No this isn't about "stupid fats." It's a stupid study, in my opinion.
I try to give research scientists the benefit of the doubt, because I've done lab research myself, and I know how difficult it can be to get reliable results. It's even more complex today than it was when I was in graduate school.
Nevertheless, I think this study, reported in Science Daily, really takes the cake. The SD title is "High-Fat Meals a No-No for Asthma Patients, Researchers Find."
So what did the researchers do?
They fed two different meals to 40 people with asthma and measured any resulting inflammation. Diet 1 was 1000 calories, 52% fat, and consisted of fast-food burgers and hash brown potatoes. Diet 2 was 200 calories, 13% fat, and consisted of reduced-fat yogurt.
They found that people eating diet 1 had more inflammation. So they concluded that the inflammation was caused by fat!
How can you possibly assign blame when the diets differed in so many ways?
An equally valid headline might have been "High-calorie meals a no-no for asthma patients" or "Hash-brown potatoes a no-no for asthma patients" or "Dairy products good for asthma patients" or "Eating lots of fat in combination with lots of carbohyrate a no-no for asthma patients" or "Hamburger buns a no-no for asthma patients."
Instead, they focused on the one ingredient they probably started out believing would be bad and ignored the rest.
This study was presented at the American Thoracic Society 2o10 conference in New Orleans.
One of the researchers said, "This is the first study to show that a high fat meal increases airway inflammation." No it didn't. It showed that a high-fat, high-calorie, high-carbohydrate, commercial junk-food meal increased airway inflammation.
Unfortunately, headlines are all that many people read and remember. Keep in mind that headlines can be misleading. Before accepting the conclusions in any study you think might be important for you, read as much of the full text as you are able to and then make up your own mind.
We can't depend on other people to inform us correctly. We have to take control ourselves.
Monday, May 17, 2010
Friday, May 7, 2010
ACCORD again
A couple of years ago, it was reported that intensive treatment of type 2 diabetes, aiming for a hemoglobin A1c level below 6, increased cardiovascular events compared with patients aiming for an A1c between 7 and 7.9. The study was called ACCORD, and the glucose arm of the study was stopped early because of the excess deaths in the intensive-treatment group.
On the basis of this one study, a lot of doctors told their diabetes patients who had A1c values in the normal ranges that they were too low and they should attempt to get them higher!
They seemed to apply this advice to everyone with type 2, even though the patients in the ACCORD study were older (between 40 and 79 years), had had diabetes for a median of 10 years, and already had signs of heart disease or had several risk factors for heart disease.
I've previously discussed the ACCORD trial here, here, and here.
A conservative interpretation of the study was that aiming for a normal A1c might be harmful in older people with longstanding type 2 and pre-existing signs of or risk factors for cardiovascular disese but it would be OK for younger people who had recently been diagnosed. The idea was that if damage from high blood glucose levels has already been done, it may be too late to help by getting those levels down.
Another interpretation was that these people had been put on traditional high-carbohydrate American Diabetes Association diets, so they needed a lot of drugs to get their A1cs in normal ranges, and it was the combination of so many drugs that caused the increased cardiac events.
Another interpretation was that they'd brought the A1cs down too quickly, and that was what caused the harm.
And another was that the intensive-control group had more serious incidents of hypoglycemia.
Now comes a new interpretation of this study that says that those who were actually able to reach the normal A1c goals had lower rates of cardiovascular events. It was the patients who were unable to reach the goals despite the intensive treatment who had increased rates of cardiovascular events.
Mortality was greater in the intensive-treatment group only when the A1c was above 7.
The new interpretation was published in the May 2010 issue of Diabetes Care.
None of the mainstream analyses of the ACCORD study have suggested that instead of intensive treatment with drugs, patients might benefit by using lower-carb diets to get their A1c levels down. We know that works. Why can't the cardiologists understand it?
I think one thing the back-and-forth recommendations resulting from the ACCORD trial tell us is that we shouldn't forget to use common sense. If we're discussing treatment of a mentally compromised relative who is 99 and unable to understand why he shouldn't eat huge dishes of ice cream and chocolate sauce, perhaps trying to enforce a low-carb diet so the poor man would have no enjoyment in life wouldn't make sense.
One vision that haunts me is the description of an old diabetic woman in a nursing home. Everyone else got ice cream for dessert, and the nurses said, "You can't have ice cream because you are diabetic." The old woman cried all during dessert because she wanted the ice cream so much. That's cruel. Especially because they were probably stuffing her with starches like bread and potatoes.
But if we're still pretty healthy and able to manage our diabetes diet ourselves, and if we understand how harmful high blood glucose levels can be, we should make an effort to get the best A1c levels we can manage, even if some study shows that this might be harmful to some people.
We shouldn't reverse our treatment plan on the basis of one study, which is what the doctors who told all their type 2 patients to get their A1cs higher did. One study doesn't prove much. The study might have been poorly designed. The population studied might not be representative of the population as a whole, or it might not match your own situation (a study of 80-year-old male veterans might not apply to a 40-year old woman). The statistics used might have been faulty. The treatment in the study might have been different from what you are using.
There are many reasons that one study might be misleading. It's only consistent results that are significant. We shouldn't totally ignore any study. But we need to take them with a grain of salt.
On the basis of this one study, a lot of doctors told their diabetes patients who had A1c values in the normal ranges that they were too low and they should attempt to get them higher!
They seemed to apply this advice to everyone with type 2, even though the patients in the ACCORD study were older (between 40 and 79 years), had had diabetes for a median of 10 years, and already had signs of heart disease or had several risk factors for heart disease.
I've previously discussed the ACCORD trial here, here, and here.
A conservative interpretation of the study was that aiming for a normal A1c might be harmful in older people with longstanding type 2 and pre-existing signs of or risk factors for cardiovascular disese but it would be OK for younger people who had recently been diagnosed. The idea was that if damage from high blood glucose levels has already been done, it may be too late to help by getting those levels down.
Another interpretation was that these people had been put on traditional high-carbohydrate American Diabetes Association diets, so they needed a lot of drugs to get their A1cs in normal ranges, and it was the combination of so many drugs that caused the increased cardiac events.
Another interpretation was that they'd brought the A1cs down too quickly, and that was what caused the harm.
And another was that the intensive-control group had more serious incidents of hypoglycemia.
Now comes a new interpretation of this study that says that those who were actually able to reach the normal A1c goals had lower rates of cardiovascular events. It was the patients who were unable to reach the goals despite the intensive treatment who had increased rates of cardiovascular events.
Mortality was greater in the intensive-treatment group only when the A1c was above 7.
The new interpretation was published in the May 2010 issue of Diabetes Care.
None of the mainstream analyses of the ACCORD study have suggested that instead of intensive treatment with drugs, patients might benefit by using lower-carb diets to get their A1c levels down. We know that works. Why can't the cardiologists understand it?
I think one thing the back-and-forth recommendations resulting from the ACCORD trial tell us is that we shouldn't forget to use common sense. If we're discussing treatment of a mentally compromised relative who is 99 and unable to understand why he shouldn't eat huge dishes of ice cream and chocolate sauce, perhaps trying to enforce a low-carb diet so the poor man would have no enjoyment in life wouldn't make sense.
One vision that haunts me is the description of an old diabetic woman in a nursing home. Everyone else got ice cream for dessert, and the nurses said, "You can't have ice cream because you are diabetic." The old woman cried all during dessert because she wanted the ice cream so much. That's cruel. Especially because they were probably stuffing her with starches like bread and potatoes.
But if we're still pretty healthy and able to manage our diabetes diet ourselves, and if we understand how harmful high blood glucose levels can be, we should make an effort to get the best A1c levels we can manage, even if some study shows that this might be harmful to some people.
