Monday, July 9, 2018

Intestinal modification for glucose control

A lot of research is being done on the effect of the duodenum on diabetes control.

The duodenum is the first part of the small intestine. Food empties from the stomach into the duodenum and then continues down the intestine. When a type of gastric bypass called Roux-en-Y is done, the duodenum is bypassed. And because glucose control improves after this operation, even before the patient has lost any weight, some researchers wondered if something produced by the duodenum was controlling blood glucose levels.

Various approaches to deal with this have been tried.

One, called he duodenal-jejunal sleeve bypass, or EndoBarrier, is a removable plastic tube that is implanted endoscopically. The tube prevents nutrients from contacting the duodenum.

The EndoBarrier has been used outside the United States with positive results, but preliminary US studies were terminated after a higher-then-expected number of liver abscesses, and some other countries have also terminated their approval of the device. Efforts to revive use of the device are underway.

The second procedure, called duodenal mucosa resurfacing, or DMR, introduces a heated balloon into the duodenum. The company says the heated water modifies the cells of the duodenum in a positive way to reduce hemoglobin A1c levels and markers of insulin resistance. It is approved in Europe but not yet in the United States.

And the third procedure uses a pill that releases substances that temporarily coat the duodenum. The active ingredient is sucralfate (Carafate), which is already approved for control of ulcers. The researchers have further engineered the sucralfate (called LuCI for luminal coating of the intestine) so that it adheres to the intestine even when it's not acidic, because normal intestine is not as acidic as ulcers. After a 24 hours, the LuCI dissipates.

Because the LuCI coats the intestine, nutrients are absorbed more slowly, and this can reduce glucose peaks, the researchers say.

So far, research has been in animals, and this treatment has not yet been approved by the FDA.

So none of these new procedures sound perfect, but it's a new approach that sound promising, and maybe new creative approaches to altering nutrient-duodenum contact will be developed.

Tuesday, July 3, 2018

Diet Trends

This is a good article. At least it was today. The site has more than one article at links, and it's possible that in the future it will go somewhere else. The one I'm referring to is "Faulty Studies Mean Everything You Know About Nutrition Is Wrong" by Dan Robitzsk.

I  hate those "everything you know is wrong" titles, which are clickbait, but he makes some good points and discusses the problem that one day the press says fat is bad and the next day they say it's good, and most people don't have the time or statistical background to plow through the studies that are cited to support any dietary view and so don't know what to eat. 

For the past few decades, we've been bombarded with messages telling us to cut out the fat. Now the tide is turning, and high-fat ketogenic diets are "in" and its supporters say carbohydrates are poison. (I've been on a low-carb diet for more than 20 years, starting when it went against the advice of most medical organizations. What will I do if these organizations make a switch and tell me I'm right? I'll have to find new battles to fight).

Dietary patterns tend to go in cycles, and I suspect the ketogenic diet will grow in popularity and then will be supplanted by something else. What diet? Who knows.

I think the diet I grew up with was probably pretty healthy, and in those days (1950s) childhood obesity wasn't common. Our family's diet wasn't vegetarian. It wasn't low fat. It wasn't high in pasta and other carbohydrates. It wasn't ketogenic. A typical meal would consist of some meat or fish, a vegetable seasoned with butter, some kind of potato, a piece of bread, and a glass of whole milk. Sometimes salad. For dessert we could have some ice cream.


We weren't usually allowed to snack between meals except for fruit, and sodas were a rare treat. In the summer we could have a treat if the Good Humor truck came down our street, and my little brother used to sit on the front steps with a dime clutched in his hand listening for the jingle-jingle of the Good Humor man. We could have bought a candy bar with our 10-cent allowance, but I preferred to buy a comic book or save the money.


I suspect my friends ate the same way that we did, but of course people in different areas of the country or different ethnic groups or different incomes would have eaten differently.

I doubt we'll return to the diet I grew up with, as too many people today eat all their meals in restaurants or order takeout food, and kids today mostly have more spending money so they can buy a lot of treats. But let's hope we transition to a diet that is healthier than the junk that too many people eat today, and that the diet will be affordable for all.

I suspect the next trend will be an expansion of farmers markets and more "whole food," meaning unprocessed food. Eating less processed food is one thing proponents of various diets agree on.Will working couples have the time to prepare this food? I don't know. Perhaps if studies show that doing so will improve the health of their children they would figure out how to make the time.

So I'm not a seer. The next trend might be something completely different. What do you think the next diet trend will be?

Thursday, June 21, 2018

Toothpaste and Type 2

Did your toothpaste give you diabetes?

Well, OK, that's a bit of a stretch. But some new research has shown that the white pigment titanium dioxide is associated with type 2 diabetes. And titanium dioxide is often used to make toothpaste white as well as its use in other products such as drinks, foods, and medications. The full article can be seen here.

