Thursday, January 2, 2020

Insulin Clearance

I recently came across this paper on insulin clearance. It's a little technical but discusses the insulin-degrading enzye (IDE) and how it affects type 2 diabetes.

As we all know, insulin makes blood glucose (BG) go down, and glucagon makes it go up. In most cases, the absolute amount of these hormones is not as important as their ratio. But other hormones can affect BG levels as well. For example, the hormone somatostatin inhibits the secretion of both insulin and glucagon as well as other hormones.

And IDE can also affect BG levels by degrading insulin in the liver.

So if, for some reason, you were producing too much insulin and not enough glucagon, IDE could help to control the excessive insulin levels. This is called insulin clearance, and it seems to decline with the progression of type 2 diabetes. Lower levels of IDE are found in obesity and type 2 diabetes. Less insulin clearance would result in higher insulin levels, and these could cause insulin resistance.

However, there's no agreement on whether lower levels of IDE are because insulin levels are declining or insulin resitance is increasing (essentially reducing the levels of effective insulin) or whether they are the result of dysfunction in the liver.

From a practical point of view, it doesn't matter that much what causes the decline in IDE levels. What matters to us is how this decline affects our BG levels. The authors found that exercise can increase IDE levels.

One interesting thing about all this is as an illustration of how complex the control of BG levels is. Many hormones and enzymes are involved, and we may have differences in the effectiveness of the various hormones and enzymes. Is it any wonder that we don't always see the same results from some drug or diet? Results of big clinical studies are reported as averages. But there are usually outliers.

We have to constantly experiment, keep records, and work out what is best for us. It's a lot of work, but it's worth that effort. Good control now will mean fewer problems in the future.

Wednesday, January 1, 2020

Helping Obese Mice (humor)

OK, I admit it. I'm a worrier. I worry about big issues, like climate change. But I also worry about smaller issues, like what I would do if we had five straight days of snow so I couldn't get out and I was almost out of toilet paper and coffee.

[Correction: Being out of coffee is a big issue.]

But one thing I don't worry about a lot is obese mice. As long as they don't eat all my food, I don't care how svelte my resident mice are. So when I saw an article titled "Watermelon supplements bring health benefits to obese mice," I didn't exactly race to the supermarket to buy watermelon for my live-in mice.

I did wonder why the researchers even thought about giving mice watermelon in the first place. Were they sitting around in the shade some hot day eating watermelon when one of them said, "Say, I wonder if watermelon would solve the urgent national problem of obese mice? Might they have a better self-image if they were healthier after eating this fruit?"

Then I read on. "The study was funded by the National Watermelon Promotion Board."  Ah, that explains it.

Food industry groups support research that takes some product they're pushing, extracting something from it, and giving a lot of the extract to mice or people, hoping it will show some benefit. If it doesn't, you'll never hear about it: "Kale extract doesn't help diabetics" is a headline you'll never see in your newspaper, ever. If it does help, the story will be trumpeted everywhere: "Kale extract may cure diabetes in platypuses." Even if the effect is miniscule and the test organism rare, the PR experts hope you won't remember the details, just "cure diabetes," so you'll buy a lot of it.

Thus unless you're losing sleep over the problems of fat mice, when you see news stories lauding some common food as an obesity or diabetes treatment, see who sponsored the study. If it's a food industry group, take the findings with a grain of salt.

Unless, of course, you're on a low-salt diet.

Thursday, December 19, 2019

Ultraprocessed Foods

Nutrition research seems to follow fads, just like diets. Not long ago, everyone was into intermittent fasting. Now it's so-called ultraprocessed foods.

A recent observational study in France linked consumption of ultraprocessed foods and risk of type 2 diabetes. And another observational French study linked consumption of ultraprocessed foods to increased mortality. Both studies lasted for some years and relied on 24-hour dietary records.  An earlier study linked consumption of ultraprocessed food with cancer.

