3rd Thursday Update

November 20, 2014

 


How not to write a headline

The titles of research papers, and even the titles of articles summarizing them, tend to be awkwardly lengthy. Health-news websites which link to such things usually shorten the titles considerably. Because link titles exist for the sole purpose of inducing people to click on them, the shortened title is usually crafted to make it sound edgy and provocative, even at the cost of badly misrepresenting what the linked article actually says. The problem with this approach is that not everyone who sees the misleading headline actually clicks on the link, so the false impression created by the headline persists in the minds of all the people who saw it.

An example I saw today was on the Science News website: "Exercise Regimens: Little Benefit for Diabetes?". I suppose that question mark on the end is supposed to let them off the hook for putting such an irresponsible message out there, but I don't think that's a good enough excuse.

What the article actually says is that, owing to unfortunate genetic factors, 20% of diabetes patients are unable to obtain from exercise the benefit of increased insulin sensitivity (and therefore improved glycemic control) which 80% of diabetes patients are able to obtain from exercise.

What the article did not say was that any diabetes patients were unable to obtain from exercise the benefit of improved cardiovascular health. Everyone needs that benefit, and diabetes patients need it more than anyone else does, given that diabetes is notoriously hard on the cardiovascular system. So, even if you know for a fact that you are among the unlucky 20% of diabetes patients whose insulin sensitivity is not improved by exercise, you still need exercise for other reasons.

And even if improved insulin sensitivity were the only health benefit provided by exercise, it's still hard to argue that "large benefit for 80% of patients" can be fairly abbreviated as "little benefit".

 


About brown fat

These days I'm seeing a lot of health news about "brown fat", often in connection with diabetes and obesity. I thought it was time for me to educate myself a little on the subject, and share with you whatever I can learn on the subject.

It used to be that we didn't hear much about brown fat, because brown fat supposedly existed only in the bodies of animals that hibernate and, in humans, only in the bodies of infants. The general assumption was that human adults didn't have brown fat in their bodies, or at least not enough of it for this tissue to have much impact on our health. Lately that assumption has been overturned: apparently adult humans have a significant amount of brown fat, and it could be important to our health.

Brown fat (or "brown adipose tissue", sometimes abbreviated as BAT) is fat which consists of brown fat cells ("adipocytes") rather than the familiar white variety. It turns out that brown fat cells are very different from white fat cells, and serve a different function in the body. (In fact, brown fat cells are actually a modified type of muscle cell.)

White fat cells exist for the purpose of storing chemical energy. They store it in the form of a single, large fat droplet, which happens to be white in color.

Brown fat cells, by contrast, exist for the purpose of using chemical energy for heat-generation ("thermogenesis"). They do store fat, too, although not so much of it, and they store it in the form of numerous small droplets. But the real purpose of the brown fat cell is not to store chemical energy but to burn it. And they don't just burn fat -- they can absorb glucose from the bloodstream, and burn that as well.

Just to clarify: all cells generate at least a little bit of heat, because of the mitochondria (microscopic chemical power-plants) that the cells contain. But brown fat cells contain an abnormally large number of mitochondria, so they generate much more heat than other cells do.

The heavy concentration of mitochondria in brown fat cells also accounts for the brown coloration: iron compounds in the mitochondria darken the cells. Another factor causing brown fat tissue to be brown is a heavy concentration of microscopic blood vessels (the high rate of energy usage requires a high rate of blood flow). With all those blood vessels and iron-rich mitochondria, brown fat cannot look anything like white fat.

Hibernating animals use their brown fat to burn energy and maintain body heat during their prolonged winter rest. Human infants use it the same way, because infants have a harder time maintaining body heat than adults do. A baby's body has a high surface-to-volume ratio, and a comparative lack of muscle tissue; these and other factors make babies highly vulnerable to heat loss. Without brown fat, it would be difficult for humans to avoid dying of hypothermia during infancy.

It was assumed for a long time that, in adults, brown fat disappears, because the brown fat cells turn into white fat cells. Not so, apparently: brown fat cells are so different from white fat cells that the former cannot turn into the latter. However, because the adult body no longer needs to use brown fat to maintain body heat, the brown fat cells are largely deactivated: they lose a lot of their mitochondria, and the brown fat becomes pale enough that it's hard to recognize it for what it is. Also, deposits of brown fat in adults are concentrated in seemingly unlikely places: the neck and upper chest, between the shoulder blades, and around the kidneys. And some adults have very little of the stuff. It was difficult to study (or even find) brown fat in adults until advanced medical scanning technology became available, so it's no wonder researchers overlooked it for many years.

