4th Thursday Update

February 26, 2015

The weather madness continues: I went for a run today in sunny, 74-degree weather. This is not February as we know it!

 


Food, exercise, blood sugar, and surprises

I know I tend to create the impression that I've entirely figured out the mysteries of blood sugar: I expect a meal with a given amount of carbohydrate to drive my post-prandial blood glucose to a certain level -- with an adjustment downward if I've already had my workout for the day (or upward if I haven't). It's all pretty predictable. If I'm mindful of how many carbs I've taken in and how much exercise I've done, then surely my glucose meter won't surprise me.

Actually, it does work out that way a lot of the time -- even most of the time. My usual routine is to run at noon and eat lunch after I'm done. A low-carb lunch right after running will typically give me a post-prandial test result of 100-115, and a moderate-carb lunch more in the 120-130 range. (But a high-carb lunch is likely to push me near to the vicinity of 150, especially after no exercise. That's why I try to get out of participating in the taking-Kevin-out-to-lunch-for-his-birthday kind of office events, where I'm going to have to skip working out and sit in front of a platter of nachos for an hour.)

However, I should admit that predictability and diabetes do not go hand in hand. Your glucose meter can always surprise you. Just when you think you've got your patterns figured out, you will have a high test result when it should be low, or a low result when you're expecting it to be high. Then you have to try to figure out why.

Although it's certainly worth trying to figure out why you get a test result that doesn't make much sense under the circumstances (just in case you overlooked something significant), a lot of the time you're going to draw a blank. One day you'll get an unexpectedly high result after exercise and a low-carb meal; the next day you'll get an unexpectedly low result after no exercise and a higher-carb meal. No predictive scheme is perfect when it comes to variations in blood glucose levels, probably because blood sugar can be affected by factors we normally wouldn't consider as relevant.

Also, when we discover a factor which seems to be relevant, it doesn't always turn out to work the way we think it does.

A study at the University of Missouri has "compared young women who habitually skip breakfast to those who routinely eat breakfast and found that their metabolic responses to eating a high-protein breakfast were different. Specifically, the habitual breakfast skippers experienced poorer glucose control throughout the day when they consumed a high-protein breakfast, whereas those who typically ate a high-carbohydrate breakfast had improved glucose control after they ate a high-protein breakfast."

Wait a minute, let me untangle that sentence. Changing to a high-protein breakfast resulted in poorer glucose control for those who had been in the habit of skipping breakfast. But changing to a high-protein breakfast resulted in improved glucose control in those who had been in the habit of eating a high-carb breakfast. In other words, a specific dietary change had harmful effects on one group and helpful effects on another, depending on what their breakfast habits had been up to that point.

The researchers confess themselves unable to explain the result, but they see it as being all about the protein, and they hope that, if everyone gets into the habit of eating a high-protein breakfast, it will eventually prove beneficial to everyone regardless of their previous breakfast habits.

Might this amateur observer point out a possible explanation for the peculiar pattern in the data? The "high-protein breakfast" in the study consisted of this egg-and-lean-beef wrap:

We are told this wrap delivers 30 grams of protein, but we're not told how much carbohydrate is in the big tortilla wrapped around it. Typically those things run pretty high -- 45 grams of carbohydrate or more. Maybe a lower-carb wrap was used in this case, but there's a limit to how low you can get the carb content of such a thing.

My inclination is to forget about the protein for a minute, and ask what the exact change in carb consumption was for the two groups of young women compared in the study. Those who were in the habit of skipping breakfast were used to getting zero grams of carbohydrate in the morning. The experiment increased their morning carb consumption, so their glucose control became worse instead of better. Meanwhile, the other group had been in the habit eating a high-carb breakfast (probably cereal, toast, orange juice -- all very high in carbs). In their case, the experiment decreased their morning carb consumption, so their glucose control became better instead of worse.

Perhaps I'm looking at this wrong. Perhaps I would not propose this explanation of the results if I knew more about the details of the experiment. Perhaps the researchers carefully considered total carb consumption, and controlled for it adequately. However, when researchers seem to be overlooking the obvious, it isn't my habit to assume they couldn't possibly be doing anything of the sort. Clearly they thought protein was the issue, and if they were fixated on protein, it would not be too surprising if they ignored the role of carbohydrate.

So, what I'm taking away from this research report, at least for now, is that scientists who thought they were uncovering something new about protein were in fact rediscovering something old about carbohydrate.

