skip to main |
skip to sidebar
Most of us understand the importance of insulin in controlling our blood glucose (BG) levels. When our BG levels get too high, we can bring them down by injecting insulin. Insulin is made in and secreted by the beta cells in the pancreas.
Many of us are also aware that another hormone, glucagon, helps bring BG levels up when they get too low. Glucagon is made in and secreted by the alpha cells in the pancreas.
In nondiabetics and people with type 2 diabetes or early type 1 diabetes, glucagon automatically gets secreted when BG levels get too low. But people with longstanding type 1 diabetes often stop producing much glucagon and need glucagon shots to bring up a serious low.
Insulin and glucagon are like the accelerator and brake on your car. And it's the ratio of the two, rather than the absolute amount, that is important. If you have almost no insulin, you might be able to have normal BG levels if you also had almost no glucagon.
In fact, a study done in 1981 in a man who had no pancreas, showed that BG levels could be maintained at about 100 without insulin as long as they didn't give the man glucagon.
The problem is that when the beta cells give out, the alpha cells don't give out as well. In fact, they often secrete even more glucagon than they would in a nondiabetic. Glucagon tells the liver to produce and secrete glucose, so the BG levels stay high even when you don't eat.
Most diabetes researchers focus on beta cells and insulin production, but some are studying the alpha cells and glucagon production as well. A recent study found that hyperglucagonemia (too much glucagon in the blood) actually precedes the decline in insulin secretion seen in diabetes.
These researchers infused rats with a lot of glucose for 10 days. After initial high BG levels, the rats adapted and maintained normal BG levels for 4 days. But then their BG levels started to go up, and by 10 days 89% of the rats had high BG levels.
This isn't surprising. The traditional view is that coping with a lot of glucose and producing a lot of insulin can "exhaust" the beta cells; this is called glucotoxicity.
But the researchers found that the rats weren't producing any more insulin than normal. Instead, their glucagon levels increased fivefold. Thus endogenous glucose production, production of glucose by the liver, was what was making the BG levels go up. And infusing them with anti-glucagon antibodies made their BG levels return to normal.
That is surprising.
The authors conclude that glucotoxicity may first manifest as alpha cell malfunction, before any deficit in beta cells and insulin secretion is seen. This is a new way of looking at how diabetes procedes.
A few months earlier, another paper showed that glutamate (or glutamic acid), an important neurotransmitter in brain and pancreas, is secreted from alpha cells along with glucagon. The glutamate contributes to beta cell destruction; it doesn't affect the alpha cells.
Hence, if you're secreting more glucagon, you'd also be secreting more glutamate, thus accelerating beta cell loss and insulin production when you needed more to oppose the extra glucagon.
The authors also found that the protein GLT1 (glial glutamate transporter 1) could protect the beta cells, and they are working on finding other beta-cell-protective compounds.
Neither of these discoveries will result in an instant cure for type 2 diabetes. The first was done in rodents, and the second was done in isolated human cells. Before they can be translated into actual diabetes treatments, they'd have to be replicated in humans, not isolated cells or rats, and treatments that turned down the alpha cells would have to be developed.
However, for decades, researchers have been studying how type 2 diabetes evolves, and they're still not sure. Of course it's all terribly complex. But is it possible people are looking in the wrong places? Maybe it's time for some new ways of looking at an old problem.
Focusing on the alpha cells is one such approach. Let's hope this work continues.
I follow a low-carb (LC) diet to help control my type 2 diabetes. I can understand that this approach is very difficult for some people, and some with relatively mild type 2 can control despite eating more carbs.
But I'm always amazed at the closed-minded comments I often see in blogs of anti-low-carbers. Here's one, commenting on a photograph of a LC breakfast posted with a blog:
"There's nothing on the plate that I consider breakfast food."
The photograph seems to show bacon, ham, eggs, sausage, tomato, and mushroom.
I wonder why the poster feels that he needs special foods for breakfast. And apparently that special "breakfast food" should have a lot of carbohydrate, and little protein. That makes no sense. Most people are more insulin resistant at breakfast, and many studies have shown that blood glucose levels rise more after breakfast than after other meals. So if you feel a need for a daily allotment of orange juice, skim milk, toast, jam, and cereal, it would make more sense to eat it for supper, not breakfast.
Of course, this poster is not alone. Many people have irrational prejudices about "breakfast food." For instance, most Americans think bacon and ham are OK for breakfast. But if you say you had chicken or lamb chops, they'll think you're odd. Most Americans would consider Danish pastry or toast and jam to be suitable breakfast food. But if you say you had cheesecake or blueberry pie, they'll think you're odd.
What's the difference? Bacon, ham, chicken, and lamb are all meats. Danish, toast and jam, cheesecake, and blueberry pie are all sweetened starches.
It was the Kellogg brothers at the turn of the 20th century who pushed dry "breakfast cereals," at first primarily corn flakes, on the American public. At that time, rich people tended to eat meat and eggs for breakfast. Poor people ate starches, often boiled into porridge. Farm breakfasts tended to include a little of everything: meat, eggs, milk, pancakes, potatoes, breads, and pies. The farmers needed a lot of energy when facing long hours of backbreaking work and tended to eat the lighter meals like cereal in the evening.
