Happy New Year

Tuesday, December 31, 2013

 

I have some drinking to do at the moment, but I'll get back to you in the year 2014!

 


Taking Family History to Extremes

Monday, December 30, 2013

 


Neanderthals & Diabetes

Lately I've been hearing a lot about "Neanderthal genes". When you submit a sample to a lab for genetic testing, one of the results they give you these days is a figure telling you how much of your DNA is "Neanderthal DNA" (it's usually in the range of 2% to 4% if you're of European background).

And now a gene variant which has been linked to diabetes is reported to be part of the Neanderthal genome. So who are these Neanderthals, and why do they want to give us diabetes?

"Neanderthal" is a place name: it means "Neander Valley", located in Germany near Dusseldorf. Mine workers at a limestone quarry found a skeleton there in 1856; they took it to be the remains of a bear, but naturalists who assembled the bones found that it looked very close to human -- although noticeably larger and more robustly built. Eventually it was identified as a separate species, Homo neanderthalensis (some argue that it is really a subspecies of humans, and should be called Homo sapiens neanderthalensis). Some other skulls that had been found earlier, in Belgium and Gibraltar, were also identified as Neanderthals. Apparently the Neanderthals had been spread across Europe, but were not found to the south -- they never lived in Africa, for example (which is why African people these days carry little or no "Neanderthal DNA"). But Neanderthals coexisted with Homo sapiens in Europe for many years, until they went extinct somewhere between 45,000 and 30,000 years ago.

Because we tend to think of the word "Neanderthal" as synonymous with "primitive and stupid", it is worth mentioning that the Neanderthals have been somewhat misrepresented in popular culture. Classic textbook illustrations of Neanderthals have generally made them look more like furry animals than people, so we tend to assume that they had no human traits.

Also, there was a tendency to represent Neanderthals as having very dark skin -- which was odd, as they were purely European rather than African; could this choice possibly a reflect an unconscious assumption that anything "inferior" couldn't be white?

More modern reconstructions of the Neanderthal tend to look more recognizably human (and European) -- such as this:

...and this:

Oh, wait -- wrong picture, that's actually Chuck Norris.

But there is really no reason to assume that Neanderthals were inferior, or less than human. They are known to have used tools, and to have buried their dead ceremonially -- both of these things suggesting that they probably used language, too, in order to communicate ideas about such matters. Their skulls were larger than our own, so there's no reason to assume they were small-brained dopes. If they were left behind by history, it isn't necessarily because they were inferior beings who couldn't get their act together. Any number of things could have caused them to go extinct; there's a good chance that we killed them, either deliberately (through warfare) or accidentally (by giving them diseases they couldn't handle, which is pretty much what happened when Europeans first came to the Americas).

However, for many years Neanderthals coexisted with our bunch. During that time, did the two kinds of humans interbreed? For a long time it was thought that they didn't, and some still argue for that position, claiming that the so-called "Neanderthal genes" already existed in Europe before the Neanderthals branched off from us, and that's why we have them today. But most researchers accept that some interbreeding occurred. Anyway, however they got into the modern human genome, Neanderthal genes do exist in modern humans, and are most common in Europe, less common in Asia, and least common in Africa. If a Neanderthal gene has unfortunate health consequences, having roots in Europe increases your risk.

Apparently such a problematic Neanderthal gene has been identified. It's called SLC16A11, and it was identified by researchers from Boston who were trying to account for the unusually high incidence of Type 2 diabetes in Latin American populations, especially in Mexico. The problematic Neanderthal gene variant of SLC16A11 is common in that population, for some unknown reason, and having that gene variant increases your risk of diabetes by 25%. That's if you inherit it from just one of your parents; if you inherit it from both of your parents, this increases your risk of diabetes by 50%.

How does the Neanderthal version of SLC16A11 cause diabetes? The researchers report: "SLC16A11 is part of a family of genes that code for proteins that transport metabolites — molecules involved in the body's various chemical reactions. The SIGMA Type 2 Diabetes Consortium paper reports that SLC16A11 is expressed in the liver, in a cellular structure called the endoplasmic reticulum. The researchers went on to show that altering the levels of the SLC16A11 protein can change the amount of a type of fat that has previously been implicated in the risk of diabetes. These findings have led the team to hypothesize that SLC16A11 may be involved in the transport of an unknown metabolite that affects fat levels in cells and thereby increases risk of type 2 diabetes."

Why this Neanderthal variant of the gene should be especially common in Mexico is not known. Mexicans don't have an unusually high incidence of Neanderthal genes in general, just an unusually high incidence of this one. Perhaps an unusually high proportion of the Spanish Conquistadors carried this gene, and seeded the population generously with it.

As for how the gene became established among Neanderthals in the first place, it may very well be that the gene had advantages as well as disadvantages. Perhaps the gene's impact on fat metabolism in the liver made it easier to survive a famine. That it causes problems when food is abundant may not have mattered too much to the Neanderthals, if food was usually not abundant for them.

I feel the need to point out a few facts about this new gene:

  1. The newly-discovered gene is not the one and only explanation for diabetes; several other genes have been found to contribute to the problem. It does seem to be an unusually important factor in causing diabetes, however, especially in Mexico.
  2. The fact that the gene affects fat levels in your cells does not mean nothing else affects fat levels in your cells. Even if you inherited a copy of this gene (or, worse, two copies of it) you can probably still do something about it by changing your habits. As I've said before, try not to see your genes as your inescapable fate -- see them instead as the particular set of challenges you must deal with.

 


Don't Fear Your Genes!

Friday, December 27, 2013

 


The Genome as Poker Hand

I recently came across a vivid metaphor which helps us understand why our usual, naive picture of what a gene is doesn't work. We are used to thinking that there is "a gene for" every imaginable trait, and that each of us has a set of traits rigidly determined (at conception) by whatever set of genes we inherited from our parents. Genes are not actually that simple, but how do you explain that to people?

Well, look at this way: the set of genes you inherited is like a hand of cards that you were dealt. The significance of any one of them varies with the situation. It would be silly to ask whether a given card was good or bad, except with reference to the other cards you're holding (and also with reference to the cards which other participants in the game are holding). A ten of hearts, considered in isolation, has no fixed value of its own. It might be highly desirable within the context of this hand:

A ten of hearts would not seem so desirable in the context of this hand:

A given card has only a situational value, not an inherent value. Its worth is determined by what else is going on in the game.

