Wednesday, December 21, 2011
Many of us are also aware that another hormone, glucagon, helps bring BG levels up when they get too low. Glucagon is made in and secreted by the alpha cells in the pancreas.
In nondiabetics and people with type 2 diabetes or early type 1 diabetes, glucagon automatically gets secreted when BG levels get too low. But people with longstanding type 1 diabetes often stop producing much glucagon and need glucagon shots to bring up a serious low.
Insulin and glucagon are like the accelerator and brake on your car. And it's the ratio of the two, rather than the absolute amount, that is important. If you have almost no insulin, you might be able to have normal BG levels if you also had almost no glucagon.
In fact, a study done in 1981 in a man who had no pancreas, showed that BG levels could be maintained at about 100 without insulin as long as they didn't give the man glucagon.
The problem is that when the beta cells give out, the alpha cells don't give out as well. In fact, they often secrete even more glucagon than they would in a nondiabetic. Glucagon tells the liver to produce and secrete glucose, so the BG levels stay high even when you don't eat.
Most diabetes researchers focus on beta cells and insulin production, but some are studying the alpha cells and glucagon production as well. A recent study found that hyperglucagonemia (too much glucagon in the blood) actually precedes the decline in insulin secretion seen in diabetes.
These researchers infused rats with a lot of glucose for 10 days. After initial high BG levels, the rats adapted and maintained normal BG levels for 4 days. But then their BG levels started to go up, and by 10 days 89% of the rats had high BG levels.
This isn't surprising. The traditional view is that coping with a lot of glucose and producing a lot of insulin can "exhaust" the beta cells; this is called glucotoxicity.
But the researchers found that the rats weren't producing any more insulin than normal. Instead, their glucagon levels increased fivefold. Thus endogenous glucose production, production of glucose by the liver, was what was making the BG levels go up. And infusing them with anti-glucagon antibodies made their BG levels return to normal.
That is surprising.
The authors conclude that glucotoxicity may first manifest as alpha cell malfunction, before any deficit in beta cells and insulin secretion is seen. This is a new way of looking at how diabetes procedes.
A few months earlier, another paper showed that glutamate (or glutamic acid), an important neurotransmitter in brain and pancreas, is secreted from alpha cells along with glucagon. The glutamate contributes to beta cell destruction; it doesn't affect the alpha cells.
Hence, if you're secreting more glucagon, you'd also be secreting more glutamate, thus accelerating beta cell loss and insulin production when you needed more to oppose the extra glucagon.
The authors also found that the protein GLT1 (glial glutamate transporter 1) could protect the beta cells, and they are working on finding other beta-cell-protective compounds.
Neither of these discoveries will result in an instant cure for type 2 diabetes. The first was done in rodents, and the second was done in isolated human cells. Before they can be translated into actual diabetes treatments, they'd have to be replicated in humans, not isolated cells or rats, and treatments that turned down the alpha cells would have to be developed.
However, for decades, researchers have been studying how type 2 diabetes evolves, and they're still not sure. Of course it's all terribly complex. But is it possible people are looking in the wrong places? Maybe it's time for some new ways of looking at an old problem.
Focusing on the alpha cells is one such approach. Let's hope this work continues.
Tuesday, December 20, 2011
But I'm always amazed at the closed-minded comments I often see in blogs of anti-low-carbers. Here's one, commenting on a photograph of a LC breakfast posted with a blog:
"There's nothing on the plate that I consider breakfast food."
The photograph seems to show bacon, ham, eggs, sausage, tomato, and mushroom.
I wonder why the poster feels that he needs special foods for breakfast. And apparently that special "breakfast food" should have a lot of carbohydrate, and little protein. That makes no sense. Most people are more insulin resistant at breakfast, and many studies have shown that blood glucose levels rise more after breakfast than after other meals. So if you feel a need for a daily allotment of orange juice, skim milk, toast, jam, and cereal, it would make more sense to eat it for supper, not breakfast.
Of course, this poster is not alone. Many people have irrational prejudices about "breakfast food." For instance, most Americans think bacon and ham are OK for breakfast. But if you say you had chicken or lamb chops, they'll think you're odd. Most Americans would consider Danish pastry or toast and jam to be suitable breakfast food. But if you say you had cheesecake or blueberry pie, they'll think you're odd.
What's the difference? Bacon, ham, chicken, and lamb are all meats. Danish, toast and jam, cheesecake, and blueberry pie are all sweetened starches.
It was the Kellogg brothers at the turn of the 20th century who pushed dry "breakfast cereals," at first primarily corn flakes, on the American public. At that time, rich people tended to eat meat and eggs for breakfast. Poor people ate starches, often boiled into porridge. Farm breakfasts tended to include a little of everything: meat, eggs, milk, pancakes, potatoes, breads, and pies. The farmers needed a lot of energy when facing long hours of backbreaking work and tended to eat the lighter meals like cereal in the evening.
By now, several generations of Americans have grown up thinking that breakfast has to include a dry cereal, often sweetened, and milk. But why do we have to mindlessly accept that there should be special "breakfast food"? We're smarter than that, aren't we?
In the rural area where I live, most people still conform to older patterns of eating. But in urban areas, it seems people are getting more creative with their meals, as described here. (The trend toward daylong snacking does not sound healthy, however, as commercial snacks are usually highly processed.) Nevertheless, the reporter reveals his underlying bias when he refers to eating nontraditional meals as "weird."
When we have diabetes, we need to eat the foods that keep our blood glucose levels down, whether they're considered "breakfast food" or "lunch food" or "dinner food." We can't let old patterns get in the way.
Lamb chops and broccoli for breakfast anyone?
Friday, November 25, 2011
Because Lowe has done research with Big Pharma (including diabetes research), he provides a different point of view from the common "Big Pharma is evil and doesn't want to cure diseases" point of view found in many patient blogs. I think it's important to look at both sides of any issue, and Lowe often points out the difficulties of various chemical approaches to solving some drug problem. Most of them are over my head, but this one was interesting.
He links to another blog that has a series on mouse models, for those who are interested.
Many of the comments on Lowe's post are from other researchers, and it's interesting to see that unlike the popular press, the researchers are cautious about using mouse results. Even different strains of mice can show different results with the same drug.
One interesting comment was that when you put a human tumor into a mouse and some drug cures the tumor in that mouse it's possible that the drug simply kills human cells and hence would be dangerous in humans.
I think most of us understand that mouse studies often don't pan out to be human treatments. They are only suggestive. If only the popular press could show some restraint, patients wouldn't be told over and over again that some new cure was on the way, only to be disappointed when they never hear about it again.
According to Grandin, someone's cat loved watching the water swirl around when a toilet was flushed. The cat couldn't figure out how to flush itself, but it had noticed that when there was paper in the toilet, it was more apt to be flushed.
So the cat tore up toilet paper and threw it in the toilet and waited expectantly.
This is a perfect example of the difference between association and cause. The cat correctly noted that toilet paper was associated with toilet flushing. But the cat incorrectly decided that toilet paper caused toilet flushing.
Of course, flushing didn't cause toilet paper any more than toilet paper caused flushing. It was a third factor, pulling the handle on the toilet, that caused the flushing.
