4th Thursday Update

May 26, 2016


Management by walking around

The company I work for used to be a part of a much larger and more famous corporation, and once upon a time there was a management philosophy in that corporation known as "management by walking around", the core concept of which was that high-level executives should get in touch with what was really going on within their organizations by wandering about the place at random, noticing employees engaged in tasks, and stopping to talk with them about what they were doing. The idea was that this simple reality-check would often reveal to the executive that there was some kind of surprising disconnection between the highest priorities of the corporation and the tasks its employees were actually spending most of their time on. Management by walking around was seen as a simple cure for the commonplace problem of a company's operations failing to support its goals, without management realizing it.

I won't try to judge the degree to which this management philosophy is actually put into practice today (or was in the past) in large corporations. Managing corporate behemoths is not our concern on this blog. Managing diabetes is, however -- and diabetes is, in some ways, as difficult to manage as any corporate behemoth ever was. Can management by walking around have an application to diabetes management? I think it can -- provided we understand that the "walking around" part is what's important, not the "stopping to talk" part.

Recent research from Canada finds that urban neighborhoods which are more conducive to pedestrian activity ("those with high population density, high numbers of destinations within walking distance of residential areas, and well-connected streets") not only had higher rates of walking and bicycle use, they also had lower rates of obesity and diabetes. Apparently, people get healthier when they spend more time walking around.

I don't happen to live in the kind of dense urban neighborhood where such basic destinations as grocery stores and drug stores are easy to walk to. I live half-way up a very steep hill which makes any kind of local walking a sweaty, time-consuming workout. In theory I could walk to the supermarket, and in fact I did it once, but only a complete absence of transportation alternatives would make me devote that much time and energy to grocery shopping in the future. I might go for a stroll after dinner in the summertime, but any sort of walking more purposeful than that would be impractical. So, if I'm going to get any walking-around time in, it will need to something I'm setting aside as an exercise activity, not something that just happens naturally as a regular consequence of my routine daily activities.

In other words, like a lot of people, I need a reason to walk around, and therefore I need to give myself a reason to walk around. My solution to that problem, lately, has been nature photography.

Some months back I invested in a fairly serious camera -- a Nikon D5300. It has an 18-200 mm zoom lens, and this very wide range of focal lengths gives it a lot of versatility. For example, it can take very wide-angle shots of the landscape...

...or telephoto shots of animals at a distance...

...or extreme close-ups of flowers (and their pollinators).

And, of course, when you're out there walking around, looking for photo opportunities, you sometimes have an opportunity to see interesting and unusual things happening. Yesterday evening, in the local state park, I saw what I thought at first as a helicopter rescue operation. Such things do happen in the park, after all; people sometimes hurt themselves in the park when they are far from roads, and helicopter-based evacuation is the only practical option. I have seen such rescues happening. In this case, however, it was the county sheriff's department conducting a training exercise on helicopter rescues.

A hovering helicopter was repeatedly hoisting up two guys on the ground, sometimes separately and sometimes together.

The 200 mm extension of the zoom range made it possible for me to get shots which make it appear I was much closer (dangerously closer) to the action than I actually was.

As I'm now 59, and heavy-duty workouts (such as this evening's 9.3-mile trail run) are inevitably becoming harder on the body than they once would have been, I feel the need to cultivate habits which will at least get me moving around outdoors, even if not in a heavily strenuous way. Walking around taking pictures of the world I live in seems like a pretty good long-term solution to the problem.


Unhappy marriage as therapy

I remember, as a child, reading a letter in the Ann Landers advice column, from a woman who boasted of the way she nagged her husband constantly in order to force him to adopt better health habits. She advised other woman to nag their husbands, on the grounds that "you'll add years to his life". To which the pragmatic Ann Landers replied, "Who wants more years like that?".

At least the letter-writer appears to have a valid point, so far as it goes: researchers are reporting that marital unhappiness (in men, not women) correlates with a lower risk of diabetes, and with better success in managing diabetes if it develops. So far, researchers have found that happy marriages equate with better health -- and for women, that's still true. But men do better, in terms of diabetes, if their wives are making them miserable. "The most surprising finding was that, for men, an increase in negative marital quality lowered the risk of developing diabetes and increased the chances of managing the disease after its onset. Diabetes requires frequent monitoring that the wives could be prodding the husband to do, boosting his health but also increasing marital strain over time."

This seems like something we will have to let patients decide, on an individual basis. If the price of living longer is having to endure constant personal criticism from the person best qualified to make it hurt, do you want to pay that price?