We shouldn't reverse our treatment plan on the basis of one study, which is what the doctors who told all their type 2 patients to get their A1cs higher did. One study doesn't prove much. The study might have been poorly designed. The population studied might not be representative of the population as a whole, or it might not match your own situation (a study of 80-year-old male veterans might not apply to a 40-year old woman). The statistics used might have been faulty. The treatment in the study might have been different from what you are using.
There are many reasons that one study might be misleading. It's only consistent results that are significant. We shouldn't totally ignore any study. But we need to take them with a grain of salt.
Sunday, May 2, 2010
Saturated Fat and the Popular Press
The May issue of the mainstream magazine Scientific American had an article saying that dietary carbohydrates are more important than fats in terms of heart disease risk.
Wow!
Many people thought the news would never reach the mainstream press. But it finally has. The article cites the recent meta-analysis by Krauss and colleagues that suggested that the amount of saturated fat in the diet is not related to heart disease.
I would note several caveats. First, although some of the studies in the meta-analysis used food diaries to assess intake, others used the ubiquitous "food frequency questionnaires," which may not be accurate, as discussed here.
Second, Krauss et al. suggested that the effect of saturated fat may depend on what people substitute for the saturated fat. (This assumes that no one would want to decrease calories by simply eating less saturated fat, which is what makes the most sense to me.) Eating more unsaturated fat may decrease heart disease rates, whereas eating more carbohydrates may increase heart disease rates. Not everyone agrees with this, however.
Finally, the Scientific American article says it's mostly highly processed carbohydrates that are the villains, and the author writes, "some high-fiber carbohydrates are unquestionably good for the body." Many people do, in fact, question that statement, especially in relation to people with diabetes.
The author of the Scientific American article is not urging people to pig out on saturated fats. She says that current studies "do not suggest that saturated fats are not so bad; they indicate that carbohydrates could be worse."
It takes a long time for generally accepted ideas to be thrown out. Further studies may convince people that the "healthy whole grains" that people (including those with diabetes) are currently being urged to make the focus of their diets are just as bad as white bread, pasta, and sodas.
But for now, every little nail hammered into the brittle saturated fat hypothesis of heart disease helps. Saying that high-glycemic-index carbohydrates may increase heart disease risk is a step toward accepting the idea that all carbohydrates may do the same, especially in people with a genetic propensity to insulin resistance.
Publicizing the evidence in a mainstream popular magazine will help to spread the news, because the popular press operates with a herd mentality. If one mainstream news outlet carries a story, everyone else has to report on it too.
In fact, just today I got in the mail a copy of the Harvard Medical School Focus, which included a brief comment titled "For Heart Health: More Polyunsaturated Fat, Fewer Refined Carbohydrates." This discusses both the Krauss paper cited above and another paper that supports the idea that substituting polyunsaturated fat for saturated fat instead of carbohydrate will reduce heart disease risks.
Perhaps the brittle saturated fat hypothesis of heart disease it will soon be shattered.
Wow!
Many people thought the news would never reach the mainstream press. But it finally has. The article cites the recent meta-analysis by Krauss and colleagues that suggested that the amount of saturated fat in the diet is not related to heart disease.
I would note several caveats. First, although some of the studies in the meta-analysis used food diaries to assess intake, others used the ubiquitous "food frequency questionnaires," which may not be accurate, as discussed here.
Second, Krauss et al. suggested that the effect of saturated fat may depend on what people substitute for the saturated fat. (This assumes that no one would want to decrease calories by simply eating less saturated fat, which is what makes the most sense to me.) Eating more unsaturated fat may decrease heart disease rates, whereas eating more carbohydrates may increase heart disease rates. Not everyone agrees with this, however.
Finally, the Scientific American article says it's mostly highly processed carbohydrates that are the villains, and the author writes, "some high-fiber carbohydrates are unquestionably good for the body." Many people do, in fact, question that statement, especially in relation to people with diabetes.
The author of the Scientific American article is not urging people to pig out on saturated fats. She says that current studies "do not suggest that saturated fats are not so bad; they indicate that carbohydrates could be worse."
It takes a long time for generally accepted ideas to be thrown out. Further studies may convince people that the "healthy whole grains" that people (including those with diabetes) are currently being urged to make the focus of their diets are just as bad as white bread, pasta, and sodas.
But for now, every little nail hammered into the brittle saturated fat hypothesis of heart disease helps. Saying that high-glycemic-index carbohydrates may increase heart disease risk is a step toward accepting the idea that all carbohydrates may do the same, especially in people with a genetic propensity to insulin resistance.
Publicizing the evidence in a mainstream popular magazine will help to spread the news, because the popular press operates with a herd mentality. If one mainstream news outlet carries a story, everyone else has to report on it too.
In fact, just today I got in the mail a copy of the Harvard Medical School Focus, which included a brief comment titled "For Heart Health: More Polyunsaturated Fat, Fewer Refined Carbohydrates." This discusses both the Krauss paper cited above and another paper that supports the idea that substituting polyunsaturated fat for saturated fat instead of carbohydrate will reduce heart disease risks.
Perhaps the brittle saturated fat hypothesis of heart disease it will soon be shattered.
Saturday, April 3, 2010
Is Dieting a Sport?
One thing that annoys me (well, OK, a lot of things annoy me; I'm becoming a curmudgeon) is when people approach dieting like a team sport.
You pick your favorite diet, and then you defend that diet come heck or high water. When a scientific paper supporting your diet choice is published, you crow. When a scientific paper supporting some other diet is published, you ignore it.
A couple of recent papers concerning the impact of saturated fat on heart disease illustrate this unscientific approach by some people in the science-discussing community.
In January, a study titled Meta-analysis of prospective cohort studies evaluating the association of saturated fat with cardiovascular disease was published online ahead of print publication. The study concluded that "there is no significant evidence for concluding that dietary saturated fat is associated with an increased risk of CHD or CVD."
The study was pretty much ignored by the mainstream science press, which tends to support the official American Heart Association low-fat approach to heart health. The New York Times didn't mention it. The various popular science summary services like Science Daily and EurekAlert also didn't report on it.
As diabetes blogger David Mendosa wrote, "I couldn't find any mainstream articles about it today. Not one of the four sources that I rely on heavily for leads to new studies has carried a word about this one."
But response in the low-carb community was immediate. People on low-carb diets tend to eat a lot of fat, often including a lot of saturated fat. Blog after blog reported on this study, and some of the bloggers made fun of the "low fatters" and patted each other on the back for following the "correct" diet.
More recently, another paper, titled Effects on Coronary Heart Disease of Increasing Polyunsaturated Fat in Place of Saturated Fat: A Systematic Review and Meta-Analysis of Randomized Controlled Trials was published online. This paper concluded that replacing saturated fat with unsaturated fat could reduce the risk of having a coronary heart disease "event" almost 20%.
This study was picked up by the science reporting services like Science Daily, but to date, I haven't seen a single one of the sites or blogs that publicized the "no effect of saturated fat" study mention this other study, and I've been looking.
To be fair, I get the URLs of some lipid blogs from the links in other blogs, and because people tend to link to blogs that agree with them, they do tend to read each other's posts and come to similar conclusions. But I find this business of ignoring the studies you don't agree with sad.
This isn't science. This is religion, or politics . . . or sports. When I was a child, I was a big supporter of the Washington Senators, the team that ended up in the basement year after year. The big excitement was whether they'd end up last, as usual, or perhaps claw their way up to next-to-last. So I know what it's like to root for a loser. You grasp at straws.
For example, Dean Ornish, who advocates an extremely low fat diet to prevent heart disease, was once asked about the fact that when your fat intake is low, your HDL cholesterol, the "good" cholesterol, goes down as well as your LDL, the "bad" cholesterol, so the ratio remains the same or even gets worse.
He said well, maybe when you're not eating fat, you don't need HDL.
