Monday, Monday

Monday, March 31, 2014

 


Weather

After a rainy Saturday, the weather was sunny on Sunday, and I thought I would renew my acquaintance with the state park where I used to be in the habit of trail-running every weekend. Lately I've been less enthusiastic, owing to a horrible experience there in August, where I got up close and personal with poison oak while doing volunteer trail-clearing work. It strained my love-affair with the park, to be honest. I've gone back there since, but the old magic wasn't happening for me. On recent weekends I haven't been there at all. I thought it was high time I went back there, and had a nice long run.

So I went there, and the lushness of the place -- in bright sunshine, with the recent rain still glistening on every leaf and blade of grass -- was spectacular. It was nice to be back. But when I got to those places where the entire trail was one broad puddle, I slogged through the water and mud rather than step off the trail to get in among the poison-oak leaves. Once burned (almost beyond recognition), twice shy!

I ended up doing a long route through the park -- 9.4 miles. I had the stamina to do it. The only catch was that, despite the bright sunshine, it wasn't warm. There was a cool breeze, and by the time I was done I'd lost a lot of body heat. I felt a little feverish for the rest of the day and evening. And I guess there was another catch: I felt a bit stiff and sore today. Still, I managed to do a pretty long run today, too, and my yoga class in the evening smoothed out the rough edges, or at least so I hope.

It's a reminder of the passing of time that, as I get older, any challenging physical activity has a little more of a traumatic impact on me than it would have a few years earlier. Only a little more, I hasten to add. Yeah, I was feeling too sore to go running at lunchtime -- but there was a torrential rain then anyway. And when it cleared up late in the day, I felt able to go for a 5.4-mile run (with steep hill-climbs) after work. I can still do what I need to do, even if it's not quite as easy for me to do it as it once would have been.

And I certainly get enough reminders of what I'm trying to avoid. Someone I work with (about my age, I think, or at least not a great deal older) died of a heart attack over the weekend. I'm 56, and it would be absurd for me to pretend that this isn't something that could happen to me. I need to do what I can to prevent it. And I am doing what I can to prevent it. But I guess it does me no harm to pay attention to life's frequent reminders that the risk is real.

 


An Unsurprising Development

A long article in the New England Journal of Medicine describes a study comparing "Intensive Medical Therapy" (that is, lots o' drugs) with two forms of weight-loss surgery (gastric bypass and sleeve gastrectomy) and found that, based on 3-year outcomes, surgery was the better option.

Not studied: lifestyle-based diabetes management. We don't need to know how well that works.

Yeah, I know all the reasons researchers would give for not thinking that lifestyle-based diabetes management needed to be looked into (or even could be looked into, given the difficulty of finding patients who were willing to do it for three years.) But I find it worrisome that "medical therapy" is being defined in such a way that only drugs count. What I'm doing isn't medical therapy, because my doctor isn't doing it for me. Therefore, what I'm doing doesn't matter. It shouldn't be studied, and it shouldn't be mentioned. Nobody needs to know that a third option exists. Just tell people to sign up for the drugs, or sign up for the surgery.

What drives me crazy is knowing that more people would might be willing to try it if they knew it was a valid option.

 


The Whole Shebang

Friday, March 28, 2014

 


"Holistic Medicine" is one of those terms that makes me flinch even though I have some sympathy for some of the ideas behind it.

Here's a description of holistic medicine, from the website of the American Holistic Medical Association:

"Holistic medicine is the art and science of healing that addresses care of the whole person -- body, mind, and spirit. The practice of holistic medicine integrates conventional and complementary therapies to promote optimal health, and prevent and treat disease by addressing contributing factors. Holistic healthcare practitioners strive to meet the patient with grace, kindness, acceptance, and spirit without condition, as love is life's most powerful healer. In practice, this means that each person is seen as a unique individual, rather than an example of a particular disease. Disease is understood to be the result of physical, emotional, spiritual, social and environmental imbalance. Healing, therefore, takes place naturally when these aspects of life are brought into proper balance. The role of the practitioner is as guide, mentor and role model; the patient must do the work -- changing lifestyle, beliefs and old habits in order to facilitate healing. All appropriate methods may be used, from medication to meditation."

Where do I begin? There is so much there which irritates me, but is so superficially positive that it makes me look bad to say that I'm irritated by it.

They sort of lost me where they defined the whole person as "body, mind, and spirit" without explaining how the third of those items differs from the second. The word "spiritual" always drives me crazy, because everyone uses it and nobody knows what it means. To the extent it is definable at all, it probably means something like "the feelings I think I should have about the things I wish I believed". As soon as someone uses the word "spiritual", I feel as if they're holding up a sign that says: "I'm about to utter a bunch of vague, dreamy nonsense, and it's your job to pretend you take it just as seriously as I'm pretending to take it". When the conversation goes there, you just know you're going to be spending a long time smiling weakly and nodding. If you want to think I'm a terrible person for feeling that way, you go right ahead; I just can't help feeling that people talk about the spiritual life in order to avoid having to talk about something more threatening, such as, for example, life.

Also disturbing to me: the implication that your relationship with your doctor should be so personal, so intimate, that it will probably lead eventually to joint custody of a child.

And yet, and yet! Leaving aside all the cringe-inducing babble, there is something at the core of this which does speak to me.

A patient is indeed "a unique individual, rather than an example of a particular disease", and an individual body is made up of a fantastically complicated set of interacting systems. Treating a disease in isolation, disregarding its involvement with every other aspect of the patient's health, cannot possibly be the best way to proceed.

Here's an example: researchers at the University of Adelaide (in Australia) just published a study of erectile dysfunction which found that a lot of men can correct this problem through lifestyle changes rather than drugs (and that the lifestyle changes also improve the results of those who do use drugs).

You can choose to look at erectile dysfunction as a very simple, mechanical problem which should be addressed with a narrowly focused chemical solution. But erectile dysfunction is not just a simple, mechanical problem to be treated in isolation. It is, according to the study authors, "a very serious issue because it's a marker of underlying cardiovascular disease, and it often occurs before heart conditions become apparent". Erectile dysfunction is a warning sign of a general failure of health, and that general failure needs to be addressed. Addressing it might or might not be enough by itself to solve the immediate problem, but it needs to be addressed.

A lot of what passes for diabetes therapy amounts to a kind of diabetic Viagra: addressing the obvious problem and ignoring the hidden one. I can't believe that's the best approach, even if the more embarrassing aspects of the holistic alternative make me think that the ideal approach has not yet been found.

 


More Normal than Normal!

