Monday, December 28, 2009

Biased Reports

Now that Santa has come and gone and we don't need to worry about being good for another year, I can stop worrying that I might say something unkind in a season of joy and get back to sniping about the biased reporting we see every day.

This time it's a study suggesting that a diet high in methionine might increase your risk of Alzheimer's disease. According to the ScienceDaily summary, foods typically high in methionine include red meats, fish, beans, eggs, garlic, lentils, onions, yogurt, and seeds.

So does the researcher interviewed for the article suggest that people eat less fish, beans, lentils, and garlic?

Of course not. Instead he blames the problem on red meat:

"But people who have a diet high in red meat, for instance, could be more at risk because they are more likely to develop this high level of circulating homocysteine, [lead researcher Domenico Pratico] said."

Well, he did at least say "for instance," but you know that most readers will come away with the idea that "artery-clogging red meat" will cause Alzheimer's, and they'll forget that fish, beans, lentils, and garlic may have the same effect.

Sometimes I think it's hopeless. These people aren't real scientists, who seek the truth, whether it's what they were expecting or not. Instead, these people start out with a preconception of what healthy eating is and then do experiments to try to prove they're right. When the answers don't come out the way they want them to, sometimes they don't publish them.

I was once in a study of the cholesterol-lowering drugs Lipitor vs Zocor. At the time, Lipitor was gaining market share, and the Zocor people hoped to prove that even though Lipitor might be better for the general public, Zocor would be better for people with diabetes.

However, according to a nurse, it turned out that Lipitor worked better for the people with diabetes. And as far as I know, the results of this study have never been published.

I hope the people who read this blog are smarter than average and know how to read between the lines in these popular science reports.

We'll never get the answers if we have to rely on these biased popular reports.

Tuesday, December 22, 2009

Quick Chocolate Cake

The holiday season is difficult for many of us, as we watch our friends gobble down allegedly delicious holiday foods. So I thought I'd mention an instant LC chocolate cake recipe I got somewhere. Can't remember where, so I can't give credit.

The nice thing about this recipe is that it's incredibly fast, so if you suddenly get hit by a yen for something sweet and chocolate but you wisely don't keep stuff like that in the house, you can whip up a batch of this in minutes.

1/4 cup nut flour (or wheat bran or rice bran)
2 tablespoons cocoa powder
1/4 teaspoon baking powder
3 to 5 packets of sweetener
2 tablespoons melted butter, or sour cream
1 tablespoon water or DaVinci syrup, any flavor)
1 egg

Mix everything together in a 2-cup microwavable glass cup and cover with plastic wrap. Cut a small slit in the center of the wrap to vent. Put in microwave for about a minute.

That's it! I'm lazy, so I usually don't bother to cover with plastic wrap and it turns out OK. I also don't see a reason to waste the DaVinci syrup, as this is plenty sweet (5 packets of sweetener made it too sweet for me), and the chocolate flavor is intense so who needs more?

You can gussy this up by adding chunked nuts. Or you could add a LC icing or swirls of whipped cream.

I never particularly liked chocolate cake; I was more of an icing person. And I preferred fruit pie to cake. But I do occasionally feel chocolate-dessert deprived, and then I whip up a batch of this and feel satisfied for another month or so.

Sunday, November 22, 2009

Serotonin and Insulin Secretion

Most of us have heard of serotonin (5-hydroxytryptamine, or 5-HT) as a neurotransmitter. It's the compound that is affected by the SSRI antidepressants.

Nerves use neurotransmitters to transmit messages from one nerve cell to the next. The nerve's signal arrives at the end of one nerve, which then secretes a neurotransmitter. This diffuses across the tiny space between the nerves and is taken up by the next nerve. The neurotransmitter is then reabsorbed by the first nerve and can be used again. The reabsorption also prevents the signal from becoming permanent.

The SSRIs slow down the reuptake of the neurotransmitter so its effects last longer. Serotonin can affect mood, and low levels can cause depression. Hence keeping it around longer by means of the SSRI drugs can reduce depression.

So what does all this have to do with diabetes?

A fascinating new article that appeared in the open-access journal
PLOS recently shows that serotonin in beta cells is required for insulin secretion. A summary of the article appears here.

Apparently it's been known for 30 years that serotonin is synthesized in beta cells and cosecreted from the beta cells along with insulin, but no one knew why, and most textbooks -- even comprehensive ones -- didn't even mention this fact.

But this German research group showed that mice unable to produce serotonin outside the nervous system became diabetic. Infusing them with serotonin corrected the problem.

So all we have to do is take serotonin tabs and all our problems will disappear? Unfortunately, no.

The crucial factor here is whether the serotonin is inside the cell or outside the cell. High serotonin inside the cell stimulates insulin release. High serotonin outside the cell inhibits insulin release. It's the ratio that is important.

So when internal serotonin levels are high, insulin and serotonin are cosecreted. The secreted serotonin then inhibits further insulin release. Gradually the secreted serotonin is taken up again by the beta cells, until there's more inside the cell than outside the cell. Then the cell can secrete more insulin.

The authors postulate that this system is responsible for the well-known insulin pulses that occur in nondiabetic people between meals. This pulsating pattern is lost in people with type 2 diabetes.

This research is also fascinating for a more general reason. Most water-soluble hormones like serotonin, histamine, and the catecholamines were thought to work at the surface of the cell. They bind to a surface receptor in the membrane, causing conformational changes that affect the metabolism inside the cell. This is true of insulin, for example.

Other hormones, the lipid-soluble ones like thyroid hormone and the steroid hormones, get inside the cell and bind receptors in the nucleus, changing the expression of genes.

But this study showed that serotonin works inside the beta cell in a very different way. It doesn't just bind to a receptor. Instead it works by actually forming bonds with other compounds in the cell, called
serotonylation. This action is very different from the way serotonin works as a neurotransmitter.

Serotonylation had previously been found in platelet-forming cells and in smooth muscle cells. Finding it in beta cells suggests that it may turn out to be a general property in many kinds of cells.

This will open the door to a lot more research on how hormones work as well as research to find new drugs that work to control hormone action.

And I hope it results in new treatments for diabetes of all kinds.

Saturday, November 21, 2009

Glitazones and Weight Gain

Many people who take a glitazone drug -- pioglitazone (Actos) or rosiglitazone (Avandia), also known as TZDs (thiazolidinediones) -- find that the drug works well to lower their blood glucose (BG) levels, but it also seems to make them gain weight.

Some doctors will say that the weight gain is simply fluid retention, which is a known side effect of the TZDs. That did happen to me when I was in a short clinical study of Avandia. I put on about 6 pounds during the study, but I lost them without effort when I went off the drug at the end of the study.

But the TZDs are also supposed to trigger the differentiation of precursor cells into new fat cells. The new, small fat cells aren't stuffed with fat like some of the older, large fat cells, and they're more responsive to insulin. Hence they take up more glucose, and this keeps the BG levels down.

Several recent studies have shed more light on the weight gain that occurs with the TZDs.

One study, published in the Journal of Biological Chemistry, showed that in obese mice, at least, rosiglitazone increased the expression of the VLDL receptor gene in fat cells. VLDL is the type of cholesterol particle that carries fats from the liver to the various organs that use it.

With more VLDL receptors on the fat cells, more VLDL would get bound to the fat cells, which would take up more fat. And the mice did, in fact, get fatter than the control mice, although their insulin resistance decreased.

They also showed that in certain mutant mice that couldn't bind VLDL, the effect on insulin resistance was preserved, but the mice didn't gain any weight, meaning it would be possible in theory to separate the effects on BG levels from weight gain.

Another study, in the journal
Clinical Endocrinology and Metabolism, showed that pioglitazone treatment enlarges subcutaneous fat cells in insulin-resistant patients.

This is rather ironic, because obesity-related insulin resistance is associated with large fat cells, and TZD therapy is supposed to result in the birth of smaller fat cells. But in this study, although insulin resistance decreased, the size of the fat cells increased with the TZD treatment.

The TZDs work by stimulating a nuclear transcription factor called
PPAR gamma. A third article described a study in humans in which they separated patients into TZD responders and TZD nonresponders. Previous studies had suggested that about 30% of patients do not respond to the TZDs.