A gene, like a playing card, has a value determined by what else is going on in the game. Simply having a gene means nothing if the gene is not expressed. And gene expression (that is, how strongly a gene is activated, or when it is activated -- if it is ever activated at all) is determined by other factors, such as which other genes you have, and what environment you're in, or how you are living.

A bizarre example of how gene expression can change things is the locust -- a kind of grasshopper known for swarming, rapid movement, and voracious feeding. But the locust, even though it is behaviorally and also anatomically different from other grasshoppers, is not a separate species of grasshopper. It is an ordinary grasshopper going through a "phase change". That change (which is a response to environmental factors associated with a food shortage) is triggered by hormones which change gene expression. The grasshopper doesn't acquire any new genes; it's just a matter of genes which are usually dormant being expressed in a given situation. But that alteration in gene expression is enough to alter (within a few days) the body proportions, flying ability, and feeding behavior of the grasshopper... to the extent that it appears to be a different species entirely.

Humans, being considerably larger than grasshoppers, are not able to morph quite so dramatically and rapidly as a result of alterations in gene expression. That doesn't mean we are incapable of change, in response to a change in our environment or our habitual behavior.

I think that our oversimplified picture of genes as the biological equivalent of fate has had an unfortunate impact on patients -- and often on their doctors as well. The idea that our medical destiny was more or less carved in stone the moment egg met sperm is simply not valid. We can change. I'm not trying to offer up locusts as inspirational role models, but you see what I mean, right?

Type 2 diabetes is often seen as an inescapable sequence of bad things which, once launched, can only continue moving in the same undesirable direction. Diabetes patients can't hope to change what's going on, because the body has no choice but to follow the script that's written in our DNA.

But we don't know that, we've simply assumed it! And some diabetes patients have shown that it's possible for things to get better rather than worse.



The Christmas Beast is Dead

Thursday, December 26, 2013

 


The Ghost of Christmas Immediately Past

Ah, here we are, with Christmas safely over with, and the holiday treats receding into the past (or at least to a safe distance). All we have to do now is slay the Christmas monster, and get our test results back where they ought to be.

My fasting test wasn't great this morning, but I doubt I've ever had a great fasting test the day after Christmas; the important thing is to get back on track quickly. A nice long trail-run is a good way to do that, but the weather needs to cooperate. It certainly did today: it was clear, calm, and beautiful, and the temperature was in the high 60s all day. So I went to the state park and did an 8.3 mile loop through the place.

One of the highlights of the run was charging through, and scattering, a group of about a dozen wild turkeys. I know that there are people who hunt wild turkeys, and even consider them especially elusive prey (requiring, among other things, unusually thorough use of camouflage), but I find that a little hard to understand. When you venture into the woods around here, the really challenging thing would not be to find a turkey, but to avoid tripping over one. Maybe the turkeys are more wary in other parts of the country. You wouldn't think hunters would pride themselves on bagging something that's about as uncommon as a Toyota and about as hard to sneak up on as a dairy-cow.

The trails were busy today, and not just with turkeys. A lot of people were out there taking advantage of the beautiful weather to burn off some of their Christmas calories. You can't really do it in a day, but you have to start somewhere, don't you? There seemed to be a spirit of camaraderie among the people there, a tendency to call out encouragement to strangers they passed on the trails, and a tendency to exchange smiles which seemed to combine a cheery celebration of the fact that everybody was outdoors exercising with a sheepish acknowledgement of why everybody was doing so.


Christmas Here We Come!

Friday, December 20, 2013

 


A Very Christmassy Week

Like an asteroid hurtling earthward, Christmas is heading straight for us at top speed. And somehow there always turns out to be a little more to it than we were expecting, and a little more activity to fit into our December than there seems to be room for.

The Christmas-party situation where I work is complicated. Different divisions, and different departments within those divisions, have Christmas parties at different times. And my band of Christmas musicians (from various divisions at the site) are asked to participate in a lot of these events.

We've been doing the Christmas-music thing at work for 17 years now (I'm the only member of it who has participated in it for all 17 of those years). I'm not exactly "in charge of it", but I'm the one who organizes it, recruits musicians, and sets up rehearsals. I used to be in charge of the sheet-music too, but this year an orchestral musician who understands such things better than I do produced a new set of arrangements -- more difficult, but better. I was playing some harmony parts this time (which I'm not naturally good at, because I'm a melody player and I get lost easily when I don't have the tune); also, we added some new Christmas songs to our set list this year.

So, I've felt a little overwhelmed over the last few days, trying to be ready to do this. We had performances at parties yesterday and today, and this morning we strolled around the site and played at ten different locations, so that each department would get a chance to hear us.

And, of course, everywhere we went people were offering us cookies, fudge, and cake. It's that time of year, of course, but when you go around playing music for people for free, and they have treats, the first thought that enters their heads is that they should offer them to you. It was actually a good time to be carrying around a fiddle and bow -- because you need to keep your hands clean when you're playing that instrument and it's best not to be handling food. This gave me a built-in excuse, and made it easy for me to turn down their offers.

It was nice that I managed to fit in an outdoor run today, after three days in a row of evening gym workouts (I couldn't exercise outdoors in the daytime because my schedule wasn't cooperating even though the weather was). This time I was lucky enough to get outdoors before it got cold and dark.

When you're managing diabetes, the Christmas season is not entirely your friend. However, with a little effort and a little luck, you can keep it from derailing your program completely.

 


Christmas Panic!

Wednesday, December 18, 2013

Sorry, by I'm just too focused on preparations for Christmas parties tomorrow and Friday to do a proper blog post. I'm playing a bunch of Christmas music, in unfamiliar arrangements, for a party tomorrow, and I'm trying to carve out some serious practice time tonight. I'll get back to you when I can!

 


Unreliable Insulin

Tuesday, December 2013

 


Even with the Same Amount of Insulin!

Somebody recently entered this as a Google search phrase: "cannot control diabetes anymore lately after 25 years even with same amount of insulin".

Clearly, someone out there is badly confused and needs my help!

To a lot of people, the situation described in that question is genuinely puzzling. But to me, it's about as puzzling as finding that you can't afford to buy lobster any more, even with the same amount of money as you used to spend on it 25 years ago. You can't expect insulin to have the same degree of effectiveness forever, any more than you can expect money to have the same amount of purchasing power forever.