Thursday, March 27, 2014

 


Looking slightly beyond the headline

"HbA1c Levels Don't Aid in CVD Risk Prediction" reads the Medscape headline. But Medscape was summarizing a JAMA press release entitled "Blood Glucose Measure Appears to Provide Little Benefit in Predicting Risk of Cardiovascular Disease". And that press release was summarizing a JAMA paper entitled "Glycated Hemoglobin Measurement and Prediction of Cardiovascular Disease".

The progression of the titles is significant, I think: as a scientific paper is digested for an increasingly broad audience, the headline evolves in a particular direction. The title of the original paper merely indicates the subject matter, without telegraphing any conclusion about it. The title of the press release suggests a tentative conclusion. The title of the popular article states a bold conclusion, with no qualifiers -- and that bold conclusion is a little problematic, as we shall see.

The object of the study was to see whether prediction of a patient's risk of cardiovascular disease becomes any more accurate if the result of the patient's hemoglobin A1c test is added to the mix of factors that are used to determine risk (age, weight, cholesterol levels, and so on). The answer turns out to be no. Or rather, the answer turns out to be that including A1c in the calculation improves the accuracy of risk assessment by such a trivial amount that it's not worth doing.

This seems a bit surprising, doesn't it? Diabetes is so notorious as a risk factor for cardiovascular disease that some doctors think diabetes could be fairly described as "a form of heart disease characterized by elevated blood glucose". Wouldn't you expect the high A1c levels typical of diabetes patients to result in a strong association between A1c and CVD risk?

Yes, but there's a catch here: the study didn't include diabetes patients!

The point of the study was to see whether variations in A1c results among non-diabetic patients were useful as an indicator of CVD risk. And it turns out they're not useful.

Properly understood, that's actually good news for some diabetes patients. For this diabetes patient, anyway.

Although my A1c results have been low enough to fall within the "normal" spectrum for that test (it was 5.5% last time I was tested), it wasn't as low as the typical non-diabetic person's A1c (5.0%, or even lower), and I've been wondering if real success in staying healthy with diabetes required one not only to barely qualify as "normal" but to be within the lower half of the normal range. Did one have to be more normal than normal, so to speak, to be truly safe?

Apparently not. Even for people without diabetes, A1c is variable, and lower is slightly better, but the variations don't have a big enough impact on CVD risk to be worth making a fuss over. Being anywhere within the normal range, it seems, is good enough for all practical purposes.

Which is good news for me. So long as I can keep hitting the "normal" window, I don't have to do any better than that.

I'm less cheery about the way the study has been presented to the public. To summarize the results of the study as "HbA1c Levels Don't Aid in CVD Risk Prediction" is highly misleading, because the study excluded diabetes patients, so the conclusion applies only to those comparatively minor variations in A1c results that fall within the normal range. The study certainly didn't find that having an A1c level of 10% wasn't risky -- and couldn't have found that, because the study didn't look at anyone with a level nearly that high. If a study on drug abuse looked only at marijuana, excluding cocaine, heroin, and methamphetamine... would it be appropriate to describe the study's findings under the headline, "Drug Abuse Has Little Impact on Health, Families"?

 


Competing with Reality

Wednesday, March 26, 2014

 


When life gets in the way

It's easy to make plans for what you're going to do in terms of diabetes management, but the business of daily life has a way of interfering with those plans. Any diabetes management program has to compete with pretty much the rest of the real world.

This competition isn't avoidable (unless you're a reclusive billionaire who never has to answer to anyone or leave his gated compound for any reason), so the trick we have to learn is how to come up with some kind of reasonable compromise when competition from real life makes it impossible to execute our plan as originally conceived.

Compromise isn't something I have a natural gift for. I tend to have an all-or-nothing attitude. There was a scene in "Annie Hall" where Woody Allen refuses to go into a movie theater late, just after the film has started. Diane Keaton upbraids him for making such a fuss over missing the opening credits of a film that's in French anyway, and the audience is supposed to take her side, and think, "of course it's nutty for him to insist on seeing a film from the start or not at all!" But the truth is that I was sitting there thinking: "of course you can't go into a movie after it's already started!". I realize this isn't a good time to be comparing oneself to Woody Allen, and perhaps I should emphasize that missing the start of a movie is the only issue I'm siding with him on. But anyway, I do have that all-or-nothing mentality: settling for a compromise doesn't come naturally. I tend to feel that "good enough" is not good enough. But in terms of diabetes management, you often need to settle for good enough.

Yesterday's workout was in the gym (and therefore not as intense as a real run outdoors on real hills), so I felt that for today's workout I needed the real thing. But it rained all morning, and I was tempted to say, "that's it -- I can't face doing a long run in the rain, so I can't run today".

But I checked the weather-radar map on a weather website, and I could see a clearing trend coming, and the rain was already getting lighter. I figured I could handle starting my usual lunchtime run in a light rain, especially as it seemed clear that the rain would stop soon. So I did that, and it worked out: it was drizzling during the first mile, but not enough to soak my clothes and give me a chill. And then it stopped. And the sky even cleared briefly, and all the wet greenery around me was dazzlingly bright in the sudden sunshine. Also, I passed two wild turkeys who were extending their tail feathers in full display (probably to dry them off), which was startling and impressive. So I ended up being glad I went outside. That is, I'm glad I resisted the temptation to dismiss the run as an impossibility today, just because conditions weren't just right for it.

After lunch, just when I was about due to do my one-hour post-prandial test, my boss dropped by my office to talk about a complicated problem, and I wasn't about to interrupt the conversation to do a blood test. I'm not keeping it a secret from him that I have diabetes, but I don't want to put it on display, either. I want him to know about it but also forget about it. So, although I usually do a test 60 minutes after eating, I ended up doing it 90 minutes after eating this time. I don't like to do glucose testing in an inconsistent way, because I think you end up with less meaningful data that way. But some data is better than no data, and I suppose if I was down to 104 at 90 minutes, I couldn't have been too terribly high at 60 minutes. I'm glad I resisted the temptation to dismiss the test as an impossibility today, just because conditions weren't quite right for it.

I realize that not everyone shares my all-or-nothing attitude, so for a lot of people it's no trouble at all to compromise diabetes-management plans whenever circumstances are inconvenient. But if you do have that all-or-nothing attitude, it can be very tempting to take the nothing. I think one of the reasons people often give up on diabetes management altogether (the so-called "diabetic burnout" problem) is that they become too frustrated by their inability to make it work exactly the way they wanted it to work. If you find yourself throwing up your hands at the impossibility of making diabetes management fit neatly into the business of life, maybe you should settle for making it fit not-very-neatly into the business of life.

 


Ants Again!

Tuesday, March 25, 2014

 


This is how rumors get started

When I look at the search strings that resulted in a reference to my blog, I'm never surprised to find questions about ants. A lot of people have the idea that the best way to tell if you have diabetes is by observing how much ants like your urine. But the search string I saw today took this to a whole new level: "is it true that by eating ant can kill diabetes".