They found that in insulin sensitive people, those without insulin resistance, feeding resulted in the expression of many genes involved with glucose metabolism. This response was blunted in people with insulin resistance.

In the insulin resistant people who responded to a TZD, the drug caused an increase in the genes that were stimulated in the insulin sensitive people. In the insulin resistant nonresponders, the expression of the same genes was not changed.

But they also noted that fat cell gene expression in muscle increased after TZD treatment, especially in those people who responded to the drug, suggesting that the decrease in insulin resistance in the drug responders was caused by more fat cells in the muscle tissue.

Hence they suggested that the fat infiltration often seen in the muscles of insulin resistant persons may not, in fact, be causing the insulin resistance. Rather, they suggest, the fat cells are absorbing extra calories from overeating and are attempting to reduce the insulin resistance.

All these studies -- and I'm sure there are many more -- are consistent in suggesting that the TZDs
do work by increasing the amount of fat in the body, both subcutaneous fat and fat in muscle tissue, and perhaps elsewhere as well.

They are consistent in suggesting that the TZDs work by stimulating this increased amount of fat while at the same time reducing insulin resistance. If you're taking one of these drugs and you gain weight, don't let your doctor tell you that you're not watching your portion sizes. The drug is probably causing the weight gain.

However, the one study suggested that these two effects could be separated, although no one knows how yet.

The last study also notes the difference between drug responders and nonresponders. The TZDs don't work for everyone.

Most drugs can have both good and bad effects. For example, it turns out that the fat cell precursor cells that the TZDs stimulate to differentiate into baby fat cells are the same ones that can be turned into bone-forming cells. When you produce more fat cells, you produce fewer bone-producing cells. Hence the TZDs can contribute to bone loss, or osteoporosis.

As with all drugs, we need to weigh the pros and cons of the TZDs in light of our own particular situation. First, do they work to reduce BG levels when we take them? Or are we nonresponders? No point in risking side effects if the drug isn't working for us.

Second, are we unhappy with the amount of weight gain that results from the drugs?

Third, are we at high risk for osteoporosis so even a small loss of bone-producing cells might have terrible consequences?

Diabetes is complicated, and there are no simple answers. But the more we understand about how these drugs work, the better the decisions we can make about which drug or drugs work best for our own particular physiology.

Friday, November 20, 2009

On the Popular Press

Does the popular science press help us all by spreading the word about new research? Or is it causing harm by distorting the facts?

I spent 8 years as a reporter/editor working for a small daily newspaper in Vermont, and I'm familiar with the stock complaints about the press. We heard them every day.

"You're blowing it out of proportion." Or "You just want to sell papers." Or "You misquoted me." I was once accused of misquoting a politician because I reported only what he said at a meeting and not what he had intended to say!

So I hate to jump on the "tar the press" bandwagon myself. But sometimes things really go too far.

One thing that has angered me lately is the tendency of the popular science press to blame everything on fast-food gluttony. Whenever there's an article about overeating, for example, they illustrate it with a gargantuan cheeseburger accompanied by a bucketful of French fries. Don't they know it's possible to overeat on chicken and tofu as well?

A recent Science Daily article here really went too far. This one concerned a study showing that a high-calorie diet may accelerate age-related disease. The article was illustrated by a man with a huge plate of french fries. He was eating with his hands, which were covered in catsup. There was also catsup on his face, as if he'd been grabbing the fries and stuffing them in so fast that he got catsup all over everything.

Apparently I wasn't the only person who was fed up with this sort of thing. I see that the current iteration of the story illustrates the other extreme: a plate with very little food: one shrimp, a third of a spear of asparagus, and a mushroom.

And it's not just the popular press that blames everything on fast-food gluttony. Scientists themselves tend to single out those factors.

This Science Daily story was about a study showing that people in their 60s today have more disabilities than previous generations. What do the researchers blame this situation on? Immigrants and fat people, of course.

They say that "disabilities may be linked with the changing racial and ethnic makeup of the group that recently reached or will soon be reaching its 60s, with the most rapid growth projected to be among African Americans and Hispanics -- groups with significantly higher rates of obesity and lower socioeconomic status, both of which are associated with higher risk for functional limitations and disabilities.

It's true that very extreme obesity would be likely to make people less likely to walk a quarter of a mile or climb steps. But a lot of people in the "obese" category of BMI are as fit as their thinner counterparts. Maybe the real change is that no one, thin or fat, tends to walk anywhere these days when most people have cars.

And finally, popular science writers obviously don't do any fact checking of science press releases at all. A currently hot topic in the popular press is a recent study in which some researchers did MRI on some mummies and found evidence of heart disease, as reported here. The reporters were agog.

As one said, this new study challenged "longstanding assumptions that cardiovascular disease is mainly a malady of modern societies." But low-carb author Michael Eades discussed the evidence for cardiovascular disease among ancient Egyptians in his book Protein Power, first published in 1996. And apparently the first report of aortic calcification in ancient Egyptians occurred in 1852, as a result of a study by a scientist named Czermack, as discussed in the book Mummies, Disease, and Ancient Cultures.

Let's see. That's only about 150 years ago, but scientists continued to believe that cardiovascular disease is "often attributed to urbanization, fast-food diets, smoking and sedentary lifestyles characteristic of Western societies," according to the Wall Street Journal article. Notice the reference to fast-food diets again. The assumption of the reporter is that all of society's ills are caused by fast food.

Because the Egyptians didn't have fast food, as far as we know, however, they then blame it on the fact that the upper classes (and of course the lower classes, who ate mostly bread and onions, weren't mummified) ate meat "from cattle, ducks, and geese." Again, the bias is that the only healthy diet is one devoid of meat.

I'm quite aware that the reporters who write these popular science article are most likely under tight deadlines. Maybe they have to produce X number of stories per day in order to keep their jobs, so they don't have time to do even quick Internet research on the topic, and they simply print the press releases that flood in every day.

Nevertheless, the biases that are so obvious not just among the science reporters but among the scientists as well (surely they knew that finding evidence of cardiovascular disease in mummies was nothing new; what was new was the technique they used to find it) makes the rest of us sceptical about anything we read.

I think the science reporters and even the scientists who do the research are shooting themselves in the foot.

Tuesday, October 13, 2009

Misleading the Public

A recent article in the New York Times focused on the safety of ground beef. Apparently a lot of ground beef includes bits and pieces cut from parts of the animal that are likely to be contaminated with feces, and thus E. coli.

Not all the meat is tested before sale, increasing the chances that you'll get sick from eating it unless you cook it to death.

But another comment in the article didn't seem to arouse much comment. According to the Times article, "To finish off the Smiths’ ground beef, Cargill added bread crumbs and spices, fashioned it into patties, froze them and packed them 18 to a carton."

Bread crumbs? In ground beef? What's going on here?

According to the article, "The listed ingredients revealed little of how the meat was made. There was just one meat product listed: 'Beef.' "

When I first read this, I thought it meant that the only ingredient listed was beef, and I was outraged, thinking of all the people who have wheat allergies that could be triggered by even small amounts of wheat. Other people apparently also read the sentence that way.

But on rereading, I suspected that what the author really meant was that the only kind of meat listed on the label was beef. And I assume the bread crumbs were also listed.

I'm still angry. If I buy ground beef (and I only buy it at the local general store, which I know grinds its own), I expect to get ground beef, not ground beef plus a lot of fillers. And what about people with serious wheat allergies who eat hamburgers at parties, or at restaurants, if the ground beef comes from one of these companies that add bread crumbs to them?

We really can't trust anyone when it comes to food labels.

Another example is the new high-fiber sugar substitute sold under the Splenda label.

One problem with most commercial sugar substitutes is that they because the sugar substitutes are so intensely sweet, they need some kind of bulking agent so you can pour it out of the container. Without the bulking agent, much of the sweetener might stick to the side of the package.

And unfortunately for those of us with diabetes, the bulking agent is often glucose (listed as dextrose, which some people don't realize is the same thing) or maltodextrin, which consists of 3 to 19 glucose molecules strung together and acts essentially the same as glucose in the gut.

So when I saw that Splenda was offering a new "high fiber" form, and the ingredients were simply "soluble corn fiber and sucralose," I was thrilled. At last someone had figured out that you could use fiber instead of maltodextrin or glucose as a bulking agent.