But finding the best diet for people with diabetes shouldn't be pursued like this. We need to look at all the evidence, whether it supports our preconceived notions or not.
In fact, these two studies are not that far apart in their conclusions. What the first study said was that there was no significant evidence for linking saturated fat with heart disease. But they hinted at the results of the second study: "More data are needed to elucidate whether CVD risks are likely to be influenced by the specific nutrients used to replace saturated fat."
And the second study concluded that yes, it does matter what you replace the saturated fat with. Replace it with carbohydrate, and people's risk goes up. Replace it with unsaturated fat, and people's risk goes down.
Both studies were meta-analyses, and like many people, I'm not a big fan of meta-analyses, as I discussed here. Nevertheless, they hint at possible relationships.
And I don't think we should sit around throwing darts and this study or that study and maintaining the ideas we've had for decades. What we need to do is to look at all the evidence and try to interpret it in the best way we can given today's scientific and statistical tools. We need to try to find out why different studies seem to give different results and figure out how we can apply those findings to individual patients.
When I was in graduate school, forced to read a little in the history of biology, one thing that struck me was that often when there were two different schools of thought on some topic, it turned out they were both wrong. The answer turned out to be something else, which they couldn't have known because the technology for testing for that thing had not yet been developed.
So it's possible that a similar thing applies to research on dietary fats. Maybe it's not the saturation/unsaturation of the fats that is important but how fresh they are. Maybe it's the degree to which the fats are oxidized, or glycated because of high blood glucose, or modified in some other way that makes the most difference in heart disease.
Maybe the type of fat depends on what you're doing with that fat. Unsaturated fats, expecially the omega-3 fats found in fish, are easily oxidized when warm. This is what causes the "fishy" smell when fish sit around before you cook them. Using fish oil for frying would be a bad idea. The best fats for frying are the saturated fats. But most studies don't ask about how the various fats were used, or how fresh they were.
Maybe we can tolerate any kind of fat when it's not modified by food additives or the many chemical pollutants in our environment. Even organic food and bottled water are not free from contaminants, especially when the water is bottled in plastic.
Maybe we can tolerate almost any kind of fat in limited quantities, but when we overwhelm our metabolism with huge amounts of any kind of fat we'll see our heart health decline.
If it turns out that any type of food does, indeed, affect heart disease, we need to study why that food has that effect. We need to determine if it's eating any of the suspect food or eating a tremendous amount of that food that is important.
We need to abandon more studies designed to prove some preconceived notion (fat is bad, or fat is good) and instead encourage studies that show why different studies appear to give different results. Was it study design? Poor use of statistics? Poor choice of patient populations? Poor choice of endpoints?
You can look at short-term effects or long-term effects. You can lump together all cardiovascular events, including mortality, or you can study only mortality, or you can separate strokes from heart attacks, or you can try to study them all. In the latter case you need gargantuan overall sample sizes to have statistical significance in all the groups. And that means very expensive studies, especially if it's a long-term study.
You can study saturated fat from meat, butter, chicken, and coconut oil or you can study saturated fat from fast-food burgers, luncheon meats, hot dogs, french fries, potato chips, and southern fried chicken. The latter sources are apt to be associated with other behaviors such as eating a lot of processed convenience foods and drinking lots of sodas. So is it the effect of saturated fat that you're measuring or an overall unhealthy eating pattern?
So until we find the best possible diet, what do I think is the best diet for both preventing heart disease and controlling diabetes?
A l0w-carb diet. I've been following a low-carb diet for about 14 years.
But if you start out on a "standard American diet" that is high in both carbs and fats, I think the best approach is to drastically reduce the carbs and not replace them with anything. This way, your percentage of fat will increase; a typical low-carb diet includes about 60% fat. But your calories will go down.
In fact, studies have shown that when most people switch from a typical American diet to a low-carb diet, they reduce calories without thinking about it. This is because a low-carb diet tends to reduce hunger, so you don't want as much food.
Simply losing weight (not that the process itself is simple) improves blood pressure and blood glucose levels in most people. So if you reduce the carbs and don't replace them with a lot of other calories, you're apt to lose weight.
If not replacing the carbs with anything means that you're hungry, you can eat a little extra protein. Or even have a little extra fat. Just don't make a big effort to replace those 1000 calories a day you were eating in the form of bread, mashed potatoes, and doughnuts with something else.
I don't know why, when the press keeps blathering about the "obesity epidemic" the nutrition researchers hone in on replacing fat calories with something else. Do they want to keep people fat?
Come on, people. Let's stop bickering and use our brains and figure out how to make us all as healthy as we can be.
You pick your favorite diet, and then you defend that diet come heck or high water. When a scientific paper supporting your diet choice is published, you crow. When a scientific paper supporting some other diet is published, you ignore it.
A couple of recent papers concerning the impact of saturated fat on heart disease illustrate this unscientific approach by some people in the science-discussing community.
In January, a study titled Meta-analysis of prospective cohort studies evaluating the association of saturated fat with cardiovascular disease was published online ahead of print publication. The study concluded that "there is no significant evidence for concluding that dietary saturated fat is associated with an increased risk of CHD or CVD."
The study was pretty much ignored by the mainstream science press, which tends to support the official American Heart Association low-fat approach to heart health. The New York Times didn't mention it. The various popular science summary services like Science Daily and EurekAlert also didn't report on it.
As diabetes blogger David Mendosa wrote, "I couldn't find any mainstream articles about it today. Not one of the four sources that I rely on heavily for leads to new studies has carried a word about this one."
But response in the low-carb community was immediate. People on low-carb diets tend to eat a lot of fat, often including a lot of saturated fat. Blog after blog reported on this study, and some of the bloggers made fun of the "low fatters" and patted each other on the back for following the "correct" diet.
More recently, another paper, titled Effects on Coronary Heart Disease of Increasing Polyunsaturated Fat in Place of Saturated Fat: A Systematic Review and Meta-Analysis of Randomized Controlled Trials was published online. This paper concluded that replacing saturated fat with unsaturated fat could reduce the risk of having a coronary heart disease "event" almost 20%.
This study was picked up by the science reporting services like Science Daily, but to date, I haven't seen a single one of the sites or blogs that publicized the "no effect of saturated fat" study mention this other study, and I've been looking.
To be fair, I get the URLs of some lipid blogs from the links in other blogs, and because people tend to link to blogs that agree with them, they do tend to read each other's posts and come to similar conclusions. But I find this business of ignoring the studies you don't agree with sad.
This isn't science. This is religion, or politics . . . or sports. When I was a child, I was a big supporter of the Washington Senators, the team that ended up in the basement year after year. The big excitement was whether they'd end up last, as usual, or perhaps claw their way up to next-to-last. So I know what it's like to root for a loser. You grasp at straws.
For example, Dean Ornish, who advocates an extremely low fat diet to prevent heart disease, was once asked about the fact that when your fat intake is low, your HDL cholesterol, the "good" cholesterol, goes down as well as your LDL, the "bad" cholesterol, so the ratio remains the same or even gets worse.
He said well, maybe when you're not eating fat, you don't need HDL.
But finding the best diet for people with diabetes shouldn't be pursued like this. We need to look at all the evidence, whether it supports our preconceived notions or not.
In fact, these two studies are not that far apart in their conclusions. What the first study said was that there was no significant evidence for linking saturated fat with heart disease. But they hinted at the results of the second study: "More data are needed to elucidate whether CVD risks are likely to be influenced by the specific nutrients used to replace saturated fat."
And the second study concluded that yes, it does matter what you replace the saturated fat with. Replace it with carbohydrate, and people's risk goes up. Replace it with unsaturated fat, and people's risk goes down.
Both studies were meta-analyses, and like many people, I'm not a big fan of meta-analyses, as I discussed here. Nevertheless, they hint at possible relationships.