Many of our scientific interpretations are like the cat's. If we see a fat person eating more than a thin person, most people conclude that overeating causes obesity. But perhaps obesity causes increased appetite, or perhaps a third factor that no one has discovered yet causes both obesity and increased appetite.
Whenever we see research that shows that two factors are associated, we should think of this cat story. Does the research provide any evidence that one factor caused the other, or is the researcher simply thinking like the cat because of a preconceived notion?
Gary Taubes is challenging the catlike assumption that because fat people tend to eat a lot and not exercise much, it's their behavior that is causing their obesity. Instead, he says it's insulin that is making the body store fat instead of burning it, and the resulting energy deficit makes the person want to eat more and exercise less.
The blogosphere is filled with people debating this theory. I won't go through it all here.
My point here is simply that we should keep this graphic cat story in mind as we evaluate evidence. Surely we humans can be smarter than a cat!
Tuesday, August 2, 2011
GLP-1 has positive effects on insulin secretion, and the drug exenatide (Byetta) works by mimicking natural GLP-1. Because GLP-1 can help people with diabetes, it was thought that drugs that inhibit DPP-4, which would keep GLP-1 in the circulation longer, would also help people with diabetes.
Several DPP-4 inhibitors, the "gliptins" have been developed and include Januvia (sitagliptin) and Trajenta (linagliptin). They do reduce A1c levels somewhat, although they don't appear to be as effective as the GLP1-mimetics.
And one problem with such drugs is that DPP-4 affects many different proteins, and the inhibitors seem to reduce the effectiveness of the immune system, which could be deleterious.
DPP-4 exists as a membrane-bound protein and also free in solution. Both forms break down GLP-1.
But now European researchers report that DPP-4 is an adipokine that impairs insulin sensitivity.
An adipokine is a cytokine secreted by adipose tissue. A cytokine is similar to a hormone; it is a signalling molecule. Many of these substances have been discovered only recently and not everyone agrees about which should be called hormones and which cytokines. The important thing is that they're secreted by one type of cell and can affect others.
The European researchers found that the levels of DPP-4 were higher in persons with more fat cells, and in those with larger fat cells. Also, the production of DPP-4 in obese persons was fivefold higher in visceral adipose tissue (the tissue around organs that is associated with metabolic syndrome) than it was in subcutaneous fat. There were no regional differences in lean subjects.
After weight loss, the release of DPP-4 reverted to levels similar to those of lean subjects.
If DPP-4 is an adipokine that impairs insulin sensitivity, then it makes sense that the DPP-4 inhibitors would improve insulin sensitivity and lower BG levels. It's not clear at this time which of the DPP-4 effects would be more important.
But this could be the link between obesity and insulin resistance, or it could simply be one of many links between the two conditions. Perhaps this report will stimulate more research in this area.
Thursday, July 28, 2011
1. ScienceDaily (June 14, 2011) — People who use a mist inhaler to deliver a drug widely prescribed in more than 55 countries to treat chronic obstructive pulmonary disease (COPD) may be 52 percent more likely to die, new Johns Hopkins-led research suggests.
2. ScienceDaily (June 13, 2011) — An inhaler designed to help chronic bronchitis and emphysema sufferers breathe could be significantly increasing their risk of dying, according to new research by the University of East Anglia (UEA) and three US universities.
Right you are! The Hopkins PR department didn't even mention the UK university and the UK university dismissed Hopkins as just one of three US universities.
These press releases that get published by Science Daily and then picked up by newspapers are released not only when some research group has a real breakthrough, not only when some research group has something slightly new to say, but often whenever a clever PR person at the research center can figure out how to put a positive spin on something that might or might not be confirmed with future research.
The lead invariably mentions the institution. The next few paragraphs often describe the researchers and give all their titles. I usually skip reading all this. Then there are a few paragraphs giving background, for example, giving the differences between type 1 and type 2 or once again describing the "obesity epidemic."
The real news is often far down in the article, sometimes only a sentence or two. Then come quotes from the researchers saying how important this work is and how it either suggests the need for more research (the researchers want more grants) or suggests the need for the development of new drugs on the basis of the work (the researchers want to patent something).
[These two articles did have more meat than some others, and the safety concerns are, in fact, newsworthy. It was the leads that were so obviously PR-department generated.]
When science news is spun just like political news or "sold" by PR departments like a new type of plastic kitchenware, how can we trust anything we read on these news sources? There are zillions of scientific journals out there today, and no one can read even the tables of contents of them all. We have to trust science journalists to notice the important stuff and let us know about it.
But if all they do is reprint press releases from PR departments, is there any point? I suppose these press releases are better than nothing. They do alert us to the possibility there's something new there, and they usually give links to the source, so we can check it out ourselves.
But wouldn't it be wonderful if we could read real science news without having to scrutinize it for spin?
It's today's fad mantra. Want to lose weight? Eat more fruits and vegetables. Feeling sad? Eat more fruits and vegetables. Credit card maxed out? Eat more fruits and vegetables.
Sometimes I think we should just make it one word: fruitsandvegetables.
When I read one article that claimed that people in previous centuries ate lots of fruitsandvegetables my tolerance limit was reached.
Sure, there wasn't as much junk food in past centuries. But then, as now, poor people couldn't afford expensive fruits, or even vegetables unless they grew their own. Oranges were considered a rare luxury. Then, as now, poor people had to eat a lot of starches like bread and potatoes to get sufficient calories.
Even rich people didn't feast on lots of fruitsandvegetables. Here's a menu from Queen Victoria's household on her 80th birthday. I don't see a lot of fruits there. A few vegetables, but mostly meat and fish and eggs.
Here's an article describing what people ate in Boston restaurants in the 19th century. Like Queen Victoria's household menu, the restaurants seemed heavy on lots of meat courses, thick sauces, and pastry. Certainly not what today's nutritionists would recommend. Not a lot of emphasis on salads. Fruit was offered at the end, but only after a pastry course.
Here's another 19th century menu so heavy on meats that it makes me slightly nauseous to read it . . . and I'm on a low-carb diet! They do offer some fruit at the end, but by that time you'd probably be so stuffed with meat, game birds, lobster, and fish that you wouldn't have much room to stuff yourself with fruit.
I have nothing against eating more vegetables, limiting them to the low-carb ones like greens and other above-ground vegetables except peas and corn if you have diabetes. But fruits are full of sugar. If you have diabetes, it's not a good idea to eat a lot of fruit.
It's time we came to our senses and got rid of the fruitsandvegetables mantra. It's time we stopped thinking of some past Golden Age when everyone ate lots of lean meat (people in the 19th century would have guffawed at the idea of lean meat; they added bacon or lard to meat to make it juicier) and fruitsandvegetables and low-fat dairy and had glowing skin and never got fat.
Let's separate fruits from vegetables and eat less of the former and more of the latter. Let's focus on the carb counts of foods rather than whether they're fruitsandvegetables or other things.
Let's control our diabetes by finding out what foods make our blood glucose levels go up instead of listening to idiotic fad mantras.
We're smarter than fruitsandvegetables, right?
Saturday, July 2, 2011
But too many scientists get stuck in a groove, and they can't be budged from the current dogma, even when the evidence doesn't support their beliefs.