But because I'm not too swift, it took me a bit to notice the nutritional facts, which said there were 2 grams of carbohydrate and 1 gram of fiber. Wait a minute! If only 1 gram is fiber, what is the rest of the carbohydrate?

The other versions of Splenda list 1 gram of carbohydrate, so it looked as if instead of substituting fiber for maltodextrin/glucose, they'd simply added fiber to the regular stuff and not listed the maltodextrin/glucose on the label.

So I wrote to the manufacturers and asked, "Your new Splenda with fiber contains 2 g of carbs and only 1 g of fiber. What is the other gram of carbohydrate? Maltodextrin?"

In response, I got a canned response giving the sugar equivalents for Splenda and never even mentioning the new high-fiber product. So OK, they're not going to help. I searched the Internet for answers.

According to one site, "Corn syrup is being relabeled as "Soluble Corn Fiber" in foods and artificial sweeteners, possibly to avoid consumer health concerns about high fructose corn syrup."

And from the cached page of the company that produces it, Promitor (they've removed the original page), "Soluble Corn Fiber may be labeled as “soluble corn fiber” or alternatively, it may be labeled as “corn syrup” or “corn syrup solids” depending on whether it is liquid or dry."

In other words, they take corn syrup, which includes some soluble fiber, and process it to maximize the amount of fiber and then use that as the bulking agent. Their site says that soluble corn fiber is 70% fiber, so obviously 30% is something else.

The 50:50 breakdown on the label (2 g of carbs and 1 g of fiber), instead of 70:30, is probably due to rounding. If you have 2 g of carbs that are 70% fiber, that would be 1.4 g of fiber, and if you're not using decimal places, this would round to 1. The 0.6 g of nonfiber would also round to 1.

But what isn't fiber is most likely maltodextrin and glucose, but they don't have to say that on the label, and most consumers don't t realize that they're eating corn syrup. I didn't.

Various discussions of the soluble corn fiber note that it can be used for "consumer-friendly labels." I would describe them as "consumer-deceiving labels."

I don't like it when a company tries to deceive me with "consumer friendly" terms, making me think there's no corn syrup in what I'm eating, so I'm not planning to buy any more Splenda.

Type 2 Testing

I posted a blogpost at Health Central on testing in type 2, and on the basis of the number of comments I received, I gather this is a pretty hot topic for a lot of people. You can see it here.

Back Again

I recently returned from a short trip to southern France, which was great. But unfortunately I and my traveling companion both returned with some kind of virus, which we probably got on the crowded plane, and I've been under the weather since then, not trusting my brain to write anything very worthwhile.

However, I'm finally seeing the light at the end of the tunnel and I've started tackling the stacking of 3 cords of wood. Maybe that's helping to cure me.

France was great for someone on a low-carb diet, as the French aren't as fat-phobic as most Americans. My first meal, in a small town along the coast, was the only thing they were serving at that hour (restaurants serve only from noon to 2 p.m., which we didn't know): a large assortment of delicious cold cuts, pates, and a green salad. I was in heaven.

Also, meals didn't come with huge mounds of mashed potatoes or rice, and corn. Of course all the meals come with bread, but I only tasted that. Some was delicious and some was mediocre, not as good as the stuff I used to make using Julia Child's bread recipe and King Arthur flour. A popular "dessert" in France is cheese, and I was able to substitute that for the sweet dessert that came along with full-course meals. Breakfast at the B&B included yogurt and "fruits rouges" (berries), cheese, and sausage along with bread and homemade jam, which I tasted.

But the woman couldn't grasp the concept of a LC diet and assumed I was gluten intolerant. When she finally grasped that I was diabetic, she then assumed I could eat other starches, just not sugar. Oh well. I survived.

I was stuffing myself with fatty cheeses along with other LC food, and when I got home I discovered I'd lost 2 pounds.

I think I need to get a grant to return to France to study this phenomenon.

Friday, September 4, 2009

Inflammation and Heart Disease

We all know that chronic inflammation is a bad thing, and many of us try to eat antinflammatory foods or we take supplements that are supposed to reduce inflammation.

But like everything in human biology, inflammation may not be as simple as some people think.

In the short term, inflammation is usually a good thing. It's what protects us from infection. When you cut your skin, it usually hurts and becomes hot and red. Sometimes it swells. This is a sign of inflammation. (Doctors sometimes refer to rubor, calor, dolor, and tumor, referring to red, heat, pain, and swelling.)

What happens is that the wound releases signals that tell the body to send white blood cells to the area to repair the damage, removing dead tissue and replacing it with new tissue. Local blood vessels dilate and become leaky, allowing fluids and white blood cells to exit and get to the wound. This results in swelling, heat, and redness.

Again, short-term inflammation is a good thing. It's chronic inflammation that is supposed to contribute to chronic diseases such as diabetes and heart disease.

But a paper published last month showed that among an obscure tribe in the Amazon, chronic inflammation is the norm, but heart disease is rare.

According to the scientists, the Tsimane tribe still live a traditional lifestyle, fishing, hunting and gathering, growing crops, and also growing and using tobacco, although they smoke much less than Americans who smoke. Most of them die from infections or parasitic diseases. About three-quarters harbor intestinal worms or protozoa. Their life expectancy at birth is only 43 years.

Chronic inflammation is prevalent, and they have high levels of C-reactive protein (CRP), which is often used as a marker of inflammation in the Western world.
The Tsimane also have low HDL levels, which is supposed to mean high risk of heart disease.

But the Tsimane had almost none.
Not a single adult, even the elderly ones, showed signs of peripheral artery disease, a sign of atherosclerosis. Peripheral artery disease increases with age in every other population studied.

The scientists reported that no one died of a heart attack during the 7 years that they were studying the population, which consisted of about 9000 people.

What this suggests is that chronic inflammation alone is not enough to trigger heart disease in a population living a traditional lifestyle. That means they're pretty lean and get plenty of exercise every day just obtaining their food. Their food is fresh.

Of course, many of them died from infectious diseases before they were old enough to be at higher risk of heart attacks and type 2 diabetes.

And one of the flaws of this study is that the authors do not indicate how many people were in each age group for which they reported data. There were only several hundred people in the whole samples
(they did more of the simple tests like blood pressure than the more complicated ones), sometimes even less, and they report the results as percentages, so you have no idea how many people were in each age group.

Nevertheless, I think it illustrates one of the flaws to the American approach to health. Too many people focus on one or two factors, try to control those with drugs, and then expect chronic diseases to go away.

It doesn't happen like this.

Our entire lifestyle makes a difference. We can't pop antioxidant and anti-inflammatory pills and think the risk of cardiovascular disease will evaporate. We need to try to live more like the Tsimane, getting exercise as we go about our daily lives and eating real foods that are as fresh as possible.

One would hope that it's not the parasites that are protecting the Tsimane from heart disease. But that's also possible. Some people theorize that allergies in the developed world have risen because our parasite loads are so low. Maybe parasites also help our arteries. One never knows. As I said, human biology is never simple.

Another possibility discussed by the authors is that the Tsimane are somehow protected by genetic differences. In my opinion, that's always a way to explain the results when they don't come out as you expected they would.

This article also illustrates another issue: the effect of preconceptions by the scientists doing the study. Most people today think thin is good. They think eating a low-fat diet is good, especially if it's vegetarian.

And the title of this article is "Inflammation and Infection Do Not Promote Arterial Aging and Cardiovascular Disease Risk Factors Among Lean Horticulturalists." In other words, they're saying, "Well, these risk factors might not work if the rest of your lifestyle is healthy, like being thin and eating a plant-based diet."

They could just as easily have said, ". . . Among Tobacco-Using Hunters With High Parasite Loads," or "Well, these risk factors might not work if you smoke, eat meat, and have a lot of worms."

Many people read only the titles of articles, and perhaps the abstracts. So any biased generalizations made there can mislead a lot of people. It takes much longer to plow through the full text of an article. But sometimes it's necessary to learn what it really shows.

Monday, August 24, 2009

Some Progress

Many of us whine about doctors' lack of understanding of the diabetes research that we read. One reason for this knowledge gap is that current standards for medical education don't require that medical students be give significant instruction in some areas -- for example, statistics, nutrition, and disease prevention rather than disease treatment.

