later on. One wouldn't expect this to have any influence on the father's risk of becoming diabetic, yet it apparently does. At least, that is what some researchers are reporting, based on an analysis of data from Quebec. "We observed that the incident of diabetes was 33% greater in men whose partner has gestational diabetes compared with men whose partners did not have gestational diabetes."

Okay, so what's going on here?

Gestational diabetes appears to be Type 2 diabetes, manifesting itself ahead of schedule (in young women who would have developed it anyway, later in life) because the physical stress or physical changes occurring during pregnancy overstrain the endocrine system. The women who develop gestational diabetes are probably women with a genetic predisposition to Type 2 diabetes; if they'd had no children, they wouldn't have got a preview of what nature had in store for them after their child-bearing years.

How could this have any impact on their husbands, though? Here it's important to remember that Type 2 diabetes has both a genetic component and a lifestyle component. Perhaps couples tend to share the same eating habits and exercise habits, or at least closely enough for their shared lifestyle to have a measurable impact on their health risks.

Because the fathers would not have the same genetic factors as their wives, we wouldn't expect them to have the same risk of becoming diabetic, and they don't. Having a wife with gestational diabetes only ups your Type 2 risk by 33% -- but being a wife with gestational diabetes ups it by 700%! The impact of living with someone who is destined to develop Type 2 later on has a comparatively modest impact, but it does have enough of an impact for researchers to be able to measure it.

I hasten to add that this doesn't mean the genetic component of diabetes risk is huge and the lifestyle component is small. It's doubtful that the fathers in the study ate exactly what their waves ate and got exactly the amount of exercise that their wives did. The similarity of their lifestyles might not have been very close. But it was close enough to make a difference to the outcome.


Bariatric surgery for diabetes -- how successful?

Bariatric surgery (that is, weight-loss surgery) has been shown to have a dramatic impact on Type 2 diabetes patients; many become non-diabetic shortly after surgery. But how long does this effect last?

For a while there was no way to know, because bariatric surgery is a recent innovation. However, there are now a fair number of diabetes patients around who had the surgery years ago. A new study from London (a mighty small study, but perhaps meaningful nevertheless) has found that bariatric surgery works better than "conventional" treatment (that is, drugs galore) at the five-year mark. Specifically, 50% of patients were non-diabetic five years after surgery, compared to 0% of patients after five years of pharmaceuticals.

Okay, I guess I'm supposed to be impressed. Most of the world probably is impressed. But I'm still non-diabetic after fourteen years of neither drugs nor surgery, so I'm not exactly overawed by learning that the surgical operation has an awesome 50% success rate -- even if that is pretty good compared to what the drugstore-cowboy approach achieves. And my approach is a lot cheaper than either of those (provided you ignore the high cost of exercise clothing, anyway!).


Half the population is either diabetic or getting there

An analysis of statistics from 2011-2012 shows that about half the US population has diabetes or pre-diabetes (that's 12-14% for diabetes, and 37-38% for pre-diabetes). Some have called this "a glimmer of hope" because the recent trend toward an increase in diabetes prevalence seems to be leveling off. Maybe it won't get much worse than this.

The distinction between diabetes and pre-diabetes is largely a legal fiction: it matters to the bean-counters at your health insurance company, but it doesn't have a great deal of impact on reality. It would be more honest if we described "pre-diabetes" as "Type 2 diabetes that hasn't got very far out of control yet".

I guess the good news here -- the silver lining that I always look for -- is that people who feel "isolated" by being diabetic are not as isolated as they think. Being diabetic doesn't really give you a minority status anymore. Half the country is in the same boat. Maybe this will eventually lead to people making up their minds to deal with the problem a little more effectively than we have been so far.


Grinding down fiber is not a good thing

Whatever else might be causing the increase in Type 2 diabetes prevalence during modern times, it has long been suspected that excessive "refinement" of grains has something to do with it. Milling of wheat to produce fine, powdery flour has resulted in tiny, easily-digested starch particles becoming a big part of the human diet.

A new study finds that the "bioaccessiblity" of starch (that is, the ease and rapidity with which the digestive process can extract glucose from a high-carb food) is strongly affected by the fine milling of grains. Compared to coarsely ground grains, the powdered variety cause a sharper glucose spike (and a more exaggerated insulin response, along with other undesirable physiological effects). This difference in the body's response to smaller starch-particles suggest that they represent a risk factor for Type 2 diabetes.

Grittier grains might be a good bet for people trying to avoid becoming diabetic.

For people who already are diabetic, coarser grains aren't necessarily good -- they're just less problematic than fine white flour.

I've said it before and I'll say it again: don't be too ready to jump on the "whole grain" bandwagon, and assume that any high-carb food is okay for you so long as it says "whole wheat" on the label, or something similar. Often these things are only a tiny bit better than the alternative; let your glucose meter, not an advertising claim, tell you whether or not a particular kind of bread won't spike you too much.