And I don't think we should sit around throwing darts and this study or that study and maintaining the ideas we've had for decades. What we need to do is to look at all the evidence and try to interpret it in the best way we can given today's scientific and statistical tools. We need to try to find out why different studies seem to give different results and figure out how we can apply those findings to individual patients.
When I was in graduate school, forced to read a little in the history of biology, one thing that struck me was that often when there were two different schools of thought on some topic, it turned out they were both wrong. The answer turned out to be something else, which they couldn't have known because the technology for testing for that thing had not yet been developed.
So it's possible that a similar thing applies to research on dietary fats. Maybe it's not the saturation/unsaturation of the fats that is important but how fresh they are. Maybe it's the degree to which the fats are oxidized, or glycated because of high blood glucose, or modified in some other way that makes the most difference in heart disease.
Maybe the type of fat depends on what you're doing with that fat. Unsaturated fats, expecially the omega-3 fats found in fish, are easily oxidized when warm. This is what causes the "fishy" smell when fish sit around before you cook them. Using fish oil for frying would be a bad idea. The best fats for frying are the saturated fats. But most studies don't ask about how the various fats were used, or how fresh they were.
Maybe we can tolerate any kind of fat when it's not modified by food additives or the many chemical pollutants in our environment. Even organic food and bottled water are not free from contaminants, especially when the water is bottled in plastic.
Maybe we can tolerate almost any kind of fat in limited quantities, but when we overwhelm our metabolism with huge amounts of any kind of fat we'll see our heart health decline.
If it turns out that any type of food does, indeed, affect heart disease, we need to study why that food has that effect. We need to determine if it's eating any of the suspect food or eating a tremendous amount of that food that is important.
We need to abandon more studies designed to prove some preconceived notion (fat is bad, or fat is good) and instead encourage studies that show why different studies appear to give different results. Was it study design? Poor use of statistics? Poor choice of patient populations? Poor choice of endpoints?
You can look at short-term effects or long-term effects. You can lump together all cardiovascular events, including mortality, or you can study only mortality, or you can separate strokes from heart attacks, or you can try to study them all. In the latter case you need gargantuan overall sample sizes to have statistical significance in all the groups. And that means very expensive studies, especially if it's a long-term study.
You can study saturated fat from meat, butter, chicken, and coconut oil or you can study saturated fat from fast-food burgers, luncheon meats, hot dogs, french fries, potato chips, and southern fried chicken. The latter sources are apt to be associated with other behaviors such as eating a lot of processed convenience foods and drinking lots of sodas. So is it the effect of saturated fat that you're measuring or an overall unhealthy eating pattern?
So until we find the best possible diet, what do I think is the best diet for both preventing heart disease and controlling diabetes?
A l0w-carb diet. I've been following a low-carb diet for about 14 years.
But if you start out on a "standard American diet" that is high in both carbs and fats, I think the best approach is to drastically reduce the carbs and not replace them with anything. This way, your percentage of fat will increase; a typical low-carb diet includes about 60% fat. But your calories will go down.
In fact, studies have shown that when most people switch from a typical American diet to a low-carb diet, they reduce calories without thinking about it. This is because a low-carb diet tends to reduce hunger, so you don't want as much food.
Simply losing weight (not that the process itself is simple) improves blood pressure and blood glucose levels in most people. So if you reduce the carbs and don't replace them with a lot of other calories, you're apt to lose weight.
If not replacing the carbs with anything means that you're hungry, you can eat a little extra protein. Or even have a little extra fat. Just don't make a big effort to replace those 1000 calories a day you were eating in the form of bread, mashed potatoes, and doughnuts with something else.
I don't know why, when the press keeps blathering about the "obesity epidemic" the nutrition researchers hone in on replacing fat calories with something else. Do they want to keep people fat?
Come on, people. Let's stop bickering and use our brains and figure out how to make us all as healthy as we can be.
Monday, March 15, 2010
ADVANCE and NAVIGATOR
The Internet is abuzz with the latest results from a couple of those massive trials that physicians who practice "evidence-based medicine" require before they'll believe in any treatment.
Although I understand why such studies are needed, I hate them, because they're studying a huge, diverse population of patients who may differ a lot in their baseline characteristics, even though the mean is usually all you can see.
Unless the outcome is black and white, for example, 100% of the patients who took the new drug dropped dead within 2 weeks, you need statistics to evaluate the study. Quite often, individual patients may be harmed or helped, but the published conclusion refers only to the average impact, as I noted here. Then physicians apply these average results to everyone.
A good example of this is the blood glucose (BG) arm of the ACCORD study, which was stopped early a couple of years ago because it appeared that the patients who used intensive treatment with a lot of drugs and lowered their A1cs to a mean of 6.5% had higher mortality than those who used standard treatment and had A1cs of about 7.3%.
This was despite the fact that patients in both groups had mortality rates lower than those of most people with diabetes.
In fact, the patients in the ACCORD study were older, had had type 2 for at least 10 years, had other risk factors for heart disease, and started with mean A1cs of 8.3. This means they had probably had poor control for years. Yet doctors are applying the conclusions to everyone.
Many patients are now reporting that their doctors tell them that their excellent A1c levels in the 5s are too low and they should increase them until they're over 7!
Furthermore, like most patients, the ACCORD patients were told to follow an ADA-type diet with less than 30% total fat and less than 10% saturated fat. This means they undoubtedly increased their consumption of carbohydrates, most likely the kind most Americans eat: potatoes, rice, white bread, processed fat-free foods. Yet a recent meta-analysis showed that there is no significant evidence to conclude that saturated fat causes heart disease. Some studies showed an increase when saturated fat was reduced, and others showed an increase. This averaged out to no effect.
The authors suggested that it might depend on what you substitute for the saturated fat, as studies with substitution of unsaturated fat tended to reduce heart disease and mortality and studies with substitution of carbohydrate tended to increase it, although no studies have been done that would actually prove this.
Yet replacing saturated fat with carbohydrate is undoubtedly what people in ACCORD were told to do, and those in the intensive treatment arm of the study got more intensive nutritional counseling and hence probably ate more carbohydrate.
Now the other two arms of the ACCORD study have been published. The blood pressure arm showed that reducing the systolic blood pressure below 120 resulted in no better cardiovascular outcomes than using fewer drugs to keep the systolic blood pressure below 140. The lower blood pressures did result in fewer strokes.
This is the same patient population as the BG arm of the study, and the same caveats apply: longstanding diabetes in an elderly population with coexisting medical problems (34% had already had a cardiovascular event), relatively high starting A1cs and fasting BG levels over 170, and multiple blood pressure drugs given to reach the goal. Also, twice as many of the intensively treated patients gained more than 10 kg during the study.
The final arm of the study was designed to see whether adding a fibrate drug to the treatment of patients already taking a statin would reduce cardiovascular events. The fibrates (they used fenofibrate) reduce triglycerides and increase HDL levels.
Again, they found no significant effect but a suggestion that the drug might help in patients who began with triglyceride levels over 204 and HDL levels under 34. Men appeared to do better and women appeared to do worse on the fibrate. Such studies can show differences that appear to be real but aren't statistically significant.
Again: same population and same caveats.
Another study, the NAVIGATOR study, was reported at the same time. This study started with patients who had prediabetes, with mean A1cs of 5.8 and also either preexisting heart disease or cardiovascular risk factors. They tested whether using valsartan (Diovan), an angiotensin-receptor inhibitor that lowers blood pressure, would reduce progression from prediabetes to diabetes. Similar drugs had been shown in the past to do so.
Again, all the patients were given "lifestyle modification" advice, although the papers don't specify exactly what that was other than the usual ADA line of reducing total and saturated fat and increasing exercise. You have to go to an Appendix, which most people won't read, and then to a reference to a Finnish study they cite to see what type of dietary advice was given.