A fairly recent (well, OK, it was June 5; I get behind in my reading) editorial in the journal Science suggests that medical education in some of these areas may improve if the recomendations of the Association of American Medical Colleges and the Howard Hughes Medical Institute are followed. (The full text is free if you register.)

The report, titled Scientific Foundations for Future Physicians, says that "physicians must have a firm grounding in the biomedical sciences and understand their relation to the physical sciences and mathematics. For physicians to be prepared for inquisitive, critical thinking and lifelong learning, they should also be able to incorporate the methods of science into their practice, including skeptical and critical analysis."

Wow! Skeptical and critical analysis instead of listening to drug reps and reading medical magazine summaries. Wouldn't that be wonderful!

To achieve these goals, the groups recommend changing medical education starting in the undergraduate years: "Students should arrive at medical school prepared in the sciences, including some areas not currently required, such as statistics and biochemistry."

The idea is that if first-year studenst already have a grounding in the basics, then medical school can focus on more advanced concepts, for example, "the synergistic relationships among biomedical science, research, and clinical medicine."

They also recommend more emphasis in medical school on "the physical sciences and mathematics in biomedical research and clinical practice."

They also recommend assessing incoming students by their competency, rather than according to what courses they've taken. This should allow creative students to design their own ways of learning rather than forcing them into taking certain undergraduate courses.

Whether or not these recommendations will be followed of course no one knows. And even if they are, it will take a long time before physicians trained with the new guidelines -- better equipped to do critical statistical analyses of the latest blockbuster study of a new kind of cholesterol drug, for example -- constitute a significant percentage of the practicing physician population.

Even when they do, the problem that even a physician with a firm grasp of physical sciences, statistics, mathematics, and biochemistry as well as medicine and with a burning desire to do critical analyses still needs to have the time to do it. Not all physicans spend their afternoons on the golf course. Many of them are overworked.

Still, just the idea that people in the field are recognizing the deficiencies in the training of physicians is a good thing. Let's hope something comes of it.


For anyone not subscribed to Health Central, here are links to my most recent posts there.

Thinking Outside the Box is about how success in diabetes control often stems from being able to think outside the box, applying what you learn to your own individual physiology rather than following the cookie cutter advice you may get from your health care team.

Is Type 2 Diabetes Your Fault? discusses the myth that "you brought it on yourself." Needless to say, it stimulated a lot of discussion.

Finally, Avoiding Diabetes, is an allegedly humorous post about how to avoid getting diabetes. When I read the Comments, I wondered if some people had taken it seriously!


I'm afraid I've been absent lately, working through a Blogger Identity Crisis.

I've been thinking about how to deal with two blogs, this one and the one at Health Central. Initially, I was using this site for longer posts and writing shorter versions of the same thing for Health Central. But that came to be too much of a chore, figuring out how to say the same thing in a briefer way, and I found I was sometimes putting off writing something for just that reason.

So I've decided to abandon that approach and write brief, more general posts for Health Central, discussing the things people always want to seem to talk about, like diet, feeling overwhelmed, exercise, trying to lose weight, whether or not to take meds, etc. I also promised to write diabetes humor posts for them.

At this site I'll focus more on new research, both in-depth discussions and brief notes about research or other items that catch my eye.

I'll be assuming that anyone reading this blog is intelligent, already knows at least a little about diabetes, and wants to understand things in greater depth. I hope this works and I won't need to undergo another Blogger Identity Crisis!

Thursday, July 23, 2009

Are Grains Healthy?

Several studies have shown that the so-called Mediterranean Diet is healthy.

This is not surprising, because as interpreted by various groups, it consists mostly of whole foods instead of a lot of processed junk, and you can show that almost any reasonable diet is healthy if you compare it to the "standard American diet" that is high in trans fat and processed carbohydrates.

Definitions of the diet do differ.

As interpreted by the American Heart Association, the key features of the diet include "
high consumption of fruits, vegetables, bread and other cereals, potatoes, beans, nuts and seeds"; emphasis on olive oil in place of other fats; low to moderate consumption of dairy products, fish and poultry, with little red meat, and eggs only zero to four times a week; and low to moderate amounts of wine. They suggest that the diet may have too much fat.

A WebMD article says the Mediterranean Diet features "fresh fruits and vegetables, whole grains, nuts and seeds, legumes, seafood, yogurt, olive oil, and small amounts of wine for heart health."

A New England Journal of Medicine article described the diet as being "rich in vegetables and low in red meat, with poultry and fish replacing beef and lamb," with olive oil and "a handful" of nuts as the main source of fat.

It's clear that different people interpret the "Mediterranean Diet" differently, although they all seem to agree that it is high in vegetables and low in beef. But there are many components to the diet, and it hasn't been clear if the healthy aspects of the diet (for people in general, not necessarily people with diabetes) are because of all the components, some of them, or maybe just one or two.

So when a statistical study of the components of the diet was recently published, showing that some of the Mediterranean Diet components didn't seem to have any effect on mortality at all, I was expecting an avalanche of blog posts commenting on this.

I'm still waiting.

Most of the blog posts and articles I found simply restated what the researchers had reported in their publicity releases, without comment.

The study showed that consumption of cereals, dairy products, and fish had very little effect on the mortality of the participants in the 8-year study in Greece. In fact, in this study, increased fish and seafood consumption slightly increased mortality, although this increase was not statistically significant. But we've been bombarded with messages telling us to eat more "healthy whole grains," fish, and low-fat dairy if we want to be healthy.

Of course, the authors of the study couldn't believe that whole grains aren't healthy, so they suggested that the lack of effect of cereals might be because they didn't separate out processed cereals and whole grains.

It's possible that's true.

It's also possible that when the results of a study don't fit the preconceptions, the authors find some reason to explain it. When the results are what they expect, they accept the study as proof of their pre-existing theories.

The study did show that both low alcohol consumption and high alcohol consumption were associated with a statistically significant increase in mortality compared with moderate alcohol consumption.

They said high consumption of vegetables, legumes, fruits and nuts (which for some odd reasons they lumped together), and olive oil and low consumption of meat and "meat products" (which would included luncheon meats) were associated with reduced mortality.

Then they said that none of these results were statistically significant. This lack of statistical significance is not mentioned in the press releases.

Because the researchers were expecting the results they found for vegetables, legumes, fruits and nuts, olive oil, and meat (although they were not statistically significant), they didn't try to interpret them. For example, "meat" is a broad category. It's possible that some meats such as luncheon meats are unhealthy and other meats such as lean beef are not. Maybe nuts are beneficial but fruits are not, but because they grouped them together, there's no way to know.

Although they called the diet Mediterranean, you notice that all these foods that showed benefit are real, whole foods that hunters and gatherers could eat, rather than processed garbage. You could just as well eat these foods and call it a Whole Foods Diet or a Traditional Diet or a Neolithic Diet. Hunters and gatherers probably eat all the meat they can get, but their hunts are not always successful. Olive oil is processed but in a minimal way. You could get the same monounsaturated fat by eating the olives themselves.

I'm not a big fan of any nutritional studies because most of them are based on food recall forms. I often can't remember what I had for lunch. There's no way I can remember what I ate for the past few days or the past month or so. Nutritional researchers claim they've tested the recall and it's reasonably accurate, but I'm not convinced.

Furthermore, we're all individuals. High fruit consumption might be beneficial for people without diabetes (certainly better than high banana split consumption), but a lot of fruit will raises the blood sugar of people with diabetes.

I suppose this study is a first step. Perhaps future studies will be able to refine these results.

In the meantime, follow the advice we patients so often give. Don't accept any diet as the "best diet" until you see how it affects you individually. If your nutritionist tells you to eat a lot of "healthy whole grains," try a few whole grains and see what it does to your blood glucose levels 1 and 2 hours after you've eaten them.

Then make up your own mind.

Tuesday, July 14, 2009


The readers of this blog are intelligent, so I don't think I need to comment a lot on this.

What's sad is that the people who write the headlines are so gullible. When I worked for a small daily newspaper and we got press releases, we always edited the BS out. Today, people seem to reproduce online what everyone sends them.

Science Daily does a lot of that. Sometimes you have to look hard to find out what's new in one of their articles, which focus on the names of all the scientists involved, the institution where they worked, the fact that the results were published in "prestigious" journals, and suggestions that this research opens the way for new drugs to treat diabetes.

