Fourth Thursday Update

Thursday, June 24, 2014

Last week, the main thing interfering with exercise at work was a broken water-heater. This week, there was a slightly more challenging issue: a mountain lion was spotted on the company property. That sort of thing makes you a little inhibited about going outside for a lunchtime run. I decided to run in the evening, off the property. To be sure, the route I chose instead wasn't guaranteed to be a lion-free zone, but I was on well-traveled roads, with enough vehicular traffic to scare the major predators away.

Not that being on well-traveled roads is always a safe option. A cyclist tried pretty hard to kill me. He overtook me from behind at close range and at high speed, without calling out the traditional "on your left!" warning. Not knowing he was there, I moved into his way, and he had to do an emergency swerve around me. Shouted obscenities ensued. (None of them from me; I was too shocked to make a sound.) Maybe I should have taken my chances with the mountain lions. They eat you sometimes, but they don't insult you much.

I know that there are cyclists whose mission in life is to make everyone hate cyclists, but I'm not exactly clear on what their motivation is. He looked like a serious competitive cyclist, though, so maybe he just thinks hating everyone is the normal human condition.


Diabetes is Unfair to Women!

Ladies, you knew it would turn out this way, didn't you? Apparently diabetes, or at least one of its major health consequences, is harder on women than it is on men.

Diabetes can harm our health in a variety of ways, but the biggest problem with diabetes is that it raises the risk of cardiovascular disease. Heart attacks, heart failure, ischemic strokes -- diabetes makes you more likely to experience these and other serious problems with your circulatory system. If you don't have diabetes, such problems are more common in men than in women, at least up to a certain age. But diabetes, which heightens the risk of such problems for men, heightens it more in women, so that women with diabetes actually have more cardiovascular problems than men with diabetes.

This insight comes from Pendar Farahani at Queen's University (painstaking examination of the university's website reveals that it is located in Kingston, Ontario, Canada -- why are so many university websites reluctant to admit where on the planet their school is located?), who says, "Women with diabetes have a considerably higher rate of cardiovascular-related illness and death than men with diabetes. This pattern is likely related to poorer control of cardiovascular risk factors."

It seems that women who try to tame their cardiovascular risk factors following a diabetes diagnosis tend to be less successful at it than men are, particularly in terms of cholesterol reduction. For example, only 64% of women in this situation succeed at reducing their LDL cholesterol adequately, versus 81% of men.

Why should that be? Apparently it has something to do with the fact that, these days, doctors treat high cholesterol with statin drugs, and women are less able to tolerate those drugs than men are. The more unpleasant side effects of statins (such as muscle pain) occur more often in women than in men, so women are less likely than men to comply with statin-based treatment requirements.

Dr. Farahini adds, "The findings suggest the need for gender-based evaluation and treatment of cardiovascular risk factors in these patients. We need further study into the gender disparities to tailor drug interventions and we need to increase the inclusion of women in clinical trials." So there you have it! Problems with drug-based therapies should not lead us to consider drugless therapies; they should send us on a search for different drugs.

So, eventually, doctors will be offering blue pills for men and pink pills for women. So long as the pink pills work about as well as the blue pills, no one will ask if either pill is as effective as exercise.


Gut-bugs and Diabetes

The human intestinal tract is home to a thriving population of bacteria, and although we might be inclined to think of them as parasites, we might not find it so easy to live without them. They play an important role in digestion, and apparently they benefit us in other ways as well. It seems to make a big difference to our health what kinds of microbes are dominant in there.

There is some evidence that a microbial imbalance contributes to the development of Type 2 diabetes, and some pharmaceutical companies have been developing new drugs known as "microbiome modulators", which alter the balance of different kinds of microbes in the intestinal tract. One such drug, which hasn't had an unpronounceable or comical name assigned to it yet, and is known temporarily as NM504, was developed by a company called MicroBiome Therapeutics. Dr. Mark Heiman, the chief scientific officer of that firm, says: "We believe that modern Western diets contribute to development of Type 2 diabetes, in part because they change the habitat of the microorganisms that reside in the gut. This shifts the microbial populations that live there in ways that affect metabolic health."