Brown fat has attracted a lot of research interest lately because of the possibility that reactivating brown fat within the adult body, so that it is constantly burning calories (and extracting glucose from the bloodstream for that purpose) could provide a way to prevent or treat obesity, diabetes, and other health problems.

Up to a point, this makes sense to me. Arctic explorers and mountain-climbers in the Himalayas, who are exposed to constant cold for extended periods, tend to lose weight dramatically even on a high-calorie diet, because their bodies are obliged to burn energy to maintain body heat. (Presumably their brown fat becomes vigorously activated during the ordeal.) And one small study found that activating brown fat through exposure to cold caused test subjects to experience increased insulin sensitivity and improved glucose control.

Have you noticed the obvious catch? Brown fat is activated by exposure to cold. The reason brown fat is deactivated in adults is that most of us don't need it to avoid freezing to death. If activating your brown fat requires exposure to serious cold, that might not be a lifestyle change everyone will want to make, even for the sake of weight loss or diabetic control.

Admittedly, the guys in those pictures from the Shackleton expedition look so cheery that it's hard to believe they weren't having a good time...

...but let's face it, anybody can make himself look buoyant long enough to pose for a snapshot. What if, in reality, the frostbite got old after a while?

Well, of course medical researchers are not planning to use hypothermia as a therapy (at least, I hope they're not). Most of them are now seeking ways to activate brown fat (and take advantage of its calorie-burning and glucose-eliminating capabilities) without having to freeze the patient. This probably means finding a drug which can mimic whatever chemical signals the body sends to brown fat (during prolonged cold exposure) to activate it.

Researchers are currently excited because they have discovered a hitherto-unknown signaling pathway which (1) activates brown fat, and (2) does not depend on insulin or sensitivity to insulin. Whether they can actually make a drug to manipulate this signaling pathway, and activate brown fat at will, remains to be seen. It would take a long time to introduce such a drug, partly because of concerns that activating brown fat in this way might have unforeseen and undesirable consequences.

We shouldn't get too carried away with the idea that activating brown fat is the solution to our problems. There could be a downside to activation of brown fat. In fact, there almost has to be a downside: why does the body only activate brown fat when it's absolutely necessary to protect against hypothermia, if leaving it active all the time would be entirely beneficial? Maybe there's a reason why the body deactivates brown fat whenever you're not freezing. There is some evidence that activation of brown fat promotes plaque buildup on arterial walls; this (rather than old people shoveling snow off their driveways) could be the real reason for the increase in cardiovascular mortality during the winter.

Most research into brown fat is done on mice, and the few studies done on humans have been exceedingly small, so all conclusions about what brown fat does (and what it could do, with a little help from the pharmacy) is extremely tentative. But it's a "hot" field right now, because the idea of fat as a solution rather than a problem is deeply appealing to people. It sounds like a sort of pharmaceutical Holy Grail: anyone who can make a drug that causes people to burn up calories (without doing anything!) is pretty likely to get rich.

So, I'm expecting to hear more and more about brown fat over the next few years, but I am skeptical that, for most of us, it will lead to anything useful.




Meanwhile...

 


2nd Thursday Update

November 13, 2014

 


Nature's plan for us

We tend to use the word "natural" as if it meant "benevolent" -- as if the natural world were doing its best to make our lives beautiful, comfortable, and of long duration. Whatever is right and proper we call "natural"; whatever is sick and twisted we call "unnatural". If anything is going wrong with human health (physical or mental), it is because we are departing from nature's way. The secret of leading a good life, a healthy life, is to align ourselves with nature's plan.

I can go along with that way of looking at things, up to a point. Certainly it can be a bad idea to disregard nature. Human physiology is what it is, and obviously it must be better adapted to some ways of living than others. Creating artificial living conditions always entails a risk of placing ourselves in a situation which the human body can't properly cope with. Sometimes "unnatural" really does mean unhealthy. That is why those who argue in favor of re-creating older ways of life, for the sake of improved health, can usually make a plausible case for themselves. Advocates of paleolithic diets, barefoot running, and other practices can always argue that these practices are automatically healthier, because human beings are adapted for them. If we can align ourselves with nature's plan, we'll do much better.

I'm not a complete sucker for the Disney view of nature, however. Nature's plan is not necessarily the ideal plan. In fact, nature's plan is not really a plan. Whatever works, works. Whatever leads to an increase rather than a decrease in the prevalence of particular genes within a local population is nature's definition of success. An organism may be beautiful or ugly, vicious or harmless; if it leaves more offspring (and there could be many reasons why it does or doesn't), it wins. That's the plan, to the extent that there is one.