This is apparent in the eternal debate about the best diet. One problem is that people are different, they interpret diets differently, they keep track of what they're actually eating differently, they have different exercise patterns, they take different drugs, and so on and so on. But focus on "evidence-based medicine" means physicians won't believe anything unless it's been proved in a double-blinded controlled randomized trial.
And because such trials involve large groups of people, some of them usually respond one way and others respond in another way, and only statistical analysis will show whether the intervention worked on average. It says nothing about how the intervention will work on any individual patient in the future.
Nevertheless, what bothers me is the tendency of the scientists doing these trials to interpret the results in the light of their own biases. One such ploy when your intervention didn't work is to suggest that you didn't intervene hard enough.
For example, when a study of l0w-fat diets resulted in no benefit, the researchers said maybe the fat content wasn't low enough, that the study should be repeated with even less fat in the diet. It didn't seem to occur to them that perhaps lowering the fat content of the diet wasn't helpful.
A recent study shows the same type of reasoning. This study showed that adding moderate exercise (walking) to diet in people with type 2 diabetes resulted in no benefit for hemoglobin A1c. The first explanation by the lead author of the study was that "the activity chosen, walking, was suboptimal."
In other words, if the exercise you used shows no benefit, maybe more exercise will help.
A lot of studies have shown that exercise doesn't contribute to weight loss. Just Google "exercise, weight loss, doesn't help" for a smorgasbord of articles. Often, exercise just makes you hungrier. Other studies have shown that diet and exercise do work better for overall fitness than either diet or exercise alone.
Exercise helps the cardiovascular system and is certainly a good thing to get. (So why am I sitting here typing instead of finishing the wood stacking I started this morning? Answer: I'm human, just like you.)
I'm not suggesting that exercise is bad. What bothers me is the knee-jerk reaction of some science investigators. "My study doesn't support my hypothesis, so maybe the study wasn't done right" instead of "My study doesn't support my hypothesis, so maybe the hypothesis is wrong."
If everyone thought like this, we'd never make any progress.
Luckily, there are always a few brave souls who dare to defy the current dogma. They're usually laughed at when they start, and some of them give up. Some persist. And they're the ones who end up with the Nobel Prizes.
Sunday, June 26, 2011
From a story on statins in the New York Times discussing the fact that statins increase risk of diabetes:
"Exactly how statins may increase diabetes risk isn’t entirely clear, though animal studies suggest that statins can increase muscle resistance to insulin, resulting in higher levels of circulating blood sugar. Dr. Kausik notes that the patients in the studies were diagnosed with diabetes because of elevated blood sugar levels, but that the long-term consequences of higher blood sugar levels triggered by statin use aren’t known.
" 'Diabetes is defined by blood glucose levels, but none of us are absolutely certain if this is going to carry the same risk as if you traditionally developed diabetes,' Dr. Kausik said.
["Dr. Kausik" is Dr. Kausik Ray, professor of cardiovascular disease prevention at St. George’s University of London and senior author on the paper. Apparently the reporter couldn't even get the name right, so perhaps she also misquoted the doctor. Or maybe she refers to doctors as "Dr. Bob" or "Dr. Mary."]
A high blood glucose level is a high blood glucose level. It doesn't matter what caused it. The good doctor's statement makes as much sense as saying that high blood pressure caused by some drug has different consequences from high blood pressure caused by stress or genetics. It's the high blood pressure, or the high blood glucose, that causes the complications.
One could argue that high blood glucose levels caused by insulin resistance were riskier than high blood glucose levels caused by autoimmunity if you think it's the insulin resistance rather than the high blood glucose levels that are harmful in type 2.
But Dr. Ray said statins increase insulin resistance, so the diabetes they cause is like type 2.
With stupid reasoning like this, it's a miracle any of us survive our doctors' treatments! Remind me to avoid St. George's University of London.
I found it interesting that Dr. Steven Nissen, the one who pressed to have Avandia removed from the market because it increases heart disease risks, is arguing that people shouldn't stop taking statins even though they increase diabetes risks, and diabetes increases heart disease risks.
Thursday, June 16, 2011
"One in five rural elders do not participate in either moderate or vigorous physical activity in their leisure time."
Gasp! No vigorous physical activity in leisure time. I was shocked.
So I called my friend Hortensia Supergranny, who spent a lifetime working in a factory and now, at 94, is retired and spends a lot of time baking cakes and pies for local fund-raising events. When she's not baking, she's knitting winter clothing for low-income children or helping neighbors who can't do chores themselves. Every afternoon at 4, she sits down for a cup of tea.
"Hortensia," I asked, "How many minutes of vigorous physical activity did you get yesterday? For instance, did you go to Senior Lacrosse or play Touch Football or anything? The University of California seems to think that's how you should spend your leisure time if you want to be healthy."
"Well, gosh," she answered. "I'd hate to be unhealthy. But after I fisished the Times crossword early yesterday morning, I baked 10 pies and 3 cakes and then motored over to Fritzie's house, cooked dinner for him and did a few loads of laundry. I don't know when I'd have time for the lacrosse."
"Well, you could cut out the cup of tea," I suggested. "The University of California thinks we need to use our leisure time wisely, with lots of vigorous physical activity."
"Vigorous physical activity in our leisure time?" Hortensia responded. "Have you looked up the term leisure lately?"
"Well, no," I had to admit. "I always thought it had something to do with vigorous physical activity. But I suppose with your experience with crosswords, you probably consult the dictionary more often than I do."
"I did have to look up a new word in 1976," she admitted. "Not since then. But sorry, I've got to go. The cakes are coming out of the oven and I'm in charge at the school fund-raiser in a few minutes. Gotta go."
She hung up, and I found a dictionary and looked up the work leisure. According to Webster, it means "freedom provided by the cessation of activities." I guess the University of California doesn't know that. Maybe they don't have time to consult dictionaries because they're spending so much time in vigorous physical activity. Or maybe they sold all their dictionaries at yard sales when the state had so many budget problems.
Maybe we should change the name of when we're not employed from leisure time to forced labor. Or we could have Leisure Police going around making sure rural elders were getting enough vigorous physical activity when they weren't working.
In the meantime, now that we know how important it is, everyone should urge Granny to get out on the football field every day instead of lounging around drinking tea!
Tuesday, June 14, 2011
The enzyme in question is called, not very creatively, insulin-degrading enzyme, or IDE. When you secrete insulin after eating carbohydrate (or protein), if there were no way to remove insulin from your system, you'd end up with more insulin than you needed after the blood glucose (BG) levels had returned to normal. So in healthy people, there's a delicate balance between the amount of insulin being put into the system and the amount that is removed.
IDE isn't the only way insulin levels can be lowered, but it's an important one. And because genetic manipulation is difficult in humans and has potentially damaging consequences, the researchers are developing drugs that inhibit IDE either totally or partially and are planning human trials of such drugs.
The researchers showed that mice who lacked IDE through genetic manipulation had higher insulin levels and were "more efficient" at controlling their BG levels.
But as these mice aged, they became insulin resistant, gained weight, and lost control of their BG levels. In other words, they developed classic type 2 diabetes.