Now, this was a small pilot study (a pilot study is a small study done to try to see if it's worthwhile to do a larger study), only 11 participants, three without diabetes, four with type 2 diabetes (T2), and four with T2 plus pancreatitis. The researchers looked at their pancreases and found titanium dioxide nanoparticles in all the patients with T2 and none of the controls.

Remember that association is not causation. But the fact that the crystals were found in none of the three controls is suggestive. Obviously, as the cliche goes, "more research is needed" with larger numbers of people studied. 

However, this study is consistent with the idea that perhaps one reason diabetes rates have increased so much is related to the increase in various toxins in our environment. Titanium dioxide is considered safe, but maybe it isn't, even though it's approved as a food additive.

Another study, in vitro and in flies, suggested that titanium dioxide reduces glucose transport across the intestinal epithelium.

So how many other "safe" chemicals are we ingesting as well? 


Wednesday, March 28, 2018

Glucose Outside and Inside Cells

When we speak of glucose levels, we're usually referring to the levels of glucose in the blood, or blood glucose (BG). And this level is important, because the glucose in the blood travels throughout the body to provide nourishment for our cells. It can also react chemically with tissues that are exposed to blood, for instance the endothelial cells that line the blood vessels, and damage them, especially when BG levels are high.

However, BG isn't the whole story. The level of glucose inside cells is also important. Outside of research studies, we don't measure this. But because too much glucose within the cells could cause damage, many types of cells won't take up glucose unless they have insulin to facilitate its transport across the cell membrane.

This is where insulin resistance comes in. Insulin resistance can be protective, keeping too much glucose from getting in some cells when it's not needed. In 2015, I blogged about the benefits of insulin resistance in the heart.

Insulin resistance can also function as a way to get glucose to tissues that need it. For example, when you have an infection or trauma, or when you're starving, or when you're in late pregnancy, your muscles become insulin resistant. This means the muscles won't grab all the glucose, thus making more glucose available for the cells that really need it, such as the site of infection or trauma, or the brain when you're starving. In late pregnancy, it ensures that the mother doesn't grab all the glucose and leave the developing baby with too little.

In other words, insulin resistance is a mechanism to select which tissues get glucose. If you're starving, you want to make sure the brain has enough glucose, because even though the brain can function on mostly ketones, derived from the breakdown of fat, it still needs a little bit of glucose. No point in wasting it on muscles.

However, if you're starving you still want to be able to hunt and gather, so the body overrides the insulin resistance in working muscle so  you can run after that impala and get a decent meal.

When it comes to obesity, the basic dogma goes like this: For some reason, maybe genetic, you have more insulin resistance than normal. The insulin resistance means you have to produce more insulin than normal. And the high insulin levels make you gain weight. The increased weight makes you even more insulin resistant. So you have a vicious cycle going.

This means that in terms of obesity, insulin resistance is bad and you should do whatever you can to reduce it.

But there's some evidence that maybe we have it backward. Maybe it's insulin sensitivity that makes you gain weight and the ensuing insulin resistance is the body's effort to control this weight gain.

Grizzly bears are very insulin sensitive in the late summer and fall when they're packing on the pounds. Then when they're snoozing in their dens, they become insulin resistant and lose weight by burning their stored fat.

There's some indication that a similar effect, minus the winterlong snoozing, can occur in humans. One study in 1991 showed that among the Pima Indians, known for their high diabetes rates in modern times, the ones with the most insulin resistance put on the least weight (other studies showed exceptions to this concept in some ethnic groups).

This all makes sense. If you're insulin sensitive, your cells will take up more glucose, and with more glucose in the cells, the body can make and store more fat. You might have less insulin in the blood, but that insulin will be effective in keeping the stored fat in place.

So what do we really need for health?

What we really need is for our cells to not only take up glucose from the blood, reducing BG, but to burn that glucose in the cells, so the internal glucose levels don't get too high. We can burn all the glucose that gets taken up by not eating more than necessary, and by working our muscles to burn a little extra. Exercise is good but less effective than diet when it comes to controlling weight.

This sounds a lot like "diet and exercise," and for eons that has been the standard treatment for type 2 diabetes. Of course, we'd all like a pill that would allow us to overeat as most Americans do while simultaneously making us slim and muscular. But so far, no such pills have emerged.

So all this blather about insulin resistance has no practical application. But it should give you a new perspective on the issue of insulin resistance.

Thursday, March 22, 2018

Could Salt Cause Obesity?

Could a high-salt diet lead to obesity?

Intuitively it makes sense. Most populations still eating traditional diets do eat salt, but often not as much as is found in Western diets, and such populations have low rates of diabetes. When they move from rural to urban environments and are exposed to salty Western food, they tend to gain weight.

(I did once read about an isolated group somewhere in South America, maybe the Yanomami, that didn't use salt; instead they burned a plant to get a calcium compound and used the ashes to flavor their food. When the anthropologists offered them some salty food, they said yuch and threw it away. But by the next day they'd changed their mind and were soon begging for more. I can't find the article I read, and perhaps the writer was exaggerating, but it does suggest that salt is addictive.)