It's nice that the pork researchers are supporting low-carb diets, but the constant barrage of specific food "cures" or "preventatives" for diabetes is making patients confused and cynical and harming them in the long run.

I've posted a satirical take on the same article here.

Sunday, June 28, 2009

Lantus and Cancer

Everyone seems to be talking about the recent report that insulin glargine (Lantus) might increase cancer rates. Needless to say, this is very upsetting news to a lot of people, although Lantus has been linked with cancer in the past.

But like most news stories, the facts aren't as simple as the summaries would indicate. If you like reading all the details, they're available here in full text, free.

The method of publishing these papers was interesting. Apparently the first study was submitted to the journal Diabetolgia last year. But the editors decided not to publish it without further evidence. So they commissioned three additional studies to see if the results could be reproduced. Those plus the original article are the four articles available at the journal’s Web site.

Was this irresponsible or responsible? Not publishing results suggesting some bad side effect of a drug might mean that people were harmed because they didn’t know about it. On the other hand, publishing preliminary results suggesting some bad side effect of a drug might mean that people were harmed because the huge publicity in the popular press that usually follows such news would scare patients who could be helped by the drug so they’d stop taking it.

This happened with the drug rosiglitazone (Avandia) last year. One analysis suggested that it caused heart disease, there was a huge glut of articles and blogposts saying Avandia could kill you, and a lot of people stopped taking it. Their A1cs then increased, and high A1cs also increase the risk of heart disease.

So it’s sort of a damned if you do and damned if you don’t situation.

Most patients don’t have the statistical skills to analyze research articles, especially meta-analyses, which try to combine results of numerous trials to see if they can come to overall conclusions. Because the patient populations, time frames, and endpoints being studied in different studies differ, this is difficult to do, and it’s easy to disagree with the results of a meta-analysis.

But regardless of whether or not we approve of the journal’s method of dealing with the Lantus-cancer articles, there are some things patients should understand.

In the editorial accompanying the articles, the authors make a few interesting points:

1. Type 2 diabetes is associated with increased rates of cancer of the colon, breast, and pancreas. People with type 2 diabetes have insulin resistance and hence need more insulin, either produced by their own beta cells or injected.

2. Cancers of the colon, breast, and pancreas have been associated with increased circulating levels of insulin in nondiabetic people. Obviously they wouldn’t be injecting insulin. They’re probably insulin resistant.

3. Metformin reduces the rates of cancer of the colon and pancreas but not cancer of the breast and prostate. (Metformin also seems to reduce the pancreatitis that can result from sitagliptin [Januvia].)

4. Insulin is a growth factor for both healthy cells and cancer cells in cell culture.

5. Evidence suggests that insulin doesn’t cause cancer, but it may increase the rate of growth of cancer cells that have been caused by something else.

6. Most elderly people have some early cancer cells. For example, 90% of men older than 90 years have prostate cancer cells. (The body often keeps these cells in check, or even destroys them.)

7. One early insulin analogue, B10Asp, was found to increase cancer growth in rodents and was never marketed. But "B10Asp would have passed the carcinogenicty testing to which insulin glargine was subjected and would now be in clinical use."

8. Lantus increases mitogenic potency (mitogenic means it causes cell division or transformation into another cell type, for example, a malignant one) six to eight times. The short-acting insulins (e.g., Novolog and Humalog) have little effect. Detemir (Levemir) seems to reduce the mitogenic potency in vitro, but the authors say that because of technical difficulties, this was difficult to measure.

There were all kinds of confusing factors in the four studies published by Diabetologia. For instance, they classified everyone diagnosed when older than 30 as type 2. We know that a lot of type 1s and LADAs aren’t diagnosed until later in life.

In the German study, the patients receiving regular insulin were taking larger doses than the patients taking insulin analogues. In another study, those taking only Lantus were older than those taking Lantus plus a bolus insulin. The ones taking only a basal insulin were most likely type 2s, who would need large doses of insulin, and we know that cancer rates increase with age among all groups.

In their editorial, the authors conclude that

1. “There is no evidence that insulin, however formulated, causes cancer.”

2. But “the growth of some tumor cells lines is clearly enhanced by insulin.”

3. “Circulating levels of endogenous insulin appear to be associated with cancer risk in obesity and other insulin-resistant conditions, including type 2 diabetes.”

4. “There is no evidence of harm in type 1 diabetes, or in males, or in premenopausal breast cancer.”

5. “On current evidence, the short-acting analogues do not appear to present a potential problem.”

In other words, there is evidence that very high levels of insulin, no matter what the source, may increase the growth of pre-existing cancers. People with insulin resistance (metabolic syndrome or type 2 diabetes) are at increased risk whether or not they inject insulin of any kind.

Hence, for us, the best approach would be to do whatever we can to reduce the amount of insulin that we need. Reducing our insulin resistance through exercise and, if possible, weight loss should help.

Another approach, available to everyone regardless of ability to exercise or lose weight, is to reduce the amount of carbohydrate we eat.

The less carbohydrate you eat, the less insulin you need. The less insulin you need (either your own or injected), the lower your risks of encouraging the growth of cancer cells. It seems me this is pretty easy to understand.

But some people don't seem to be able to grasp this. How long will it be before the American Diabetes Association stops telling people with type 2 diabetes to eat more carbohydrate and “Make starch the star”?

Saturday, June 27, 2009

Body Build and Diabetes

You can't tell if someone is diabetic simply by looking at them.

Yet a lot of people still think you can. They buy into the idea that eating too much and exercising too little causes obesity and obesity causes type 2 diabetes. Hence, if shown a bunch of photos of strangers, many would predict that the fat ones had diabetes and the thin ones didn't.

It is true that being overweight is
associated with type 2 diabetes, and many people with the disease are, in fact, overweight. But not everyone who is overweight, or even obese, has diabetes, and not everyone who has type 2 diabetes is overweight.

While filing sometime recently, I came across a popular press article that I had found fascinating.

A British newspaper had asked 10 people between the ages of 35 and 50 who had never been diagnosed with diabetes to take "a blood test." The test was simply a
fingerstick test in a home-type meter. If the participants said they hadn't eaten (most likely not rigorously controlled, so it wasn't a real fasting test but closer to a premeal test), any result over 5.9 mmol/L (106 mg/dL) was considered suggestive of diabetes. If they said they'd eaten recently, the cutoff was 8.9 mmol/dL (160 mg.mL).

If the results were over these limits, the people were told to see their physician for more rigorous tests. They don't say which readings were
premeal and which were after eating, so one person with a reading of 8.9 mmol/L (160 mg/dL) was labeled diabetic and another with a reading of 9.1 (164 mg/dL) was labeled "needs investigation." Probably the former reading was premeal and the latter was after eating.

Here's the interesting part. They then photographed the participants wearing gym togs, so you can compare their body builds with high blood glucose (
BG) readings. It's also interesting to compare the body builds with the BMIs.

In this tiny sample, there were a lot of results that go against "common knowledge."

One person labeled obese (
BMI 34) had normal BG levels. A person with a BMI of 22 had high BG levels. A woman with a pear shape, which is supposed to be healthy (it's the apple shape with most of the weight in the stomach that is thought to be dangerous), had high BG levels. A woman with a lot of risk factors had normal BG levels. A vegetarian was obese. And the woman with the lowest BG reading said she got no exercise at all.

Scroll down through the initial text, which is the usual popular press stuff about diabetes, and try looking at the photos before you read the descriptions underneath them to see how your predictions compare with the facts.

Many of these participants had relatives with diabetes, which is probably one reason they volunteered for the tests. And they were relatively young. Some of those who tested normal with this fairly uncontrolled test may develop diabetes when they get older.

But it's still interesting to see how different people are and how misleading body build can be as a predictor of diabetes.

The sad thing is that because of the constant barrage of news stories saying that obesity is the cause of type 2 diabetes, many people (probably most people) believe it. And that includes a lot of physicians, who might not bother to do
BG tests on someone who was thin, said they "ate healthy" (whatever that means), and got regular exercise.

With the advent of home meters, it's easy to test friends and relatives if you think they might be at risk. Just make certain you use fresh lancets when you do, as well as cleaning off the tip of the finger pricker, to avoid passing on any blood-borne diseases. Even better, ask them to get their own finger-pricking devices.