A small study of patients with prediabetes found that the drug known as NM504 improved glucose tolerance in these patients even if they made no changes in their diet.

Maybe the claimed benefits of NM504 will stand up under scrutiny, and maybe the won't. But if researchers can figure out precisely what it is about the Western diet that promotes undesirable changes in the gut biome, maybe we don't need to take special drugs to counteract the consequences of the diet; maybe we just need to make adjustments in the diet.

No, wait -- I'm getting talking crazy here. We need more drugs! Give us our drugs! NOW!


Third Thursday Update

Thursday, June 19, 2014

The water heater in the locker-room at work was broken, so I decided not to run at lunchtime and then suffer through a cold shower afterward. For a change of pace, I did a hike instead of a run after work. It was on steep trails in the state park, so it definitely counted as a workout.


Let me try to answer some of the questions which people out there seem to have about diabetes, based on their Google searches...

"fructosamine level chart equate to a1c"

The fructosamine test is a diagnostic test which seeks to quantify a patient's comparative success at diabetes control, by looking for evidence of "glycation" (unwanted bonding of sugars to proteins) in the blood. The more familiar hemoglobin A1c test looks at glycation of hemoglobin in red blood cells; the less familiar fructosamine test measures glycation of proteins (mainly albumin) found the blood serum. Because albumin in the blood serum doesn't last as long as hemoglobin in the red blood cells, the result of a fructosamine test reflects blood conditions during the past two weeks (not the past two to three months, as in the case of the A1c test).

Because the fructosamine test reflects only recent conditions in the blood, it is used to look at comparatively short-term trends (for example, your doctor might order a fructosamine test to get an idea of how well a new medication -- or new dosage level -- is working for you).

Relating the results of the fructosamine and A1c tests to each other, and to glucose test results, is a mighty tricky business. These tests measure different things, and although those things are connected, the mathematical relationship between them appears to be different for different people. The conversion formulas are generally given as follows:

(A1c X 28.7) – 46.7 = estimated average glucose in mg/dl (or divide by 18, for the equivalent in mmol/l).

(A1c - 1.61) X 58.82 = fructosamine in umol.

Still, I'm sure it is misleading to offer a table of equivalents for the three tests. I'll do it, because that is the question being asked, but please don't take this too literally. It's a rough indicator, no more:

A1c, % Est. Avg Glucose, mg/dL Fructosamine, umol
5 97 199
5.5 111 229
6 126 258
6.5 140 288
7 154 317
7.5 169 346
8 183 375
9 212 435
10 240 494
11 269 552
12 298 611

"what would cause your blood sugar to go from 85 to 128 after a nap"

The body has a kind of protective mechanism which is designed to prevent hypoglycemic episodes during sleep. Obviously, there's a lot of potential for hypoglycemia during sleep, because people tend to sleep for several hours, during which time they are not eating, and also not conscious (so the feelings which would normally stimulate a hypoglycemic person to do something about it are not going to be perceived). Anyway, if your glucose level starts dropping a little too fast during sleep, the pancreas releases a hormone called glucagon, which stimulates the liver to release stored sugar into the bloodstream to correct the problem.

It's a great system, so long as you don't have Type 2 diabetes. If you have Type 2 diabetes, the liver's attempt to correct the problem is effectively an over-correction, because your system can't quite cope with the amount of stored sugar your liver releases in this situation, and your blood sugar rises more than you would like it to.

"how quickly does one get diabetes after an a1c reading of 6.2"

Probably somewhere between two weeks and twenty years.

There is absolutely no knowing how long you can coast along in a pre-diabetic state (with an A1c result which is slightly elevated, but not elevated enough for a diabetes diagnosis) before becoming "officially" diabetic.