It turns out to be the usual low fat with "lots of whole grains, fruits and vegetable." Many Americans told to eat lots of whole grains are apt to eat whole-wheat bread (which isn't whole grain) and to drink more orange juice and eat more apples and bananas, and maybe more peas and corn. Very few will up their intake of kale and broccoli and other low-carb veggies.
It turned out that the low-fat high-carb diet plus increased exercise plus the drug reduced the progression to type 2 diabetes from 36.8% to 33.1%, which they calculate is a 13% reduction in the "absolute hazard difference using an exponential model," but a pretty small absolute reduction. It didn't affect the rate of cardiovascular events.
The second arm of the NAVIGATOR trial involved the same patient population and the drug nateglinide (Starlix), which is a sulfonylurea-type drug that increases insulin secretion by the beta cells but for a shorter period than the traditional sulfs.
The rationale was that high postprandial BG levels are said to lead to beta cell deterioration, and higher A1cs are associated with increased heart disease. They tested whether or not this drug would reduce progression from prediabetes to diabetes and whether it would affect cardiovascular events.
They found it did neither.
Do these studies mean there's no point in trying to control our diabetes?
Not at all. What they really show is that you can't give people with longstanding diabetes or even a diabetic tendency and either preexisting heart disease or a lot of heart disease risk factors a low fat, and hence very high carbohydrate, diet, try to control the resulting high BG levels with a lot of drugs, and expect the heart disease to go away.
Furthermore, even though you tell people to eat lots of vegetables and whole grains, you know that in the general population, most of them -- if they modify their diet at all -- will eat high-glycemic foods, low-fat processed convenience foods, and sugary fruits. If they show the dietician that their fat consumption is down, the dietician will probably tell them they're doing great.
No one has tested whether or not trying to control diabetes with lower-carb diets and fewer drugs would reduce heart disease rates.
But I'm afraid that the results of these trials will make a lot of people simply throw up their hands and give up, figuring that heart attacks are inevitable, no matter what they do.
Even if the results from a lower-carb study showed fewer cardiovascular events, I'm afraid most Americans wouldn't make significant changes in their diets. An intelligent woman with type 2 once told me she had trouble eating just a couple of potato chips. I asked why she bought potato chips (she lived alone). She said, "Because I like potato chips."
Well, who doesn't. I also used to like blueberry pie (I probably wouldn't like it now, because it would seem overwhelmingly sweet with relatively little taste) and homemade bread slathered with butter and homemade jam. But I don't eat those things now.
What we need to learn to do is to become gourmets, seeking out foods with a lot of taste and not a lot of carbohydrate, like berries, or exotic fresh vegetables from a farmers market. This is a lot more fun and cheaper than paying $500 a month for a lot of pills to try to cover the damage from eating ho-hum potato chips and packaged snack cakes.
The intelligent people who read this blog will understand this. I worry about the other millions of people in the country who don't have access to good information. I worry about the overworked GPs who don't have time to slog through long statistical studies and try to figure out what an "absolute hazard difference using an exponential model" is.
Many of the details, like the actual dietary advice, in these papers are difficult, if not impossible, to find. If you make an effort to download the full study protocol of the ACCORD study, you find that patients were taught carb counting but it doesn't say how many carbs they were supposed to eat. They were taught self-monitoring of BG, and how to titrate their drugs according to the results. They were apparently not taught how to "titrate" their carb consumption according to the results.
And the authors are often sloppy. For example, sometimes they give both mean and median A1c. Sometimes they give only one. Sometimes they don't indicate which one they calculated.
I worry that the busy physicians will just read the headlines in medical magazines and the New York Times ("Diabetes Heart Treatments May Cause Harm") and conclude that they shouldn't try to treat diabetic patients with high blood pressure, high BG levels, or high lipid levels. Why bother, because they might be sued if they caused harm.
As studies become old, people who write about them tend to simplify, ignoring the many caveats that apply to the studies. For example, Gina Kolata wrote in the recent New York Times story, "It was discovered 2 years ago that rigorously controlling blood sugar did not prevent heart disease or deaths in people with type 2 diabetes." What that study actually showed was that "rigorously controlling blood sugar with a lot of drugs to cover a high-carb diet did not prevent heart disease or death in elderly patients with preexisting heart disease or at least two cardiovascular risk factors and long-standing poorly controlled diabetes."
But how many physicians have retained Kolata's interpretation? I suspect a lot. I've mentioned the many patients whose doctors told them that their diet-controlled A1cs of 5.6 were too low and they should try to get them up to 7!
I would agree that if someone had an A1c of 5.6 only because they were on 7 different expensive medications with a lot of potential side effects, it would make sense to stop several of the drugs and let the A1c go up a bit, especially if the patient was elderly with several other medical problems treated with even more drugs.
But if someone has an A1c of 4.8 because of strict diet control and a lot of exercise, and if that person doesn't go low (after all, nondiabetics don't go low when they have low A1cs), there's absolutely no reason to tell that person to increase the A1c.
Applying a "rule" for the wrong reasons is the type of faulty logic that has caused harm in a lot of diabetic patients. I know some who have been told by registered dieticians that they should put raisins in their oatmeal "to get the carb counts up."
The reason for the high-carb ADA diet is not to eat a lot of carbohydrate; it's to eat less fat. The idea is that when you eat more carbohydrate, you'll eat less fat. But adding carbohydrate to a meal instead of substituting carbohydrate for fat won't reach the ADA goals (which many people today don't agree with anyway). It will just add calories, increase insulin levels, and promote even more fat gain.
So will patients with type 2 diabetes soon be told to get their blood pressure up, not worry about lipid levels, and pay no attention to postprandial BG levels?
I certainly hope not.
The full texts of the New England Journal of Medicine articles cited are available free here.
Although I understand why such studies are needed, I hate them, because they're studying a huge, diverse population of patients who may differ a lot in their baseline characteristics, even though the mean is usually all you can see.
Unless the outcome is black and white, for example, 100% of the patients who took the new drug dropped dead within 2 weeks, you need statistics to evaluate the study. Quite often, individual patients may be harmed or helped, but the published conclusion refers only to the average impact, as I noted here. Then physicians apply these average results to everyone.
A good example of this is the blood glucose (BG) arm of the ACCORD study, which was stopped early a couple of years ago because it appeared that the patients who used intensive treatment with a lot of drugs and lowered their A1cs to a mean of 6.5% had higher mortality than those who used standard treatment and had A1cs of about 7.3%.
This was despite the fact that patients in both groups had mortality rates lower than those of most people with diabetes.
In fact, the patients in the ACCORD study were older, had had type 2 for at least 10 years, had other risk factors for heart disease, and started with mean A1cs of 8.3. This means they had probably had poor control for years. Yet doctors are applying the conclusions to everyone.
Many patients are now reporting that their doctors tell them that their excellent A1c levels in the 5s are too low and they should increase them until they're over 7!
Furthermore, like most patients, the ACCORD patients were told to follow an ADA-type diet with less than 30% total fat and less than 10% saturated fat. This means they undoubtedly increased their consumption of carbohydrates, most likely the kind most Americans eat: potatoes, rice, white bread, processed fat-free foods. Yet a recent meta-analysis showed that there is no significant evidence to conclude that saturated fat causes heart disease. Some studies showed an increase when saturated fat was reduced, and others showed an increase. This averaged out to no effect.
The authors suggested that it might depend on what you substitute for the saturated fat, as studies with substitution of unsaturated fat tended to reduce heart disease and mortality and studies with substitution of carbohydrate tended to increase it, although no studies have been done that would actually prove this.