The focus of news reports of the Mayo research is on the possibility of developing drugs that would inhibit IDE, a new approach to controlling type 2 diabetes. But I think the research is interesting for another reason: It suggests that anything that increases insulin levels in the short term may result in insulin resistance and type 2 diabetes in the long term.
Chronic high insulin levels in these mice made them become diabetic. You can also produce higher insulin levels by injecting insulin or by taking sulfonylurea drugs that cause your pancreas to secrete more insulin. Could long-term use of sulfonylureas or insulin cause a loss of effectiveness for the same reason?
Another thing that increases insulin levels is eating carbohydrate foods. And for the past 40 years or so, Americans have been bombarded by messages urging them to eat less fat and more carbohydrate. Many have. And diabetes rates are skyrocketing.
Someone with a healthy pancreas that is able to cope with huge carbohydrate overloads can tolerate them, at least in the short run. But as we age, everything tends to wear out. And that's when type 2 diabetes becomes even more prevalent.
The elderly mice were found to have fewer insulin receptors on their cells. With fewer receptors, they needed more insulin to do the same job. In other words, they had insulin resistance.
This downregulation of a receptor when the substance it binds is present in excess is not unusual. Nor is the opposite, upregulation of a receptor when the substance is present at low levels. The cells are constantly trying to maintain the status quo, avoiding being overwhelmed by a sudden influx of something or not getting enough of something that is rare.
A classic example of this is the adaptation to caffeine. Caffeine normally binds to receptors called adenosine receptors. When the adenosine receptors bind adenosine, you tend to get sleepy. Caffeine can also bind to the adenosine receptors and block the binding of adenosine. But the caffeine-receptor complex doesn't make you sleepy. So by keeping adenosine from binding, the coffee makes you feel more alert.
There's just one problem with this. When you ingest caffeine regularly, the body starts making even more adenosine receptors, hoping it can bind the usual amount of adenosine. This means that if you drink caffeinated beverages chronically, you'll need even more caffeine to block the sleep-inducing receptors. Then the body makes more receptors. So then you have to ingest even more caffeine to feel more alert. Eventually, you have to ingest caffeine just to stay awake. You're addicted.
A similar phenomenon could be occurring with insulin. When insulin levels are always high, the body may produce fewer insulin receptors, causing insulin resistance, meaning you need those high insulin levels in order to have normal responses. This theory was proposed in the past, but most evidence suggested that insulin resistance is caused by postreceptor effects, meaning effects that occur after insulin binds to the receptor.
But what if short-term hyperinsulinemia causes insulin resistance via postreceptor effects but very long term hyperinsulinemia causes insulin resistance via downregulation of the receptors? The mice who developed diabetes were 6 months old, but this is fairly elderly for a mouse. Mice generally live only 1 or 2 years, sometimes a little more, depending on the breed.
If so, then eating a high-carbohydrate diet for years and years might cause diabetes, especially if carbs were eaten pretty constantly throughout the day. People eating traditional high-starch diets and maintaining traditional lifestyles, with lots of exercise, don't all develop diabetes. But they don't usually snack all day, and their active lifestyles burn a lot of glucose, so their BG levels don't stay high for very long. And when BG levels aren't high, insulin secretion isn't stimulated.
Many Americans, on the other hand, seem to be constantly snacking. That means constant higher-than-fasting BG levels, even when those levels are not diabetic. Higher BG levels stimulate the secretion of insulin. And constant hyperinsulinemia could cause downregulation of the receptors.
When you're fasting, insulin is normally secreted in pulses, about every 15 minutes. Some researchers have found that pulsatile insulin secretion doesn't increase insulin resistance, but constant infusion of insulin does. Normally the body is in fasting condition overnight and before the next meal. But if one snacks constantly, the insulin levels might be constantly high, with less pulsatility.
A substance losing its effectiveness with time is not limited to insulin. High doses of niacin, much larger than those needed for its vitamin effects, are very effective in reducing lipid levels, especially free fatty acids. Niacin also increases levels of HDL.
A continuous infusion of niacin for more than 5 hours lowered free fatty acids. But when the infusion was increased to 24 hours, there was a "rebound" effect, in which the free fatty acids increased to the level of the controls. In this case, the rebound was not caused by downregulation, but by an increase in lipolysis, the hydrolysis of fats to produce free fatty acids. The researchers showed that this was caused by changes in gene expression.
But the result was the same. Constant high levels of a substance cause the body to try to reduce those levels. In this case, free fatty acids. In the case of insulin resistance, the increased glucose uptake that results from insulin action.
In the case of niacin, researchers found that during the niacin infusion, glucose metabolism was improved. But when they stopped the infusion and the free fatty acid levels rebounded to much higher than normal, insulin resistance resulted.
So many things can cause insulin resistance it's very difficult to tease out the most important causes. But every clue helps. Sometime someone will figure it all out. In the meantime, even if you're not ready to try a low-carbohydrate diet, limiting snacks and limiting the amount of carbohydrate you eat would be a good idea.
Monday, May 30, 2011
Most of the stories simply reprint the press release used by Science Daily and EurekAlert and other popular science-news alerting services. These tell you that the new form of LDL is glycated and it turns LDL into small, dense LDL, the kind that is more easily taken up by the arterial wall to form plaque.
Interestingly, metformin seems to block the formation of MGmin-LDL.
But what exactly is MGmin-LDL?
The MG stands for methylglyoxal, which is a highly reactive side product of glycolysis (the aerobic metabolism of glucose). MG reacts with proteins and is one way cells produce AGEs, or advanced glycation end products, which are glycated proteins that cause a lot of the side effects associated with diabetes.
MG is known to cause AGEs in a lot of proteins, including enzymes and DNA transcription factors, and has even been implicated as a cause of insulin resistance. MG has also been used as a marker of oxidative stress. We know that glycated proteins are not effective. Glycation of serum albumin (not necessarily by MG) seems to decrease insulin secretion. Glycation of LDL reduces its uptake by the LDL receptor. And so forth.
The higher your blood glucose (BG) levels, the more MG you make and the more glycation of protein occurs. One study showed that MG levels reflected the level of postprandial BG levels and suggested that high postprandial levels are as important as hemoglobin A1c levels when it comes to causing complications.
In fact, the idea that MG reacts with LDL is not new. It was shown in 1998, and possible even earlier, that MG reacts with LDL. However, each new research project adds new information, and the current one emphasized the atherogenicity of the MG-LDL complex.
The min in the MGmin-LDL stands for minimally modified, meaning that they didn't carry out the reactions to such an extent that the product was not physiological. They modified it so that it was present in concentrations they thought would actually occur in a human.
It's interesting that the popular, and generic, drug metformin reduces the level of MGmin-LDL. It may do this by blocking the formation of MG.
Because MG is formed as a byproduct of glycolysis, the more glucose that goes through the glycolytic pathway, the more MG you'll be apt to make. But glucose not only source of MG. Other compounds, including ketones, can also be broken down into MG.