Another study, this one in the United States, admitted people to the NIH Clinical Center for two weeks and fed them different diets. They could eat a much as they wanted. The researchers found that the people ate about 500 more calories a day when fed the ultraprocessed diets, and their weight increased correspondingly. They gained an average of 2 pounds over the 2 weeks on the ultraprocessed diet and lost 2 pounds on the unprocessed diet. Interestingly, when they ate more, they ate more carbohydrate and fat but not more protein.

The full text of the study is here.

What I found interesting in the first cited study was the description in the article and supplementary material about what the researchers consider to be ultraprocessed. Ultraprocessed foods are those undergoing multiple physical, biological, and/or chemical processes and generally containing food additives. They usually go through several physical and chemical processes such as extruding, molding, prefrying, and hydrogenation. Flavoring agents, colors, emulsifiers, humectants, nonsugar sweeteners, and other cosmetic additives are often added.

Other categories are unprocessed and minimally processed foods, culinary ingredients, and processed foods, including canned vegetables with added salt, sugar-coated dried fruits, cheeses, meat products processsed only by salting, and unpackaged breads.

Examples of ultraprocessed foods include sugary drinks, diet sodas, and energy drinks; flavored or artificially sweetened yogurts; dairy desserts, cream cheese, and milkshakes with texturizer, emulsifant, colorant, or other cosmetic additives; sauces like mayonnaise or ketchup containing emulsifiers, flavor enhancers, or other additives; instant powder soups; flavored and artificially sweetened fruit compotes; fish fingers and processed meat with added nitrites; prebaked breads with added dextrose, preservatives or emulsifiers; industrially packed cookies, cakes and candies; chips and crackers made with ingredients other than potatoes, oil and salt.

Most people eat most of these foods.

I make my own yogurt or kefir from whole milk and add strawberries. But according to this definition, it would be considered ultraprocessed because I use artificial sugar.

The authors point out that because ultraprocessed foods often have longer shelf lives because of added preservatives, they may stay for long periods in their packaging, favoring migration of materials in contact with food, such as bisphenol A, which has been associated with increased type 2 diabetes risk.

It's clear that you're better off eating whole foods; cooking at home instead of eating in restaurants (or take-out), where you don't know what's in the food; and avoiding convenience foods, which are usually ultraprocessed and often packaged in plastic.

But not everyone has that option. Someone who has a full-time job and also cares for children or elderly relatives, or both, probably doesn't have the time to prepare meals from scratch at home all the time. The answer is to do what you can. As they say, "Perfection is the enemy of the good."

Sunday, December 15, 2019

Soaked (Marinated) Vegetables

Sometimes one wants something a little crunchy, as well as tasty, and this fills the bill for me. I don't know where the recipe came from, so I can't give credit. I think a friend or relative took a Chinese cooking course and passed this on.

You can use turnips, radishes, cucumbers (boil whole for one minute), Chinese string beans, carrots (keep a long time), cabbage (short time), green pepper (short time), celery cabbage stems, etc. I like turnips or peeled broccoli stems.

2 cups water
2 tablespoons sherry
2 tablespoons vinegar
2 tablespoons sugar (I use erythritol)
4 teaspoons salt
2 to 3 dried red chiles
3 cloves garlic
(szechuan peppercorns)

Wash vegetables. Cut into pieces if large.

Fill quart jar half full with soaking solution. Drop vegetables in. Keep in fridge at least 1 day. Then it keeps for about a week.

As you eat some of the vegetables, you can add more with a small portion of soaking solution.

I find this satisfies any cravings for something to chew on between meals. It's salty, slightly sweet, and slightly hot. You can experiment with vegetables until you find some you like.

Saturday, November 30, 2019

Growing on Carbon Dioxide

Scientists have developed a strain of E. coli that is able to produce all its cell mass from carbon dioxide. Of course, plants do this, using energy from the sun. But other organisms, including humans, normally can't. They consume other organisms, plants or animals, and use the chemicals from their food to grow. Some of the food is used to produce energy, and some is used to produce mass.