Yet replacing saturated fat with carbohydrate is undoubtedly what people in ACCORD were told to do, and those in the intensive treatment arm of the study got more intensive nutritional counseling and hence probably ate more carbohydrate.
Now the other two arms of the ACCORD study have been published. The blood pressure arm showed that reducing the systolic blood pressure below 120 resulted in no better cardiovascular outcomes than using fewer drugs to keep the systolic blood pressure below 140. The lower blood pressures did result in fewer strokes.
This is the same patient population as the BG arm of the study, and the same caveats apply: longstanding diabetes in an elderly population with coexisting medical problems (34% had already had a cardiovascular event), relatively high starting A1cs and fasting BG levels over 170, and multiple blood pressure drugs given to reach the goal. Also, twice as many of the intensively treated patients gained more than 10 kg during the study.
The final arm of the study was designed to see whether adding a fibrate drug to the treatment of patients already taking a statin would reduce cardiovascular events. The fibrates (they used fenofibrate) reduce triglycerides and increase HDL levels.
Again, they found no significant effect but a suggestion that the drug might help in patients who began with triglyceride levels over 204 and HDL levels under 34. Men appeared to do better and women appeared to do worse on the fibrate. Such studies can show differences that appear to be real but aren't statistically significant.
Again: same population and same caveats.
Another study, the NAVIGATOR study, was reported at the same time. This study started with patients who had prediabetes, with mean A1cs of 5.8 and also either preexisting heart disease or cardiovascular risk factors. They tested whether using valsartan (Diovan), an angiotensin-receptor inhibitor that lowers blood pressure, would reduce progression from prediabetes to diabetes. Similar drugs had been shown in the past to do so.
Again, all the patients were given "lifestyle modification" advice, although the papers don't specify exactly what that was other than the usual ADA line of reducing total and saturated fat and increasing exercise. You have to go to an Appendix, which most people won't read, and then to a reference to a Finnish study they cite to see what type of dietary advice was given.
It turns out to be the usual low fat with "lots of whole grains, fruits and vegetable." Many Americans told to eat lots of whole grains are apt to eat whole-wheat bread (which isn't whole grain) and to drink more orange juice and eat more apples and bananas, and maybe more peas and corn. Very few will up their intake of kale and broccoli and other low-carb veggies.
It turned out that the low-fat high-carb diet plus increased exercise plus the drug reduced the progression to type 2 diabetes from 36.8% to 33.1%, which they calculate is a 13% reduction in the "absolute hazard difference using an exponential model," but a pretty small absolute reduction. It didn't affect the rate of cardiovascular events.
The second arm of the NAVIGATOR trial involved the same patient population and the drug nateglinide (Starlix), which is a sulfonylurea-type drug that increases insulin secretion by the beta cells but for a shorter period than the traditional sulfs.
The rationale was that high postprandial BG levels are said to lead to beta cell deterioration, and higher A1cs are associated with increased heart disease. They tested whether or not this drug would reduce progression from prediabetes to diabetes and whether it would affect cardiovascular events.
They found it did neither.
Do these studies mean there's no point in trying to control our diabetes?
Not at all. What they really show is that you can't give people with longstanding diabetes or even a diabetic tendency and either preexisting heart disease or a lot of heart disease risk factors a low fat, and hence very high carbohydrate, diet, try to control the resulting high BG levels with a lot of drugs, and expect the heart disease to go away.
Furthermore, even though you tell people to eat lots of vegetables and whole grains, you know that in the general population, most of them -- if they modify their diet at all -- will eat high-glycemic foods, low-fat processed convenience foods, and sugary fruits. If they show the dietician that their fat consumption is down, the dietician will probably tell them they're doing great.
No one has tested whether or not trying to control diabetes with lower-carb diets and fewer drugs would reduce heart disease rates.
But I'm afraid that the results of these trials will make a lot of people simply throw up their hands and give up, figuring that heart attacks are inevitable, no matter what they do.
Even if the results from a lower-carb study showed fewer cardiovascular events, I'm afraid most Americans wouldn't make significant changes in their diets. An intelligent woman with type 2 once told me she had trouble eating just a couple of potato chips. I asked why she bought potato chips (she lived alone). She said, "Because I like potato chips."
Well, who doesn't. I also used to like blueberry pie (I probably wouldn't like it now, because it would seem overwhelmingly sweet with relatively little taste) and homemade bread slathered with butter and homemade jam. But I don't eat those things now.
What we need to learn to do is to become gourmets, seeking out foods with a lot of taste and not a lot of carbohydrate, like berries, or exotic fresh vegetables from a farmers market. This is a lot more fun and cheaper than paying $500 a month for a lot of pills to try to cover the damage from eating ho-hum potato chips and packaged snack cakes.
The intelligent people who read this blog will understand this. I worry about the other millions of people in the country who don't have access to good information. I worry about the overworked GPs who don't have time to slog through long statistical studies and try to figure out what an "absolute hazard difference using an exponential model" is.
Many of the details, like the actual dietary advice, in these papers are difficult, if not impossible, to find. If you make an effort to download the full study protocol of the ACCORD study, you find that patients were taught carb counting but it doesn't say how many carbs they were supposed to eat. They were taught self-monitoring of BG, and how to titrate their drugs according to the results. They were apparently not taught how to "titrate" their carb consumption according to the results.
And the authors are often sloppy. For example, sometimes they give both mean and median A1c. Sometimes they give only one. Sometimes they don't indicate which one they calculated.
I worry that the busy physicians will just read the headlines in medical magazines and the New York Times ("Diabetes Heart Treatments May Cause Harm") and conclude that they shouldn't try to treat diabetic patients with high blood pressure, high BG levels, or high lipid levels. Why bother, because they might be sued if they caused harm.
As studies become old, people who write about them tend to simplify, ignoring the many caveats that apply to the studies. For example, Gina Kolata wrote in the recent New York Times story, "It was discovered 2 years ago that rigorously controlling blood sugar did not prevent heart disease or deaths in people with type 2 diabetes." What that study actually showed was that "rigorously controlling blood sugar with a lot of drugs to cover a high-carb diet did not prevent heart disease or death in elderly patients with preexisting heart disease or at least two cardiovascular risk factors and long-standing poorly controlled diabetes."
But how many physicians have retained Kolata's interpretation? I suspect a lot. I've mentioned the many patients whose doctors told them that their diet-controlled A1cs of 5.6 were too low and they should try to get them up to 7!
I would agree that if someone had an A1c of 5.6 only because they were on 7 different expensive medications with a lot of potential side effects, it would make sense to stop several of the drugs and let the A1c go up a bit, especially if the patient was elderly with several other medical problems treated with even more drugs.
But if someone has an A1c of 4.8 because of strict diet control and a lot of exercise, and if that person doesn't go low (after all, nondiabetics don't go low when they have low A1cs), there's absolutely no reason to tell that person to increase the A1c.
Applying a "rule" for the wrong reasons is the type of faulty logic that has caused harm in a lot of diabetic patients. I know some who have been told by registered dieticians that they should put raisins in their oatmeal "to get the carb counts up."
The reason for the high-carb ADA diet is not to eat a lot of carbohydrate; it's to eat less fat. The idea is that when you eat more carbohydrate, you'll eat less fat. But adding carbohydrate to a meal instead of substituting carbohydrate for fat won't reach the ADA goals (which many people today don't agree with anyway). It will just add calories, increase insulin levels, and promote even more fat gain.
So will patients with type 2 diabetes soon be told to get their blood pressure up, not worry about lipid levels, and pay no attention to postprandial BG levels?
I certainly hope not.
The full texts of the New England Journal of Medicine articles cited are available free here.
Friday, March 5, 2010
Ancient Bacteria
It's generally agreed that low-grade chronic inflammation is related to metabolic syndrome, cardiovascular disease, and type 2 diabetes. But no one knows what causes this generalized inflammation.