And if you can increase a man's lifespan by making him wish he'd died young, are you going to?

I don't think those are decisions that the medical profession can make on behalf of anybody.


People claiming to be healthy

Medscape it claiming to be shocked to find that two thirds of Americans rate their own health as very good or excellent, even though a lot of Americans have chronic health problems. "More Americans suffer psychological distress today than 10 years ago, yet two thirds rate their overall health as very good or excellent, according to "early release" data from the National Health Interview Survey released yesterday by the Centers for Disease Control and Prevention's National Center for Health Statistics. According to the 2015 data, the percentage of adults aged 18 years or older who said they experienced serious psychological distress in the past month rose to 3.6%, up from 2.9% a decade ago in 2005. Yet, 66.1% of Americans of all ages report they are in very good or excellent health."

Okay, wait a minute. How is it a contradiction for 66.1% of Americans to think they're healthy even though 3.6% of them have recently experienced serious psychological distress? It seems to me that, if 66.1% of people say they're healthy, that leaves 33.9% of them not saying they're healthy, and presumably the 3.6% of people who are in psychological distress fit somewhere into that 33.9%.

Medscape goes on to point out that 30.4% of Americans are obese. Okay, but maybe they, too, fit into that 33.9% of people not claiming to be healthy.

Admittedly, a lot of Americans would not think that "psychological distress" counted as a health problem, and some of them wouldn't think obesity counted as a health problem, either, a least until it had produced some kind of specific disease condition. But even if no one was making such assumptions, problems that affect less than a third of the population do not make it unreasonable for two thirds of the population to say they're in good health.


3rd Thursday Update

May 19, 2016


All aboard for unintended consequences!

Every medical treatment aims to change one bad thing that's going on within the human body, in the hope that this can be done without accidentally changing something else which isn't bad and shouldn't be changed. Generally speaking, we cannot expect any treatment to accomplish this flawlessly -- some kind of "side effect" is to be expected. Therefore, all medical treatments need to be evaluated carefully in terms of risk/benefit analysis. How likely is Drug X to have an undesirable effect? How bad will that effect be if it happens? What benefit does the patient get in exchange for taking that risk?

If a drug causes 10% of patients to experience low-level muscle soreness, but it reverses congestive heart failure, doctors are not going to be leery of recommending it to patients whose lives can probably be saved by it. Small risk, big benefit: the choice is clear.

That's not a very realistic example, however. Most real drugs involve more serious risks than that, and less dramatic benefits. This makes it hard for medical organizations, and agencies such as the Food and Drug Administration, to make decisions about whether a given treatment is "worth it". Sometimes they approve a treatment and then change their minds, because new and unwelcome clinical information came to light.

Even exercise can't be said to be free of side-effects. Several of its side-effects are beneficial ones, but still, there's no denying that you can hurt yourself exercising, and exercise can cause cumulative trauma over the long haul. Certainly exercise doesn't get any easier with age. Yesterday someone at the office asked me why I was limping; I hadn't been conscious of doing it, but I realized that my right heel tends to get sore after a run these days, and that was what he'd spotted. I was able to do a long trail-run after work tonight, and my heel didn't bother me during the run itself, but it did feel sore afterwards. If it wasn't my right heel, it would be something else: when you run regularly, you're always dealing with sore muscle or joint someplace. I've had problems with hips, knees, shins, and calf muscles. These problems have never become incapacitating -- I've always found ways to work through them, and I've been using yoga to alleviate them. Still, I suppose the day will come when I won't be able to exercise, or at least won't be able to do it the way I have been. Even a therapy that works is not guaranteed to work forever.

Anyway, because medical treatments usually involve an unintended consequence of one kind or another, I think it's best to read the fine print when medical research breakthroughs are being reported about promising new treatments, or newly discovered biochemical pathways which could be used to create a new treatment. We should never hear about a treatment having some very desirable impact on lab rats without asking "but what else does it do?".

Currently there is a lot of excitement among medical researchers about "brown" fat cells (that is, fat cells which burn fat instead of storing it) and especially about the possibility of turning ordinary white fat cells (which store fat instead of burning it) into the brown variety. The obvious reason for the excitement is that transforming white fat cells into brown fat cells would result in weight loss; a drug which brought this about could be sold as a an obesity treatment, and make billions of dollars.