The endocrine system (which releases hormones in varying amounts at various times, in order to control active processes going on throughout the body) should not be thought of in terms of absolutes. That is, it's a mistake to assume that a given amount of insulin equals normal glycemic levels. That a particular amount of insulin used to be all you needed has no bearing on how much insulin is going to get the job done today. I don't mean to suggest that the endocrine system is affected by inflation -- but that might be the only thing the endocrine system isn't affected by. The endocrine system is a damned complicated thing.

A lot of factors are going to play a role in determining how much insulin is enough to keep your diabetes under control. An especially important factor is insulin sensitivity. The effectiveness of whatever insulin you inject (or produce in your pancreas) is going to be determined by how sensitively your cells respond to insulin. Insulin is supposed to trigger insulin receptors on the exterior walls of your cells, so that "transporter proteins" called GLUT4 transporters drag glucose from the surrounding bloodstream into the interior of the cell. But how efficiently does that process actually work? In some cases, not efficiently at all, because of "insulin resistance" (that is, impaired sensitivity to insulin).

Insulin resistance has long been associated with Type 2 diabetes; the disease seems to be caused by it, or by a combination of insulin resistance and reduced production of insulin. But whether or not you have Type 2, your sensitivity to insulin is bound to fluctuate. Many things (including inflammation, and any health condition which can trigger an inflammatory response -- which includes such unlikely things as gum disease, lack of sleep, and obesity) can cause insulin resistance to increase to a greater or lesser degree. (The main thing that reduces insulin resistance is exercise.) So, even if you're taking the same amount of insulin as you used to take, it is pretty likely that the effectiveness of a given dose of insulin will change over time, owing to your changing sensitivity to insulin. And you want to keep that sensitivity high, if you possibly can.

Also, the insulin you take is not equal to the insulin you make (that must be the worst allusion to a Beatles lyric ever, but it was unplanned, I swear). Even Type 1 patients often produce some amount of insulin, and Type 2 patients produce more -- just not enough, in either case. But any insulin you produce does add to the total amount of insulin in your system, and if you begin to produce less of it, the amount of compensatory insulin you must inject to produce the same level of glycemic control inevitably increases.

Other factors also influence the net result of taking insulin. Glucagon, the hormone which can be thought of as "anti-insulin" because it increases blood sugar instead of reducing it, is obviously an important factor. If your body starts producing more glucagon, then whatever insulin you take is going to be counter-acted, at least partially, by glucagon and its effects. Glucagon stimulates the liver to release stored sugar into the bloodstream; it has the beneficial effect of protecting you from hypoglycemia while you sleep, but also has the less helpful effect of pushing up your blood sugar when it doesn't need pushing up.

Anyway, diabetes patients need to wrap their minds around a crucial concept: X amount of insulin does not equal Y amount of glycemic normality. The effectiveness of a given dosage of insulin is subject to change over time.

If the amount of insulin that worked for you 25 years ago is no longer enough, you need to experiment and find out what does work for you now. There is no use searching for the answer on the internet, to see if someone has done enough research on people just like you to tell you what's right. You need to find out for yourself what works for you, and experimentation is the only path to wisdom in that case. (But make sure your experimentation includes exercise, because that's what make a given amount of insulin do more for you.)

 


Don't Get Too Comfortable!

Monday, December 16, 2013

 


Creaky Old Me

I was feeling a little old today, when I went outside for my lunchtime run. Not as old as Beethoven, who's having his 243rd birthday today, but old. A little sore in the joints, a little stiff in the muscles. I felt as if I ought to feel a little more springy, as the weather was a lot milder than last week (it wasn't a challenge at all to run in shorts). But when I was doing a little preliminary stretching before the run, my body really wasn't in the mood to stretch.

In particular, when I tried to do what is known in yoga as Uttanasana (a standing forward bend, with your legs straight but your body folded in the middle like a taco, and your hands touching the ground in front of your feet), I fell pretty far short of perfection.

That's how you're supposed to look when you do it, but I came about three inches short of reaching the ground with my hands. I kept standing upright and then bending down again, getting a little closer to touching the ground each time. I did get there eventually, but it seemed to take a lot more tries than it should have.

But maybe the thing to focus on is that I eventually got there. I was able to touch the ground before I took off on my run. And I had a good run -- I didn't feel sore during it or after it, and it was a beautiful, sunny winter day; maybe those are things to focus on, too.

I'm 56, for heaven's sake: it shouldn't be expecting myself to be able to loosen up instantly. For people of a certain age (and I'm pretty sure I'm "of a certain age" now), it's perfectly normal to have to work harder at limbering up to do something physical. The options seem to be limited to two: adjusting to it, or giving up on doing anything anymore.

On Saturday I was going to a Christmas party that basically was a big, crowded jam session for Irish musicians. I was worried that playing for a long time might trigger a flareup in my right shoulder, which has been bothering me since Thanksgiving. But I've been doing a new physical therapy exercise for it that seems to be helping, and I'm very relieved to report that I played till midnight and suffered no ill effects.

Some people continue doing the things after 50 that they did before 50, and a lot of people don't. It's very easy and tempting to assume that, if any particular physical activity is harder to do now than it was a few years ago, that means you are now too old for that sort of thing, and should give up on it. But there's a distinction to be made between "harder than it used to be" and "impossible".

In my yoga class tonight, some poses were harder for me than they used to be; some stretches found me not as stretchy as I remember myself being in years past. It is extremely tempting to tell yourself, "stop kidding yourself, you can't do this any more". The truth is that I can do it -- the only thing that's changed is that, these days, doing it is more difficult and uncomfortable. But what is likely to happen to me if I give up on doing everything that isn't as easy and comfortable as it once was?

Beware your comfort zone! It's a dangerous place.

 


A Visit from a Fat Smoker

Friday, December 13, 2013

The cold wave really is over -- I was able to go for a lunchtime run in shorts and a short-sleeved shirt, and I had no regrets. It was a beautiful, clear, sunny winter day; the temperature was around 55 F.

It's supposed to be pretty warm tomorrow, too -- and I hope that's true, because I'm going to be playing music outdoors, and that can be hell if your hands get too cold.