If you don't think salt is addictive, try to eat just one potato chip.

It's been found that salt increases appetite, and now there's some scientific evidence that salt could lead to obesity through increasing leptin resistance. Leptin turns down your appetite when your fat stores are sufficient for your needs, and if you have leptin resistance, you have a big appetite even though your body is already storing plenty of fat.

For those interested in the mechanism, it seems that salt increases to aldose reductase pathway in the liver and hypothalamus. (The aldose reductase pathway is also involved in some diabetes complications.)

This pathway results in the production of fructose, which then causes insulin resistance. And blocking fructose metabolism blocks the effects of a high-salt diet.

In humans, a high-salt diet causes insulin resistance after only 5 days, and this study showed that in Japan, salt and calorie intake were correlated. In mice, a high-salt diet makes the mice eat more than usual. In the Japanese study in humans, the researchers showed that salt intake can be shown to be correlated with BMI, and high salt intake predicted diabetes and nonalcoholic fatty liver disease.

Could it be that too much salt, rather than too much fat or too much carbohydrate, is the real reason for the rise in obesity in America? Most Americans eat a lot of their meals away from home. And restaurant food and street food tend to be salty as well as sweet and fatty. If the salt makes you eat more, then you get more sugar and fat and calories, and you put on weight.

We all know that correlation does not mean causation, but when there's some proof of a mechanism, it becomes more likely.

Wouldn't it be ironic if it turns out that it's salt that is driving the increase in obesity? Of course you need calories to gain weight, but if the salt makes you eat more calories, then we can blame the salt.

And the fix is obvious.



Monday, March 19, 2018

Does Amyloid Clog Beta Cells?

When the beta cells produce insulin, they also produce a protein called IAPP. This stands for islet amyloid polypeptide, and the IAPP is secreted along with the insulin. IAPP is also known as amylin.

Amyloids are proteins that tend to clump when present in excess, and various amyloids contribute to diseases such as Parkinson's (alpha-synuclein clumps) and Alzheimer's (beta-amyloid clumps). The IAPP also clumps, and this causes the beta cells to decline and eventually die, resulting in diabetes.

Now researchers have found where the clumping occurs. It seems be in the tubes that let newly synthesized proteins leave the site of their synthesis (the endoplasmic reticulum) and emerge into the cytoplasm. When these tubes are clogged, insulin can't be released and the whole system gets gummed up.

One interesting thing is that the clumping of amyloids occurs more often when the proteins are present in excess. This means that if you're producing a lot of insulin, you're also producing a lot of IAPP, and the probability of amyloid clumping increases.

"What happens is that as demand for insulin increases, you get more and more IAPP production, and the more you make, the more likely it is to aggregate,” says the lead author of the cited paper Can Kayatekin. “So, the idea is that as you make more IAPP, it starts poisoning the very cells that are producing it.”

Now, what makes you produce a lot of insulin? Eating a lot of carbohydrate, of course. So this could be one way in which high-carbohydrate diets can increase the risk of diabetes.

However, ascertaining where the clogging occurs wasn't the only thing these researchers found. They also found an unclogger called STE24 in yeast and ZMPSTE24 in humans that snips off the clogging IAPP and opens up the channel again. This article has a nice illustration of the declogger.

This research like so much, alas, has no immediate application except to confirm the idea that a very high carbohydrate diet is probably not good for anyone. Sometimes it's the basic research that eventually leads to real advances in treatment, and further research could lead to methods of getting  unclogging enzymes to beta cells so insulin production could go on as it should.



Friday, March 9, 2018

Right Before Our Eyes?

I sometimes don't see something that is right in front of me.

For instance, this morning I was looking for some zhoug, a spicy Yemenite sauce that I like on top of cheese. I usually keep sauces in the back of the fridge, so that's where I looked. It wasn't there. Had I taken it out already? Nope. Had thieves broken into the house to steal my zhoug? Not likely.

I finally found it in the front of the fridge, right before my eyes.

Another time I spent hours looking for a book. I knew what part of the bookcase it should be in and looked and looked and couldn't find it. Did the thieves I thought took my zhoug also take Richard Feinman's book? Not likely.

I finally found it right where I'd been looking. I'd remembered that it had a white cover, but in fact it had a blue cover.

Well, what does all this have to do with diabetes? It made me wonder how many other things we think are missing are right before our eyes. Could we be looking in all the wrong places for the cause of type 2 diabetes? Is the real cause staring us in the face but we don't see it because we're expecting something else?

For decades we've been told that type 2 is caused by obesity, so the focus is there. But what if the real cause is something else, something that causes both obesity and diabetes (so they are related) but we're not seeing it because we're so focussed on weight?

I'm not sure how this concept will help the average patient; I just hope that some creative soul deciphers the puzzle so we can end this scourge before the prevalence is 100%.