Humans are born with a fair amount of brown fat, for the simple reason that babies are small, and have a high surface-to-volume ratio -- which makes it harder for babies than adults to maintain body heat. Brown fat cells in babies burn fat for the heat energy it releases. Adults tend to lose most of their brown fat -- but what if they could turn a large share of their white fat cells into brown fat, so that their bodies were constantly burning up fat instead of retaining it? Air-conditioning would have to become more aggressive under this scenario, but it would probably be a pretty effective way of controlling body weight. When I heard about this, I thought it sounded like a concept worth investigating.

Today I read a report on some proof-of-concept testing going on in this area -- a report of the kind I usually categorize mentally as the "It Works In Mice!" genre. The Science Daily summary begins: "Researchers have uncovered a new molecular pathway for stimulating the body to burn fat -- a discovery that could help fight obesity, diabetes and cardiovascular disease. In a study published in the journal Genes & Development, a team led by researchers from the Department of Biochemistry at McGill University focus on a protein known as folliculin and its role in regulating the activity of fat cells. By knocking out the gene that produces folliculin in fat cells in mice, the researchers triggered a series of biomolecular signals that switched the cells from storing fat to burning it."

I had never heard of this protein called folliculin, but the name suggested to me that it must have some kind of connection with hair follicles. (It does, but I'll get to the connection later.) Curious to learn more, I followed a link back to an abstract of the original research paper, which turns out to describe the findings with a slight but significant difference in the opening line: "The tumor suppressor folliculin (FLCN) forms a repressor complex with AMP-activated protein kinase (AMPK)..."

Now just a god-damned minute! Folliculin is a tumor-suppressor? And the researchers are inactivating it?

I looked up folliculin. It is thought to be a tumor-suppressor because a defect in the gene for folliculin is known to cause a genetic disease which results in tumor formation in hair-follicles (and also in the lungs, and sometimes in other organs).

Call me paranoid, but it's hard for me to get excited about a potential obesity drug which works by eliminating a protein which is supposed to suppress tumor formation! Would you want to be the first in line to take a drug which knocks out folliculin, knowing that people without normal folliculin production end up getting what amounts to Hair Cancer? Obviously some people would, but not me!

I feel more or less the same way about research into potential cures that involve restoring telomeres (the little structures on the end of chromosomes, similar to the aglets on the end of a shoelace, which serve to protect the DNA strand from fraying). If the only thing the telomeres did was protect the integrity of our DNA, I'd be all for restoring them when they get worn down to the nub. The trouble is, telomeres have another function: they are supposed to fight cancer, by placing an upper limit on how many times a cell can divide. What if a drug which restores telomeres also has the fringe benefit of enabling micro-tumors to grow without limit?

I don't think I'm going to be the first in line for that drug, either.

It's easy to feel, as a mere spectator to medical research (albeit a spectator with a personal stake in the results) that scientists ought to just develop a drug which cures an illness and does absolutely nothing else, but human physiology is a mighty complicated system to be interfering with; we should not expect to find many options for consequence-free intervention. That is why it is still necessary, this late in history, to adopt a bias in favor of less treatment rather than more treatment, and also in favor of well-studied treatments rather than new and exciting ones.


2nd Thursday Update

May 12, 2016

I was surprised that my fasting result was as high as 106 this morning, but the combination of a late dinner last night and not enough sleep could have played a role in the matter. At least my result after dinner was good.

While trail-running tonight, climbing the first steep hill, I wondered if I would have to cut the run short, because my back was bothering me, and going uphill seemed to put an extra strain on it. I came to feel that part of the problem was that I was holding my back too rigidly straight, and that making an effort to swing my hips more, to rotate my spine left and right a bit, might give me relief. I tried it. Not only did it make my back feel better, it made running seem less effortful. I don't know if I was actually going any faster, but it felt as if I was going faster without working as hard. And it took me till now to learn this? What's wrong with me?


Melatonin & diabetes

Melatonin is a hormone which the body produces to regulate the day/night cycle of human metabolism (the dark of night triggers a boost in melatonin production). Babies develop a regular cycle of melatonin production within about ten days after they are born, and thereafter this determines their hours of sleep. During the teenage years, the timing of melatonin release is delayed, and sleep times adjust accordingly. Melatonin production decreases as we age, which apparently is why difficulty with sleeping is more common in older people. Many people who suffer from insomnia use melatonin supplements to help them fall asleep.

None of this information makes it sound as if melatonin could be relevant to diabetes, but apparently it is. Pretty much everything is relevant to diabetes, it seems; there is a connection of one sort or another between diabetes and just about every aspect of the processes by which the body regulates its own functioning.