However, the pre-diabetic state itself is by no means harmless. It essentially means that your endocrine system is struggling to keep your blood sugar out of the diabetic range, and is having a very hard time keeping a lid on the problem. The endocrine system's standard coping mechanism in this situation (hyperinsulinemia, meaning the release of abnormally large doses of insulin into the bloodstream on a chronic basis) is not at all a good thing in the long run; it tends to promote cardiovascular disease -- even if you never become officially diabetic.

Any indication that you are in the process of becoming diabetic should be seen as a call to immediate action, not as an omen that action might be required some day. It's easier to get this kind of thing under control if you don't wait until it's officially out of control.

"diabetic reading 325 should i take insulin"

You should certainly do something. Depending on your situation, insulin might or might not be the right thing for you to do. You need to talk to your doctor about what your options are, and what the risks and benefits of the different options are. But 325 (I assume we're talking about glucose in mg/dl) is not a good place to be for long.

"is it possible to turn around a reading of 360 glucose"

I don't know of any reason why not. There is no arbitrary glucose level beyond which no one returns. It's very dangerous to think in those terms anyway. It is very typical for diabetes patients, having heard so many ugly stories about how intractable the disease is, to assume that unless their diabetes is very mild and was caught very early, it will prove impossible to control. Their pessimism (and that of their doctors, often) becomes a self-fulfilling prophecy, because they give up too easily as soon as they run into a rough patch. You know what they say: if you think you can't do something, then you're right.

"does glucometer measure diabetes inspidus"

No. Strictly speaking, "diabetes" by itself doesn't refer to problems with blood sugar; it refers to any disease which is associated with excessive urination. Only diabetes mellitus relates to blood sugar. Diabetes inspidus is an unrelated hormonal problem which causes excessive production of urine without elevated blood sugar. A glucometer wouldn't tell you anything about it.

By the way, "insipidus" means "lacking flavor", and it refers to the disappointingly bland flavor of the urine of patients with diabetes insipidus. "Mellitus" means "honey-like", in reference to the sweeter taste of urine from diabetes mellitus patients. Obviously these terms go back a long way. Modern doctors do not taste the urine of their patients. We have lab equipment for that now, and I'm sure that is something for which modern doctors are deeply grateful.

"is glycation the result of hyperinsulinemia"

No. Glycation is the result of sugar in the blood. Some glycation goes on in everybody, but in most people the body is able to correct for it by recycling its glycated proteins. In people with diabetes, glycation occurs at a heightened rate, simply because more sugar is present in the blood, so the body isn't able to recycle proteins fast enough to prevent glycation from building up.

Hyperinsulinemia is the body's way of trying to get high blood sugar under control. When this doesn't entirely work, blood sugar goes up, but the hyperinsulinemia continues for as long as the body can keep doing it. So, elevated glycation often occurs in people with elevated insulin, but it's not a case of the insulin causing the glycation, it's a case of the insulin trying to prevent glycation and not fully succeeding.

"how long with diabetes before sweet urine"

There's no way to predict that. It depend on how well you control your blood sugar. If your blood sugar gets far enough out of control that is rises above your "renal threshold" (the point at which the kidneys are overwhelmed by the amount of sugar in the blood), at least some of your blood sugar will leak through your kidneys into the urine. The renal threshold is different in different people; it is usually something like 160 to 180 mg/dl, but it can be lower in some people, especially children and pregnant women.

"is it possible to pee out all the excess sugar in the body and still be diabetic free"

No. Even when you get above the renal threshold and blood sugar leaks through the kidneys into the urine, this doesn't bring your blood sugar down to normal. It only brings your blood sugar down to the renal threshold -- which is still high enough to be called diabetes.

A class of drugs known as SGLT2 inhibitors (dapagliflozin is an example) operate by lowering the renal threshold, so that sugar starts leaking into the urine before it gets extremely high. Still, this approach is only a method of keeping diabetes under reasonably good control; it doesn't make you "diabetic free".