I don't really know why my glucose numbers were so low today; I didn't practice any unusual carb restriction or do an exceptional amount of exercise. Sometimes it just happens that way. And sometimes your numbers are unusually high for no apparent reason, too. That can be frustrating, if you're taking your diabetes management seriously and you want to know what's going on and why. However, a little unpredictability is probably a good thing: it keeps us paying attention.

 


'Twas the Friday the 13th Before Christmas!

Today I learned an interesting thing about "A Visit from St. Nicholas" (better known by its opening line, 'Twas the Night Before Christmas), published anonymously in 1823 and later attributed to Clement Clarke Moore. The poem evidently paved the way for Christmas to be accepted as a religious holiday in the USA -- against long-standing opposition by religious conservatives.

In those days, most American Christians were Protestants, and they originally looked upon Christmas celebrations as highly improper. To them, Christmas as a religious holiday was a strictly Catholic concept, and therefore primitive and stupid and vulgar. Protestants tended to see Catholicism as pre-Christian folklore dressed up in Christian drag, and they thought Christmas was an especially obvious example of that. Clearly the Catholics were taking over the tradition of winter-solstice festivals, which dated back to the Roman Saturnalia, and pretending they valued it for its religious significance! They were just trying to appeal to the public! (Protestants of that day were pretty sure it was wrong for anyone to try to appeal to anybody, ever.) Poets and novelists, of all people, labored to overcome this resistance; Moore redefined Christmas in America, as Dickens would later do in England.

By 1823, Protestants were weakening in their resistance to Christmas as a religious holiday, but it was still enough of a sore point that Moore shifted the arrival of St. Nicholas from Christmas to the night before, thus making the whole thing just a tiny bit more palatable. Evidently it worked; the poem became very popular, and its vision of Christmas Eve began to be accepted as if things had always been that way.

Now here we are 190 years later, and American religious conservatives are trying to stir up anxiety about an imaginary "war on Christmas". Under the circumstances, it is charming to be reminded that the only people who have ever engaged in actual, organized opposition to the Christmas holiday have been American religious conservatives. Well, you know what they say: those who do not remember history are doomed to say stupid things about it on television.

Of course, if Moore were writing his poem today, he might make a few alterations, perhaps placing less emphasis on the abdominal obesity of St. Nicholas, and almost certainly not presenting him as a heavy smoker. And perhaps that business about the visions of sugar plums could be toned down a bit. But that was 1823. And I suspect the kids didn't get sugar plums on any other day of the year.

I realize that Moore's authorship has been disputed (some think Henry Livingston actually wrote the poem), but the case against Moore as author seems to be pretty feeble. It is claimed, for example, that Moore would never have presented St. Nicholas as a smoker because Moore was a sour puritan who condemned tobacco in his poem "The Wine Drinker" -- but that poem turns out to be a satire about people who condemn vices which they secretly practice themselves! A sampling:

I'll drink my glass of generous wine;
And what concern is it of thine
Thou self-erected censor pale,
Forever watching to assail
Each honest, open-hearted fellow
Who takes his liquor ripe and mellow,
And feels delight, in moderate measure,
With chosen friends to share his pleasure?
...
If ev'ry good must be refus'd
That may by mortals be abus'd,
E'en abstinence may be excess,
And prove a curse, when meant to bless.

I think you'd have to be pretty dense to interpret Moore's portrayal of the temperance movement as an endorsement of it. But that's the problem with satire: dopey people think you're expressing the very attitude you're trying to ridicule. Anyway, I'm leaning toward accepting that Moore really was the author of the famous Christmas poem which has been attributed to him. And I'll agree to look the other way in regard to the sugar plums -- and even the smoking, so long as it only happens one night a year!

 


The Gore-Tex Menace!

Thursday, December 12, 2013

 


News from Sweden

A friend of mine is going on a business trip which will take him to Sweden (a beautiful country to visit in the summer, I'm told). But he's going to arrive there in January, and isn't sure he's ready to face the Nordic winter of perpetual darkness, bitter cold, and nationwide depression. I told him he'll probably be okay as long as he stays in bars all the time like everyone else. And I begged him to bring me a souvenir I've been trying to lay my hands on for a long time: a bottle of Swedish bubble-bath soap.

He was surprised by this request, until I explained to him that the Swedish phrase that means "bath foam" looks very funny on a product label, at least to English speakers.

I really think a nice colorful bottle of Bad Skum would dress up my bland bathroom decor like nothing else could, so I hope he'll bring some home with him. It might turn out that customs officials or the security people at the airport have some kind of rule against allowing travelers to carry Bad Skum into the USA, but all I really need is the empty bottle and I'll fill it with something domestic that looks about right.

Yeah, I'm that superficial when it comes to skum.

Meanwhile, there's news from Sweden: researchers at the University of Uppsala (located, conveniently enough, in Uppsala, Sweden -- which is about 50 miles north of Stockholm) have found yet another Cause Of Diabetes to throw on the pile: exposure to perfluorinated compounds.

Perhaps you're wondering what perfluorinated compounds are. I admit I hadn't heard of them either. They're a family of toxic chemicals which are widely used in industrial and commercial products. These compounds are typically used to make materials fire-resistant or water-repellant; they are also used in non-stick cookware. With these compounds used in so many of the products we use daily, including clothing and food-preparation products, we're all being exposed to perfluorinated compounds. The Swedish researchers tested over a thousand people in their 70s and found that pretty much all of them had detectable levels of these compounds in their blood.

However, some people had more perfluorinated compounds in their blood than others -- and the ones who were carrying the largest load of these compounds were also more likely to have diabetes.

So there you are: proof positive that perfluorinated compounds cause diabetes!

Actually, no: that isn't proof positive of anything. It's just a correlation (and I'm not sure how strong the correlation is, because the report I've read on the research gives no specifics). But even if the correlation is strong, there could be explanations for it other than the disease being caused by the compounds under study. Maybe diabetes patients happen to wear more Gore-Tex than the average person, for some reason. But the perfluorinated compounds are definitely under suspicion -- especially perfluorononanoic acid or PFNA, which showed the strongest correlation with diabetes. I don't know what to suggest if you want to avoid exposure to PFNA, because it doesn't seem to be used in consumer products directly -- it is used industrially to produce other chemicals. We are exposed to it mainly because it leaks into the environment, and it doesn't break down there because of its strong carbon-fluorine bonds. It shows up in wildlife (in 2005, it was found in generous amounts in bottlenose dolphins in Delaware Bay).