No, I don't believe there's any evidence that eating ant can kill diabetes. I mean, eat ants if you like them, but don't expect it to cure you of anything besides popularity.

It's really time we left the ants behind, folks, at least in regard to diabetes. Three thousand years ago, the behavior of swarming insects might have provided an interesting clue to the nature of diabetes, but it was never an especially reliable diagnostic tool, and we have much more precise measurement technology available to us now.

But that question about eating ants to cure diabetes is a clue to the strange conclusions people draw from an association of any kind between two things. Once you get the idea into your head that diabetes has something to do with ants, it's a short leap from there (in some people's minds, anyway) to the idea that curing diabetes might also have something to do with ants. Eat ants; problem solved!

A silly example, I realize, but my study of the questions people ask about diabetes has revealed a lot of very odd conclusions people are obviously drawing form the association of diabetes with something else -- perhaps anything else.

For example, a lot of people, having gotten the idea into their heads that diabetes is the problem of having sugar in your urine, also think that diabetes will not be a problem once you can somehow get the sugar out of your urine. Actually, sugar in the urine is just a telltale sign that you have diabetes and that it's getting pretty far out of control. You can be diabetic without having sugary urine, and in any case, urine isn't the real area of concern. When diabetes harms your health, it isn't because you're urine isn't all it should be. What's going on in your blood is the real issue.

We are pattern-seeking animals, and we feel a strong impulse to read meaning into every connection we observe (or think we observe) between two things. It doesn't matter that we don't really understand the connection (or that, for all we know, the connection is a mere coincidence). We have perceived a connection, and it has to mean something. So let's just guess at what the meaning is!

One of the problems with this kind of magical thinking is that it sets us up to be deceived and exploited. Quack cures, anti-vaccine hysteria, and all sorts of other dangerous nonsense can be sold to us pretty easily, so long as we are willing to let somebody sell us on their interpretation of a perceived (or imagined) connection between unrelated things.

So, when you find yourself associating diabetes with something else, always ask yourself what you think the nature of that connection is, and how you know you're right about your interpretation of it. Maybe ants aren't the important thing here. Maybe urine isn't the important thing here, either.

 


Mind Games

Monday, March 24, 2014

 



I'm not sure it's a great idea to do this, but maybe I should try to give you some idea of my thought process when I'm pushing myself to do a heavy-duty workout.

Strenuous exercise is the cornerstone of my diabetes-management system, and yet strenuous exercise is so much the opposite of what most people (me, to name one) usually feel naturally inclined to do... that there seems to be a paradox involved here. How is it that I'm so consistently doing what doesn't come naturally? Perhaps some of my readers are wondering how that kind of thing is done. How does one overcome the strong natural resistance which most people feel about doing hard exercise?

The answer, at least in regard to today's run (which I can promise you was very difficult, with a steep hill-climb that seemed to go on forever) was that I was thinking past the workout itself. As I was talking myself into choosing that route (when easier ones were readily available to me), I was thinking past the workout itself. The issue was not how I wanted to feel during my lunchtime run (that consideration would have argued for a shorter and less hilly route), but rather how I wanted to feel after the run, and what kind of post-prandial test result I wanted to get after lunch.

On another day a shorter run might have been all right, but this was a Monday following a weekend which was in some ways a continuation of St. Patrick's Day. On Saturday I had played Irish music at a delayed St. Patrick's Day celebration, and this celebration included a substantial amount of eating and an even more substantial amount of drinking. I wasn't at all sure that my 5-mile run on Sunday had done enough to make up for my Saturday indulgences (and Saturday, I should mention, had been my exercise-free rest day for the week, so the day had combined the deadly sins of gluttony and sloth). So, I felt that I had a lot of transgressions to compensate for today.

Even so, when I went outside for my lunchtime run, I still had options, and had not made up my mind which route I was going to choose. I ended up choosing the toughest option I had time for, simply because I felt it was appropriate to the circumstances (I had a St. Patrick's Day party to make up for, after all).

How did I keep myself going through the rather unpleasant hill-climbs? Partly by resigning myself to the necessity of the thing ("you don't really have a choice, so stop fretting about whether this is the choice you would make if you had one"), and partly by distracting myself. I have a vivid imagination, so it wasn't hard for me to imagine vivid and emotionally-charged scenes to take my mind off the actual challenge before me. Instead, I imagined myself in a frightening situation: singing to an audience.

On a few occasions I have sung to a small audience at a party, but in general I have zero confidence as a singer, and the thought of singing to a concert audience that is expecting great things is a thought quite frightening enough to take my mind off the physical discomfort of my actual situation. So, that's what I thought about as I was doing the steepest climb. However difficult it was to breathe as I struggled up the steepest slope, I thought of it as the struggle to sing very long phrases with no place to sneak in a catch-breath.

I don't have any idea whether this kind of worst-case-scenario thinking can be useful to others as a means of distracting themselves from the horror of the immediate situation (that is, the horror of finding yourself engaged in exercise, when you'd rather do something else, perhaps anything else). My real point is that you need to find some kind of mind-game that is useful to you in this situation.

Almost 100% of diabetes management consists of doing things you'd rather not. I don't know what kind of mental trick you can play on yourself that will enable you to do right now the things you'd just as soon never do at all... but it's necessary to find that trick and start using it on yourself. At this point it's become second-nature to use such tricks on myself, but I've been managing diabetes without meds for 13 years. It's harder for beginners, I realize that. But beginners have to find something that works for them, and put it to use.

 


Do Something!

Thursday, March 20, 2014

 


Someone Googled this phrase recently: "my blood sugar levels are rising and my a1c is high but my doctor won't do anything about it". Google referred them to my site. In case I still have their attention, I might as well share my thoughts on this.

Superficially, the situation sounds very sad (and also sounds like medical malpractice), but we would need to know a lot more about what's going on here before we could conclude that the doctor in the case is actually doing anything wrong.

I wonder what else might be wrong with this patient. I wrote recently about "therapeutic competition", the situation in which doctors are trying to treat everything that's wrong with a person, but the treatment for one condition makes another condition worse. In such cases, doctors sometimes have to decide to concentrate on treating whatever condition is the biggest immediate threat.

Suppose that this is an elderly patient struggling with multiple chronic conditions, including some kind of dangerous cardiovascular ailment. In such a case, getting blood sugar under control is not the highest priority, and might conflict with more pressing concerns. (And, to be more blunt than I really want to, the long-term consequences of not getting blood sugar under control might not matter, if the patient has no real prospect of a long-term future).

But suppose this patient is not at the end of a long life, and is not burdened with multiple serious ailments that compete for the doctor's attention. Suppose this is simply an ordinary, middle-aged diabetes patient whose blood sugar levels are rising but whose doctor "won't do anything about it". What then?