Hence, just to be on the safe side, the best way to reduce the levels of MG might be simply to eat less food of all kinds. But we have to eat something, so eating less of the glucose-forming foods would most likely be the most effective in reducing the levels of MG. We know that high BG levels increase glycation of all kinds of proteins, as illustrated above, whether through MG or other mechanisms. Some of these proteins are needed to keep our bodies in top working order. Glycating them means they can't do their job.
It's hard to give up the carby foods we love. But to me, it doesn't make sense to risk getting complications just for the temporary pleasure of eating rice or toast and jam.
Tuesday, April 26, 2011
"People do lose weight, but not for the reasons put forth by those who champion such plans. The weight loss comes partly from eating fewer calories and partly because in this day and age, eliminating carbohydrates means eliminating calorie dense, highly processed foods (most of which contain high fructose corn syrup (HFCS)."
Huh? You mean eating fewer calories and eliminating highly processed foods full of HFCS is a bad thing? Maybe I don't understand this because I never went to medical school, but I thought when you wanted to lose weight, eating fewer calories was your goal, and everyone is saying today that we should eliminate highly processed foods.
Then this sage goes on to say, "I can't imagine why anyone would follow a diet -- any diet -- that takes entire food groups away from you. There's no reason to give up great foods like pasta, potatoes, beans and corn to lose weight or to be healthier. Giving up these foods is one of the main reasons that the Atkins diet is not a diet that can be sustained for the long term."
One could also say, "There's no reason to give up great foods like whole-fat milk and yogurt, steaks, and heavy cream to lose weight or to be healthier. Giving up these foods is one of the main reasons that low-saturated-fat diets cannot be sustained for the long term."
Because people like this author think that low-carb diets consist of nothing but rib roasts and cream cheese with no vegetables, they're prejudiced about them, label them "fad diets," and then use ridiculous logic to support their preconceptions.
Another stupid argument warns people with diabetes not to go on low-carb diets because their blood sugar might go down, as if that were a terrible thing. Of course people should be warned to keep track of their blood sugar and if it goes down too much to consult their doctors about reducing their medications. But for someone with a disease that causes high blood sugar to avoid a diet because it would make blood sugar go down is ridiculous.
One can only hope that physicians like this use better logic with the non-nutritional aspects of their practices. Would they say, "I don't want you to use chemotherapy because it might make your cancer cells shrink too much"? Or would they tell people who were gluten-intolerant, "There's no reason to give up great foods like bread and cereal to be healthier. Giving up these foods is one of the main reasons that gluten-free diets are not diets that can be sustained for the long term."
No one really wants to give up "great foods" like potatoes, bread, corn, and peas. But sometimes when you have a chronic disease like diabetes, you have to make difficult choices. Would you rather eat "great foods" or would you rather have your eyesight?
Friday, April 15, 2011
The popular news stories about caffeine and BGs can be confusing. Some say that caffeine is bad for BG control. Others say it's good. For example, heavy coffee drinkers are at lower risk of developing diabetes than light users or coffee abstainers.
What's going on here?
James D. Lane's recent review in a new science journal, the Journal of Caffeine Research, attempted to bring some order to these conflicting views by doing a meta-analysis of the various studies of caffeine and insulin resistance and BG control.
There does seem to be good evidence that high caffeine doses cause an increase in insulin resistance (IR) in healthy, nondiabetic adults. In a healthy, nondiabetic person, however, an increase in insulin resistance wouldn't necessarily mean higher BG levels. They'd just secrete more insulin to cover the increased IR.
When you have diabetes, however, and you can't just secrete more insulin, then an increase in IR usually results in an increase in BG levels. And, indeed, research has shown higher BG levels in people with type 2 diabetes after drinking coffee.
According to Lane, more than 17 studies in nondiabetic adults from 1968 through 2010 have demonstrated transient increases in IR with moderate caffeine doses (equivalent to 2 or 3 cups of brewed coffee) in both habitual caffeine consumers and abstainers. Different studies used different methods, but the results were consistent. Thirteen of 14 studies measuring the glucose response after a carbohydrate challenge found an increase in insulin resistance with caffeine. (Those who want more details can consult the references in the Lane paper, which is free full text online.)
Many studies used pure caffeine in amounts designed to replicate the amounts in coffee, and some of the caffeine doses were infused intravenously, hardly a physiological situation, although I've sometimes thought mainlining my coffee would get me going faster in the morning.
So Terry Graham and colleagues at the University of Guelph, Ontario, studied the effects of drinking coffee, to try to mimic the real-world effect of caffeine. They also studied the effect of fat. As reported here, they found that both fat and caffeine independently increased insulin resistance and glucose levels in the 10 young healthy men in the study. The caffeinated coffee had the greatest effect alone. Both together had an even greater effect than either one alone.
Both caffeinated and decaffeinated coffee increased levels of glucagon-like peptide-1 (GLP-1).
Graham explained that coffee alone won't raise BG levels. It only increases BG levels when you eat carbs. And even drinking the coffee at the same time you eat the carbs won't have much effect. But when you drink coffee, wait a bit, and then eat carbs, your BGs will go higher. The researchers had previously shown that this effect persists through a second meal and occurs with low-glycemic-index as well as high-glycemic-index carbohydrates.
Lane concluded from the meta-analysis that "Caffeine in coffee, tea, or soft drinks causes transient insulin resistance that can produce exaggerated glucose and insulin responses when carbohydrate is consumed" [italics mine].
This qualifier made me wonder what the effect would be in people on low-carb diets. The Graham group used 75 grams of carbohydrate in their test meals. Many people on low-carb diets eat only 30 to 50 carbohydrate grams a day. Would the caffeine be important in them?
To test this question in myself I adopted the following procedure.
1. Drink my usual 2 cups of strong espresso (or decaf another day) on arising.
2. Measure BG every hour until 2 hours after lunch.
3. Wait an hour after the coffee. Then eat 26 home roasted almonds.
4. Eat a poached egg with butter an hour after the almonds (so I'd have some protein to keep me until lunch) and take oral meds, including extended-release metformin.
5. Have lunch. I had 3 oz beef, 6 spears of asparagus with 1 tsp olive oil and a few slivers of red pepper, cracker-sized wedge of LC wrap with butter, half cup of plain kefir with a few nuts.
An hour after eating lunch and measuring, I took my standard walk, about 1.4 miles.
Here are the results:
2_____104____86___ egg and ER metformin
*I was absorbed in something else and forgot to test here.
At hour 2 (1 hour after eating nuts), I thought maybe the coffee was having an effect, but at hour 3 the readings were almost identical. Graham said that research has shown that caffeine doesn't affect gastric emptying, so this could be random variation.
Because my BG was higher before lunch on the decaf day than it was on the caffeine day, although the 1-hour postlunch BGs were similar, the rise was almost twice as much on the caffeine day.
Finally, perhaps the real peak might have occurred at 1.5 hours after eating the almonds and might have been higher with the caffeine (I'd planned to measure every 30 minutes, but then I got lazy).
But if so, it came down fast enough, so I concluded that for me and my diet, the effect of the caffeine was not large enough to persuade me to give up the pleasure I get from drinking black coffee.
Because we're all slightly different physiologically, with different sensitivities to chemicals and different diets, anyone who is concerned about the effects of caffeine should try a similar test themselves. If you want, you could let us know what you found.