1st Thursday Update

September 3, 2015

Uh-oh... it's getting to be that time of year...

As sunset times get earlier and earlier (7:38 PM today -- when it was exactly an hour later, just one month ago!), it is becoming impractical to continue my evening trail-runs at the state park. I can't get there early enough to be sure I'll still have some daylight left at the end. I went for a hike there yesterday after work, and found that, even early in the hike, I was catching only the last of the day's sunshine.

Of course, I'm all for twilight in a general way -- running at sunset has a special atmosphere to it, and it's a relief to be running as the air is starting to cool off.

However! If you're going to go for a long run, you want to feel confident that you're not going to be stumbling around in the dark during the final mile.

The terrain is too rough for that to be safe. Clearly, trail-running is going to be a weekend-only thing until next summer.

Of course, one of the advantages of exercising outdoors is that it puts you in touch with nature's cycles in a way that nothing else does.


By the way: I'm not against science!

Because I am so often critical of the questionable ways in which health research is conducted and financed (and selectively cited as a justification for policy decisions actually motivated by something else)... because of all that, it might look as if I'm an opponent of medical science. Or, if that is putting it too strongly, it might look as if I am seeking some alternative version of medical science, something which sounds kind of "sciency" but accepts unverified claims. Something which welcomes traditional wisdom, and maybe even alternative ways of knowing. Well, forget that! I don't think there are any alternative ways of knowing.

There are alternative ways of guessing, certainly. But the only way to find out if a guess is worth anything is to test it rigorously against reality and see how well it fits. There is nothing "alternative" about that process; that is quite simply science. If you want to know how something in nature actually works, science is the only game in town. The alternative ways of knowing are strictly for people who would prefer to accept someone's untested guess about how nature works.

Because science is about testing guesses, and because the testing process is far more important than the guessing process, even a guess made for silly reasons sometimes turns out to be right. Practitioners of traditional medicine from China to the Amazon have spent years treating people with various substances for various medical conditions; it would be surprising if they never found anything that actually helped. But that doesn't mean all the medicines they use actually help (or that a traditional medicine which alleviates one condition also alleviates the other conditions it is prescribed for).

Anybody can make a guess, and some guesses are lucky, but only science can sort out the lucky guesses from the unlucky ones. Guesses that haven't been put through the sorting process are called "alternative". Hence the riddle: what do you call alternative medicine that has been shown to be effective? (Answer: medicine.)

Not everyone wants to see guesses put to the test. Some people would prefer to accept whatever guess makes a good story, and would rather not risk the unpleasantness of discovering that a story they like was tested and it failed. They become uncomfortable with too much discussion of evidence; they ask others to be "open-minded", a quality which apparently boils down to a polite willingness to accept an unlikely story without checking it.

And yet: these people want it both ways. They want to see themselves as being reasonable and even scientific. Often they fall back on conspiracy theories: the apparent debunking of a claim wasn't legitimate; it was done by people who claimed to be skeptical scientists, but were actually working as hired goons for Big Pharma. True science, honest science (if it were allowed to be done at all) would support the claim!

No one is more concerned than I am by the way medical research is increasingly financed by those with a commercial stake in getting one result rather than another, but this problem manifests itself mainly in studies claiming to show that a new proprietary pharmaceutical reduces blood pressure, not in studies finding that some herb or other doesn't reduce blood pressure. The biggest problem created by the influence of drug-company money on medical research is a tendency to study the wrong issues and ask the wrong questions. Researchers are asking themselves how they can make the next billion-dollar drug, and seldom if ever asking themselves how they can help people be less dependent on drugs.

Science is only a process, of course, and its work is never done, so there are plenty of things science has not explained yet. It's difficult to get to the bottom of a scientific question -- especially one related to human health, if you're not going to raise people in cages and do dangerous experiments on them. So, yes, there are important gaps in medical science waiting to be filled. If you want to complain that "scientists don't know everything!", you're right -- scientists don't know everything. But the anti-science people don't know anything; given a choice between incomplete truth and complete fiction, I have to bet on the former. I'll be damned if I'm going to support the latest celebrity airhead trying to convince people that they shouldn't vaccinate their children because reasons.

I have certainly been known to criticize the way the health care industry uses iffy science to justify whatever they're planning to do. But the solution to that kind of problem is more and better science, not a retreat from science. A lot of people seem to think that we ought to chuck this "science" thing, and start over with something more appealing. I'm not on their side. I don't care how strongly they feel that we can cure diabetes by eating an ounce of chrysanthemum seeds every day. Feelings are not what this is about. Finding out what actually works is what this is about.

I just thought I should underline that point. Are we clear?


Smoking and diabetes

Who could possibly have guessed that smoking and diabetes in combination were more harmful than diabetes alone? And yet, that is what the latest study finds. Apparently smoking adds about 55% to the mortality risk of a diabetes patient.

Knock it off.


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