Acute, localized inflammation is a good thing. It's what walls off an infection, "eats" the offending organism, and then digests it with the help of heavy-duty oxidants. Then, when things are working right, the body repairs the damage, and the cells that have been doing all this leave the scene.
Chronic inflammation, on the other hand, is not a good thing, and the more scientists can find out about it, the better.
Hence I was intrigued by a recent paper in Nature that proposed a totally new idea and confirmed an old idea. You can read a popularized description here, or a link to the original paper here.
When we are invaded by pathogens, the body mounts what is called the innate immune response. This is a nonspecific response triggered by certain chemicals on the surface of many organisms that are unique to them and are not found on our own cells. The body sends out cells called macrophages to engulf the offending organisms and sends chemical signals to recruit other cell types to help rid the body of the organisms and then repair any damage that occurred.
This response is more primitive than the adaptive immune response that uses antibodies and is more specific than the innate immune response.
Usually, the cause of the response is clear, as bacteria or viruses or other pathogens can be found in the blood. But sometimes people seem to have such a response when no pathogens can be found. This puzzled scientists for a long time.
But Carl Hauser and colleagues, the authors of the Nature paper, came up with a fascinating hypothesis. It is generally accepted that mitochondria, known as the "powerhouses of the cell" because they are where most of the cell's energy is produced, were originally bacteria that invaded the cells of other organisms and adapted to the benefit of both.
Mitochondria have their own DNA, which comes only from the mother.
Hauser and colleagues wondered if perhaps trauma that destroys cells could release mitochondria from the damaged cells into the bloodstream. Then, because the mitochondria are descended from bacteria, they might have surface molecules that our bodies would interpret as foreign, so we would mount an innate immune response, just as we do to other bacteria.
His researched suggested that this does indeed happen.
It explains why severe trauma patients sometimes get reactions that look like severe infections when no signs of infecting organisms can be found.
And I wonder if less severe chronic trauma could cause just enough of an innate immune response to trigger chronic disease. For example, we know that chronic gum disease can increase blood glucose levels, along with various signs if inflammation. Could this be because the gum disease is causing gum cells to break down and release mitochondria?
Could other hidden infections be doing the same? By reducing various chronic infections, could we reduce people's chance of getting type 2 diabetes?
I find this research exciting, not because it offers an immediate chance for a cure of type 2 diabetes, but because it's a new idea and I find new paradigm-shifting ideas much more fascinating than huge studies of drugs that rely on statistics to prove anything. Even then, although the statistics can show that the drug worked on average, it can never show whether or not it will help you in particular, as I discussed here.
Creative new ideas can suggest new research paths that may some day lead to real cures.
.
Acute, localized inflammation is a good thing. It's what walls off an infection, "eats" the offending organism, and then digests it with the help of heavy-duty oxidants. Then, when things are working right, the body repairs the damage, and the cells that have been doing all this leave the scene.
Chronic inflammation, on the other hand, is not a good thing, and the more scientists can find out about it, the better.
Hence I was intrigued by a recent paper in Nature that proposed a totally new idea and confirmed an old idea. You can read a popularized description here, or a link to the original paper here.
When we are invaded by pathogens, the body mounts what is called the innate immune response. This is a nonspecific response triggered by certain chemicals on the surface of many organisms that are unique to them and are not found on our own cells. The body sends out cells called macrophages to engulf the offending organisms and sends chemical signals to recruit other cell types to help rid the body of the organisms and then repair any damage that occurred.
This response is more primitive than the adaptive immune response that uses antibodies and is more specific than the innate immune response.
Usually, the cause of the response is clear, as bacteria or viruses or other pathogens can be found in the blood. But sometimes people seem to have such a response when no pathogens can be found. This puzzled scientists for a long time.
But Carl Hauser and colleagues, the authors of the Nature paper, came up with a fascinating hypothesis. It is generally accepted that mitochondria, known as the "powerhouses of the cell" because they are where most of the cell's energy is produced, were originally bacteria that invaded the cells of other organisms and adapted to the benefit of both.
Mitochondria have their own DNA, which comes only from the mother.
Hauser and colleagues wondered if perhaps trauma that destroys cells could release mitochondria from the damaged cells into the bloodstream. Then, because the mitochondria are descended from bacteria, they might have surface molecules that our bodies would interpret as foreign, so we would mount an innate immune response, just as we do to other bacteria.
His researched suggested that this does indeed happen.
It explains why severe trauma patients sometimes get reactions that look like severe infections when no signs of infecting organisms can be found.
And I wonder if less severe chronic trauma could cause just enough of an innate immune response to trigger chronic disease. For example, we know that chronic gum disease can increase blood glucose levels, along with various signs if inflammation. Could this be because the gum disease is causing gum cells to break down and release mitochondria?
Could other hidden infections be doing the same? By reducing various chronic infections, could we reduce people's chance of getting type 2 diabetes?
I find this research exciting, not because it offers an immediate chance for a cure of type 2 diabetes, but because it's a new idea and I find new paradigm-shifting ideas much more fascinating than huge studies of drugs that rely on statistics to prove anything. Even then, although the statistics can show that the drug worked on average, it can never show whether or not it will help you in particular, as I discussed here.
Creative new ideas can suggest new research paths that may some day lead to real cures.
.
Monday, March 1, 2010
Slow Progress
One thing that annoys me is how long it takes for new ideas and new research results to filter down to practitioners. At this rate I will have died of old age before they figure out a better way to treat type 2 diabetes.
When I was first diagnosed in 1996, because I had been a biology major and had done some research in biochemistry, I wanted to learn more about the science of type 2 diabetes.
I was puzzled because the nurse practitioner who diagnosed me told me to follow the American Diabetes Association (ADA) diet, which was chock-a-block full of carbohydrates. I knew that diabetes was caused by an inability to process carbohydrates. So why were they telling me to eat more of them? It made no sense.
So I went to the library. Remember libraries? They were places with books and preceded Internet searches and Google and all that. The library didn't have much of interest, so I searched the interlibrary loan catalogs and found and ordered a book called Insulin, edited by F. M. and S. J. H. Ashcroft. It was published in 1992, which means it was probably written around 1990, as the publishing process does take time.
The book was very interesting. A chapter author named Erol Cerasi said he and others had done a study of a large group of obese and nonobese subects both with and without diabetes and studied insulin resistance (IR) and insulin secretion.
They found that only beta-cell responsiveness could distinguish the diabetic from nondiabetic subjects. The IR could only distinguish obese from nonobese subjects.
In other words, if you're obese, you'll have IR, but you won't necessarily have diabetes. If you have diabetes, your beta cells won't secrete enough insulin, whether or not you're overweight.
They concluded that "the diabetic state is much more closely related to a failure of the secretion of insulin than to diminished efficiency of the circulating hormone level," that is, beta cell defects are more important than IR in causing type 2.
Another group did a similar study and found that those who progressed from prediabetes to diabetes had decreased insulin responses to glucose at the beginning of the study.
Yet people with type 2 diabetes continued to be told that their obesity had caused IR and the IR had caused the diabetes.
Recently, 23 years after the research published by Cerasi and others, there was a report of a study of 13 new genes increasing the risk of type 2 diabetes. The authors of the study said they were "intrigued" by the finding that most of these genes affect beta cell secretion rather than insulin resistance.
"Beta cell impairment may play a larger role in type 2 diabetes than previously recognized," the authors said, as if this was a totally new idea.
It is true that there's so much diabetes research published that no researcher can have read all of it. One report or one person's opinion isn't considered proof of anything, but it should suggest something, so researchers shouldn't be stunned 23 years later to discover the same thing.
Why is it that an amateur researcher, a newly diagnosed patient, can find information a professional apparently cannot? I'm sure the Cerasi papers were not the only ones to come to the same conclusion, and the other researchers had 23 years in which to look.