Meanwhile, another study suggests that people with Type 2 diabetes will do better (in terms of glycemic control) if they have a big breakfast and a small dinner, and not the other way around. "The mechanism of better glucose tolerance after high-energy breakfast than after an identical dinner may be in part the result of clock regulation that triggers higher beta cell responsiveness and insulin secretion in the morning, and both a lower rate of breakdown of insulin by the liver and the increase in insulin-mediated muscle glucose uptake in the morning. Thus, recommending a higher energy load at breakfast, when beta cell responsiveness and insulin-mediated muscle glucose uptake are at optimal levels, seems an adequate strategy to decrease post-meal glucose spikes in patients with type 2 diabetes....High energy intake at breakfast is associated with significant reduction in overall post-meal glucose levels in diabetic patients over the entire day. This dietary adjustment may have a therapeutic advantage for the achievement of optimal metabolic control and may have the potential for being preventive for cardiovascular and other complications of type 2 diabetes."

My personal experience inclines me to agree that breakfast is the best opportunity to "get away" with a an indulgent meal; my post-prandial results show that my system can deal with carbs a lot better in the morning than later in the day.

However! I have heard from people with Type 2 diabetes who find that this isn't true for them: they say that they get bigger glucose spikes, not smaller ones, after the morning meal.

So, I really have to caution against interpreting any report from the experts as being relevant to your personal experience of diabetes. The big-breakfast-small-dinner approach may indeed be the best plan for that statistical gremlin known as The Average Patient. But who knows if you're The Average Patient, or not?

It's certainly worth experimenting, to see if shifting your daily calories toward breakfast and away from dinner yields better results in your case. But if it doesn't work for you, don't pursue it. It's never a good plan for non-average people to insist on doing what works for average people, if it doesn't work for them.

 


3rd Thursday Update

February 19, 2015

 


What's up with sleep loss and diabetes?

Sleep is one of life's great mysteries, and I remember puzzling over it as a small child. Why on earth do we have to spend a third of every day in a state of unconsciousness? Clearly the body "needs" sleep for some reason (it can't be just a human cultural convention, if animals do it too), but it's hard to imagine a purpose for it that is very specific or convincing.

The best answer available to us so far is that the body in general, and the brain in particular, have basic maintenance tasks which need doing every day, and these tasks can be done most efficiently and safely when the body is inactive and the conscious mind is shut down. It seems that the brain sorts and shuffles through stored memory every night (performing a sort of hard-drive cleanup), and that this function requires unconsciousness. Why should the process require unconsciousness? Probably because perceiving the process would be dangerously hallucinatory -- not the sort of thing you'd want to experience while operating heavy machinery. Dreams, which occur when people are emerging from the state of deep sleep, may be an artifact of this memory-management process: a few of those hallucinatory perceptions can be captured by our re-emerging consciousness, and the subconscious mind promptly "makes sense" of that disturbing glimpse of mental chaos by imposing a false narrative continuity on it. (As a child, I had a vivid dream about standing at the helm of a big ship; as I remembered it after waking, as the ship plowed forward, it grew smaller and smaller, until it was just a tiny wooden plank on which I washed ashore. The "actual" dream content probably consisted of separate visions of a ship and a plank; my subconscious mind then bridged the gap between those two fragments by constructing the narrative of the gradually-shrinking vessel.)

No doubt the body is doing other things besides memory-management while you're asleep -- perhaps a lot of other custodial tasks, such as recycling of proteins and healing of injured tissues, are performed mainly while we sleep. At any rate, the body operates differently during the sleep state, and this involves changes to body chemistry. Metabolic functions are altered during sleep. And, if you miss out on sleep, those metabolic alterations don't occur -- and that can have an impact on health.

The University of Chicago has long been known for research into the health effects of sleep deprivation. They were the first to show that chronic loss of sleep over even a comparatively short period can trigger "metabolic syndrome" (an unhealthy set of physical changes, including loss of sensitivity to insulin, which promote Type 2 diabetes). Many studies have confirmed a link between loss of sleep and Type 2 diabetes (for example, the disease is more common in shift-workers). But why, exactly, should loss of sleep have that effect? What might be happening to body chemistry during sleep which protects us from becoming diabetic -- and fails to protect us if we don't get enough sleep? Some new research from the University of Chicago aims to answer that question.