Because type 2 diabetes usually starts with elevated
postmeal BG levels, measuring after a large meal, especially a carby meal, would be the best place to start. People can have normal fasting BG levels and elevated postmeal levels for years before they get a diagnosis. The earlier they learn they're at risk, the easier it will be to take corrective action, like limiting the carbohydrate content of their meals.

And if you are testing relatives, don't ignore the thin ones who exercise. Diabetes is a complex disease, and it happens to apparently healthy people too.

Thursday, June 11, 2009

Monday, June 1, 2009

Right on!

Sometimes a cartoon says it all. This one does it for me.

It's funny, but it's also sad. So many small discoveries are magnified by PR departments and then news media that the public has become cynical about every new discovery.

Some day we'll find cures for cancer, AIDS, and diabetes, and people will read the stories in the newspaper or see them on TV and think, "Yeah, right. Next week they'll announce that the cure causes something even worse."

Sadly, this sort of thing has been going on for a long time, and I doubt that it will change in the near future.

Tuesday, May 26, 2009

On Antioxidants

For a long time, many people have suggested that one reason we age is that we basically "rust" with time.

Rust is formed when oxygen reacts with iron, and the "aging as rusting" idea is that reactive oxygen compounds in our bodies, called
free radicals or reactive oxygen species (ROS), react with important compounds in our body and destroy their effectiveness.

Hence a lot of people have been taking huge doses of antioxidants in the hopes that this will make them healthier.

But recently, a news article that was ricocheting around the Internet said that when you take high doses of antioxidants (the researchers studied vitamins C [1000 mg] and E [400 mg] taken for 4 weeks), the beneficial effects of exercise are eliminated. This study was performed in nondiabetic healthy young men.

On the basis of this news report, some people probably decided to throw their antioxidants away.

But wait a minute! There are a lot of studies out there suggesting that antioxidants can help people with diabetes. What's going on here? Are antioxidants good or bad?

ROS are formed in our cells when we metabolize our food to produce the energy we need to live (or when we metabolize the glucose or fatty acids stored in the body to be used when we're not eating). The process of producing energy is not 100% efficient, and the ROS are the result of this inefficiency.

ROS are extremely reactive, and if not neutralized, they can cause damage to our cells. Our body knows this, so it produces antioxidants to neutralize the ROS. The more ROS we produce, the more endogenous antioxidants we make. This is called mitohormesis.

Beta cells, however, produce fewer antioxidants than other cells, and for this reason, they're much more susceptible to cell damage from ROS. When the damage is severe, the beta cells commit suicide, a process called
apoptosis. Chemicals used to make rodents diabetic (streptozotocin and alloxan) use ROS to kill the beta cells.

Why do beta cells produce fewer antioxidants than other cells? Is this just an accident of nature, or is there a good reason? I'd tend to vote for the latter, as the body usually has reasons for doing things, even when we don't always understand those reasons.

People with diabetes have even lower levels of endogenous antioxidants than nondiabetics, so researchers have suggested that antioxidants might be a good idea for people with diabetes. In fact, entire books have been written on this topic.

It has been suggested that people who develop complications may be especially deficient in endogenous antioxidant production, and those who do not despite poor control may be more fortunate in their natural production of these natural antioxidants.

Although in vitro and animal studies (e.g., here) have shown benefits of adding antioxidants, so far no major studies have shown major benefits in humans with diabetes. One question is how we define benefits. Do we mean A1c levels? Lipid levels? Diabetes prevention? Less insulin resistance? Decrease in cardiovascular disease rates? Increased longevity? Nicer hair?

In fact, sometimes the addition of antioxidants has been shown to be deleterious.
One study even suggested that taking one common antioxidant (N-acetylcysteine, or NAC) might cause pulmonary hypertension (high blood pressure in the arteries that take blood to the lungs).

Nothing is ever black and white when it comes to diabetes, and this is certainly true of antioxidants. Although ROS can have deleterious effects on a cell, they can also have positive effects.

For example, scavenger cells use ROS to destroy bacteria and damaged cells, including cancer cells. Using
too much of an antioxidant might lessen the effectiveness of this beneficial effect. You could think of ROS as rifles. When you use the rifles to kill bad guys like rabid panthers, that's positive (for us, that is; not for the panthers). When you use the rifles to kill good guys like innocent people, that's negative.

Some chemotherapy to treat cancer works by producing ROS that destroy the cancer cells. So some people say you shouldn't take antioxidants if you're undergoing chemotherapy. Others say that taking antioxidants helps prevent side effects from the therapy. This issue has not yet been resolved.

And recently it has been discovered that ROS are not just harmful byproducts of reactions in cells. They can also act as signaling molecules.

In fact, ROS can increase the production of insulin
in the beta cell. The ROS alone won't stimulate insulin production, but it will augment the response triggered by glucose. Perhaps this is one reason beta cells don't produce as many antioxidants as other cells. The increase in insulin sensitivity seen after exercise also seems to be triggered by ROS, which explains why antioxidants might abolish the benefit.

Insulin secretion itself seems to increase the production of ROS. Studies have shown
that compounds such as diazoxide and calcium channel blockers, which inhibit insulin secretion, improve beta cell function in humans.

This would argue for limiting anything that causes high insulin secretion, for example, high-carbohydrate diets.

When you have insulin resistance, you produce even more insulin than normal until you wear your beta cells out. Perhaps it's the ROS that are causing the damage.

This is all fascinating (well, at least I think so). But what does it mean for us?

In healthy people, the production of ROS and the production of antioxidants to neutralize unwanted ROS should be in balance. When the system becomes unbalanced, it's called
oxidative stress. But if we have type 2 diabetes, we know that something in our bodies is out of balance and we probably have less antioxidants than normal, so perhaps we need to help the cells restore the balance by taking some antioxidants.

The cited exercise study was performed on nondiabetic men. It's possible that because they were already producing sufficient antioxidants, further antioxidants were harmful. In people with diabetes who were deficient in antioxidants, the results might have been different.

Ideally, we'd be able to take just enough antioxidants to keep the beta cells from committing suicide, but not so much that the ROS wouldn't be able to augment the insulin response to glucose and protect us from cancer and infections. Needless to say, no one knows how much antioxidant this would be.

The timing and location of the antioxidants are also important. We may need antioxidants in one part of a cell but not in another. When functioning properly, our endogenous antioxidant systems would be able to control this. Taking antioxidants in pills probably can't.

Cells use short bursts of ROS to stimulate insulin production, but chronic production of ROS is harmful. This is analogous to the situation with glucose and fatty acids. Short-term increases in fatty acids or glucose will increase insulin production. But chronically high levels of fatty acids or glucose will cause insulin resistance.

In fact, when you have chronic oxidative stress (chronic production of ROS), your body starts producing more endogenous antioxidants, and this can be sufficient to reduce the secretion of insulin.

So how can we decrease the chronic production of ROS?
Preventing the formation of ROS in the first place would be likely to work better than trying to destroy just the right amount after they're formed.

The most important factor is to keep our blood glucose levels as close to normal as we can. Beta cells (and also endothelial cells) don't need insulin to take up glucose, so the more glucose there is in the blood, the higher the levels will be in these cells. The higher the levels of glucose in the cells, the more glucose they burn and the more ROS they produce.

ROS are formed when we metabolize our food. So the less food we eat, the fewer ROS we produce. Perhaps this is one reason why when overweight people (being overweight is one of several contributors to insulin resistance; about 50% is genetic) are put on a very low calorie diet, their BGs improve even before they've lost any weight.

However, we need to eat in order to live. Fasting is not a long-term solution.

I think taking a few antioxidant supplements might be a good idea, but overdoing it might not. It might also be wise to think about stopping the antioxidants if one were on chemotherapy.

Of course, it's always better to get your vitamins and other beneficial compounds in food. This is how we evolved to get them, so we're probably designed to absorb small amounts of antioxidants as we slowly digest our food rather than getting huge amounts from a pill all at once.

Sometimes, taking a lot of a substance shuts off the body's endogenous production of that substance. It probably thinks, "Gosh, I'm getting all this antioxidant from that pill. Why should I bother to make it myself?"

Furthermore, many vitamins and supplements these days come from China, which lacks the strict qualtity control we would like to see.