Second Thursday Update

Thursday, June 12, 2014


Cause of Diabetes #2589

You know what causes diabetes? Things. Things in general. Perhaps all things. But certainly most things. If you're going to live in a world of things -- if you're going to spend your life surrounded by things, most of which cause diabetes -- you're at pretty high risk of developing the disease one way or another.

Not many months go by without researchers finding evidence for some causal mechanism for diabetes which everyone else had been overlooking. Wouldn't you know it, these discoveries usually turn out to involve "targets" -- that is, some protein or gene whose evil influence promotes diabetes but might some day be nullified, if only we can spend enough research-&-development money creating a drug to counteract it.

Sorry, am I sounding cynical? I don't know that any of these breakthroughs are faked up for the sake of attracting grant money, but I have to wonder how it can be that so many different things seemingly cause diabetes. It seems improbable that all these discoveries are going to stand up to scrutiny during follow-up research.

The diabetes-causation breakthrough I read about today (aside from the one about milk proteins causing diabetes) has to do with, of all things, oxygen-deprivation. Specifically, oxygen-deprivation within fat cells.

Researchers at the University of California in San Diego have been trying to figure out how obesity causes a type of chronic inflammation which impairs insulin sensitivity and promotes Type 2 diabetes. They have worked out a chain of causation for diabetes that goes like this:

The researchers found that a sustained high-fat diet in mice (sorry, did I forget to tell you we were talking about mice here?) produced the chain of events described above.

The researchers are, of course, very much focused on possible chemical interventions: "The elucidation of this sequence also revealed two potential therapeutic targets: ANT2 and HIF-1alpha. The researchers suggest that inhibiting either could blunt, or even reverse, the damaging cellular sequence. Indeed, they found that mice genetically engineered to lack HIF-1alpha in their adipocytes were protected from high-fat diet-induced inflammation, insulin resistance and elevated glucose levels."

Well, we'll see about that. The odds are high that any drug which nullifies ANT2 and HIF-1alpha in humans would have effects besides the ones we would want them to have. Maybe this will lead ultimately to new diabetes drugs, and maybe it won't.

Meanwhile, in my usual contrarian way, I'm wondering about other implications of the research. Instead of figuring out how to nullify the "target" compounds ANT2 and HIF-1alpha, maybe we should think about keeping the fat cells from generating them in the first place. Perhaps we should focus on the hypoxia which is occurring in fat cells and triggering the release of those problematic compounds.

It's worth noting that hypoxia in cells might be caused by other things besides a high-fat diet. One obvious possibility is OSA (obstructive sleep apnea) -- a disruption of breathing during sleep which is strongly associated with Type 2 diabetes. (My own diabetes diagnosis occurred not long after I developed a serious problem with OSA.) If OSA patients are suffering frequent episodes of hypoxia while sleeping, this would seemingly trigger the same scenario experienced by mice on a high-fat diet, as described above. Maybe that explains why alleviating OSA also tends to alleviate diabetes.

Another obvious possibility: stop eating a high-fat diet, if you have diabetes. But there's a catch: it's hard to develop a low-fat diet that isn't also a high-carb diet. Like many people with Type 2 diabetes, I find myself feeling a bit trapped between the disadvantages of a high-fat diet (which tends to be bad for weight control) and the disadvantages of a high-carb diet (which tends to be bad for glucose control). However, since my rather high fat diet in recent years has caused me to gain enough weight that glucose control is difficult anyway (not today, but often), I guess it's time to bite the bullet, and cut fat even if (for a while) it makes glucose control difficult. It's difficult anyway!


Anti-side-effect drugs!

Lipitor, a statin drug which reduces serum cholesterol, has been promoted as the wonder-drug to end all wonder-drugs, but it has a slight flaw: it tends to promote the development of diabetes. Because the ultimate purpose of lipitor is to reduce the risk of coronary heart disease, and diabetes is an important risk factor for coronary heart disease, doctors find this side-effect a little troubling.

But never fear! Researchers at McMaster University (in Ontario, Canada, in case you haven't heard of it either) have found that you can counteract the diabetes-promoting side effects of lipitor by taking it in combination with glyburide. The second drug suppresses the side effects of the first!