The effect in someone on a low-fat high-carb diet might be quite different. And the effect on most Americans, who eat a lot of carbohydrate and fat as well as a lot of caffeine, especially in today's world where coffee houses are so popular, might be more significant.
The mechanism of the increased IR from caffeine is not known. There are two major hypotheses. The first is that it's because of interference with adenosine receptors on cells. Adenosine is involved in insulin-mediated glucose transport as well as playing a role in sleepiness.
One reason coffee keeps us awake is that blocking the adenosine receptors means adenosine can't bind to the receptors and make us sleepy. Blocking the receptors also seems to reduce inflammation and affect IR. Some research has shown that blocking the receptors decreases IR. Other research shows the opposite. And a study cited by Lane suggested that adenosine receptors had no effect.
The picture is further complicated by the fact that there are different subtypes of adenosine receptors on different cells, and the caffeine may have different effects in different tissues.
The other hypothesis is that caffeine increases the release of stress hormones like cortisol and epinephrine (adrenaline), counterregulatory hormones known to increase BG levels. There is some evidence for this effect, but more research needs to be done.
Finally, there's the paradoxical evidence that heavy coffee users are at much lower risk of getting type 2 diabetes. Those who drink 7 cups a day have half the risk of those who drink 2 or less.
Perhaps there's something in coffee other than caffeine that is causing this protection. In some studies, decaffeinated coffee reduced risk as much as caffeinated.
Common sense suggests that people who drink a lot of coffee probably drink fewer sodas.
But now a study at the University of California at Los Angeles, reported in January, suggests that a hormone-binding protein called SHBG (sex-hormone binding globulin) may be involved. The levels of SHBG in postmenopausal women were increased by caffeine; decaffeinated coffee and tea had no effect.
So far, this is just a hypothesis, but it's one more clue in this complex picture. When it comes to diet and type 2 diabetes control, nothing seems to be simple.
Thursday, March 17, 2011
But most drugs also have minor effects. Sometimes your doctor is aware of these but doesn't tell you because the incidence of these effects is low and the doctor doesn't want to worry you. This is often true of the muscle weakness and memory problems that statins can cause.
Sometimes even your doctor isn't aware of the minor side effects.
Sometimes no one has yet discovered some side effects. This can be because you have to be on a drug for a certain amount of time before these side effects show up. It can be because no one has noticed the link between a particular drug and some side effect.
Or it can be because drugs can interact with other drugs, and when you're taking a lot of different drugs -- say a diabetes drug, a blood pressure drug, a lipid-lowering drug, an anti-reflux drug, an antidepressant, a beta blocker, an antihistamine, an osteoporosis drug, and an asthma drug -- and you complain of fatigue, it's not immediately clear which one of these drugs or which combination is causing that problem.
One relatively unknown drug-hormone interaction was first reported in 2006.
It seems that metformin suppresses thyroid-stimulating hormone (TSH; also called thyrotropin), the hormone that is generally tested to ascertain your thyroid function.
When your thyroid hormones (called T4 and T3) are too low, your pituitary gland secretes TSH. The TSH then tells the thyroid gland to secrete more T4 and T3.
Thus a high TSH level suggests low thyroid, and a low TSH level suggests high thyroid.
Your doctor often tests the T4 and T3 levels too, but often not. If the TSH is in the normal range, your doctor may assume your thyroid levels are fine and refuse to do more testing.
The normal ranges are controversial. The usual range is said to be about 0.4 to 5 microunits per milliliter. But some people say the cutoff on the high end should be lower, about 2.5. And graphs in endocrinology books show that the average TSH level in people considered to have healthy thyroid control is only 1.1, with very few in the upper ranges.
The new research shows that metformin therapy suppresses TSH levels. Two studies showed that it did this without affecting T4 and T3 levels. A third found that free T4 levels increased as TSH went down.
Most of the T4 and T3 in your blood is bound to proteins. The free (unbound) levels of the hormones are the active hormones, and that's what the free T4 (fT4) and free T3 (fT3) measure.
No one yet understands the mechanism of the TSH reduction by metformin. It's especially puzzling because it doesn't seem to be linked with the thyroid hormone level. And the metformin has no effect on TSH in people who have no thyroid problems.
But what it does mean for you is that if you're on metformin you should be aware of this link. Let's say you're on thyroid medication and then you start taking metformin. Your TSH goes down, and your doctor may worry that your thyroid is now too high and might reduce your dose.
But what if it's just a result of the metformin? Then you'd end up with a thyroid level that was too low.
So if you're on metformin and your TSH test doesn't seem to agree with how you're feeling, discuss this interaction with your doctor and have your T4 and T3 levels tested as well as the TSH. It could be that the lower TSH is caused by the metformin and notw higher thyroid levels.
Does this mean that metformin could interact with other lab tests? It's possible. The metformin-TSH interaction was only noticed in 2006, more than 10 years after the drug first became available.
Does this mean that other drugs could interact with the TSH test? It's possible.
We need to be vigilant about all the drugs we take, and if something seems wrong, we need to try to figure it out. Sometimes the published science reports can't tell us.
Trust your body. You know it better than anyone else. And don't let some doctor tell you that your symptoms are all in your head because there's no evidence for what you're saying. Maybe you're right and the current literature is wrong.
Saturday, February 26, 2011
That often seems to happen. I'm doing a test that requires measuring blood glucose (BG) at a specific time, and just as I'm about to do so, the phone rings, and it's an important call I can't ignore. Or I want to compare BG control on two consecutive days, do a whole slew of tests on day 1 and then on day 2 come down with the flu, which makes any BG measurements useless.
I've always had A1c levels that seem to be higher than what I'd expect on the basis of my BG readings. Because of this, I even spent more than $500 on continuous glucose monitor sensors (a kind friend gave me the meter) to make sure I wasn't going high at some unexpected time when I wasn't measuring.
I wasn't. The results were what I'd expect. Fastings were 70 to 90, and going over 130 was rare. But my A1c was always around 6, which calculates to an average BG of 130, which means I'd be going way over 130 a lot of the time to balance the lower fastings.
I tested my two different meters (Ultra and Freestyle), and they agreed quite well with each other and with my hospital lab.
I know there's some individual variation in red blood cell (RBC) lifetimes, and an increased lifetime could raise A1c, because the longer a RBC has been in your body, the more likely it is to be glycated.
So when I read, as reported here, that low iron can make your A1c higher than it should be, I decided to try taking iron-containing multivitamins a couple of weeks before my next A1c. I usually use iron-free vitamins, because iron can contribute to cardiac problems, and people with diabetes are at increased risk of that.
The theory is that if you're iron-deficient, you won't produce reticulocytes, or new RBCs, as fast as you should, so your body will let the older, more-glycated RBCs live longer. If you take iron, you'll produce more new, glycation-free RBCs, so your A1c will be lower.
I did the test, and the results seemed to confirm the theory. My A1c dropped to 5.3, which is about what I'd expect.
But then I read the fine print. Apparently the A1c machine at the local hospital had broken, so they sent all the samples to the Mayo Clinic. So was the lower A1c because of the iron? Or was it because Mayo was using a different type of test that gave different results. I didn't know.