It is impossible to know, on the basis of the stated complaint, how high the patient's blood sugar is, or whether the doctor is truly refusing to "do anything about it". It's not even clear what the patient wants the doctor to do about it.

But it might be useful for the patient to ponder this question: why is this a problem that the doctor has to do something about?

The time for your doctor to do something about your diabetes is when you've done everything that you can do about it, and your best efforts can't bring the situation under control.

It may come to that -- your insulin productivity may decline so deeply that getting control of the situation without prescription meds of some kind becomes impossible. But are you sure you've reached that point? Probably not. And until you do reach that point, what your doctor can "do about" your glycemic control is not as significant as what you can do about it.

Your doctor cannot follow you around all day, saying such things as "don't you dare reach for that muffin, it's big enough to use as furniture!" and "no, you damned well don't want fries with that!".

Nor can your doctor monitor your daily activity level, and offer such helpful suggestions as, "maybe you ought to go outdoors now, for a nice long run -- based on what you had for lunch, I'd say you need it!".

What your doctor can do for you is pull out the mighty prescription pad, and give you legal permission to go to the pharmacy and pick up a bottle of pills or a vial of something injectable. But the success or failure of this is still going to depend largely on what you do. For one thing, you have to remember to take the medication (all your doctor can do is give you a lawful opportunity to purchase it). And even if you take the medication, it's not going to work out well in the long run if you assume that taking it entitles you to have that footstool-sized muffin, and exempts you from going outside and moving your body around.

Anyway: don't ask yourself why your doctor isn't doing something about your rising blood sugar without asking yourself why you aren't doing something about it.

 


All Roads Lead to Diabetes

Wednesday, March 19, 2014

 


Two New Diabetic Pathways!

I continue to be amazed at the number of things that can go wrong to make someone diabetic. Dozens of different gene variants have been found to increase the risk of becoming diabetic. Many different health problems and bad habits also increase the risk. And researchers keep finding new signaling pathways within the body which, when they go awry, result in diabetes. It seems that the reason diabetes is so common is that there are unlimited number of ways to trigger it.

This is a pretty weird situation, if you think about it. The body's system for regulating blood sugar is extremely important, yet also extremely fragile, with countless possible ways to fail. This is not true for most other crucial regulatory functions in the body. For example, the mechanism that causes blood to clot can fail, but there seems to be only one genetic defect that causes that, and it doesn't happen often (about 20,000 Americans have hemophilia -- a pretty modest number compared to the 25 million with diabetes). And blood clotting is not a simple process! It's hard to believe glycemic regulation is so much more complicated than blood clotting that the complexity of the process explains its extreme vulnerability.

Anyway, it seems as if researchers find new pathways to diabetes every few weeks. And I leaned about two new ones today. Researchers are interested in them mainly because may lead to the discovery of the next billion-dollar drug. I'm interested in them more because I would like to understand the disease better.

The first of these pathways has to do with a problem which causes beta cells in the pancreas to produce insufficient insulin. The problem has to do with a "switching protein" called p35, which inhibits insulin production (when blood sugar is already low, p35 prevents excessive insulin secretion from triggering hypoglycemia). But when blood sugar is high, another protein SIK2 is supposed to "switch off" p35, so that insulin production can go up. The body therefore responds to high blood sugar by increasing production of SIK2. Apparently, in diabetes patients, this reactive increase in SIK2 doesn't happen, so insulin production continues to be inhibited. The obvious pharmaceutical intervention: create a drug which either mimics SIK2 or forces the body to make more of it. (And hope that the drug doesn't have any other effects we don't want.)

The second pathway doesn't relate to insulin secretion from the pancreas -- it relates to glucose secretion from the liver. The liver also does its part to protect us from hypoglycemia, by releasing stored glucose into the bloodstream as needed. The liver is stimulated to secrete glucose by lipids known as phosphatidic acids. A defect in the gene AGPAT2 can cause excessive production of phosphatidic acids (by first causing excessive production of two liver enzymes which stimulate production of those acids). This goes on even when blood sugar is already high. The over-abundant phosphatidic acids cause the liver to dump sugar into the bloodstream. The obvious pharmaceutical intervention: suppress the enzymes that produce phosphatidic acids. (And hope that the drug doesn't have any other effects we don't want.)

I wonder how many more new diabetic pathways will be discovered this year. The trouble with having so many possible failure mechanisms which can cause diabetes is that, even though this gives researchers lots of potential drug targets, it also raises the possibility that the resulting drugs will work for some patients and not others. If there are dozens of ways to become diabetic, and dozens of possible remedies, the odds of any one remedy being the right one for you might be slim!

 


St. Patrick's Day: the Aftermath

Tuesday, March 18, 2014

Spring is upon us, at least in California, where the March weather has been ridiculously warm. For my lunchtime run today it was clear and sunny and 72 degrees. (That's 22 degrees Celsius, for those of you who live in scientifically advanced countries.) It's forecast to be even warmer tomorrow.

I took yesterday off to head down to San Francisco and points west to play Irish music at a couple of St. Patrick's Day celebrations. Even in San Francisco it was warm, which is pretty unusual for March. San Francisco is a narrow peninsula with the ocean on one side and a large bay on the other, so it's normally a lot cooler and foggier there than anyplace else in northern California. But walking from the parking garage to the pub, wearing a very light windbreaker, I felt that I was too warmly dressed for the occasion.

I felt good during today's run -- the weather was too beautiful to feel any other way, even while struggling up the ridiculously steep hills which the misguided city council apparently installed here -- but all those blossoms on the trees and shrubs reminded my vividly that allergy season is about to get into full swing. As of today, I started taking Claritin to prepare myself for the pollen onslaught. Ten milligrams a day should see me through -- from now till June.

Is it hypocritical for me to treat my allergies with pills, when I don't want to treat my diabetes that way? Not necessarily. I've never said that the unmedicated approach is always best for diabetes; I've only said that it's better to use the unmedicated approach if you can make it work. There isn't an unmedicated approach I can take that deals effectively with my allergy problems.

Well, in a way there is. My seasonal allergies became less severe once I made it a practice to exercise outdoors frequently. But they haven't gone away completely, and they're extremely irritating... and irritation isn't one of the things I like.

 


The Wine/Diabetes Nexus

I am so used to reading that everything in life is made worse by diabetes -- if you have diabetes, then every potential bad thing in life is likelier to strike you (including paper cuts, bad dreams, and costly automotive repairs) -- that I'm always cheered up when I learn that something which benefits the non-diabetic population also benefits people with diabetes. But this doesn't happen often. Usually it's all gloom and doom. Hey, diabetes patients: here's something that's good for everyone but you!