Melatonin does not simply determine when you get sleepy. (That's the tricky thing about endocrinology: no hormone ever does just one thing.) Melatonin also has an impact on other ways in which the body adjusts itself to the day/night cycle. Everything that goes on when we're sleeping is of importance to diabetes, because this is a period when we're neither eating (thus adding sugar to the blood) nor physically active (thus subtracting sugar from the blood), and therefore our blood glucose level needs to be controlled entirely by the body's automatic processes. If those processes aren't working quite right, blood sugar tends to drift well above or below the normal range.

Type 2 diabetes (and specifically the diminished sensitivity to insulin which drives it) is notoriously linked with sleep problems. For reasons unknown, sleep deprivation suppresses insulin sensitivity, thus promoting Type diabetes. This, however, isn't the reason melatonin has a direct bearing on Type 2 diabetes.

It turns out that melatonin plays a role in the body's production of insulin. Regardless of how sensitive you are to insulin, it is a problem to be producing abnormally low amounts of the stuff -- and in certain circumstances, melatonin can cause you to produce too little insulin.

The beta cells in the pancreas (which produce our insulin supply) are wired to reduce their production of insulin when stimulated by melatonin. The reason for this is that, during the long night-time fast, no sugar is entering he bloodstream as a result of digestion, so less insulin is needed. Therefore, when the beta cell's melatonin receptors (known as MTNR1B receptors) are stimulated by melatonin, they produce a reaction which inhibits the production of "cAMP", or cyclic adenosine monophosphate, the signaling molecule which triggers the cell to generate insulin. In short, the effect of melatonin on beta cells is to make them produce less insulin.

However, according to research recently published in Cell Metabolism, a common genetic variation (up to 30% of people have it) causes the MTNR1B receptors to be extra-sensitive to melatonin; people with this genetic variant inhibit insulin production, in response to the nightly release of melatonin, more than is healthy. The strong association between this genetic variation and Type 2 diabetes indicates that the genetic variation is a causal factor in the disease.

However, the researchers note that over a hundred different genetic variants are associated with Type 2 diabetes, so there isn't any single genetic factor which is "the cause" of the condition. Many people with Type 2 diabetes do not have an abnormal sensitivity to melatonin in their beta cells -- they have some other genetic issue which makes them vulnerable to becoming diabetic.

However, if you're diabetic, and you're taking melatonin supplements to get to sleep, and you're getting high fasting glucose test results in the morning, maybe it's worth looking into this -- to see if your fasting numbers improve, if you stop taking melatonin in the evenings to get to sleep. If you make that change and there is no difference in your fasting tests, then you needn't worry too much about having beta cells which over-react to melatonin. But if you get better fasting results when you stop taking melatonin, that's a pretty good indicator that, like a lot of other people, you have a genetic variation which makes you especially vulnerable to melatonin's tendency to drive insulin production downward.

What's interesting here, if you ask me, is that the MTNR1B genetic variation (which makes some people reduce their insulin production excessively when melatonin levels rise) is just one of over a hundred different genetic variations associated with diabetes. Not one of these genetic variations is present in everyone with diabetes, but any one of these variations might be present in a given person with diabetes.

In other words, diabetes patients vary, because the genes which made them diabetic vary. Presumably that explains why what works for one diabetes patient doesn't work for another. There are too many ways to become diabetic for there to be a single, reliable remedy for it. An approach to diabetes management which worked brilliantly for your cousin might not be right for you.

This is why I feel that diabetes patients need to treat their condition as their own personal science-fair project, and that their approach to science needs to be more experimental than theoretical. The goal of diabetes management is not to find the approach which would work for a statistically typical patient, but to find the approach which actually works for you.


1st Thursday Update

May 5, 2016


Maintenance visits

Today I had office visits to my eye doctor and my dentist on the same morning. The Honda dealer also tried to give me a service appointment today, but I figured there was only so much excitement I could cram into one day, so I'm taking my car in tomorrow instead.

My eye doctor keeps up with the latest in diagnostic testing, and in addition to the usual retinal scan (which produces creepy red and green pictures which look as if NASA took them from a space probe orbiting Mars), he gave me a new test which doesn't even have a standard clinical procedure for interpreting it yet. It uses some kind of laser scan to capture a high-contrast monochrome image of the retina which, it is hoped, will reveal diabetes-related retinal damage earlier than it can be detected by earlier scanning methods.