The next step, seemingly, if to find a third drug which you can take to suppress the side effects of glyburide (nausea, heartburn, and weight gain).

Then, of course, we will need to find a fourth drug, to suppress the side effects caused by whatever drug suppresses the side effects of the glyburide.

Repeat as needed...


First Thursday Update

Thursday, June 5, 2014


Thoughts on not going outside

Of all the things that make the modern lifestyle unhealthy for us, perhaps the one we most easily overlook is our tendency to spend almost all of our time in an artificial indoor environment.

I don't know how much difference the lack of fresh air actually makes, but the inhibition of physical movement indoors (unless you're actually in a gym) has got to be an issue. And perhaps the mental habit of feeling disconnected from nature is unhealthy, too, in a way which we haven't quite figured out yet.

Living in coastal California as I do (where there is a limit to how awful the weather is ever going to get), I have less excuse than many people for not going outside. And the only good excuse I would have for not going outside doesn't stand up to scrutiny. I am allergic to many pollens, especially from grasses, and this time of year happens to be the peak of my allergy season. (It subsides later this month.) I get asthma at this time of year, and sometimes very irritating swelling in my eyes. One would be tempted to argue that I should simply spend this time of the year indoors, hiding form all the pollen swirling around out there (especially when people with weed-whackers are stirring up a storm-front of dust, pollen, and grass-fragments).

And yet, my allergy symptoms are much less severe (now that I spend a lot of time outdoors exercising) than they used to be when I mostly stayed indoors. My symptoms now are pretty trivial. I do have a few bad days every spring, when I can't wear my contact lenses because my eyes are too irritated to tolerate them, and sometimes running becomes more of struggle than usual, because mild asthma is impairing my lung capacity a little. But these problems used to be far worse; they made me reluctant to go outdoors even for a few minutes. That was before I got the diabetes diagnosis, and started making outdoor exercise a daily habit. The more time I spend outdoors, the less I am affected by all the pollen out there.

Yesterday, after work, I realized that I had enough daylight left to go on a short hike in the nearby state park before sunset.

It's easy to assume that there's no time for that sort of thing, if you don't pay attention to the actual sunset time and plan accordingly. But if you can make the time for it, it's a great time of day to be outdoors.

One of the things I like about hiking in the park is the way the environment continually changes around you as you go along.

Even the simple act of keeping on eye on the sun's progress toward the horizon, to make sure you don't get caught there in the dark, makes you feel more connected with the natural world.

I also like the warm glow that the late-afternoon sun gives to everything.

And, of course, there's the satisfaction of spotting wildlife around you.

Even a natural phenomenon as visually unpromising as a turkey-neck can be transformed when there's a low sun illuminating it from behind.

However, I have to admit that I want my communing with nature to occur only outdoors. One morning recently I stumbled to the bathroom, opened the shower curtain, and discovered that this creature had somehow got in there:

I had been blissfully unaware that we even had scorpions in northern California, but it turns out we do. This was not a discovery about nature which I was happy to make. But, oh well: if you're going to commune with nature, you have to face the reality that not everything in nature is cute.


Inhibiting insulin breakdown

There is natural compound in the bloodstream called IDE (Insulin Degrading Enzyme), which causes insulin in the blood to break down. Researchers at Stony Brook University in New York have discovered a compound which inhibits the effect of IDE. The inhibitor is represented here in orange and white; the rest of the picture shows the IDE compound which is being inhibited by it.

The maddeningly vague press releases don't say much more about the research than that the inhibitor compound could become a useful medication for Type 2 patients, especially in the early stages of the disease, when they still have a comparatively robust production of insulin. The inhibitor compound could protect whatever insulin they are able to make, you see. (The drug would probably not be useful to Type 1 patients, or to Type 2 patients who have lost a lot of their insulin-producing capacity.)

But the full report on the research is behind a paywall, so if you want to know more about it you'd better be willing to fork over $32.

I wasn't.

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