So I did the test again. Two weeks before I gave blood, I switched to the iron-containing vitamins. This time the A1c, done at my local hospital, was 5.4.
I called the hospital lab to make sure they were still using the high-performance liquid chromatography method they'd used before. This is supposed to be the best method because it's the one used in the famous DCCT trials.
They weren't. They'd changed methods to an immunoassay. So was the result this time because of the iron? Or was it because of a different method?
I don't know. I'll have to do it all over again. I don't get labwork every three months, more like six, because it's a pain and the results are usually pretty much the same. So maybe by the time I get this resolved I'll be living in a nursing home. Who knows.
It's just one of the many frustrations of having diabetes.
On the other hand, being able to test things is one of the fun things about having diabetes. With so many other diseases, we have to let the medical people do all kinds of arcane tests and procedures. I don't know of a home MRI machine, or a home "put in your own coronary stent" kit, for example.
If I ever resolve this issue, I'll post here about it.
Wednesday, February 16, 2011
The article cites the economist John Maynard Keynes, who said, "“The difficulty lies, not in the new ideas, but in escaping from the old ones, which ramify . . . into every corner of our mind.”
And this is just what is true today. Many nutritionists just can't escape the idea that dietary fat is the cause of all our problems.
Wednesday, February 2, 2011
At the extremes, it's pretty easy to decide if someone has diabetes or not. For example, when I was diagnosed, I was having symptoms (constant thirst and urinating a lot), my random blood glucose (BG) level was over 300 mg/dL (to convert to mmol/L divide by 18) hours after my last meal, and my next-day fasting was 269. The glucose level in my urine was so high that the hospital recalibrated its machine to make sure the result was correct.
Clearly, I was diabetic.
At the other extreme, someone with a fasting BG level of 65 who goes up to 80 after drinking a huge glucose drink and has a hemoglobin A1c level of 4.2 obviously doesn't have diabetes.
In between the extremes, there are a lot of patterns that could or could not be considered to be diabetes.
The official guidelines for diagnosing diabetes are that you should be considered diabetic if
Your fasting BG level is 126 or greater on at least two occasions (less than 100 is considered normal) or
Your BG level is 200 or greater 2 hours after starting an oral glucose tolerance test (OGTT) with 75 grams of glucose (less than 140 is considered normal) or
A random BG level is greater than 200 and you're having symptoms.
Recently, some official diabetes groups are suggesting using the hemoglobin A1c test for diagnosis, with any result of 6.5 or greater confirmed by a second test considered diagnostic.
Some years ago, the diagnostic fasting levels were even higher, as some diabetes experts felt that a diagnosis of diabetes would cause harm because of the stigma against "diabetics" and because insurance companies would refuse to insure them. More recently, people have realized that diabetic complications occur even at BG levels below these diagnostic values, and the earlier people are diagnosed, the greater their chance of preventing complications.
However, regardless of where the cutoff points are set, none of these criteria are perfect. Anyone with diabetes knows that fasting BG levels can vary from day to day, and even testing fasting levels on two different days doesn't ensure that they represent a true value.
The same may be true of the OGTT. We all know that we can eat exactly the same thing on two different days at exactly the same time and get exactly the same amount of exercise, yet one day our postprandial BG levels will be higher than the other. Furthermore, because this test is time consuming, very few physicians use it for diagnosis.
And the A1c test is affected by a lot of things, including red blood cell lifetime, which can be genetic and is also affected by various hemolytic anemias, spleen damage, or major blood loss; and abnormal hemoglobin types. Furthermore, although most labs now claim to have standardized their A1c tests, in practice there's still variation from one lab to the other.
Hence one person might have normal BG levels all day long but have an abnormal A1c result, and another person might have elevated BG levels yet have a low A1c. I know someone who had fasting BG levels above 130 but an A1c in the 4s so her doctor refused to diagnose her until things got much worse.
To further complicate things, there are various different patterns of BG abnormalities. Some people may have normal fasting BG levels but go high after meals (this was formerly called impaired glucose tolerance). Others may have high fasting levels but not go very high after meals (this was formerly called impaired fasting glucose).
Some years ago official diabetes groups decided to merge both groups into a new category called prediabetes even though some people think their risks and outcomes differ.
These aren't the only patterns one can get. Some people may have a little impaired glucose tolerance and a little impaired fasting glucose.
Some may have normal fasting BG levels, go very high after meals, but come down again quickly, so they wouldn't satisfy the official requirement for high BG levels at 2 hours after an OGTT. This and this show the variation in BG levels after a high-carb breakfast in people considered nondiabetic.
But no one knows if such wide variations in BG levels might cause complications. Some people think wide variation is worse than sustained high BG levels. Yet the people shown in the cited graphs are considered nondiabetic. Their A1c levels are in normal ranges.
Other people may have temporary increases in BG levels because of some stress, such as surgery or emotional stress, and then revert to normal BG levels.
Diet can also affect your BG levels. Someone following a low-carb diet for weight loss might have normal fasting and postprandial BG levels and normal A1c levels as long as he or she followed the LC diet. An OGTT would show the underlying diabetic defect, but most doctors don't use that test these days, especially in someone with normal fasting BG levels. And these people would be grouped with the nondiabetics if they were included in any clinical trials.
Just fasting can affect your BG levels. Fasting is the ultimate low-carb diet, and after a long fast you'll test diabetic even if you're not on a standard carbohydrate-containing diet because when you don't need them, your body stops producing carbohydrate-processing enzymes. This is called starvation diabetes.
If you've been on a very low carb diet and you're given an OGTT, you'll probably test diabetic even if you're not, for the same reason.
Some people may have abnormal BG levels because of very high insulin resistance, which can sometimes be reversed with weight loss and exercise. They also have defective beta cells that aren't able to cope with the excess demand. But if they can reduce the insulin resistance, their beta cells can cope. Many overweight couch potatoes don't have diabetes because their beta cell mass simply expands to cover the increased need.
The same situation occurs during pregnancy. In most people, the beta cell mass expands during pregnancy to cover the increased need in late pregnancy. Some people have beta cells that are unable to do this, so they are diagnosed with gestational diabetes. After the baby is born and the demand is lowered, their BG levels revert to normal.
Others may have abnormal BG levels with a lot less insulin resistance and but even wimpier beta cells. And of course there can be all kinds of combinations of these two factors.
If diagnosing diabetes is difficult, diagnosing prediabetes is even more difficult because someone with full-blown diabetes like I had when I was diagnosed is unlikely to revert to normal no matter what they do. At that point we've lost so many beta cells that unless we figure out how to get them to regenerate, we're always going to have to be careful about our diet.
But in the prediabetes range, the probability of reverting to normal BG control is greater, especially if you're very overweight and hence are still producing a lot of insulin when you're diagnosed. Thus a diagnosis may be more vague. One month you'd qualify as prediabetic and then you'd lose some weight and you wouldn't. Then you'd regain the weight and you would.
Because of all this diagnostic vagueness, arbitrary cutoff points, and changing standards, any studies that purport to show that "diabetics" are at increased risk or decreased risk or should be taking X drug or avoiding Y practice are somewhat questionable. The older the study, the less relevant it's likely to be. In the old days they didn't even differentiate between type 1 (autoimmune; insulin requiring) and type 2.