Today I happened upon one of those bright exceptions. You know all those reports about how moderate alcohol consumption -- a nice Zinfandel with dinner, for example -- reduces your risk of "cardiovascular events" (heart attacks and strokes)? I was half-expecting to be told, if anyone actually looked into it, that those benefits go away if you have diabetes.

Not so, according to a report in Diabetes Care entitled "The Relationship Between Alcohol Consumption and Vascular Complications and Mortality in Individuals With Type 2 Diabetes Mellitus". According to this report, "In patients with type 2 diabetes, moderate alcohol use, particularly wine consumption, is associated with reduced risks of cardiovascular events and all-cause mortality." So there you are. Have that Zinfandel with dinner. I particularly recommend Zinfandels from Dry Creek Valley, in my own county of Sonoma (the Bella winery is a good place to start, if you can get hold of their Zinfandels, and if you can afford them).

 


The Odor/Diabetes Nexus

You know how wine enthusiasts drive you nuts talking about "notes" of this or that flavor or odor in a wine? It may seem to you that they are only pretending to be able to perceive hints of this or that in a cautious sip (the flavor of some herb or mineral you've never heard of, or perhaps the scent of an asphalt driveway washed by the first rain in October) but it is actually possible for a wine to contain a huge number of flavor/odor components. Any "organic" substance (meaning a substance containing the carbon compounds associated with living organisms) is bound to produce VOCs ("volatile organic compounds"). VOCs are carbon compounds which evaporate easily, and therefore produce a detectable scent (and in humans, at least, scent not only produces a perceptible odor but also strongly influence the perception of taste). Most of us don't focus enough on scents to become very good at recognizing them, but that doesn't mean we couldn't.

Humans rely much more on sight and hearing than on the sense of smell, but many animals are vastly more sensitive to odors than humans are (a dog with its head out the car window is experiencing a rush of sensory impressions of which human LSD-users cannot even dream). Fluctuations in human body chemistry can produce changes in human odors too subtle for humans to perceive, but animals can be trained to recognize, and react to, those changes in body chemistry. Dogs can be trained as companion animals to diabetes patients, so that they recognize by smell an extreme change in the patient's blood sugar level, and can raise an alarm. Diabetes patients have actually been saved because a properly trained companion animal recognized by smell that they were in trouble.

The trouble is that training dogs to recognize glycemic extremes by smell is time-consuming and expensive (also: dogs can't be on duty 24 hours a day, every day). What if a sensor could be developed which would detect glycemic extremes by odor -- a sensor which wouldn't cost as much as a trained dog, and could operate constantly?

Some research into analysis of human odors (with the specific goal of helping deer-hunters avoid giving themselves away by the smell of their body and breath) is resulting in sophisticated odor-measurement technologies. It looks as if this work may lead to instruments which can detect changes in odor associated with changes in blood sugar levels.

My guess is that this technology (like other technologies which attempt to get an idea of where someone's blood sugar is heading without collecting a blood sample) will always be too crude to serve as anything other than an emergency warning indicator. But we'll see!

 


When Pills Collide!

Thursday, March 13, 2014

 


Therapeutic Competition

My goodness, just yesterday I was pointing out why it might not be such a great idea to treat diabetes with drugs that promote heart failure. Trying to address one narrowly-defined problem with a treatment which causes another problem is not necessarily a good trade. You can make a case for it, if the problem being treated is a lot worse than the problem the treatment causes. (That's why we accept the unpleasant tradeoffs involved in cancer therapy.) But is anyone seriously going to argue that heart failure is not nearly as serious a problem as diabetes?

Well, it turns out that there a lot more of these tradeoffs going on in medicine than I realized. And also a lot more of these tradeoffs going on than patients realize. And a lot more of these tradeoffs going on than doctors apparently realize.

The majority of older Americans have multiple chronic health conditions, and are being treated with multiple prescription drugs. That in itself is not so surprising. But researchers at Oregon State University and Yale University have found that 22.6% of older Americans are being prescribed medications that work against each other.

The problem is known as "therapeutic competition". A common example involves patient who have both coronary heart disease (CHD) and chronic obstructive pulmonary disease (COPD). Many of these patients receive beta blockers to treat their CHD -- beta blockers which make their COPD worse! There are some kinds of beta blockers that don't have this kind of harmful interaction with COPD, so doctors do have alternatives -- they're not just exercising those alternatives, either because they haven't been given any guidance on the problem (therapeutic competition has been a largely ignored issue so far), or because they are so focused on solving one problem at a time that it doesn't occur to them to ask whether the CHD treatment is undermining the COPD treatment. (Although some doctors do prescribe the beta blockers which don't exacerbate COPD, it seems to be by chance: they don't do it any more often for patients with COPD than for patients without COPD.)

David Lee, one of the authors of the study, said "Drugs tend to focus on one disease at a time, and most physicians treat patients the same way. As a result, right now we're probably treating too many conditions with too many medications. There may be times it's best to just focus on the most serious health problem, rather than use a drug to treat a different condition that could make the more serious health problem even worse."

Another study author, Jonathon Lorgunpai: "More than 9 million older adults in the U.S. are being prescribed medications that may be causing them more harm than benefit. Not only is this potentially harmful for individual patients, it is also very wasteful for our health care system."

The task now, seemingly, is for professional medical organizations to get the word out to doctors, and give them clinical recommendations that lay out better strategies for avoiding these problems. That shouldn't take more than a few decades; in the meantime, there's something patients can do: adopt the attitude that one shouldn't take more medications than are clearly necessary.

The six diseases commonly involved in therapeutic competition are diabetes, CHD, COPD, hypertension, osteoarthritis, and depression. Considering how many diabetes patients also suffer from at least one of the other five, therapeutic competition is clearly a big issue for diabetes patients. We need to be cautious about this. If you're getting multiple prescription meds, don't be too shy to ask your doctor if your meds might possibly compete with each other, and whether different meds (or fewer meds) might be a safer bet.

 


Hidden HF

Wednesday, March 12, 2014

 


Great: another thing to worry about!

Doctors are starting to get worried about the "hidden" (or at least ignored) problem of HF in diabetes patients. And when doctors are worried, patients usually need to worry, too.

HF stands for heart failure, and I wonder what percentage of the general public believes, as I used to believe, that heart failure means that the heart stops beating. Actually, no -- that is "cardiac arrest". Heart failure is another issue.

Heart failure doesn't mean a stopped heart, it means a weak heart. It means that the heart is pumping, but not pumping strongly enough to keep the blood circulating at a rate sufficient to meet the body's needs.