The consequence of nature's very narrow, and sometimes brutal, definition of success is that nature doesn't really care if our lives are beautiful, comfortable, and of long duration. People in prehistoric times (and in primitive cultures today) may have been able to avoid many of the "diseases of affluence" which afflict first-world people today, but that does not necessarily mean that they led enviable lives. Let's face it: a lot of those people avoided chronic diseases by dying before they reached middle age. And from nature's point of view, what does it matter if you live past middle age? If you've lived long enough for your children to reach sexual maturity, you have fulfilled your part in nature's plan, and you can now get out of the way.

That sounds nasty to us -- because, in our hearts, we don't really accept nature's plan. We want something better than nature's plan. Nature may not care if we live past middle age, but we care. Nature may not care if people over fifty are comfortable, and mobile, and free of chronic disease, but we care. That is why people feel so much anxiety about one crucial question: can modern medicine, which certainly keeps people alive longer, also keep them healthy longer? And if it can't accomplish the second goal, should it accomplish the first?

What brings this to mind is a controversial article by Dr. Ezekiel J. Emanuel, physician and bioethecist, published last month in The Atlantic.

Dr. Emanuel, who is 57, explains in his article why he thinks prolonging his life past 75 would not be desirable: he expects to be a declining asset at that age. He will be less and less creative and productive, and more and more vulnerable to disabilities and unpleasant diseases. He plans to avoid the sort of life-prolonging medical treatments which will be offered to him then: no cancer treatments (or cancer screenings), no heart surgery, no flu shots, no antibiotics. He hopes that, in this way, he can let himself die relatively quickly and painlessly from whatever nature throws at him, instead of dragging out a prolonged and painful departure. (He claims that he will not change his mind about all this as age 75 approaches, but we'll see.)

As you might expect, a lot of people were hugely upset by Dr. Emanuel's article. They interpreted it as an attack on old and disabled people as useless and undesirable. Despite Emanuel's disclaimers to the effect that he was only explaining his own feelings about his own life, not recommending a social policy of discarding "unproductive" people, it is hard to overlook the creepiness of some of his arguments. He actually presents statistical analyses of the career arcs of scientists, composers, and other creative people, to demonstrate that (on average) they do their best work before 50 and then trail off into irrelevance. Maybe so... but is it valid to conclude that people who are no longer at their creative peak should no longer be alive, either? The mere fact that creativity rises and falls over the course of a lifetime tells us nothing about the value of a life. Einstein and Beethoven weren't contributing much at age three, and I assume Dr. Emanuel would not argue that their lives were pointless then.

Negative feeling about Emanuel's article ran so high that the American Medical Association just had to vote on whether or not to censure him, condemn his opinion, and withdraw some honors he had previously received. They decided not to.

So I guess Dr. Emanuel is now in the clear, and the world has survived this particular encounter with free speech. But what, if anything, should be take away from his comments on the desirability (or otherwise) of living a long life?

Certainly we can agree that, if we're going to live past 75, it's better to do so unburdened by disabilities, chronic pain, and Alzheimer's disease. But when Emanuel points out that a third of people over 85 have Alzheimer's, I can't help noticing that this means two-thirds of people over 80 don't have Alzheimer's -- which is too large a demographic for Emanuel to be calling them "outliers". If my chances of not having Alzheimer's at 80 are better than half, then maybe the fear of Alzheimer's which so many of us share is not sufficient reason to sign on to the die-at-75 program.

It's hard to deny that a lot of people who live long lives, thanks to medical advances, experience a lot of pain and difficulty during those added years. But that doesn't mean older people are necessarily miserable, or should regard themselves as guests who stayed too long after the party was clearly over.

Maybe there is another way of looking at the health problems associated with aging. Instead of asking "why should I live past age X, if a third of people past age X have disease Y?", maybe we should be asking "what can I do to make sure I'm not among the one-third of people past age X who have disease Y?".

I can't avoid feeling that Dr. Emanuel has looked at the statistics on diseases of aging as if they represented inescapable fate -- as if we can do nothing but hope to be an "outlier" (knowing that it's unlikely to happen).

What if it's possible to choose to be an outlier?

I don't mean to suggest that it's easy to make yourself into an outlier, or that being an outlier is sure to pay off. But it might work, and giving it a try might be better than giving yourself an expiration date.

Not all old people remain functional into the over-75 years, but many do. Maybe the best approach is to try hard to be among the functional. My lunchtime run today (5.4 miles on steep hills!) may or may not have bought me anything in terms of being functional in later years... but it was worth a try!

 


1st Thursday Update

November 6, 2014

 


Look, I realize this is why people move to California...