Whole, unprocessed foods also contain fiber and other beneficial substances in addition to the antioxidants. They may also contain antioxidant precursors, giving the body the raw materials to make antioxidants when and where they are needed.

But when we have diabetes and we're trying to eat less food, and perhaps omit some foods like sweet fruits that are full of antioxidants, this becomes more difficult. This is especially true as we get older and need less food to keep us going.

Some drugs some of us may be taking are reported to have antioxidant properties. These include metformin, ACE inhibitors, TZDs, statins, and calcium channel blockers. Some foods
with high levels of antioxidants include spinach, cumin, fennel, basil, and black pepper.

I myself take vitamin C (500 mg, not a huge amount). I stopped taking vitamin E because I had an uneasy feeling about it. There are many different forms of vitamin E, and I worried that taking the form found most commonly in standard vitamin E pills would shut off the production of the other, more beneficial, forms of the vitamin. You can buy vitamin E mixtures, but they're much more expensive, and who knows if they contain all the forms that we need.

I've also started taking coenzyme-Q10, which is a powerful antioxidant. I take it because I'm taking a statin, and I found my legs were getting weaker and weaker. When I tried the Q10, my muscles seemed to regain some strength. However, the effect seemed to be greatest in the first week, and now I'm wondering if taking it exogenously is shutting of my own production of this vital compound.

I also take metformin, a statin, and an ACE inhibitor, which have some antioxidant properties, and I love green vegetables, berries, and coffee, all of which contain antioxidants.

Another common antioxidant is alpha-lipoic acid. It's supposed to be especially beneificial when you have neuropathy. It also reduces insulin resistance, but the half-life in serum is so low that it can't do much unless you take an extended-release form.

I tried taking it and saw no effect on my blood glucose levels. Other people do.

Of course, I have no idea whether my own antioxidant regimen is really the best one for me, and I'm not recommending it for everyone else. There are so many unknowns in this business, and we have to make decisions on the basis of incomplete evidence.

Antioxidants are good when they are in the part of the cell that needs them, when it needs them. But when we eat antioxidants in pill form, they have to be taken up by the digestive system and then transported to the cells and taken up by those cells. Then they have to get into the particular part of the cell that needs them.

Some parts of the cell might get more than it needed (for example, the antioxidant might reduce the secretion of insulin), and other parts might not get enough, so the cell would commit suicide. We don't yet have the technology to make sure the antioxidants we ingest get where they're needed.

So helping our deficient systems along with a few antioxidants is probably a good thing. However, knowing that ROS can also have some beneficial effects, I think we should think carefully before gulping down huge amounts.

One author came to pretty much the same conclusion, although he prefers bigger words: ". . . it is now plausible that such entities have an evolutionarily orchestrated capacity to self-regulate that may be pathologically disturbed by overzealous use of antioxidants, particularly in the healthy."

Tuesday, May 12, 2009

Bromocriptine and Hibernation

The Food and Drug Administration recently approved the drug bromocriptine mesylate for use in treating diabetes.

The drug works on dopamine receptors in the brain to produce the same effects as dopamine would produce. For this reason, it's been used in dopamine-deficiency diseases like Parkinson's disease for some time.

In other words, it's not a new drug. It's a new use of an old drug.

But why, you might wonder, would a drug that works on dopamine receptors in the brain do anything for diabetes, which is a disease that causes blood glucose (BG) levels to be too high?

This is because there is some evidence that insulin resistance and obesity are regulated in part by the brain.

One example of this is the phenomenon of hibernation or, in some species, what is called torpor, a shorter period of reduced temperature and slower metabolism. Animals that hibernate typically put on a lot of weight in the late summer and fall. They also have increased insulin resistance.

People who believe that obesity is simply a case of eating too much and not exercising enough, causing obesity that in turn causes insulin resistance, would say this is what is happening in hibernating animals. There's a lot of food in the late summer and fall so the animals pig out and get fat, and the fat causes the insulin resistance, they'd argue.

But here's the interesting part. Ground squirrels normally put on a lot of weight in the fall. They also eat a lot more. But if you keep the squirrels in the laboratory and don't let them eat any more than normal, they'll put on weight anyway, mostly fat.

In other words something, most likely hormonal signals triggered by changes in daylength, are telling the squirrels to store fat. Because they're storing the fat instead of letting it hang around in the blood to be burned for energy, they have an energy deficit, and this makes them hungry.

This is consistent with the theory of weight gain described by Gary Taubes in his book Good Calories, Bad Calories. He says the "energy balance" equation so beloved of dieticians who use it to say that the only thing that matters is calories in and calories out is true, but the cause and effect have been reversed. This equation says:

Change in weight = energy in - energy out.

The dieticians would say if you change the right hand side of the equation, reducing energy in or increasing energy out, your weight will change. To some degree, this is true in extremes or for the short term, when an animal or person has no access to enough food, as in starvation, or has super willpower because of a belief that the latest diet will really work. But when food is available, the drive to eat becomes overpowering and any lost weight will be regained.

Taubes and other argue that some external force, mostly likely hormones or nervous system signals (Taubes argues that it's insulin) affects the left-hand side of the equation. This causes extreme hunger or lethargy, or both, as the body tries to balance the equation.

In other words, the net energy change is not causing the weight change, but the weight change makes the body try to balance the equation by creating an overwhelming desire to eat and aversion to exercise.

When food is available, the animal or person will thus eat more than normal and exercise less. But if you don't let them eat more than normal, they'll still store the fat. They'll just be very hungry and lethargic.

Furthermore, animals are not machines. Energy in from the same food can differ depending on the efficiency of digestion, and energy out can vary with the efficiency of transforming food into forms of energy the body can use. Some people turn excess calories into heat instead of turning them into fat.

So where does bromocriptine come into all this?

Syrian hamsters normally become insulin resistant and gain a lot of weight before they hibernate; these effects are blocked by bromocriptine. Similar effects were seen in obese women: glucose and insulin levels decreased and energy expenditure and fat burning both increased, although body weight did not change in this 8-day experiment. And other researchers
found that bromocriptine helped people with type 2 diabetes.

Some authors see hibernation as a model for insulin resistance, and the more we learn about what triggers the weight gain in hibernating animals, the more we'll know about what triggers insulin resistance and weight gain in obese humans.

They suggest that hibernators have a sliding set point. The con
cept of a set point is that the body has a certain weight that it wants to be, and if you go over or under that weight, you will have a strong urge to eat more if you're under the set point or eat less if you're over the set point. Instead of having one set point, hibernators have different set points depending on the time of year.

There are reasons to believe that bromocriptine might help people who have serious problems with obesity and insulin resistance. The drug has been around for a long time to treat other diseases, so we have a better idea of side effects than we do with brand-new drugs. And there are side effects.

The Mayo Clinic has a good outline of some of these side effects. They note that they're more apt to occur in older people, and can include confusion and hallucinations (the drug is an ergot alkaloid). This is a powerful drug, and I doubt that many physicians would prescribe it as the first choice when someone is diagnosed.

But for a person with a serious weight problem that isn't helped by other measures as well as uncontrolled BG levels, the drug might be worth a try, keeping a close watch to make sure no serious side effects occurred.

Friday, May 8, 2009

Spinning the News

Earlier this year, the Web science news site Science Daily ran a story headlined "Mice Stay Lean with High-Carb Diet."

Reading the head, I assumed the story would be about a study showing that mice who followed a high-carb, low-fat diet stayed lean while their littermates who were allowed more fat became obese.


In fact, the story reported a study showing that mice lacking a particular gene were able to stay lean despite being fed a high-carb diet. Researchers said the gene might play a role "in the prevention of obesity related to the over-consumption of high-carbohydrate foods, such as pasta, rice, soda, and sugary snacks."

In other words, the headline said the exact opposite of what the story said. And busy people who only read headlines would come away with the impression that high-carb diets kept mice (and they'd probably assume it also related to people) lean.

Four days later, Science Daily reran the exact same story. But this time the head was accurate: "Mice With Disabled Gene That Helps Turn Carbs Into Fat Stay Lean Despite Feasting on High-Carb Diet." Apparently I wasn't the only one who noticed the bad headline. Perhaps the researchers complained.