Okay, so that's what we know: a contaminant you can't escape, because it's everywhere, may be causing diabetes. Have a nice day!

We do have to take this kind of thing with a grain of salt. We don't know if these compounds really are causing diabetes, and even if they are, we don't know how big the risk factor is. If it adds to your risk by 0.001%, maybe it's not worth getting up in arms about it. Also, let's not get too excited about the idea that banning production of perfluorinated compounds will make the worldwide diabetes epidemic go away. It seems as if there are a thousand ways to become diabetic.

But, of course, if industrial toxins really are contributing to the diabetes epidemic, we might as well find out as much as we can about it.

 


Where's Diabetes?

Wednesday, December 11, 2013

California is slowly emerging from an uncharacteristic cold wave. For my lunchtime run today, I still felt it was necessary to protect myself with extra layers of clothing; maybe by tomorrow I'll be able to dispense with that. I narrowly escaped injury today, or at least indignity, when I was running fast downhill and nearly stepped into a patch of ice I wasn't expecting to encounter. This is California, there shouldn't be ice on the sidewalk! Except that there was, at least in a large patch of sidewalk which had been shaded from the sun all morning. I was able to stop myself just before planting a foot into the middle of a frictionless surface. (We usually see friction as a problem, until we run into a situation where there isn't any.)

But it has to be said that, if you dress properly for it, outdoor exercise on a cold winter day can be more exhilarating than any other kind of exercise. It was a sunny, clear, beautiful day. And the hot shower afterward was worth at least ten dollars a minute.

 


Diabetes: Not just for Americans any more!

International health organizations are expressing concern about the staggering (and growing) size of the diabetic population worldwide. According to a report in The Lancet, "The number of people with diabetes worldwide has more than doubled during the past 20 years. One of the most worrying features of this rapid increase is the emergence of type 2 diabetes in children, adolescents, and young adults... Epidemiological data predict an inexorable and unsustainable increase in global health expenditure attributable to diabetes, so disease prevention should be given high priority." The International Diabetes Federation says that "382 million people have diabetes in 2013; by 2035 this will rise to 592 million... The number of people with type 2 diabetes is increasing in every country... 80% of people with diabetes live in low- and middle-income countries."

Here is their map of the worldwide distribution of diabetes populations:

Between them, China and India account for 43% of the total diabetes population. (The USA accounts for only a paltry 6%, so let's let go of the idea that we're in the lead on this thing.) Because so many people with diabetes are living in countries where incomes are low, we are being invited to worry that the world will never be able to cope with the economic consequences of the diabetes epidemic. After all, most countries can't afford to spend the staggering amounts that America does on health care!

However, that might not be an entirely bad thing.

America may spend a ridiculous amount of money on health care, but that doesn't mean American health care is the best (in terms of metrics such as longevity and infant mortality, we've got nothing to brag about, and there is certainly no indication that we do exceptionally well at managing diabetes). So, if huge numbers of diabetes patients worldwide are going to be forced to treat their condition using less expensive treatments than Americans use, it's possible they will do better than American diabetes patients, not worse. Perhaps inexpensive diabetes patients are actually better patients; if that is the case, low-income countries with high diabetes rates may be the countries that prove it.

I'm an inexpensive diabetes patient. I use glucose test strips regularly, but that's pretty much it for me in terms of routine medical expenditures. I'm not on any oral diabetes drugs. I'm not taking insulin. I'm not taking statins for cholesterol. I'm not (at least not any more) taking ACE inhibitors for high blood pressure. Regular exercise pretty much gets the job done for me, and exercise is a lot cheaper than the diabetes treatments most American patients use.

Lifestyle-based approaches to diabetes management are not taken seriously in the USA, because it is assumed that patients won't comply with them. All the focus is on drugs. But if millions of diabetes patients worldwide are going to be living in countries that can't afford American's drug-based approach to diabetes management, maybe enough of them will succeed as inexpensive diabetes patients to make people in the USA take a fresh look at the concept.

 


Half of Two Genes

Tuesday, December 10, 2013

 


A Genetic Odd Couple

I'm going to talk a little about haploinsufficiency, but maybe you're not up on diploidy, haploidy, and haplodiploidy, so I should explain those things first.

For "diploid" organisms (a category which includes humans and most other mammals), each cell contains pairs of chromosomes, and each pair consists of one chromosome inherited from the mother and one inherited from the father. Our notions of genetic relatedness are informed by that chromosomal arrangement, but not all living things are like that.

A "haploid" organism (such as a plant) has one set of chromosomes in the cell, not pairs of each one. (Plants aren't haploid all the time; they tend to alternate between haploid and diploid generations.)

And then there are organisms which are "haplodiploid", in which the males hatch from infertile eggs and are haploid (they have one set of chromosomes), while the females hatch from fertile eggs and are diploid (they have pairs of chromosomes). The familiar examples of this are the social insects (such as bees), and their haplodiploid arrangement leads to bizarre consequences. A male "drone" has no father and cannot have sons -- but it has a grandfather and can have grandsons. The female worker-bees, meanwhile, have more genes in common with their sisters (who are all offspring of the queen bee) than they would with any children they had of their own, so in evolutionary terms they are under selective pressure to help the queen give them more sisters, instead of reproducing on their own. So the worker bees don't mate; they only serve the queen, but they end up with more of their genes reproduced than they would if they mated! This is a strange notion from a human perspective; it's hard for us to put ourselves into the mental frame of mind of a worker bee. (Working for a large corporation probably helps, though.)

Well, anyway, we office-worker-bees are diploid -- or at least, we're supposed to be. Our chromosomes come in pairs, with half of each pair from Mom and the other half from Dad, and the matched genes on the two matching chromosomes each make their contribution.

But what happens when the gene on one of the two supposedly matching chromosomes is working, and the equivalent gene on the other chromosome is not?

What happens then is a situation called "haploinsufficiency": half of the gene pair isn't getting its job done. If the gene's job is to produce a particular protein, and only one of the two copies of the gene actually functions properly in making that protein, then your cells won't produce enough of that protein. The consequence could be a disease -- and a disease which is suffered by males more than females, or the other way around, if the failing gene is associated with one sex and not the other.