There seem to be a lot of ways for the heart to get into this weakened state. Ischemic heart disease (that is, partial blockage of coronary arteries) can starve the heart muscle of oxygen and gradually damage the muscle tissue; other conditions can cause similar damage. Or, chronic hypertension may give the heart muscle too much hard work to do on a routine basis, and traumatize the muscle tissue. Problems with the coordination of different portions of the heart can play a role. Furthermore, the body's attempts to compensate for heart failure (such as enlargement of the heart) can make the problem worse in the long run.

People with HF have no "spare capacity"; their hearts are just barely getting by during periods of inactivity, and can't work harder when the body is working harder. Therefore, exercise (including mild exercise such as walking) becomes increasingly difficult or impossible. The patient easily gets exhausted and out of breath, and has coughing fits. Also, fluid tends to build up in various parts of the body (the legs, the abdomen, and in and around the lungs). Obviously all of these problems have a big impact on quality of life -- and, because they typically grow worse over time, they tend to shorten life. So, although "heart failure" isn't the sort of emergency situations the phrase seems to describe, it is a mighty serious medical problem.

The big risks factors for HF, in descending order, are ischemic heart disease, smoking, hypertension, and obesity. Diabetes is also considered a risk factor, but it's not a major one. Or is it?

Doctors are becoming concerned that a serious problem with HF in diabetes patients is going unrecognized, mainly because nobody is looking for it. Specifically, many glucose-reducing treatments for diabetes seem to be causing heart failure as a side effect, and the problem is going unrecorded because clinical trials for diabetes drugs are looking for, and recording, heart attacks and strokes, but are not looking for or recording incidence of HF. "A major concern, however, is the universal absence in any of these trials of hospital admission for heart failure as a prespecified component of their primary composite cardiovascular outcomes. In our opinion, hospital admission for heart failure is one of the most common and prognostically important cardiovascular complications of diabetes and the one cardiovascular outcome for which the risk has been shown unequivocally to be increased by certain glucose-lowering therapies."

The most serious of all diabetes complications is heart disease, so it's a bit bizarre that so many of the drugs people are taking to keep themselves safe from diabetes complications are bad for your heart. This very nasty irony is a big part of the reason why I think the unmedicated approach is preferable, if you can make it work.

 


The Gluten Thing

Tuesday, March 11, 2014

 


In the cafeteria at work today, the offerings were all pretty high-carb, and when I decided to make a sandwich, it turned out that the breads on offer looked pretty high-carb too. I decided to try some bread that was advertised as "gluten free". Unfortunately, I didn't have my reading glasses with me, so I couldn't read the carb content on the label, but I thought maybe gluten-free also meant low-carb.

I'd never tried gluten-free bread before, so I figured I might as well give it a try. The taste of the bread was so unsatisfying (more or less like a piece of unusually flimsy drywall with a crust around it) that I thought it was probably a pretty safe bet.

But my blood sugar went to 143 an hour later -- and this after a super-hilly 5.4-mile run! If the cafeteria hadn't been out of sandwich thins, I bet I would have been under 120. I decided to check again at the two-hour point, to see if the effect was prolonged. Nope: I was down to 98 by then. So the gluten-free bread didn't have a prolonged effect on my blood sugar, but it did cause a significant spike (and a higher one than I like to see). So, clearly "gluten-free" does not mean "low-carb".

So what is gluten, and why are so many people trying to avoid it? Gluten is a sticky, stretchy protein found in wheat (and some other grains), and its consistency makes gluten-rich grains particularly suitable in bread dough. In fact, making bread dough without it is a real challenge (a challenge which the gluten-free bread I sampled today did not quite meet).

Unfortunately, not everyone can tolerate gluten. Some people have an allergic reaction it. And in some people, it triggers an unpleasant auto-immune disorder of the small intestine known as celiac disease. And in some people who merely read about these problems on the internet, it triggers a conviction that they must be suffering from them. The people who have an actual physiological reaction to gluten probably make up less than 1% of the population, but the people who have a psychological reaction to it are more numerous, so there are quite a lot of people out there trying to avoid gluten, and quite a lot of food companies out there trying to make reasonably appealing gluten-free foods to serve that market.

I looked into how gluten-free breads are made, and it turns out that there are a lot of unlikely ingredients used as wheat-substitutes. Flour for gluten-free bread can be made by grinding up almonds, rice, sorghum, corn, and even beans. But the results, if my experiment today is any indication, don't taste a lot like wheat bread, and are pretty high in carbohydrate (the bread I had today was unusually thickly sliced, apparently because the powdery consistency of the bread makes it fall apart too easily if you slice it thin).

I'm not sorry I looked into this; for a long time I had assumed that gluten-free baked goods might be a useful option for diabetes patients frustrated by their inability to find a good bread that doesn't spike their blood sugar. Apparently not!

 


More Implicit Questions Answered

Monday, March 10,2014

I'm not a fan of Daylight Saving Time to begin with (to me it's like painting a wall by holding a paint-brush stationary and waving the house back and forth in front of it), but it's especially harsh when you have to begin your first Monday of the new time regime by going in to the office early for a 7 AM meeting. That dreadful meeting time was chosen because some of the participants in the meeting were joining it by phone from Scotland, and Scotland doesn't have a lot of daytime overlap with California. (And tomorrow I have to hang around for a meeting that doesn't start till 6 PM, because it included people joining by phone from China.)

Maybe my real beef isn't with Daylight Saving Time -- it's with Time.

 


Once again, I try to provide answers to the questions asked or implied by people who Googled certain diabetes-pertinent phrases and were referred to this site.

"A1c 6.2 good or bad"

The most frequently asked question of them all, for reasons that are unclear to me.

A result of 6.2% on a hemoglobin A1c test indicates, if you been diagnosed with diabetes, that your glycemic control is very good for someone with diabetes (so keep up the good work). If you have not been diagnosed with diabetes, a result of 6.2% indicates that your glycemic control isn't as good as it should be for someone without diabetes. So you need to work on bringing that number down before it starts going up.

"if your blood sugar is 6.2 average for 3 months what should be done"

The usual thing that has to be done when you're trying prevent or control Type 2 diabetes: more exercise, less carbohydrate.

"ways to lower a1c"

See above.

"does an infection affect your a1c score"

If it goes on for months, perhaps. But if a chronic infection raises your result on the A1c test, it does it by raising your blood sugar -- so don't think an infection will give you a false high reading.

"if a1c only does the last 3 months could it be higher 6 months ago"

Yes. It could also have been lower 6 months ago. It could also have been the same 6 months ago. Because the hemoglobin A1c test examines the condition of a protein in red blood cells, and red blood cells have a lifespan of about 3 months, the A1c test reveals nothing whatsoever about what was going on in your blood 6 months ago.

"123/79 blood pressure in line with a heart attack"

No, that's actually pretty good.