Researchers are finding that diabetes can start doing harm to the eye a lot earlier than they had previously thought, and technologies are being developed to help eye doctors do a better job of detecting such problems and suggesting interventions. My own scans today showed no signs of trouble. I almost feel as if my eye doctor is disappointed that he still can't find anything wrong with my retinas. He's just going to have to be patient with me!

My dental visit was fine, too. Gums in good shape. Again, I felt as if I was causing disappointment by not having anything wrong. I guess my dentist will need to be patient with me, too.


Threats to your survival: realistic and unrealistic

We human beings have a natural tendency to worry about things that might kill us someday. However, we are often hilariously incompetent at estimating the odds. We focus on unlikely risks and disregard likely ones. Whatever your favorite nightmare is, about some outlandish and horrible death which fate might have in store for you, it probably isn't going to happen. Stressing out about dying in a plane crash is a waste of time, especially if it leads you to send somebody a text on the subject while you're driving to the airport: the risk of dying in a plane crash is low, but the risk of dying in a car crash while texting is high. We should prioritize our worries a little better, and concentrate on the things that really are likely to kill us, instead of worrying pointlessly about things that won't happen anyway. (Of course, it could be that the reason we worry pointlessly about unlikely threats is that we're aware that they are unlikely, and we find it a pleasant distraction to focus on unrealistic threats instead of realistic ones.)

A great many people could accurately guess what the two leading causes of death are in the US: heart disease and cancer. Most of us will die from one of those two things -- not from plummeting elevators or killer bees. Everyone would get cancer if they lived long enough; the only reason we don't all get cancer is that a lot of us die of something else first, and that "something else" is usually heart disease. Sometimes doctors talk as if heart disease and cancer were the only two causes of death, because the others are so much less common.

Not many of us, though, would be likely to make a correct guess about what the third leading cause of death is. A new report from the BMJ says that "If medical error was a disease, it would rank as the third leading cause of death in the US." Yes, you read that right: mistakes made during medical treatments are the third most common cause of death in the US.

To be fair to those of use who were unaware of this, we're unaware of it for a good reason: medical error is usually not included in cause-of-death statistics. It isn't mentioned on death certificates, and medical records use a coding scheme (the infamous ICD-10) which sets aside codes for the most unimaginably unlikely causes of injury (including being struck by a turtle, and being burned because your water-skis caught fire) but does not have codes to capture most types of common medical error. The BMJ report is uncovering a large problem which is usually hidden from view.

An example case history: "A young woman recovered well after a successful transplant operation. However, she was readmitted for non-specific complaints that were evaluated with extensive tests, some of which were unnecessary, including a pericardiocentesis. She was discharged but came back to the hospital days later with intra-abdominal hemorrhage and cardiopulmonary arrest. An autopsy revealed that the needle inserted during the pericardiocentesis grazed the liver causing a pseudoaneurysm that resulted in subsequent rupture and death. The death certificate listed the cause of death as cardiovascular."

If you die because you were accidentally stabbed in the liver with a needle during a medical procedure -- especially an unnecessary procedure -- it is not accurate to list the cause of death as "cardiovascular". It sounds like a freakish and rare event, and yet this kind of thing happens often enough that, if it weren't being artificially excluded from the mortality statistics, it would be the third leading cause of death!

My motive for bringing this up is that I think it helps explain why the non-medicated approach to diabetes management offers a significant advantage. Medical treatment of any kind involves risks. Drugs have undesirable (and sometimes unforeseen) side effects. Surgeries go wrong. Even diagnostic tests (as in the case history above) can be dangerous. We tend to assume the risks involved in a medical intervention must be very low, or else that form of treatment wouldn't be standard practice. But obviously standard practice allows for a lot of risky things to be done, if the consequences of medical interventions gone wrong are the third leading cause of death! I think the BMJ report is a useful corrective to the widespread assumption that medical treatments aren't hazardous.

This isn't an argument against medical intervention -- it's an argument against resorting to medical intervention when you don't really need to (because some less invasive solution is available to you). Every drug you take, and every surgical procedure you undergo, adds to your risk of something going very wrong; when there's an effective a way to deal with a problem without the drugs or the surgeries, why not take advantage of it?

It used to be said that a physician's job was to keep the patient distracted while nature was carrying out the cure. That was said at a time when effective treatments were few, and nature's capacity to heal the patient was the only thing that could be relied upon. However, to a degree the principle applies even today, when there are treatments available which actually do something. The available medical treatments are more effective now than in the past, but they are not risk-free. Where satisfactory results can be achieved by natural means, they probably should be, for the sake of risk-management.


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