Thursday, March 30, 2017

Can a Drug Reverse Insulin Resistance?

A new drug seems to reverse insulin resistance in fat mice, who have normal blood glucose (BG) levels when taking the drug. Of course, we've all seen mice cured of diabetes kazillion times, but I find the approach in this case interesting.

To understand what the drug does, you have to understand a little about what causes insulin resistance, which I'll try to outline. When insulin binds to the insulin receptors on target cells, for example muscle cells, the insulin receptor phosphorylates itself. This means it adds phosphate groups. As a result, a complex chain of reactions is triggered, culminating with glucose transporters called GLUT-4 moving to the cell membrane. This allows glucose to get into the cell.

In general in the body, when something triggers a reaction, something else then slows down or stops the reaction so it won't get out of hand. For example, if you eat carbohydrate, which stimulates insulin secretion, BG falls, and that stimulates glucagon secretion, which keeps the BG from falling too low. If you get an infection, you produce chemicals that cause inflammation. But then if things are working properly, you produce chemicals that stop the inflammation when its job is done.

In the case of the insulin receptor, another enzyme called a phosphatase removes the phosphate groups that the insulin receptor added, and this slows the action down. So it made sense to look for compounds that would inhibit the phosphatase so that a little insulin would have a longer effect.

In the last half of the 20th century, scientists were investigating the effect of vanadium compounds on people with diabetes, as there were reports that it lowered BG levels. The vanadium seemed to inhibit a phosphatase. Unfortunately, because phosphatases are involved with many systems in the body and the vanadium wasn't specific to the insulin receptor, giving people enough of the vanadium compounds to be effective caused too many side effects, and interest waned.

There are many different phosphatases in the body, and what is new about this recent study is that they targeted on specific phosphatase, called LMPTP for low molecular weight protein tyrosine phosphatase. Then they looked for a small molecule that would inhibit LMPTP, and they found one. Giving this drug to the mice, they found no side effects.

One interesting thing is that blocking LMPTP only in the liver, via genetic studies, improved BG control. When one has type 2 diabetes, the liver seems to be insensitive to insulin. When BG levels are low, the liver produces glucose. When BG levels go up, insulin is supposed to stop the liver from producing glucose. But that doesn't happen in type 2. So a drug that could make the liver more sensitive to insulin sounds promising.

In fact, as I noted here, insulin resistance might be protective for the heart. So increasing insulin sensitivity in the liver while retaining it in heart muscle might be just what we need.

Science magazines have been describing this research as if the cure for type 2 diabetes has been found. Far from it.

Reversing insulin resistance might "cure" diabetes in people whose primary defect was insulin resistance, as is often the case in obese people. The studies were done in diet-induced obese mice. But it takes at least two defects to produce type 2 diabetes: insulin resistance and a defect in beta cells that makes them unable to produce the extra insulin needed to overcome that insulin resistance. In people with very little insulin production left, even reducing the insulin resistance might not be enough.

Also, as noted before, these studies are in mice, and often mouse studies don't translate into human treatments. Taking a drug from "proof of concept" to a safe drug for humans is a long process.

Nevertheless, I think this approach is interesting enough to be aware of. Perhaps it will develop into something very useful for type 2.

Wednesday, March 22, 2017

Do Diabetics Cause Global Warming?

People with type 2 diabetes have been accused of increasing health care costs. Now we're accused of contributing to global warming!

The first meme is that people with type 2 diabetes brought it on themselves by eating junk food and becoming overweight, with the weight triggering diabetes in those with a genetic susceptibility. What many don't understand is that junk food, high in both carbohydrate and fat, is cheaper than healthy food. When you have hungry children, you'll feed them what you can afford, and you'll eat the same thing yourself. This explains the apparent paradox that low-income people are often fatter than the rich, who can afford meat and fresh vegetables and fruit.

Now comes this:

"Meanwhile, an increased prevalence of diabetes may lead to more carbon emissions being generated by the health care systems treating those patients. 'Diabetes-related complications -- such as (cardiovascular disease), stroke and renal failure -- cost lives and money. Hospitalizations from such complications are also energy-intensive and increase (greenhouse gas) emissions,' according to the report."
This is from an article on diabetes and climate change. The main point of the article is that hotter climates result in more cases of diabetes. This makes no sense to me, as the Inuit have very high diabetes rates when they adopt a Western diet. 
Also, the story involves correlation, not causation. One can find all kinds of correlations that are meaningless. My favorite is the correlation between cheese consumption and fatal bedsheet-tangling accidents, from Tyler Vigan's book "Spurious Correlations." As time passes, temperatures increase. All sorts of other things also increase, like exotic pizza varieties and emmigration to Canada. Do these cause diabetes?
The article on climate change also contradicts another recent article that claims that lounging in 104-degree water for an hour results in better blood glucose control.
Does having patients in a hospital use significantly more energy than having the beds stay empty? True, if a room was empty, they might turn off the lights. But how about all the energy used by commuters driving an hour or so twice a day? (Not to mention all the fuel burned to get Trump to his weekend golfing expeditions to Florida.)
How about all the energy used by people watching giant-screen TVs? Working out at a gym instead of going outside to exercise in the fresh air? Using leaf blowers instead of raking their leaves?

What percentage of all these types of energy use would type 2 patients with complications add?

This kind of sweeping generalization can cause harm. And in our current political climate, in which some think it's OK to pick on the sick and poor, it could result in making diabetes care even more difficult. 
We have to stop blaming patients and focus on early detection and treatment of disease for everyone so no one gets complications.

Friday, March 17, 2017

Connected

Everything is connected.

No, this won't be an essay on meditation and the Oneness of Being. It's about the various organ systems in the body and how, the more we learn, the more we discover they're all connected and communicating with each other.

Physiology is usually taught around different systems: circulatory system, nervous system, skelatomuscular system, with individual organs within the systems. Of course you know they're interrelated, but one tends to think of them in isolation. The pancreas produces insulin, the liver produces bile, the stomach produces acid, and so forth.

However, as science progresses and we're able to detect things in tiny amounts, not just the large amounts that we could detect in the past, we're learning how complex it all is. For example, insulin is produced mostly by the beta cells in the pancreas. But smaller amounts of insulin can be produced by the thymus, liver, and fat and probably brain.

And various systems interact in ways that one might not think of until someone stumbles on them.

For example,  a recent paper shows that nerve growth factor (NGF), which is known to regulate the development of nerve cells, also helps to tell beta cells to release insulin. High blood glucose levels cause NGF to be released from pancreatic blood vessels, and the NGF then tells the beta cells to release insulin.

Another paper shows that the immune sytem uses gut bacteria to control glucose metabolism. An immune system molecule called interferon helps to fight infections. But a decrease in interferon-gamma can improve glucose metabolism. And when these interferon levels decrease, levels of a specific species of bacteria increase. The researchers think the bacteria are providing the link between the immune system and blood glucose control.

Another one  shows that gut bacteria can block the loss of appetite that often accompanies a stomach bug. They do this to promote the bacteria's transmission to other hosts.


Another paper shows that cutting the nerves to the kidneys reduces insulin resistance. It seems that the liver and the kidneys communicate to set glucose levels, and cutting the nerves to the kidneys makes the liver more insulin sensitive. One problem in type 2 diabetes is that because of liver insulin resistance the liver keeps pouring out glucose even when the level is already too high. Kidney function in the dogs used in the study remained normal.

Finally, a paper  shows that a brain hormone triggers fat burning in the gut. This hormone, called tachykinin, was identified 80 years ago as a peptide that triggered muscle contractions in pig intestines. It seems that this hormone is released in the brain in response to the serotonin level. Serotonin is related to mood, and low serotonin levels can cause depression. Also, some of the side effects of the drug metformin seem to be mediated by binding to serotonin receptors in the gut.

In this case, sensory cues such as food availability cause the brain to release serotonin. This tells certain neurons to release tachykinin. The tachykinin then activates a receptor in intestinal cells, and the intestines begin to burn fat.

These are just a few examples of how one organ affects another, and even our gut bacteria are involved in the communication.

There's more and more evidence that gut bacteria control a lot of things in the body. Wouldn't it be wonderful if some species could produce an  insulin-like molecule that was resistant to degradation in the gut? No evidence for that. I'm just dreaming.

Understanding all these interactions is not easy, but it means that everything in our bodies is important. We can't focus only on blood glucose levels and ignore our mental health or our intake of healthy foods that don't affect blood glucose directly but may nurture the good gut bacteria.

Our bodies know how to communicate in ways we don't yet understand. Our job is to be kind to our body so it can do its job as best it can. Enjoy life. Enjoy your friends. Enjoy your food. And stay healthy for a long, long time.



Monday, March 6, 2017

Good Glucose Control

We all know (I hope) that it's a good idea to keep our blood glucose (BG) levels as close to normal as possible. Deciding how close involves a lot of factors, balancing good BG control with enjoyment of life, economics, family preferences, and so on.