The researchers monitored various aspects of body chemistry in sleep-deprived subjects (they got an average of 4.3 hours of sleep per night), and compared them to results from "control" subjects who got a normal amount of sleep. As expected, the sleep-deprived subjects needed more insulin to achieve normal blood sugar levels -- a clear indication that they were becoming insensitive to insulin. But what else was going on which might have triggered their insulin resistance?

The researchers found that the sleep-deprived subjects also differed from the controls in other ways. The sleep-deprived subjects developed abnormally high nighttime levels of growth hormone... which led to abnormally high levels of the stress hormone noradrenaline... which caused the levels of free fatty acids in the blood to increase by 15 to 30%. The latter is crucially important, because elevated levels of free fatty acids in the blood are known to impair insulin sensitivity. The timing of the increases in all these blood components are said by the researchers to support a clear chain of causality:

  1. Sleep deprivation boosts the level of growth hormone.
  2. A higher level of growth hormone boosts the level of noradrenaline.
  3. A higher level of noradrenaline boosts the level of free fatty acids.
  4. A higher level of free fatty acids impairs sensitivity to insulin.

Insulin sensitivity was diminished by about 23% in the sleep-deprived subjects. If that doesn't sound like a huge impact, bear in mind that this was not a lengthy study -- it only took the test subjects four nights in a row of insufficient sleep to lose 23% of their insulin sensitivity. The loss could easily have become much greater if the subjects had continued in that mode on a long-term basis.

Is there hope for those of us who aren't so good at the sleeping thing? Seemingly the diabetes-promoting effect of sleep deprivation (if not other ill effects of it) could be mitigated, if we could find ways to prevent the increases in growth hormone, noradrenaline, and free fatty acids. But, on the whole, it's probably better to get some sleep...

 


Climate change: the upside!

Climate turmoil is mostly a very bad thing, of course. There is reason for concern that much of the western United States is entering a phase of profound and extremely lengthy droughts -- while much of the eastern United States is entering a phase of increasingly severe storms. But almost any kind of climate change in the world at large is bound to produce at least a temporary advantage somewhere.

So, although I'm concerned about the long-term livability of a region where rainfall is becoming rare and winter is becoming a dimly-recalled legend, I'm also trying to appreciate the more enjoyable aspects of California's current weather regime. I've lived here long enough to remember a time when it got cold in February, and I'm hearing news reports about heavy blizzards in the northeast... so I'm trying my best to savor the insanely warm and sunny weather we've been having in these parts.

Sunday in the local state park was all green grass, brilliant sunshine, and citizens enjoying some outdoor activity.

You may call it decadent to take pleasure in weather developments which are bound to be bad news in the long run... but enjoying something while it's still possible to enjoy it is pretty much what human life is about.

 


2nd Thursday Update

February 12, 2015

 


February is the new May

I went for a run today in 72-degree weather. And apparently it's just going to get warmer from here:

I guess we just need to tell ourselves that this kind of February weather is normal, that nothing strange is happening. Move along, folks! Nothing to see here!

 


Building a better insulin molecule

Trying to control your blood sugar by taking insulin injections is a little like trying to read a book by flashes of lightning. No, wait, maybe that's not the best simile I can come up with. How about trying to steer a car by grabbing the wheel once every minute, and wrenching it violently in whichever direction looks more appropriate at the moment?

Anyway, insulin injections represent abrupt and radical adjustments in what is supposed to be a continuous process of fine-tuning.

A properly functioning pancreas doesn't emit heavy blasts of insulin every hour or two (and remain inert the rest of the time). When the endocrine system is operating according to the manual, it is always doling out a little bit of insulin; the amount increases a bit when blood sugar starts to rise, and decreases a bit when blood sugar starts to fall. To prevent the insulin from exerting too strong a downward push on blood sugar, the pancreas also releases a hormone with the opposite effect (glucagon); this mutes the impact of whatever insulin is being produced, and helps prevent hypoglycemia. By changing the ratio between the amount of insulin it produces and the amount of glucagon it produces, the pancreas can make the subtlest possible adjustments to blood sugar levels.

Well, that's how it's supposed to work. When Type 1 diabetes (or even Type 2, in some severe cases) is preventing the pancreas from producing a significant amount of insulin, the patient has no choice but to inject the stuff. Unfortunately, patients can't operate the way a normal pancreas would, constantly administering small amounts of insulin and glucagon and fine-tuning the dosages. Patients just have to give themselves a shot once in a while, injecting a large amount of insulin at once, and hoping they aren't injecting too much (or too little) for the circumstances. If they've guessed wrong about when an injection is needed and how much should be injected then, their blood sugar level can take a dramatic excursion above or below the normal range.