This story illustrates the problem that faces anyone who supports a concept that isn't the dogma of the day. Many people, especially reporters in the popular press, buy into the idea that only low-fat, high-carbohydrate diets are healthy. So they interpret everything through those biased glasses.

This means that when science reporters see a research study that supports something they believe in (let's say that red meat is bad for you) they'll read it, write about it, and write a headline that supports the thesis they believe in.

An example of this is the "red meat is bad for you" hypothesis. People do studies in which they lump red meat along with luncheon meats and hot dogs, both of the latter usually packed with carbohydrate fillers, sugar, and chemicals to keep them fresh. They find people who eat any of these three things don't do well on some outcome, let's say heart disease, so they then write stories with headlines that say, "Red meat causes heart disease."

But what if the luncheon meats and hot dogs cause heart disease -- or, more accurately are related to heart disease, as many of the studies only show a relation between two factors, not causation -- and red meat does not? By lumping foods together in groups, one has no idea which of these foods is actually responsible for the effect they found.

Anyone actually taking the trouble to read the original research paper should be able to figure this out. But how many people do that? Very few. Most will rely on the science reporters to do an unbiased job.

But they don't. They choose the outcome they believe in and trumpet that.

To be fair to the reporters, I'll add that I suspect they're under a great deal of time pressure. I worked at a newspaper for 8 years, and I know what it's like to try to write a complex news story when the clock is ticking. The science reporters in this case are trying to digest extremely complex research reports and translate them into terms the general public can understand.

The scientists, on the other hand, and especially the public relations officers at the institutions where the scientists work, are trying to put a "sensational" spin on the results to make them sound more important than they really are, hoping that this will help them get more funding to do more research.

What we as patients have to do is to try to extract the truth from all this spin. It's sometimes difficult and takes a lot of time.

The physicians who treat us are also very busy people, and they too -- even those who can remember the statistics they studied years ago, if at all -- don’t have time to pour through science magazines checking to make sure the statistics are accurate.

Sometimes they’re not.

I copy edit articles for a science journal and I’m constantly amazed at the number of careless errors I find in the manuscripts that authors with advanced degrees have submitted for publication. One author using advanced statistics wasn’t distinguishing between
average and median, a very basic difference that every statistics newbie should be familiar with. Other papers give different numbers in the text and in the tables they supply to support the text. I'm sure many of these problems get through the editors and appear in print.

So our physicians also have to rely on headlines that they see in the medical magazines they read, and these headlines too may be misleading.

Just remember that you can't trust the headlines. TV sound bites and newspaper headlines are the least reliable. TV news has to be short and interesting. Newspaper headlines have to give a message in a limited amount of space. But even science news stories and journal article can have misleading titles.

If you see a headline that sounds interesting, read the story carefully. If it seems like something that will be important for you, see if you can get access to the original journal article. The abstracts of such articles are usually free. You may have to pay or wait 6 months or a year to read the full text. Or you can see if the article is at a local hospital or academic library.

You can also look around on the Internet, putting the title of the article into your favorite search engine. Perhaps someone else has read the whole thing and written a commentary on it. Or maybe some site has posted a link to the full text.

Put the names of the authors into your search engine. Sometimes scientists write very similar articles for different journals, and some slightly earlier publications may now be available without charge and will give a good indication of the methods that these researchers use in their work.

Otherwise, take any short summary with a grain of salt. It may be true. Or it may not be. Reader beware.

Monday, April 27, 2009

Still Here

I'm still here. I haven't posted anything recently because I've been "under the weather" for a week or so and I didn't trust my brain to say anything worth reading.

I'm better now but also behind in so many things. I'll be back soon.

Saturday, April 18, 2009

Hidden Clues

I get my mail in a rural mailbox by the side of the road. Earlier this year, in the middle of winter, I found that the red flag that tells the mail carrier I have mail to be picked up had disappeared.

It was not an item that anyone would bother to steal. So I figured it had been knocked off and then a plow had buried it under one of the huge mounds of snow nearby. It would turn up in the spring, I thought.

Well, spring came, sort of, and most of the mounds of snow melted (there was still a small pile of snow on April 29, after 2 days of 80-degree weather!), but there was still no sign of the red flag. As I stood looking at the largest mound, still about 6 feet high, it occurred to me that the red flag I was sure was buried there somewhere might be analogous to the cure for type 2 diabetes.

It's there somewhere, I'm sure. But maybe it's buried under a huge mound of information that is leading people to look in the wrong places. Some day we'll find it. No one knows when. Maybe in 10 years, maybe in 10 decades. It's a complex puzzle. But I know we'll find it some day, just as I was certain my red flag would turn up.

And sure enough, a week or so later, when I went down the hill to get my mail, I saw that the huge mound of snow was only 3 feet high, and then I spotted something red. It was the flag!

The key to the diabetes puzzle hasn't been lost for lack of trying. The amount of research being done on the problem is tremendous. But what if everyone is looking in all the wrong places?

For example, we know that the body needs insulin. Insulin saves lives. Before the discovery and therapeutic use of insulin, people who got type 1 diabetes died. Now they can live long and relatively healthy lives.

But there's another hormone that is also important. That hormone is glucagon. Insulin is produced by the beta cells in the pancreas. Glucagon is produced by the alpha cells.

Everything glucagon does is pretty much the opposite of what insulin does. Insulin makes blood glucose (BG) levels go down; glucagon makes them go up. Insulin tells fat cells to store fat; glucagon tells them to release fat to be burned for energy.

And it's actually the ratio of insulin to glucagon that determines what will happen with your BG levels. In other words, high glucagon levels can do the same thing as low insulin levels. And most people with type 2 diabetes have higher glucagon levels than normal.

Normally, after a meal, the increased BG levels turn down the secretion of glucagon. When you have type 2 diabetes, this doesn't happen. So glucagon tells the liver to keep pumping glucose into the blood even when BG levels are already high. This is one reason we go high after meals.

Glucagon is also responsible for the increase in BG levels people with very little insulin production see after eating protein. Insulin does more than help glucose get into cells. It also helps amino acids (the building blocks of protein) get into cells. So if you eat pure protein, a normal person secretes insulin to help the protein breakdown products get into cells to be used to make more protein.

But if you don't eat carbohydrate at the same time and your insulin levels increase, your BG levels could go too low. So the body secretes some glucagon along with the insulin. In a nondiabetic person this system works very well.

But in someone producing almost no insulin, the protein meal still stimulates the secretion of glucagon, and with no insulin to balance it, the glucagon makes BG levels go up. The same is true of other stimuli, for example, exercise, that would normally trigger the secretion of both glucagon and a balancing amount of insulin. The trigger may still work, but if you can't produce much insulin, then the ratio becomes unbalanced and your BG goes up.

As their autoimmune disease progresses, people with type 1 tend to produce less and less glucagon, and because glucagon is one of the main hormones (another one is adrenaline, or epinephrine) responsible for bringing up BG levels when you go low, people with type 1 can have more serious problems with lows. Type 2s can also go low, but they usually have a bit more of a buffer with the glucagon.

People have known about glucagon and its effects for a long time, but most of the research in the field of diabetes has focused on insulin. There is one major exception, and this is the incretins, especially those that mimic or increase the levels of GLP-1. Byetta is the incretin mimic on the market today, and others are in the works.

The incretins stimulate the secretion of insulin; they also decrease the secretion of glucagon, thus giving a "double blow" to BG levels by stimulating glucose uptake in muscle and fat and decreasing glucose production by the liver.

Of course researchers are aware of glucagon and the aberrant responses of the alpha cells in people with diabetes. But most of the research today focuses on beta cells and insulin.

What if it turns out that the alpha cells and glucagon secretion are easier to control than beta cells and insulin? What if it turns out that some other hormone, maybe even one that hasn't been discovered yet, is actually more important than insulin deficiency and insulin resistance as a cause of type 2 diabetes?

I read one paper that suggested that leptin resistance (leptin is a hormone that controls hunger) is actually more important than insulin resistance as a cause of type 2 diabetes.

Thousands of research papers on diabetes are published every year. Somewhere the answers lie hidden. Like the red flag hidden under the huge mounds of snow, the buried answer to the type 2 diabetes puzzle will emerge some day, I'm sure.

When creative minds try to look at the puzzle in new ways, we may accelerate this process.