"hypoglycemia for non medicated diabetic"

Not as big an issue as it would be for a medicated diabetic. If you're not taking any drugs that can push you into hypoglycemia, then the only hypoglycemia you're likely to experience is the sort of mild, not-dangerous, briefly unpleasant episode that absolutely anyone can experience whether they have diabetes or not.

"how long would it take to die from low blood sugar"

I cannot stress too much or too often how unreliable and unpredictable hypoglycemia is as a homicide method. Find something else, folks!

"i have to pee every one to two hours does that mean i have diabetes"

Not necessarily. Frequent urination can be a symptom of poorly-controlled diabetes, but it can also be a symptom of something else. And I'm not sure there's a universal rule about how often one must be able to go between bathroom visits to qualify as non-diabetic. The main cause of concern is if you find yourself needing to urinate more often than is normal for you.

"daily pissing count normal"

Okay, I stand corrected: there's a normal rate, and this person knows what it is. However, I'm not privy to this information, as it were.

"my blood pressure is 118/74 i am 37 years old is that good"

Yes. Especially the part about being 37 years old. Being over 50 myself, I can recommend being under 40 without reservation; it's just a terrific deal.

"my fasting blood glucose is 103 and after exercise it went to 119"

Your liver maintains a supply of stored sugar, and releases it into the bloodstream periodically to prevent lows. Exercising on an empty stomach is one of the things which can trigger the liver to release sugar in this way, so don't expect your fasting level to hold steady until you eat -- especially if you exercise in the meantime.

"my sugar was high caused me to pee on myself"

Listen, folks, there's a limit to how much I can help you! I'm just a guy with a web site.

 


Genebusters!

Thursday, March 6, 2014

 


When broken genes are good genes

A lot of health problems are caused, or made more likely to occur, by a variant in the DNA code for a gene -- a variant which causes the gene not to perform its intended function. Whatever protein that gene is supposed to produce in a cell doesn't get made. Well, actually, what usually happens is that only half of the normal amount of that protein is made, because our chromosomes come in pairs, and if you have a broken gene on one of the two chromosomes, the equivalent gene on the other chromosome is not broken. (This situation is called haploinsufficiency -- haplo meaning "half".)

Having half the normal amount of a particular protein in a cell can be a big enough problem to cause serious health consequences. Not always, though. For some proteins, you only need one working gene on one of a pair of chromosomes to get by. That is why hemophilia is a specifically male disease. One good copy of the gene that produces the protein known as clotting factor 8 is all you need to avoid hemophilia. The gene for that protein is on the X chromosome, however, which only women have two copies of. Men don't get a backup copy of the gene, so if a man has a defect on the gene for that protein, he's definitely got hemophilia. (A woman can get the disease is if she has defective copies of the gene on both X chromosomes, but that's an extremely rare coincidence.)

Once in a while, it turns out that a defective gene doesn't put you at risk of developing a disease -- it reduces your risk of developing that disease! There aren't a lot of genes like that, but the pharmaceutical industry is always hunting for them, because they have the potential to be valuable "drug targets". If it's beneficial for a particular gene to be broken, then a drug that breaks it on purpose could be a gold mine. (A gene defect which is known to provide protection against the AIDS virus is currently being investigated for possible drug applications, for example.)

The catch is that you have to make sure breaking the gene has only beneficial effects. If breaking a gene prevents one disease and causes another, it's not much of a solution.

Right now researchers think they have found a very promising target for beneficial gene-breaking. The target is a gene called SLC30A8, and it turns out that certain rare defects in this gene, resulting in haploinsufficiency of the protein it produces, reduce the risk of Type 2 diabetes by 65%, even in people seemingly at risk for the disease because of age or obesity.

Even better, it seems as if what the SLC30A8 gene does is pretty narrow, so the risk that breaking that gene on purpose will cause unforeseen health problems is probably low. (A defect in another gene called cyclin D2 is also protective against Type 2 diabetes, but that gene isn't considered a very promising drug target because it plays a role in regulating cell growth, so messing with it might turn out to cause cancer.)

So what does the SLC30A8 gene do, and why does breaking it reduce the risk of Type 2 diabetes? Well, the gene produces a protein called ZnT8. What the ZnT8 protein does is transport the element zinc into the beta cells in the pancreas (that is, the cells that produce our insulin supply). So far I have not been able to find out why we have a protein that transports zinc into beta cells, nor have I been able to find out why producing half the normal amount of that protein would be protective against Type 2 diabetes. (Perhaps nobody has figured that out yet.) But, for whatever reason, haploinsufficiency of the ZnT8 protein reduces diabetes risk considerably, so it might be very useful to create that situation artificially, using a drug.

The number of unanswered questions here is pretty large. One big one I'd like to know about: would a drug which causes haploinsufficiency of the ZnT8 protein only be useful in preventing Type 2 diabetes, or would it be useful in treating the disease after it develops?

Also, I don't know how difficult it is to develop a drug to disable the SLC30A8 gene (and specifically to disable only one copy of it on one chromosome, if I'm correct in thinking that's necessary). If this turns out to be one of those drugs that will cost you more than a heroin habit, it's hard to picture the drug being widely used, especially if it only reduces your risk of developing a disease you might not get anyway.

Still, I'll be watching this research with interest, to see what becomes of it.

 


Finding a Motive

Wednesday, March 5, 2014

 


Exercise Inspiration

Here's a weird thought for the day from SMBC:

I think by this point my own exercise inspiration is simply the force of habit. Going outside for a run at lunchtime isn't something I need to talk myself into every day; it's something I've been doing so long that it feels strange not to do it, whenever there isn't enough time, or some other circumstance gets in the way.

Today I knew that rain was expected, but went out for a run anyway. When I managed to finish my run before the rain really started (it was just misting at that point), I had a pleasant feeling of having got away with something. The run was long and it involved some very steep hill-climbing, but it seemed more like a relief than a chore to do it. It gave me some time to myself to think (and not to think about work).

It wasn't always possible for me feel that way about a hard workout. During the first year or two after my diagnosis, when I began to make exercise part of my daily routine, I used to spend the entire duration of a workout thinking about one thing: how much I hated it and wanted it to be over. And talking myself into starting the workout in the first place was a very difficult task which often longer than the workout itself did.

That was 13 years ago, so it's easy for me to forget how much more difficult exercise seemed to me then. But I try to remind myself how much more difficult an issue exercise-motivation is for people who haven't been doing it regularly for years. It's all very well to tell people that exercising regularly will become easier once they've done it consistently for a year or two, but how do they manage to keep doing it for a year or two, when it's not remotely easy for them?

People have to find their own motivation. What motivates one person is useless to another. But in general, my advice is to exercise with others. Join an exercise class, or a sports club of some kind, or find workout buddies who, despite being as unenthusiastic about exercise as you are, will agree to keep doing it as long as you keep doing it.