The developed strain of the bacterium E. coli uses carbon dioxide to produce mass, but it still needs an energy source. It can't use the sun. But it can use formate (a 1-carbon compound) to produce energy, and the formate can be produced electrochemically.

Now, I know some of us may feel that we produce cell mass (gain weight) just by breathing, or smelling food, but of course that's not really true. We need to eat if we want to gain weight or maintain what weight we already have, because we're constantly breaking down our mass in order to produce energy. This new type of bacteria can gain weight by using carbon dioxide as a carbon source.

The methods they used to get these new strains of E. coli are complex, but if you're interested, you can read the paper here.

The new strain still prefers glucose, rather than carbon dioxide, as a carbon source, so in the near future, this research will have very little practical application, but with time, these bacteria could be used to remove carbon dioxide from the atmosphere. E. coli bacteria are already used to produce human insulin, and if the bacteria could be grown even more cheaply because they didn't require food, just formate, perhaps the production of insulin would be cheaper. I say "perhaps" because Big Pharma would probably figure out some way to keep the insulin prices high.

But despite the lack of immediate application, this research is interesting and shows that bacteria can be trained to evolve in a way that produces some compound or compounds that we need. I just hope they don't develop greedy bacteria that can eat only chocolate. They might spread throughout my kitchen cabinets and decimate my supply.

Wednesday, November 20, 2019

Does Protein Damage Kidneys?

When I was diagnosed with type 2 diabetes more than 20 years ago, the accepted dogma was that protein damaged kidneys, and because people with diabetes are at high risk of kidney damage, they were told to eat more carbohydrate and less protein. Fat of all types was considered bad.

Of course, it's eating carbohydrate that makes blood glucose levels go up, and high blood glucose levels cause all kinds of complications.

In the ensuing years, studies have shown that protein does not damage healthy kidneys. If you already have kidney damage, then protein can make the damage worse. But not if you have healthy kidneys.

Now, a headline in a press release implies that protein can harm kidneys ("High-protein diets may harm your kidneys"). To be fair, it doesn't say "will harm" but "may harm," but how many readers will pick up on that?

What I found odd were some of the statements in the press release. For example, "Avoiding carbohydrates and substituting them with proteins has become a leading dogma for all those who care for their looks and health."


When did a low-carbohydrate high-protein diet become mainstream? A low-carb high-fat diet is currently popular, but the protein in such a diet is not especially high. So I went to the article cited in the press release.

It begins, "How often have you been told to eat more protein and less carbohydrates to stay healthy?" Actually, never. "This is not an emerging food culture but rather a prevailing dogma in our society. Physicians, dietitians and other health care professionals tell us constantly about the advantages of a high-protein diet."

 Again, huh? Maybe I've been living under a rock, but I've never been told this. 

"We feel compelled to eat only the meat patty of the sandwich and leave behind the bun when eating in front of others, otherwise we may lose credibility among friends and peers."

That's odd. Most of my friends and peers are still into bread and pasta. Maybe I need different friends and peers.

Since the dawn of agriculture, the authors write, the total protein intake of our ancestors was <1 g/kg body weight/day, most likely in the 0.6–0.8 g/kg/dayrange." But 0.8 g/kg is what most medical people recommend, a little more for older people who are at risk of sarcopenia, or muscle loss.

Before recent times, "obesity was never a problem," they write. That's odd. I guess they never heard of William Banting, who was obese and died in 1878. He found that it was starchy foods that made him gain weight and proposed a low-carb diet. In fact, some people call going on a low-carb diet "banting."

The next issue is what constitutes a high protein diet. If you used to have a burger, fries, and a soda for lunch and you give up the bun, the fries, and the soda and substitute salad or low-carb vegetables, your percentage of protein goes way up, but the amount is the same. And it's the amount that makes a difference for kidney function.