By now, several generations of Americans have grown up thinking that breakfast has to include a dry cereal, often sweetened, and milk. But why do we have to mindlessly accept that there should be special "breakfast food"? We're smarter than that, aren't we?
In the rural area where I live, most people still conform to older patterns of eating. But in urban areas, it seems people are getting more creative with their meals, as described here. (The trend toward daylong snacking does not sound healthy, however, as commercial snacks are usually highly processed.) Nevertheless, the reporter reveals his underlying bias when he refers to eating nontraditional meals as "weird."
When we have diabetes, we need to eat the foods that keep our blood glucose levels down, whether they're considered "breakfast food" or "lunch food" or "dinner food." We can't let old patterns get in the way.
Lamb chops and broccoli for breakfast anyone?
Derek Lowe, a chemist who has done research in the pharmaceutical industry, recently had an interesting blogpost on the problems with research done on lab mice.
Because Lowe has done research with Big Pharma (including diabetes research), he provides a different point of view from the common "Big Pharma is evil and doesn't want to cure diseases" point of view found in many patient blogs. I think it's important to look at both sides of any issue, and Lowe often points out the difficulties of various chemical approaches to solving some drug problem. Most of them are over my head, but this one was interesting.
He links to another blog that has a series on mouse models, for those who are interested.
Many of the comments on Lowe's post are from other researchers, and it's interesting to see that unlike the popular press, the researchers are cautious about using mouse results. Even different strains of mice can show different results with the same drug.
One interesting comment was that when you put a human tumor into a mouse and some drug cures the tumor in that mouse it's possible that the drug simply kills human cells and hence would be dangerous in humans.
I think most of us understand that mouse studies often don't pan out to be human treatments. They are only suggestive. If only the popular press could show some restraint, patients wouldn't be told over and over again that some new cure was on the way, only to be disappointed when they never hear about it again.
I recently read a great cat annecdote in Temple Grandin's book Animals Make Us Human.
According to Grandin, someone's cat loved watching the water swirl around when a toilet was flushed. The cat couldn't figure out how to flush itself, but it had noticed that when there was paper in the toilet, it was more apt to be flushed.
So the cat tore up toilet paper and threw it in the toilet and waited expectantly.
This is a perfect example of the difference between association and cause. The cat correctly noted that toilet paper was associated with toilet flushing. But the cat incorrectly decided that toilet paper caused toilet flushing.
Of course, flushing didn't cause toilet paper any more than toilet paper caused flushing. It was a third factor, pulling the handle on the toilet, that caused the flushing.
Many of our scientific interpretations are like the cat's. If we see a fat person eating more than a thin person, most people conclude that overeating causes obesity. But perhaps obesity causes increased appetite, or perhaps a third factor that no one has discovered yet causes both obesity and increased appetite.
Whenever we see research that shows that two factors are associated, we should think of this cat story. Does the research provide any evidence that one factor caused the other, or is the researcher simply thinking like the cat because of a preconceived notion?
Gary Taubes is challenging the catlike assumption that because fat people tend to eat a lot and not exercise much, it's their behavior that is causing their obesity. Instead, he says it's insulin that is making the body store fat instead of burning it, and the resulting energy deficit makes the person want to eat more and exercise less.
The blogosphere is filled with people debating this theory. I won't go through it all here.
My point here is simply that we should keep this graphic cat story in mind as we evaluate evidence. Surely we humans can be smarter than a cat!
DPP-4, or dipeptidyl peptidase 4, is an enzyme that breaks down certain proteins, including GLP-1, or glucagon-like peptide.
GLP-1 has positive effects on insulin secretion, and the drug exenatide (Byetta) works by mimicking natural GLP-1. Because GLP-1 can help people with diabetes, it was thought that drugs that inhibit DPP-4, which would keep GLP-1 in the circulation longer, would also help people with diabetes.
Several DPP-4 inhibitors, the "gliptins" have been developed and include Januvia (sitagliptin) and Trajenta (linagliptin). They do reduce A1c levels somewhat, although they don't appear to be as effective as the GLP1-mimetics.
And one problem with such drugs is that DPP-4 affects many different proteins, and the inhibitors seem to reduce the effectiveness of the immune system, which could be deleterious.
DPP-4 exists as a membrane-bound protein and also free in solution. Both forms break down GLP-1.
But now European researchers report that DPP-4 is an adipokine that impairs insulin sensitivity.
An adipokine is a cytokine secreted by adipose tissue. A cytokine is similar to a hormone; it is a signalling molecule. Many of these substances have been discovered only recently and not everyone agrees about which should be called hormones and which cytokines. The important thing is that they're secreted by one type of cell and can affect others.
The European researchers found that the levels of DPP-4 were higher in persons with more fat cells, and in those with larger fat cells. Also, the production of DPP-4 in obese persons was fivefold higher in visceral adipose tissue (the tissue around organs that is associated with metabolic syndrome) than it was in subcutaneous fat. There were no regional differences in lean subjects.