...and it does make it nice for those of us who exercise outdoors. (It was beautiful out there today.) But it does seem a little unnatural to be having long stretches of sunny, warm weather in November. If it wasn't for the early sunset, who would know it was autumn? This week, my company is hosting a large number of "field employees" (from all over the planet) for training sessions. These visitors from afar must think we live in an artificial universe of our own, here at the home office. (Although that's probably what field employees think about the home office of any company, no matter were it is.)

Much as I like to impress visitors from out of town, this is getting a little weird. Come on, Mother Nature: end this drought! I'll run in the rain if I have to.

 


Turning the ship around

The health care industry is a weird business, quite unlike any other business known to man. It is, at the same time, an intensely personal business, in which customers deal one-on-one with highly-trained practitioners whose professional role has changed little since the Victorian era... and also a business dominated by the interests of corporate behemoths, and strangled by insurance-company bureaucracy.

One of the effects of this odd mixture of old and new ways of running things is that it's very difficult to change any health-care policy once it has become established. To change the way the medical profession deals with an issue, you must first win the approval of the companies that have economic power over the industry, and then persuade individual doctors everywhere to stop doing what they were told to do before. The process is slow. The health care industry is like an enormous oil-tanker: when you decide to change course, you know it's going to take a long time to get the ship turned around. Adoption of a policy can sometimes be quick, even if it's based on limited or questionable information. But when there is a gap of several years before the data which justified the policy is undermined, "deadoption" of the policy can take a mighty long time.

Look at it this way: if you were a doctor who had been sternly lecturing your patients for years about saturated fat being the cause of heart disease, would you want to turn around now and say to them, "Well, I've been told that the evidence doesn't really support that idea after all, so why don't you just forget I said it"? No, you wouldn't.

Doctors have been assuming, based on a small study from 2001 ("Leuven 1"), that diabetes patients who are scheduled for surgery will do better if their blood glucose is tightly controlled (that is, maintained within a range of 80 to 110 mg/dl by means of insulin therapy). Tight glucose control for diabetic surgery patients became established as the norm -- and pretty firmly established, because eight years went by before a 2009 study found that the earlier study had looked at too narrow a selection of patients: for many diabetes patients, tight glucose control by way of insulin injections caused an increase, not a decrease, in patient mortality (owing to an increased risk of hypoglycemia). On balance, the widely-adopted policy of tight glycemic control for surgery patients had been a mistake, and should be dropped, at least for the kind of patients who were at most risk of being harmed by it.

The was in 2009. Has the policy been dropped, five years on? Apparently not -- it takes longer than that to turn the ship around. Daniel Niven, one of the researchers who found fault with the original study supporting the policy, has been frustrated that not much has changed: "It's probably best to wait for a confirmatory study before the widespread adoption of a given therapy... Our research suggests that physicians in the ICU have a hard time giving up an intervention they believe is useful... Leuven 1 was a good study, but it was performed in a narrow group of patients. Still, our profession jumped on it and extrapolated it to other groups... The passive diffusion of evidence from the medical journals to practitioners isn't going to result in practitioners discontinuing a practice that they may have done for years. Rather, what's going to need to take place is a more active effort to distribute the evidence and implement change through changes in protocols. How that's going to take place isn't clear, but the active role, as opposed to a passive role, is going to be required.".

I can't help but seeing a kind of smoking gun in the statement "how that's going to happen isn't clear", coming from a researcher who is hoping to persuade doctors to stop doing something which is known to do more harm than good.

Harvey Reich, another doctor interviewed on the subject, said "It's easy to jump on the adoption bandwagon -- especially when we see something that appears to be efficacious and has a mortality difference -- because everyone is trying to do the right thing for their patients. Often that is based on one study, and there are some limitations, but the data look good and it seems logical. But many times, the initial data look fantastic and as time goes on, things fade." Reich said that the process of deadoption is too slow: "It tends to take about a decade, which is scary."

Okay, there it is: standard medical practice can be established on the basis of one limited study, but undoing that change, after the original study has turned out to be misleading, takes ten years.

Another issue to think about here, if you ask me, is the tendency of the health care industry to adopt whatever policy is thought to help more patients than it harms, even in the case of patients who will probably be harmed. So long as the statistical model says you killed fewer people than you saved, you're doing the right thing. It's a way of thinking which is mighty hard on patients who happen not to be "average".

I'm not average myself. Everything I have been doing about my own Type 2 diabetes is off the health-care industry's radar screen. It is generally assumed that nobody is controlling diabetes by means of behavioral changes (or should be advised to try it). This assumption is based on a further assumption that no patient would do that, and therefore it would be pointless to ask any patient to give it a shot.

Diabetes patients who want to be treated in a way that's appropriate to the type of the patient they actually are, rather than the type of patient who is considered average, are going to have to educate themselves on the issues, and speak up.

 


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