But it seems that more and more things are affected by our BG levels, which should give us an incentive to put a little more effort into good control.

It's been known for a long time that keeping BG levels close to normal can reduce the risk of the complications I call "the O'Pathy sisters": retinopathy, neuropathy, and nephropathy. But there's more recent evidence that high BG levels can contribute to Alzheimer's disease. It's known that people with type 2 diabetes are at increased risk of Alzheimer's.

Glycation apparently affects an enzyme involved in Alzheimer's, and "a glycation pattern similar to that observed in AD brain homogenates could be reproduced by incubating [the enzyme] MIF with glucose." You can see the full text here.

Note that this research is complex and preliminary. So it's not something you should lose sleep over. However, it's one more hint that controlling BG levels is important.

Another recent study links poor diabetes control to heart disease. Note that the headline links heart disease to diabetes. A more accurate headline would have linked it to poorly controlled diabetes, as the text says, "When diabetes is poorly managed, your blood sugar goes up and the amount of this protein goes down." Too little of the protein in question contributes to atherosclerosis.

You can see the abstract of the study here.

Finally, a third study showed that tighter glycemic control in type 2 patients with heart failure for just 4 months helped to preserve muscle strength and lean body mass. This was not what most of us would call tight control, as the final hemoglobin A1c level was 7.6, but that was lower than the 8.4 in the controls. The free full text of that paper can be found here.

These are just a few studies, but as more studies of other functions are carried out, it's likely that the effect of good control will be duplicated.

Good control isn't always easy in today's world, but it's worth the sacrifices.

Wednesday, February 22, 2017

Nutritional Information

I was at a local coop recently and saw a new brand of tortillas. They had only a few ingredients, mostly corn, so I looked at the nutritional information. It said they had only 1 gram of carbohydrate.

At first I was ecstatic. True, the tortillas were small, but if there was only 1 g of carbohydrate, it would be wonderful. Then I looked at the fiber content. It was 2 g. Huh? Fiber is indigestible carbohydrate, so how can you have more fiber than carbs?

If the product is made in Europe, this is possible. This is because the European system lists only digestible carbs as carbohydrate, so to get what we consider total carbs, you add the carbs to the fiber. In the American system, carbohydrate means total carbs, and to get digestible carbs you subtract the fiber.

This dual system can cause problems. The GG brand crispbread used to promote their product as having zero carbs because it was made in Europe and when you subtracted the listed fiber content from the listed carb content, you got zero. After many people complained, they fixed their label.

But these tortillas were made locally. That couldn't be the answer.

Back to the coop. I found someone in charge and asked about the label. I said regular tortillas that are about twice the size of the new ones have about 20 grams of carb, so I suspected this label was a typo and it should be 10. They went into the back room and stayed there for ages and then came out and gave some kind of an answer that made no sense, so I didn't buy the tortillas. When I got home, I emailed the company.

They replied that there was an error on the label, and the total carbs should be 11, not 1. They said they'd correct it, but the next week I found the same misinformation and no sign by the coop warning people that the label was wrong. In the meantime, were people on insulin injecting the wrong amount of insulin on the basis of incorrect information?

The tortillas I usually buy contain a mixture of grains and seeds, gluten (a protein), soy flour, and cornstarch. I get them because I think they have the best taste. The package used to claim 11 grams of carb and 6 grams of fiber, for 5 grams of digestible, or net, carbs. When I eat them (which isn't often), I eat only a half, which would be about 2.5 grams of net carbs. I can deal with that.

But when I recently bought a package, I noticed that they're now advertising 8 grams of net carbs, 12 grams of carbs and 5 grams of fiber. Of course 12 minus 5 is 7, not 8, but the difference probably has to do with rounding. So if I eat half of a tortilla, I'd be getting 4 grams of net carbs. Still not enough to send me into the stratosphere, but definitely higher.

When I scrutinize the label with a magnifying glass, I see that the order of the ingredients has been changed.  Have they changed their recipe? Or do they periodically test the product with slightly differing results each time? Or were the results falsified?

After the Dreamfields, and Julian Bakery scandals, one has to be cautious. When we find a product we like and buy it regularly, most of us don't scrutinize the label every time. But it's probably a good idea to double-check from time to time.

I've tested the tortillas I usually buy (Joseph's), and in small amounts they seem to be OK for me. That doesn't mean they'd work for you. We are fortunate in having meters to do tests of new foods. I tend to be lazy, and once I've tested something I don't keep retesting. This label snafu has reminded me that perhaps I should.