The standard recommendation is about 0.8 grams of protein per kilogram of body weight, or 0.36 grams per pound. This means 56 grams per day for the average sedentary man or 46 grams per day for the average sedentary woman. But this is the minimum you need. If you get a lot of exercise, or if you're elderly, you need more.

Then you need to know if you do, in fact, have some kidney damage. Keep track of your blood creatinine levels when you get bloodwork done, and make sure your doctor also tests urine for protein. If your kidneys are healthy, you shouldn't have protein in your urine. And if your kidneys are healthy, you shouldn't worry about getting too much protein in your diet.

We should all understand that too much protein is not good for compromised kidneys, but we should also understand that low-carb diets aren't usually superhigh in protein, and calling all low-carb diets high-protein diets is misleading and may scare people into reverting to the  high-carb diets that make diabetes so difficult to control. 


Thursday, November 14, 2019

W.H.O. and Generic Insulin

The World Health Organization (W.H.O) announced on Wednesday, right before World Diabetes Day on November 14, that it will be testing and certifying generic insulin in an effort to encourage companies to produce it. Patients in many developing countries simply can't afford the cost of current brand-name insulins, which can cost 20% or more of the patient's annual income. Many die as a result.

The idea is that if the insulins are tested and certified, patients would not be afraid to use them, and more pharmaceutical companies would produce them.

In theory, generic drugs are just as good as brand-name drugs. They are tested to make sure they contain the same amount of the active ingredient. However, the buffers and other inactive ingredients don't have to be the same. So a brand-name drug might dissolve at a uniform rate whereas the generic might dissolve faster, more slowly, or erratically.

Dr. Richard Berstein, author of The Diabetes Solution and an expert on low-carbohydrate diets, always says that Glucophage ($10 to $50 a month retail for 1000 mg a day) works better than generic metformin (free to about $5 a month). So I decided to try it. With my Plan D drug plan, it cost me $25 a month; the generic was about $2. The Glucophage did give me slightly lower blood glucose levels, but I didn't think the difference was worth more than $20 a month.

I once visually compared some generic drug, I think omprazole, that came in a capsule with the brand-name drug. The brand name consisted of tiny spheres, all the same size. The generic came in random shapes of different sizes. They were obviously saving money with cheaper equipment. Would this difference have made any difference in the release of the drug? I don't know. But the FDA doesn't test this, only that the drug contains the same amount of the active ingredient.

People sometimes find that a tablet has passed through them undissolved.

I know someone who found that some drug worked well until her insurance company made her switch to a generic, and then it didn't work. A sample size of one doesn't mean much, but it could be the same for others. If a generic drug doesn't work for you, sometimes your doctor can specify the brand name, and depending on your insurance, it may be covered.

I think it's clear that brand-name drugs are usually better than the generics. The question is how much better, and whether they're worth the higher price.

If you were living in a developing country and couldn't afford insulin, you would die. So in cases like this, generic insulin would definitely be better than nothing. During World War II, Eva Saxl, who had type 1 diabetes, was trapped in Shanghai, where no insulin was available. But her husband Victor learned to make insulin from slaughterhouse pancreases, and her life was saved. Any generic insulin certified by the W.H.O. would certainly be better than what Saxl was able to make under nonsterile conditions.

Eventually, the W.H.O.-approved insulin should be available in the United States, and the competition with Big Pharma should bring insulin prices down. The current prices are obscene, and the companies that charge them have no soul.

In the meantime, if you can't afford insulin, you shouldn't ration your supply. Walmart sells older insulins for about $25 a vial. They're not as good as newer insulins because they're peaky and unpredictable, but they work. I used NPH for a few months. It peaked at noon, and I often went low then, but I looked out for lows and coped with a little regular ice cream, followed by lunch, not something I'd recommend to anyone else, but it sure tasted good.