Friday, May 26, 2017

Genes and Health

One thing that we see a lot on the internet is the person who lost a ton of weight with some diet and saw their blood glucose levels revert to normal. Then they write about their diet and imply that it will work for everyone.

But it won't. We need to find the diet that works for us.

I remember long ago, when I thought I was fat because I weighed 110 pounds (I'm small, and in college I weighed between 100 and 105), so I went on the Weight Watchers diet, which at that time was low-carb. A Hungarian colleague who saw that I was dieting said to me, "I hate to tell you this, but you don't have to diet to lose weight." I asked what you had to do. "Just give up sour cream," she said. I told her I didn't eat sour cream. She was aghast, as she put sour cream on almost everything she ate.

But that's typical of the "It works for me, so it must work for you" attitude. But we can have different genes that affect how we react to different diets.

Here is an article about a population in a remote part of Greece who eat a very high animal fat diet but have low levels of triglycerides and LDL. Now, low-carb diets reduce triglyceride levels, but they don't usually reduce LDL and sometimes make it go up. And as this wasn't a diet study, they didn't describe the participants' diets, but most Greeks don't follow low-carb diets.

So people from this area of Greece could tell others that their diet (whatever it is) reduced LDL so it should work for everyone. But it's apparently their genes, not their diet, that is important. Anyone who wishes to read the full text of the article can see it here.

Another recent article, this one in the New York Times, describes a similar situation, but in an American woman: very low levels of LDL and triglycerides. Both the woman and some of her siblings were found to have a rare gene that caused a lack of plaque in their arteries. One sibling with the gene had been a heavy smoker and had high blood pressure and type 2 diabetes but still lacked plaque in his arteries.

Again, it was no particular lifestyle that resulted in low levels of some lipids. It was their genes.

So if some diet or some exercise program or some drug makes your blood glucose return to normal, of course that's wonderful. But before proselytizing on the internet, remember that our genes may affect how we respond to any regimen. By all means, let people know the wonderful results that you got. But don't expect the same regimen to work for everyone.


Nutrition Label Errors

Nutrition labels are good for knowing how much carbohydrate is in the processed food you eat, if you eat any. Unfortunately whole foods don't come with nutritional labels.

But I've always considered the labels as approximations rather than exact numbers. They'll tell you, for example, that there's more protein than fat or whatever in some food, but they won't really tell you the exact amounts.

There are several reasons for this. First, they round the numbers off. So 3.49 grams would be listed as 3 grams and 3.5 grams would be listed as 4.

Second, they don't have to include anything with less than 5 calories or 0.5 grams. And this pertains to the serving size. So if you ate 4 servings, you could have a lot more of something than you thought.

Third, the manufacturers don't analyze every package they sell. One estimate was $750 per analysis in 1997, a lot for a loaf of bread, although they can also us nutritional tables to estimate the totals.

Finally, the nutritional content of the ingredients used to make the product can change from batch to batch and the manufacturer can't control that.

So overall, the labels are useful but not exact.

I recently came across a label that was just plain wrong. It was a sausage product and listed the ingredients as pork, water, wheat rusk, and salt and spices. So pork was the first ingredient (manufacturers are required to list ingredients according to amounts) but the label said it had no protein, as well as no carbohydrate. Huh? Pork is mostly protein and fat and rusk is mostly carbohydrate.

I telephoned the company and asked if maybe they just used pork fat and was told yes. Then I went back to the label and saw that it said one link had 150 calories, of which 50 calories were from fat. So what were the other 100 calories from. The water?

I called the company back, and now they admitted that the label was wrong. The sausage contained 4 g of carbohydrate and 19 g of protein. That totaled 146 calories, or 150 rounded up.

But what if someone used the carbohydrate and protein content to calculate bolus insulin. The calculated insulin would be incorrect, and they'd go higher than expected.

So that's yet-another reason it's so difficult for people who inject bolus insulin to keep their blood glucose levels level. I wonder how many other labels contain similar errors.

What this means is if you see a label that seems odd, don't assume it's correct. First check the numbers. Multiply grams of carbohydrate and protein by 4 and grams of fat by 9 to get calories. If they don't add up, call the company to find out. In someone without diabetes, thinking you were eating a little less carbohydrate and protein would not cause much harm. But when you're injecting bolus insulin, it could.

And because of rounding off, always take labels with a grain of salt.

Furthermore, remember that you can't always believe what someone who answers the telephone tells you. They could know about the issue, or they might not. In a large company, it sometimes pays to call twice to see if two different people have the same response.

Good control requires constant vigilance, but it's worth it in the long run.




Friday, May 12, 2017

Honoring David Mendosa

Diabetes writer David Mendosa died on May 8, only about a month after he was diagnosed with angiosarcoma in the liver. The diabetes community is mourning, with tributes at all the major diabetes sites in the United States and Europe as well as personal blogs.

David didn't want any kind of services. I was thinking of a fitting memorial for him, and I thought of this. He told me that he hoped his legacy would be his promotion of low-carbohydrate diets. He had been following one since 2007, with excellent results.

So one way to honor David would be to follow a low-carb diet for a month, or a couple of weeks, or just a week, if you haven't already been doing so. If you're already on a low-carb diet, you could make sure you're strict with the diet for a period of time to honor David. Let's face it, most of us do fall off the wagon from time to time.

Then, if you find the low-carb diet works for you, if you have better blood glucose levels and you discover that a low-carb diet doesn't mean deprivation, tell your diabetic friends. Ask them to tell their friends. Wouldn't it be wonderful if we could see an explosion in the number of diabetic people following low-carb diets in honor of David Mendosa?

A couple of caveats: if  you go suddenly from a high-carb to a low-carb diet, a period of adaptation is needed as your body builds up the enzymes needed to metabolize fat, and some people lack energy for a week or two. It's called the low-carb flu. If that happens to you, don't despair. It's temporary. Also, low-carb diets act like diuretics, so make sure you eat enough salt to retain some water.

Of course not everyone may be able to honor David in this way. For those who would prefer some other kind of donation, Caring Bridge, on which David, and then his friends and relatives, posted about his final journey is accepting donations in his memory, as is Tru Hospice Care Center, the hospice where he spent his final days.





Wednesday, May 3, 2017

David Mendosa

Many have heard already, but for those who haven't, David Mendosa, diabetes journalist, blogger, hiker, photographer, and so much more, has incurable cancer, angioscarcoma in the liver. He has recently been moved to a respite place with 24-hour care but may be able to return to his apartment if he can gain back some strength.

David wrote a chapter on Searching the Internet for my book, and it was a needed addition, as it wasn't something I had a lot of expertise with. David has been using computers since the early days and has a lot more experience with them than I do.

He was also one of the first people to have a diabetes webpage on the internet, and it has grown into a gigantic site. A friend will continue to maintain that.

He also has a blog describing various hikes, illustrated with photographs of birds and other wildlife. Many of his wildlife photos can also be found here.

David is a Buddhist and is very accepting of his situation. He has medication to control his pain. Some of his many friends in Boulder, and a niece, are supervising his care. He has become too weak to type, and telephone calls tire him out, but any who wish can follow his final journey on Caring Bridge. He has already received thousands of messages of thanks and love from all over the world.

David has said that he hopes his legacy will be his promotion of low-carb diets for people with diabetes. Even at the end, he is thinking of the well-being of fellow patients with diabetes.

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.