Researchers at Michigan State University think they have found a new example of such a condition: haploinsufficiency of a gene known as NCOA5. Apparently the NCOA5 gene produces a protein which is important in preventing liver cancer and preventing type 2 diabetes. NC0A5 haploinsufficiency is a specifically male problem, and this may explain why a common type of liver cancer is much more common in men than in women. That type of liver cancer is also associated with Type 2 diabetes, apparently because NCOA5 haploinsufficiency triggers glucose intolerance before it triggers the formation of liver tumors.

I hasten to add that NCOA5 haploinsufficiency is probably just one of many conditions which can trigger the development of Type 2 diabetes; being a male with diabetes doesn't mean you are carrying a gene that will give you liver cancer. (And even if you are carrying that gene, you won't necessarily develop liver cancer: the researchers found that the development of liver cancer depended on other factors as well, including "overexpression of interleukin-6".) Also, the researchers were looking at mice rather than men, so we shouldn't extrapolate too recklessly to what this means for us.

Anyway, I guess we can toss yet another potential cause of Type 2 diabetes onto the ever-growing stack of them. Pretty soon the list of things that don't cause Type 2 will be shorter than the list of things that do. Eventually it will probably be whittled down to garlic, sunshine, and laughter. Well, let's focus on those for now!

 


Sweet December

Monday, December 9, 2013

 


The Sugar Season

I've never seen a graph showing the rise and fall of per-capita sugar consumption in the USA over the course of a year, but I'm pretty sure that if I did, I'd be looking at a big peak in December.

I don't think it's really a Christmas thing, although Christmas is the usual excuse for it. Probably there's something about winter weather that makes us crave sweets. Even here in California, winter (or something like it) does occur. It was icy this morning, and tomorrow will be the same. I had to put on multiple layers to do my lunchtime run, and I still felt pretty cold. You come back from a run like that, and you want to indulge in something sweet. And, since my office mate and running buddy is a professional-grade chocolatier, and she brought in a tray of her Christmas chocolates to the office today, I had an opportunity to do just that.

Fortunately for me, despite an unusually high fasting result of 98 mg/dL this morning, my very tough, very hilly run today gave me a result after lunch that was also 98, and for a post-prandial result that's low. So, I figured trying her chocolates was okay under the circumstances. But the temptation would have been just as strong even if my result after lunch was elevated. It's that time of year -- we want our sugar. And we want to provide it to others, too. In December, an urge to make fancy desserts possesses even those of us who don't often feel much of need to get creative in the kitchen.

On Saturday I was at my Dad's place, working with him to do the final assembly on some Christmas treats my sister was making. I was coating balls of cookie dough in melted white chocolate, and he was decorating them with snowflake-shaped sprinkles.

Here we are, trying to look guilty about getting involved in making these very sweet confections, and also about getting ready to try one.

Maybe there's not a whole lot of point in pretending that we're not going to cut loose a bit at this time of year. It's best to try to make up for it in other ways (hard workouts, and low-carb meals when you're not eating Christmas cookies), but maybe there's just no getting around the fact that life is a little different in December. Some of us are still good diabetes patients during the holiday season -- but not a lot of us are great diabetes patients during the holiday season.

It's a time of year when saints are thin on the ground.

 

Smoothing Out Insulin

Thursday, December 5, 2013

 


People Don't Like Shots

I've never had to give myself insulin injections. The people I know who do (that is, Type 1 patients who require multiple injections per day) don't seem to be all that bothered by it. The type of subcutaneous injection technique that's used is supposedly not painful if you do it right. That said, a lot of people hate injections -- hate the very idea of injections -- and are bothered about having to do them so frequently. (Also, some people do find them painful, perhaps because their tissues have some kind of unusual reaction to them.) Any system of insulin delivery that requires fewer shots is bound to be popular.

Taking insulin orally is, unfortunately, not practical, because insulin is a digestible protein. (Strictly speaking, it's a peptide, but I've never seen a definition of "peptide" that makes it out to be anything other than a protein molecule that's smaller than usual.) Any insulin you swallow is going to be broken down by the digestive process into its constituent amino acids; by the time it hits your bloodstream it will no longer be insulin.

So, insulin pills won't work. Still, it's a pretty crude alternative method to inject a sudden blast of a hormone as powerful as insulin, in a dose meant to last for more than an hour. In a normally function human body, insulin is released gradually by the pancreas, at a carefully adjusted rate; it isn't simply dumped into the bloodstream in a series of isolated bursts, with nothing in between. For people who take insulin injections, there is never a state of equilibrium: they are cycling all day between having too much insulin and having too little. They try to match up their injection schedule with their eating schedule, to minimize the highs and lows, but even at its best, this system is about as smooth as trying to read by flashes of lightning. Insulin pumps have helped a bit, by maintaining at least some kind of minimum insulin level between injections, but they are far from a perfect solution.

Researchers in North Carolina (at North Carolina State University and the University of North Carolina) have been developing all sorts of potential solutions to the problem of making insulin delivery less spasmodic. I've mentioned before their experiments with injected sponges and nanoparticles which release insulin gradually, as the materials involved slowly break down in the body. A weakness of those technologies is that the insulin release may be gradual, but it isn't adjustable.

Now, the same researchers have come up with another technology which makes it possible to inject a large amount of insulin which remains in place at the injection site (embedded in a cloud of nanoparticles which are designed to herd together and not dissolve spontaneously). When more insulin is needed, the patient holds an ultrasound probe to the injection site, stimulating the particles to release a dose of insulin. (Apparently this takes 30 seconds for the maximum dose.)

"Each of the PLGA nanoparticles is given either a positively charged coating made of chitosan (a biocompatible material normally found in shrimp shells), or a negatively charged coating made of alginate (a biocompatible material normally found in seaweed). When the solution of coated nanoparticles is mixed together, the positively and negatively charged coatings are attracted to each other by electrostatic force to form a "nano-network." Once injected into the subcutaneous layer of the skin, that nano-network holds the nanoparticles together and prevents them from dispersing throughout the body. The coated PLGA nanoparticles are also porous. Once in the body, the insulin begins to diffuse from the nanoparticles. But the bulk of the insulin doesn't stray far – it is suspended in a de facto reservoir in the subcutaneous layer of the skin by the electrostatic force of the nano-network. This essentially creates a dose of insulin that is simply waiting to be delivered into the bloodstream."