After weight loss, the release of DPP-4 reverted to levels similar to those of lean subjects.
If DPP-4 is an adipokine that impairs insulin sensitivity, then it makes sense that the DPP-4 inhibitors would improve insulin sensitivity and lower BG levels. It's not clear at this time which of the DPP-4 effects would be more important.
But this could be the link between obesity and insulin resistance, or it could simply be one of many links between the two conditions. Perhaps this report will stimulate more research in this area.
Science Daily recently (well, sort of recently) had two stories about the same research, one put out by the PR department at Johns Hopkins and the other distributed by the PR department at the University of East Anglia, in the UK. See if you can tell which is which.
1. ScienceDaily (June 14, 2011) — People who use a mist inhaler to deliver a drug widely prescribed in more than 55 countries to treat chronic obstructive pulmonary disease (COPD) may be 52 percent more likely to die, new Johns Hopkins-led research suggests.
2. ScienceDaily (June 13, 2011) — An inhaler designed to help chronic bronchitis and emphysema sufferers breathe could be significantly increasing their risk of dying, according to new research by the University of East Anglia (UEA) and three US universities.
Right you are! The Hopkins PR department didn't even mention the UK university and the UK university dismissed Hopkins as just one of three US universities.
These press releases that get published by Science Daily and then picked up by newspapers are released not only when some research group has a real breakthrough, not only when some research group has something slightly new to say, but often whenever a clever PR person at the research center can figure out how to put a positive spin on something that might or might not be confirmed with future research.
The lead invariably mentions the institution. The next few paragraphs often describe the researchers and give all their titles. I usually skip reading all this. Then there are a few paragraphs giving background, for example, giving the differences between type 1 and type 2 or once again describing the "obesity epidemic."
The real news is often far down in the article, sometimes only a sentence or two. Then come quotes from the researchers saying how important this work is and how it either suggests the need for more research (the researchers want more grants) or suggests the need for the development of new drugs on the basis of the work (the researchers want to patent something).
[These two articles did have more meat than some others, and the safety concerns are, in fact, newsworthy. It was the leads that were so obviously PR-department generated.]
When science news is spun just like political news or "sold" by PR departments like a new type of plastic kitchenware, how can we trust anything we read on these news sources? There are zillions of scientific journals out there today, and no one can read even the tables of contents of them all. We have to trust science journalists to notice the important stuff and let us know about it.
But if all they do is reprint press releases from PR departments, is there any point? I suppose these press releases are better than nothing. They do alert us to the possibility there's something new there, and they usually give links to the source, so we can check it out ourselves.
But wouldn't it be wonderful if we could read real science news without having to scrutinize it for spin?
How many times have you read recently that you should eat more fruits and vegetables?
It's today's fad mantra. Want to lose weight? Eat more fruits and vegetables. Feeling sad? Eat more fruits and vegetables. Credit card maxed out? Eat more fruits and vegetables.
Sometimes I think we should just make it one word: fruitsandvegetables.
When I read one article that claimed that people in previous centuries ate lots of fruitsandvegetables my tolerance limit was reached.
That's idiotic!
Sure, there wasn't as much junk food in past centuries. But then, as now, poor people couldn't afford expensive fruits, or even vegetables unless they grew their own. Oranges were considered a rare luxury. Then, as now, poor people had to eat a lot of starches like bread and potatoes to get sufficient calories.
Even rich people didn't feast on lots of fruitsandvegetables. Here's a menu from Queen Victoria's household on her 80th birthday. I don't see a lot of fruits there. A few vegetables, but mostly meat and fish and eggs.
Here's an article describing what people ate in Boston restaurants in the 19th century. Like Queen Victoria's household menu, the restaurants seemed heavy on lots of meat courses, thick sauces, and pastry. Certainly not what today's nutritionists would recommend. Not a lot of emphasis on salads. Fruit was offered at the end, but only after a pastry course.
Here's another 19th century menu so heavy on meats that it makes me slightly nauseous to read it . . . and I'm on a low-carb diet! They do offer some fruit at the end, but by that time you'd probably be so stuffed with meat, game birds, lobster, and fish that you wouldn't have much room to stuff yourself with fruit.
I have nothing against eating more vegetables, limiting them to the low-carb ones like greens and other above-ground vegetables except peas and corn if you have diabetes. But fruits are full of sugar. If you have diabetes, it's not a good idea to eat a lot of fruit.
It's time we came to our senses and got rid of the fruitsandvegetables mantra. It's time we stopped thinking of some past Golden Age when everyone ate lots of lean meat (people in the 19th century would have guffawed at the idea of lean meat; they added bacon or lard to meat to make it juicier) and fruitsandvegetables and low-fat dairy and had glowing skin and never got fat.
Let's separate fruits from vegetables and eat less of the former and more of the latter. Let's focus on the carb counts of foods rather than whether they're fruitsandvegetables or other things.
Let's control our diabetes by finding out what foods make our blood glucose levels go up instead of listening to idiotic fad mantras.
We're smarter than fruitsandvegetables, right?
Posts