I personally don't put a lot of trust into studies that rely on complex statistics to show some effect. You can study 10,000 patients with type 2 and show that there's a slightly better, statistically significant benefit from some treatment (usually a drug). If you're a physician interested in prescribing that drug, that suggests that the odds of success are greater if you prescribe it. (Not taking into account the biases caused by the fact that most drug studies are sponsored by drug companies that know how to manipulate data.)
But it says nothing about whether the drug will help or harm any individual patient. And as patients, that's what we want to know.
Does that mean we should simply ignore all these massive trials? I don't think so. They do tell us something; they suggest that some treatment could help or harm.
But if your doctor tells you that all "diabetics" should be taking some drug or avoiding some drug or following some other regimen and you don't think it sounds "right for you" as the TV ads are so enamored of saying, then research it carefully.
Find out if the patients in the study sound similar to you. If they were mostly elderly white men on low-fat diets and you're a young Asian woman on a low-carb diet, you might respond differently than those patients.
Diabetes comes in many flavors. Diagnosis can be arbitrary. Statements like "All diabetics should be on aspirin" are unlikely to be true, even if supported by references to some big clinical trial.
Sunday, January 23, 2011
On one hand is the medical profession, which in general thinks statins are good things and that LDL cholesterol levels above normal ranges should be treated with statins. Recently, some have been recommending statins even for people with normal cholesterol levels but elevated levels of C-reactive protein (CRP), an indication of inflammation.
In some populations, lowering cholesterol with statins has been shown to result in lower rates of cardiovascular "events" and deaths. But some people think this isn't because of lower cholesterol levels. They suggest that the statins have some other effect as well and the lower cholesterol levels are simply a "side effect" of the drug.
At the other extreme are people who think statins are poisons. Some think no one should take a statin. Others agree they're warranted in specific populations, for example middle-aged men with previous heart attacks, but they say there's no evidence that statins help women or elderly men.
A recent Cochrane Systematic Review concluded that risks of statins are greater than benefits for those at low risk of heart disease. However, when you have diabetes, you're not considered to be at low risk.
An earlier study concluded that statins don't benefit women who have not had a heart attack and in fact may increase cardiovascular risk in this population. They say CRP levels are better predictors of heart attacks in women.
Most people agree that statins do have side effects, most commonly muscle weakness or pain, which can cause permanent damage if it's serious (rhabdomyolysis). In mild cases, taking coenzyme Q10 can sometimes help with the muscle weakness. Tendons can also be weakened by statin treatment (and treatment with other drugs like niacin that reduce cholesterol).
Beatrice Golomb of the University of California at San Diego has been studying side effects of statins and has published a comprehensive review on the topic. She says the two most common side effects are muscle weakness or pain and memory impairment.
She agrees that statin benefits outweigh risks in middle-aged men with high cholesterol and existing heart disease who tolerate the drugs, and that statins probably benefit middle-aged men with high cholesterol and "significant other risk factors for heart disease."
But she says that although those without significant risk factors for heart disease do have fewer cardiovascular deaths, there is not even a trend for lower overall death rates. In other words, fewer heart attacks and strokes but more deaths from other diseases.
Golomb says that statin benefits are not clear in middle-aged men who have heart disease or significant risks but who get side effects from statins. There is some evidence that the benefits of statins don't occur in people who get side effects.
Golomb says there is currently no evidence that statins benefit women or men over 70. They do reduce heart attacks, she says, but not overall mortality.
One problem when reading about all these studies is that different studies use different patient populations and different end points, but the news media tend to report the results without emphasizing that point.
So a drug-company-sponsored trial might be headlined as "Drug X Reduces Heart Attacks by 40%" when in fact the study showed that the drug reduced heart attacks in middle-aged men who had already had several heart attacks, had high blood pressure and high blood sugar, and smoked, and the deaths from some other disease increased with the drug. But what the public, and some physicians, will remember is "Drug X prevents heart disease."
And the confusing thing for those of us with diabetes is knowing whether or not simply having diabetes constitutes a "significant other risk factor."
Most people consider simply having diabetes to give you the same risk of cardiovascular events as people who have already had a heart attack. Is that true?
A recent Spanish research group says no, at least in the Spanish patient population they studied: 4410 patients aged 30 to 74 years, 2260 with type 2 diabetes and 2150 who had already had an acute myocardial infarction but no diabetes.
They found that the 10-year hazard ratios for the type 2 patients were significantly lower than those of the MI patients.
That's encouraging. So should we stop worrying about heart disease?
For one thing, other studies have had conflicting results. Some show that people with diabetes have heart disease death risks similar to those of nondiabetics who have had heart attacks; others show the opposite. Another study showed that prior heart attacks resulted in higher risks than diabetes among men 45 to 54 years old, but in older men, the risk was reversed.
As noted by the Spanish researchers, "Part of the discrepancy may stem from differences in the duration of diabetes, type of treatment, and baseline glucose control of diabetic patients included in the studies."
The cited studies also noted differences according to the age and sex of the patients. Furthermore, the results may depend on how you define diabetes.
Someone with type 2 diabetes who was diagnosed 5 years ago, controls blood glucose levels well, eats healthy foods, gets a lot of exercise, doesn't smoke, and makes sure to keep blood pressure and lipid levels in good ranges would be different from someone who is unfortunately probably more typical: a patient who just takes a pill or two, doesn't measure blood glucose levels, continues to smoke and spend most of the evening watching TV, eats mostly fast food or convenience foods, and has high blood pressure.
And the recent Spanish study was comparing diabetic patients with patients who had already had an acute MI, not with healthy people.
When we have type 2 diabetes, we're still at increased risk of heart disease, and we should do whatever we can to reduce that risk: Keep blood glucose levels down, monitor lipid levels and treat if necessary, monitor blood pressure and treat that if necessary, get regular exercise, and eat a healthy diet, although definitions of "healthy diet" of course depend on who you're talking to.
But all these studies illustrate the need to be vigilant when reading a popular press article stating that some study has shown something or other. First, see if you can read the journal article that the popular press story refers to. Even if you can't see the full text, you can usually see the abstract for free.
Find out what populations were studied, how various parameters were measured, and how the researchers define diabetes.
This takes a lot of time, and a firm grasp of statistics helps. So it can be frustrating when you're trying to earn a living or spend time on other projects and don't have time to pour through confusing research reports all day.
Sometimes the authors of drug-company-sponsored studies have used statistics to spin the results to make their drugs look more favorable. You sometimes need to comb through the methods and the statistics to see how the results have been biased. This takes a lot of time.
When you can't track all this down, don't ignore the health news, but take the health news you hear on TV or read in your local paper with a grain of salt. If your LDL cholesterol level is high, you might want to try a statin. Some people can take them without getting side effects. But be vigilant. If you get muscle weakness, try some coenzyme Q10, which Golomb says helps about 70% who have that problem. Some people recommend taking the coenzyme Q10 even if you don't have muscle problems.
But if the muscle pain or weakness persists, talk with y0ur doctor about other alternatives, like niacin. Muscle pain that progresses to rhabdomyolysis is serious.