Peer pressure isn't just a means of luring teenagers into doing what they shouldn't. It's also a pretty effective way to lure adults into doing what they should.

 


Protean Protein

Tuesday, March 4, 2014

 


Too much now; not enough later

Proteus was a sea-god in Greek mythology known for his shape-shifting abilities, and the word "protean" means Proteus-like in the sense of being able to assume many forms. (An actor capable of playing a wide range of different kinds of roles might be called protean, for example.)

The word protein comes from the French word proteine, which comes ultimately from the Greek word protos, meaning "first". The word originally referred to a vaguely-defined, purely theoretical substance essential to life. It is now associated with a crucial set of organic compounds consisting of amino acids chained together, compounds which fold up like origami to create molecular structures which act like tools within living cells, performing all sorts of chemical tasks that sustain life. (For example, hormones, including insulin, are proteins. So is the hemoglobin which enables red blood cells to deliver oxygen to tissues throughout the body. So is the collagen that makes connective tissues connect.)

The similarity between the words "protean" and "protein" is purely coincidental, and yet it's apt. Protein does indeed come in many shapes (that's what makes it useful as a biochemical tool), and its character also seems to change constantly. Is protein beneficial or malign? Is protein good for us or bad for us? It depends on which research study you've read most recently.

The study I read today makes the diet wars even more complicated and confusing than they already were -- which I hadn't realized was possible. It seems as if protein, or at least protein consumed in generous amounts, might be good for us at some stages of life and not others.

For generations now, people have been told that protein is good for us -- we might argue about the health effects of fat or carbohydrates in the diet, but protein is always a good thing, and you can't get too much of it. Except that some researchers think that you can get too much of it, and that a lot of us do get too much. Studies have disagreed about this, leaving the public in doubt about what to believe. (By "the public", I mean that segment of the population that tries to follow these things; most people have probably never heard that protein can be anything but good.)

A new study published in Cell Metabolism looked at the effects of protein consumption at different stages in life, and found that a high-protein diet can be helpful late in life -- and can be very harmful in middle age!

The reason for this oddity (protein is harmful for people under 65, but becomes protective for people over 65) seems to hinge on a growth hormone known as IGF-1. A high-protein diet promotes IGF-1, which can help older people (who produce much less of this protein than younger people do) prevent various kinds of degenerative conditions associated with aging. But in middle-aged people, who don't need help producing IGF-1, a high-protein diet increases the supply of IGF-1 above normal levels -- which seems to be a dangerous thing.

According to the study, a high-protein diet in middle age increases all-cause mortality by 75%, and quadruples the risk of cancer mortality. Yet it reduces mortality in people over 65!

Complicating the situation still further, a high-protein diet seems to cause a five-fold increase in the risk of diabetes, regardless of how old you are. Therefore, a high-protein diet for older people might be helpful in terms of avoiding cancer and other problem, but still increases your diabetes risk.

Yet another complication: the harmful aspect of a high-protein diet appears to relate specifically to proteins from animal foods. Vegetable protein sources seemingly don't cause the same kinds of problems that occur in connection with meat and cheese.

I have no idea how well this study will stand up under scrutiny -- and I assume there will be plenty of scrutiny. (Is it at all likely that the meat industry will take this lying down?) Expect to hear a lot more about this study. In particular, expect to hear accusations that the researchers cherry-picked the data to make it tell the story they wanted it to tell.

Still, the message seems to be pretty clear: the human diet should be less protein-rich in the middle years, and more protein-rich in the later years. We'll have to wait and see who will this system works out in the months to come.

 


Dr. Watson

Monday, March 3, 2014

 


He's Back!

A little over a year ago I wrote a piece about the eccentric biologist James Watson under the title "Great Weirdos of Science". My point was about the difficulty, in the case of a brilliant scientist who is also an obnoxious crank, to know whether his latest scientific idea is coming from the brilliant side of his personality or the crazy side. Specifically, I raised the question of whether Watson's contrarian view of anti-oxidants -- as a problem rather than a solution -- might be motivated by his decades-old professional rivalry with Linus Pauling (the patron saint of anti-oxidants).

At the time, Watson was talking specifically about the possibility that, instead of fighting cancer (as we had been led to hope), anti-oxidants interfere with the body's own cancer-fighting mechanisms. In recent years it has been widely assumed that oxidizing reactions within cells do great harm and should be neutralized as much as possible. Not so fast, Watson was saying: maybe we need those oxidizing reactions. The body uses oxidizing reactions to kill cancerous cells (just as chemotherapy does); is that a process we really want to derail?

Watson has now expanded his claims about the benefits of oxidizing reactions, and the possible harm to human health which can result if not enough oxidizing is going on. He now thinks that various chronic diseases (including Type 2 diabetes) might be caused by an insufficiency of oxidation reactions happening within cells.

The conventional view is that Type 2 diabetes develops because inflammation triggered by oxidation reactions causes pancreatic cells to make less insulin, and also causes muscle cells to be less responsive to insulin than they ought to be (because they're not making enough GLUT-4 transporter molecules). Watson, however, thinks that the inflammation and its consequences are triggered not by excessive oxidation but by insufficient oxidation.

The smoking gun in the case is exercise. Watson points out that, although exercise is known to be benefit patients with Type 2 diabetes (specifically by boosting insulin sensitivity), the precise means by which exercise achieves this effect has never been adequately explained. But exercise is known to cause the body to produce oxidants in generous amounts. If oxidants were the problem instead of the solution, why would exercise (which stimulates production of oxidants) be so beneficial for Type 2 diabetes patients? It looks as if oxidants, at least in the case of diabetes, are making a positive contribution rather than a negative one.

What might be the nature of that positive contribution? The oxidants produced by the body during exercise include hydrogen peroxide, which serves to promote disulfide bonds which are crucial to stabilizing the shape of protein molecules as they fold (proteins are like hand-tools which must be shaped properly to work properly). Without these disulfide bonds, the proteins which cells are making (including insulin and its transporter molecules) won't perform their functions. Perhaps the oxidants produced by exercise enable the body's insulin-driven glucose control mechanism to operate efficiently, by synthesizing proteins that hold their functional shapes properly.

Watson himself sees exercise as having played a crucial role in keeping him healthy into his 80s. "My capacity to remain a full-time scientist at the age of 85 years has probably been much aided by regular exercise (singles tennis)." He thinks we need to know more about how exercise does whatever it does for us, and he thinks the oxidants exercise generates are the likely explanation.

Everything he's saying makes sense to me. However, it's worth bearing in mind that James Watson is one of the weirder personalities in science, and it is by no means beyond the realm of possibility that he has gone nuts on this subject. I will be eagerly waiting to hear whether biologists with a better reputation for personal stability can confirm what he's saying about this.

 



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