Biochemists have long been trying to improve on the insulin molecule as nature gave it to us. Various artificial forms of insulin have been developed, forms which operate slower and last longer, so that the impact of insulin shots on blood sugar is not so abrupt and extreme.

But what if insulin could be engineered so that the insulin molecule itself becomes responsive to its environment, and becomes functional as a hormone only when it is needed (because blood sugar is currently high)?

A team at MIT has been developing engineered-insulin molecules which have been fitted-out with chemical add-ons which allow the insulin molecule to be activated by exposure to glucose. "Here, we prepared a derivative of insulin with a molecular switch to provide glucose-mediated activation of the insulin molecule, toward the generation of more autonomous therapy with improved blood glucose control. This modified insulin, when administered in a diabetic mouse model, restores blood glucose levels following a glucose challenge (i.e., a simulated meal) faster than both standard insulin and a clinically used long-lasting insulin derivative."

Because these engineered insulin molecules get switched on and off depending on the current level of glucose in the blood, more or less in the manner of a thermostat, they are capable of approximating the kind of continuous adjustment that a healthy pancreas would provide. Continuous glucose monitoring of mice injected with this kind of experimental insulin confirms a pancreas-like responsiveness to glucose intake.

Of course, everything works in mice. Exactly what will happen when this is tried in humans remains to be seen. But it does look pretty promising.

 


Blood pressure & Type 2

High blood pressure is associated with a heightened risk of cardiovascular disease. Type 2 diabetes is associated with a heightened risk of cardiovascular disease. Also, Type 2 diabetes is associated with a high blood pressure.

It's hard to sort out all these issues, and determine what is causing what, but it appears that both Type 2 diabetes and high blood pressure are independently associated with cardiovascular disease. The question is, if you have both Type 2 diabetes and high blood pressure (like a lot of people do), does it do any good to control your high blood pressure, or does the impact of your diabetes cancel out whatever you're gaining by controlling your blood pressure?

Apparently it is worth it for diabetes patients to control their blood pressure, according to a new study in JAMA. "The researchers found that each 10-mm Hg lower systolic BP was associated with a lower risk of mortality, cardiovascular disease events, coronary heart disease events, stroke, albuminuria (the presence of excessive protein in the urine), and retinopathy (loss of vision related to diabetes)."

For most of these problems, blood pressure reduction was about equally effective regardless of how it was achieved. (The journal authors only acknowledge pharmaceutical methods of reducing blood pressure, but I assume that running up the insanely steep hill I ran up today might also qualify as an effective "treatment".)

But how much do you have to reduce your blood pressure for the effort to pay off -- and how much difference does it make if you go lower? It appears that the most important thing is to get your systolic pressure under 140 mmHg, but you do get some additional benefit if you can get below 130: "Although proportional associations of BP-lowering treatment for most outcomes studied were diminished below a systolic BP level of 140 mm Hg, data indicated that further reduction below 130 mm Hg is associated with a lower risk of stroke, retinopathy, and albuminuria, potentially leading to net benefits for many individuals at high risk for those outcomes."

So there you have it: although Type 2 diabetes is doing its very best to give you cardiovascular problems, you can undermine its evil intentions by controlling your diabetes and controlling your blood pressure. I think it's better to use exercise as our drug of choice for both purposes -- but if you take care of these issues one way or another, you can probably avoid a lot the problems diabetes is trying to force on you.

 


1st Thursday Update

February 5, 2015

This week, my division at work is hosting a bunch of employees from distant locales for a training event. Last night we took them out for a dinner at a local brewpub. Inevitably there were a lot of liquid carbs, as well as the solid variety. So I guess my fasting test being over 100 the morning after that wasn't too surprising. But after a hard, hilly run at lunchtime, my post-prandial result was only 109, so I guess there wasn't too much harm done.

 


Tortoise defeats hare!

Aesop is said to be a slave who lived in Greece about 2600 years ago and became famous for his abilities as a story-teller. Historians aren't sure that Aesop was an actual person, and even if he was, they are confident that he didn't write all of the fables that are attributed to him. Apparently, it became conventional to attribute any fable to "Aesop", wherever it might actually have come from, and regardless of whether or not Aesop existed.