Cerasi also recommended using insulin in type 2 patients right from the beginning, to normalize blood glucose levels and reduce glucotoxicity, which he felt contributed to the IR. "Present therapeutic approaches based on initial dietary restriction followed after a period of up to several months by oral diabetic agents, seem rather unsuited" for returning the patient to mild diabetes or prediabetes.
"I propose initial, short-term (one to a few weeks) intensified insulin treatment aimed at achieving euglycemia very rapidly, in order to block down-regulation of glucose transport and inprove beta-cell function." He showed in a pilot study that when patients in whom the oral drugs had stopped working were given insulin to maintain normal BG levels for two weeks, they could then maintain good control on oral agents alone after the insulin was stopped.
Again, a recent proposal suggests essentially the same thing. Ralph DeFronzo proposed starting newly diagnosed patients with type 2 on an intensive drug regimen of metformin, a TZD, and exenatide. And he and 15 other diabetes experts proposed the same at the 2008 ADA meeting.
The ADA's response: Prove it. They just now started a 3-year study to see if early normalization of BG levels with drugs helps. But what is taking them so long? And why use drugs instead of insulin?
Other research has shown that early intensive insulin treatment is more effective than drugs in maintenance of beta cell function. So why mess around with expensive drugs that can have serious side effects when a simpler, cheaper treatment has already been shown to work?
It boggles the mind.
Another example is a 2007 paper by Frank Q. Nuttall and Mary C. Gannon. They showed in 1996 that fasting caused normalization of BG levels in people with type 2 diabetes and wondered, "Could merely a reduction in carbohydrate mimic the effect of a reduced fuel-energy diet or short-term starvation on blood glucose in people with type 2 diabetes mellitus?"
They published the results of using l0w-carb diets (20 and 30% carbohydrate), showing that BG levels and HbA1c levels were much lower. However, their request for further funding was rejected by the National Institutes of Health, which said their sample sizes were too low to show anything and "it is difficult to conceive of the diet as producing larger improvements than metformin or rosiglitazone, for example, especially if the subjects are maintaining their body weight."
"So much for open mindedness," wrote Nuttall and Gannon. The health authorities cling to their old views even in the face of new evidence. They seem to have made up their minds, and there's no more room in their tiny minds to consider alternatives.
But wait a minute. For decades, Richard K. Bernstein has been proposing low-carbohydrate diets for both type 1 and type 2 patients. His first book was published in 1984. But almost no one in the professional world listened to him either. Why did Nuttall and Gannon have to "wonder" in 1996 if the idea of reducing carbohyrate would work?
Research has been done, and it has been published, but other researchers don't seem to pay a lot of attention.
Why must the patients be the ones to ferret out the facts?
When I was first diagnosed in 1996, because I had been a biology major and had done some research in biochemistry, I wanted to learn more about the science of type 2 diabetes.
I was puzzled because the nurse practitioner who diagnosed me told me to follow the American Diabetes Association (ADA) diet, which was chock-a-block full of carbohydrates. I knew that diabetes was caused by an inability to process carbohydrates. So why were they telling me to eat more of them? It made no sense.
So I went to the library. Remember libraries? They were places with books and preceded Internet searches and Google and all that. The library didn't have much of interest, so I searched the interlibrary loan catalogs and found and ordered a book called Insulin, edited by F. M. and S. J. H. Ashcroft. It was published in 1992, which means it was probably written around 1990, as the publishing process does take time.
The book was very interesting. A chapter author named Erol Cerasi said he and others had done a study of a large group of obese and nonobese subects both with and without diabetes and studied insulin resistance (IR) and insulin secretion.
They found that only beta-cell responsiveness could distinguish the diabetic from nondiabetic subjects. The IR could only distinguish obese from nonobese subjects.
In other words, if you're obese, you'll have IR, but you won't necessarily have diabetes. If you have diabetes, your beta cells won't secrete enough insulin, whether or not you're overweight.
They concluded that "the diabetic state is much more closely related to a failure of the secretion of insulin than to diminished efficiency of the circulating hormone level," that is, beta cell defects are more important than IR in causing type 2.
Another group did a similar study and found that those who progressed from prediabetes to diabetes had decreased insulin responses to glucose at the beginning of the study.
Yet people with type 2 diabetes continued to be told that their obesity had caused IR and the IR had caused the diabetes.
Recently, 23 years after the research published by Cerasi and others, there was a report of a study of 13 new genes increasing the risk of type 2 diabetes. The authors of the study said they were "intrigued" by the finding that most of these genes affect beta cell secretion rather than insulin resistance.
"Beta cell impairment may play a larger role in type 2 diabetes than previously recognized," the authors said, as if this was a totally new idea.
It is true that there's so much diabetes research published that no researcher can have read all of it. One report or one person's opinion isn't considered proof of anything, but it should suggest something, so researchers shouldn't be stunned 23 years later to discover the same thing.
Why is it that an amateur researcher, a newly diagnosed patient, can find information a professional apparently cannot? I'm sure the Cerasi papers were not the only ones to come to the same conclusion, and the other researchers had 23 years in which to look.
Cerasi also recommended using insulin in type 2 patients right from the beginning, to normalize blood glucose levels and reduce glucotoxicity, which he felt contributed to the IR. "Present therapeutic approaches based on initial dietary restriction followed after a period of up to several months by oral diabetic agents, seem rather unsuited" for returning the patient to mild diabetes or prediabetes.
"I propose initial, short-term (one to a few weeks) intensified insulin treatment aimed at achieving euglycemia very rapidly, in order to block down-regulation of glucose transport and inprove beta-cell function." He showed in a pilot study that when patients in whom the oral drugs had stopped working were given insulin to maintain normal BG levels for two weeks, they could then maintain good control on oral agents alone after the insulin was stopped.
Again, a recent proposal suggests essentially the same thing. Ralph DeFronzo proposed starting newly diagnosed patients with type 2 on an intensive drug regimen of metformin, a TZD, and exenatide. And he and 15 other diabetes experts proposed the same at the 2008 ADA meeting.
The ADA's response: Prove it. They just now started a 3-year study to see if early normalization of BG levels with drugs helps. But what is taking them so long? And why use drugs instead of insulin?
Other research has shown that early intensive insulin treatment is more effective than drugs in maintenance of beta cell function. So why mess around with expensive drugs that can have serious side effects when a simpler, cheaper treatment has already been shown to work?
It boggles the mind.
Another example is a 2007 paper by Frank Q. Nuttall and Mary C. Gannon. They showed in 1996 that fasting caused normalization of BG levels in people with type 2 diabetes and wondered, "Could merely a reduction in carbohydrate mimic the effect of a reduced fuel-energy diet or short-term starvation on blood glucose in people with type 2 diabetes mellitus?"
They published the results of using l0w-carb diets (20 and 30% carbohydrate), showing that BG levels and HbA1c levels were much lower. However, their request for further funding was rejected by the National Institutes of Health, which said their sample sizes were too low to show anything and "it is difficult to conceive of the diet as producing larger improvements than metformin or rosiglitazone, for example, especially if the subjects are maintaining their body weight."
"So much for open mindedness," wrote Nuttall and Gannon. The health authorities cling to their old views even in the face of new evidence. They seem to have made up their minds, and there's no more room in their tiny minds to consider alternatives.
But wait a minute. For decades, Richard K. Bernstein has been proposing low-carbohydrate diets for both type 1 and type 2 patients. His first book was published in 1984. But almost no one in the professional world listened to him either. Why did Nuttall and Gannon have to "wonder" in 1996 if the idea of reducing carbohyrate would work?
Research has been done, and it has been published, but other researchers don't seem to pay a lot of attention.
Why must the patients be the ones to ferret out the facts?
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