Obviously the nanoparticles can only hold so much insulin, so you have to keep injecting them. But they last long enough that you don't have to take injections as often -- when you need more insulin, you can break out the ultrasound probe instead of the syringe. It sounds like a lot of trouble to go to, for the privilege of injecting less often (perhaps once every few days instead of several times a day), but to the people who hate giving themselves shots, it may be worth it.

It sounds as if this has only been tested on mice, though, so don't expect to see it at a pharmacy near you anytime soon.

 


Implicit Questions Answered Here

Wednesday, December 4, 2013

 


Time to have another go at answering questions implicit in Google searches which recently resulted in references to this site. Tonight I'll explore two recent examples.


"Are Fuyu persimmons good for you if you are a diabetic?"

In the naive language of pop nutrition, foods are either "good for you" or "bad for you". Every food is destined either to kill you or save you, and given the starkness of the choice, people naturally want to be told which of those two simple categories a particular food belongs in. This kind of talk always reminds me of the sheep in Animal Farm bleating their catchy slogan, "Four Legs Good, Two Legs Bad!". Do people really think it's that simple?

In a few cases, it is that simple. If you plan to go mushroom-gathering, you'd better be sure you can tell the difference between Amanita caesarea (left) and Amanita phalloides (right), because the latter is known popularly as the "death cap" mushroom, and for good reason (half of one is a fatal dose).

On the whole, though, it is not especially useful to sort foods into simple categories of "good for you" and "bad for you". The trouble with that kind of talk, especially for diabetes patients, is that it leads them to ignore the issue of serving sizes. Quite often, people with diabetes (and people advising people with diabetes) declare that one food is good and another bad because one of them has slightly less starch and slightly more fiber than the other. The difference between them isn't really that dramatic, but once you have categorized one as good and the other as bad, you're tempted to think that keeping "bad" foods off your buffet plate means you can pile on the "good" foods in unlimited quantities -- and the net result is a meal which, though it contains only "good" foods, spikes your blood sugar more than would a more modestly-scaled selection of "bad" foods.

But to return to the original question: are Fuyu persimmons "good for" people with diabetes? I recently made the assumption that they were, and it didn't work out that way. My experience is that Fuyu persimmons drive my blood sugar up more than I'm comfortable with. I had been assuming that Fuyu persimmons were equivalent to a small apple, but it turns out this isn't true. Here are the persimmon stats:


And here are the equivalent figures for an apple:

Both of these, like fruits in general, provide most of their calories in the form of sugar -- but the persimmon is considerably worse in that regard.

I'm not going to tell people with diabetes never to eat fruit, but you need to be aware that fruits are sugary foods, and you need to be aware the some fruits are more sugary than others. An apple would be a better choice, for most people with diabetes, than a persimmon.

 


"How can i have a high hemoglobin A1c if I'm in great shape?"

Here's another consequence of oversimplifying the story: the fact that obese and sedentary people have an elevated risk of Type 2 diabetes does not mean that people who are in great shape have zero risk.

It's looking more and more over time as if there are many different "failure modes" that can trigger Type 2 diabetes. That is, a variety of different things might go wrong in your body which might lead to your becoming diabetic. It isn't typical for someone in great shape to have elevated blood sugar (as indicated by an elevated A1c result), but it happens -- and I've talked to people in that situation, so I know it goes on.

It can be a very bad thing for health care when people (including doctors) oversimplify these issues. Sometimes doctors ignore warning signs of heart disease in a female patient, because they have mentally converted "heart disease is more common in men" to "heart disease is a problem only for men". (The consequence is that, although women are less likely to have a heart attack, they are more likely to die from it if it happens, because there is a longer delay before their doctors recognize what's going wrong.) Less dangerously, but more maddeningly, doctors sometimes advise diabetes patients to get in shape even though they already are; the assumption that diabetes patients are fat and immobile is so firmly established in everyone's mind that nobody seems to be capable of recognizing an exception when they see one.

Unfortunately, most of the advice I give on this site is aimed at people who developed Type 2 diabetes in the usual way: by eating too much and exercising too little. (That did the trick for me, anyway.) Anyone who developed Type 2 while being a slim and athletic person is bound to find that I haven't got a lot of useful suggestions for them, other than limiting carbohydrate intake.

But at least I won't go around saying that everyone who's diabetic is fat and needs to get in shape.

 


Seeing for Yourself

Tuesday, December 3, 2013

 


What Did the Study Really Find?

News from the world of medical research usually reaches us in translated form: someone who has looked over a scientific paper writes a summary for popular consumption. Often we have to take that person's summary at face value, because the original paper is hidden behind a paywall and we're not about to fork over 30 or 40 dollars for the privilege of examining a short paper which might turn out to be trivial. So, if we're interested in the research, we'll have to be content to take someone else's word for what it revealed.

This is an unfortunate situation, because the person writing the popular summary usually simplifies what the researchers said; sometimes nothing important is lost in the simplifying process, but if a detail that's important to you gets mangled in the process, you probably won't realize that. So, if you do have the opportunity to read the actual paper rather than someone else's gloss on it, it's a good idea to do so.

I felt the need to do that tonight, when I saw the headline "Mediterranean Diet Without Breakfast Best Choice for Diabetics". This is a summary of an interesting study in Sweden, in which people with Type 2 diabetes tried three different diets in succession, so that the researchers could compare how each diet affected their health. The study was disappointingly small (only 19 participants stayed with the study to the end), but at least everyone tried out each of the three diets.

The diets were low-fat, low-carb, and a Mediterranean plan which was sort of in between the first two. (The Mediterranean diet took the unusual approach of omitting breakfast but compensating for it with an extra-large lunch).

Popular summaries of the research make it sound as if the Mediterranean diet was the hands-down winner, but I wondered if this might be an over-simple impression of a more complicated set of data. In this case, the original paper was actually available to me, so I gave it a look.

Of course, the reason most people are content to read summaries even when the actual paper is accessible is that the actual paper is usually a lot harder to decipher. And I may have misinterpreted it -- that fact I must face -- but it seems to me that the data presented in the paper does not necessarily point to the Mediterranean diet as the best of the lot.

The graph below shows the glycemic profiles (based on six glucose tests a day) for patients on the three types of diets. The low-fat diet (the solid line) is clearly the worst, as people on that diet had higher glucose at every time of day (not so surprising, because the low-fat diet was, of course, a high-carb diet). But the comparison between low-carb and Mediterranean is ambiguous: the low-carb dieters (wide-dashed line) were higher than the Mediterranean dieters in the morning... but much lower the rest of the day.