A fable, I should mention, is a fictional anecdote illustrating a principle, but different from a parable in that the characters in a fable are animals (or sometimes plants, objects, or natural forces), whereas in a parable the characters are human. Fables, like most ancient literature, tend to be open to contradictory interpretations. Many don't state what the "moral" of the story is, and where a moral is given, it may well be an interpolation by a later author who couldn't bear to let the story remain ambiguous in its intent.

The only two of Aesop's fables that have stuck with me are the one about the fox and the grapes, and the one about the tortoise and the hare. In the former, the fox vents his frustration at not being able to reach a cluster of grapes by shouting that they are sour anyway, so who would want them? Thus our expression "sour grapes", used to lampoon those who try to disguise their disappointments in life by bad-mouthing whatever they haven't got.

The one about the tortoise and the hare is too familiar to need even a brief summary. However, I was surprised to learn that this fable has been presented in alternative versions over the years, not all of them supporting the usual interpretation of "slow and steady wins the race". In some versions, the hare abandons the race before it's over, because it is absurdly non-competitive, and then the tortoise's friends advise him to finish the race with no opponent and cynically call it a victory. In Aesop's version, however, it seems clear that the hare does finish the race, but he only does so after an ill-advised siesta. Anyway, there is enough uncertainty here to raise the question: does slow and steady win the race?

Perhaps a more pertinent question would be: if you're a slow runner, should you bother running at all?

Apparently the answer is "yes". A reader drew my attention to some research coming out of Denmark, indicating that slow-and-steady joggers gain more from their exercise, in terms of longevity, than more serious athletes who run faster and run more miles. In fact, the heavy-duty runners had no significant longevity advantage over those who didn't exercise at all; it was the low-intensity joggers who lived longest.

My first thoughts, on looking over this research very superficially, is that this is good news for me, as I'm a slow runner myself (and getting slower as the years go by). The potential down side is that I'm logging a lot more hours of running per week than the people in the study who did best. So does the study tell me that I'm doing the right thing in terms of exercise intensity, but the wrong thing in terms of total exercise time?

I should point out at once that the Danish research has serious limitations. The study involved only people who were healthy at the start, and it did not analyze cause-of-death data. It's hard to know how pertinent the findings are to anyone who is exercising at least partly for the sake of managing diabetes. If you have diabetes, and you're using regular exercise to maintain good glycemic control, perhaps that's more important than whatever problems were experienced by people in the study who ran hard and ran often.

One of the big dangers of reading medical research reports is that you are always tempted to interpret a study of people who don't have your health issues as a guide to healthy behavior in people who do have your health issues. Maybe the more heavy-duty runners gained nothing if they were disease-free from the beginning, but would have gained something if they'd had diabetes from the beginning.

I admit I have been worrying a bit lately about whether my declining running speed means I'm not getting as much benefit from exercise as I once did. If the authors of this study are to be believed, slow running is better, not worse, for your health. But there might have to be a study of people who are more like me for the question to be settled!

Incidentally, I looked up the difference between a "hare" and a "rabbit". It turns out that there are various species of the genus Lepus, and there is a convention of calling the larger one hares and the smaller ones rabbits, but that's about as specific as the distinction gets. It relaxed me a bit to finally get that terminology clear; maybe that's why my blood pressure and pulse are so low right at the moment.

 


Another complicated pathway identified!

Researchers keep discovering chemical pathways that work differently in people with and without Type 2 diabetes. The latest one, discovered by a team at Yale, relates to production of glucose by the liver. Insulin is known to damp down the release of glucose by the liver, but exactly how it does that was unclear until now. It seems that insulin suppresses lipolysis (the breakdown of fat), and one consequence of that is that there is less "acetyl CoA" produced. Because acetyl CoA stimulates the liver to release glucose, producing less of it causes the liver to release less glucose. At least, that's how it all works in people who don't have Type 2 diabetes.

In diabetes patients, inflammation in the fat tissue encourages lipolysis to occur even when insulin is trying to suppress it. So, more acetyl CoA is produced, and this triggers the liver to release more glucose.

One sign that your liver is producing too much glucose is a high fasting test result. After several hours without food, the only glucose entering your system is coming from your liver, not from your digestive tract.

The significance of this, so far as the researchers are concerned, is that it suggests the possibility of developing new medications to suppress acetyl CoA production. However, it's also possible that learning more about this pathway could help us develop better ways of managing the condition without drugs. Maybe I'm going to the only one looking at that angle, but I will definitely be looking at it.

 



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