That's an important point, because the popular summary represents it in a misleading way: "It is very interesting that the Mediterranean diet, without breakfast and with a massive lunch with wine, did not induce higher blood glucose levels than the low-fat diet lunch, despite such a large single meal." Maybe so, but it induced much higher blood glucose levels after lunch than the low-carb diet did, and that's the comparison that's worth making (the low-fat diet would be expected to produce a high after lunch!). The paper includes comparisons of the "area under a curve" for glucose, an indicator of how each diet affected blood sugar as a running average; the low-carb diet was the lowest, and the low-fat diet the highest. Purely in terms of glycemic control, the low-fat diet is clearly the best of the three.

What makes the study authors lean toward the Mediterranean diet is that it did better than the other two in terms of triglycerides (oddly enough, the diets were all alike in terms of their effect on cholesterol, but triglycerides varied).

If you ask me, the differences between the diets are less dramatic when you judge them by triglycerides, and by dinner-time the difference between the low-carb and Mediterranean diets has diminished to nothing. But, along the way, triglycerides are lower on the Mediterranean diet than on the others.

My own experience suggests that exercise is enough to take care of elevated triglycerides (my exercise program reduced my triglyceride test result from 150 mg/dL to, most recently, 49). Maybe exercise doesn't have that effect on everybody, but everyone with Type 2 diabetes should be exercising anyway, for other reasons, and if that works for them in terms of triglyceride control, then my reading of the study's data suggests that a low-carb approach would be the best diet of the three evaluated here.

My very low post-prandial result after dinner tonight was the result of having a very low-carb meal (meat and vegetables, but no starch). If I'd had some rice or noodles or bread with that, it never would have happened. I'm not saying that I want to live entirely without starch, or that I'm planning to, but for anyone who's having more trouble maintaining glycemic control than I am, it seems likely that low-carb meals should be more the rule than the exception.

Anyway, as I already admitted, I could be misunderstanding what the researchers found, but it sure looks to me as if what they found is different from what science-writers say they found.

 

Surviving Holidays

Monday, December 2, 2013

 


Meme Time!

A meme is a self-replicating cultural artifact (it can be an idea, a tune, a joke, a graffito, whatever) which spreads through society because people like repeating it. Richard Dawkins coined the term, using it as a kind of cultural equivalent of a gene (which might die out, but might also become universal if enough individuals make copies of it). These days the internet is the world's leading meme machine, but mass media in general are enthusiastic transmitters of memes, and sometimes news broadcasts on TV and radio become meme-driven to an extent which ought to be as embarrassing to the news-readers as it is irritating to the public.

We are now at the time of year when meme-driven news is at its peak, as every broadcaster takes it for granted that all Americans are interested in but one subject: Black Friday.

Black Friday refers to the day after Thanksgiving in the USA, seen by many people as the start of the Christmas shopping season -- hence the big crowds at retail stores. Although it is often said that the term refers to day when retail stores become profitable ("in the black"), that is a relatively recent concept. When the term was first used, by the Philadelphia police in 1961, the phrase referred (rather mournfully) to the traffic jams associated with the day. But if we could use a time machine to visit the Philadelphia police of 1961, we would have to say to them, "You ain't seen nothing yet!". Black Friday was a mere concept then, not yet a meme.

In recent years, the Black Friday concept has certainly become a meme. Retail stores (and the news outlets which, for some reason, love to give them free publicity) have worked hard to make Black Friday into a dramatic social happening, and they absolutely will not shut up about it. (They also keep making it begin earlier -- for many stores Black Friday actually begins on Thursday, so that store employees can't spend the holiday with their families.) Whenever the stores begin the event, they hold special sales in which the first few shoppers to arrive get large discounts on expensive items -- so that people will go to absurd lengths to be first in line. Many camp out overnight at the store entrance -- always a comfortable way to spend the night at this time of year.

When the store opens (perhaps well before dawn) there is a frantic stampede...

...and everyone races to get the big-discount items of which they know the store has created an artificial scarcity.

And you know what happens next!

Shoppers start fighting over stuff!

Then the same news broadcasters who have been heavily promoting Black Friday, as a competitive event which we should all be excited about and involved in, also run disapproving coverage of how nasty this competition becomes (as if they had not played a role in making that happen).

The weirdest aspect of all this, for me, is that the news broadcasters don't seem to have a genuine stake in any of this. Do they really get any more revenue from retail advertisers, if they repeat the Black Friday meme, than they would if they didn't? Even public radio stations, which have no retail advertisers, yammer on about Black Friday unthinkingly (which, I guess is what makes it a meme: it's self-replicating, because for some reason it never occurs to people not to repeat it).

The Black Friday meme is, to me, unpleasant and boring and stupid, and it needs to go away. Far, far way. The Andromeda galaxy is not far enough. There's no reason why we have to hear so much about this nonsense.

The Thanksgiving holiday is not supposed to be about waiting in line at a store entrance, much less about getting in fist-fights over who got the wide-screen TV. It's supposed to be about getting together with your family and overeating for most of an afternoon and evening. That's what we did, and it worked out fine. No fistfights, no police involvement.

And if I look like the oldest of the three siblings below, when I'm really the youngest of the three, at least I'm looking pretty sober. And a few years younger than my father. Darker hair, anyway -- although he's got a bit more of it.

I didn't spend the rest of the holiday weekend engaged in competitive shopping. To the extent that I did anything besides relaxing, I spent the time doing a lot of exercise to make up for my indulgence in the all-day feast on Thursday. The heaviest workout of the weekend was a 9.4-mile trail run. I was feeling a little sore in the hips from that today, but I think my yoga class tonight helped me get over that.

Anyway, I think the last thing we need to do is look for ways to make the holiday season more competitive and tension-filled. Stress is not the goal. Have fun with the holidays in whatever way you can, but don't see them as one more thing to get anxious about.

Tomorrow, at the office, we're holding our first rehearsal for the Christmas music performance some of us do every year. I'm not stressing out about that, either. I haven't practiced any of the tunes yet, and I'm not sure where I left the sheet music for it, but I'll deal with all that tomorrow. We've been doing this for 17 years, if I haven't miscalculated, and it's always worked out fine in the end.

If your holiday celebration becomes something you have to lose sleep over, you're doing it wrong.

 



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