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."

Huh?

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.


Tuesday, October 8, 2019

Changing Dietary Habits

I've had type 2 diabetes for 23 years now. When I was diagnosed, the only treatments available were sulfonylureas, metformin (which had only been approved here the year before), or insulin. And the cutoff for a diagnosis of diabetes was a fasting blood glucose (BG) level of 140 mg/dL.

Since then, myriad drugs have come on the market, including the glitazones, glutides, gliptins,  gliflozins, and meglitinides. A real tongue-twister.

Examples of these newer drugs are Actos (glitazone, or thiazolidinedione); Victoza (glutide; GLP-1 agonist); Januvia (gliptin; DPP-4 inhibitor), Invokana; (gliflozin; SGLT-2 inhibitor), and Starlix (meglitinide; long-acting sulfonylurea). Some of them are available as combinations with other diabetes drugs. Some are injectable and others are pills. Some last a week and others just a day or less.

You can find a more complete list here.

Some of these drugs can cause weight gain and others can contribute to weight loss. Some are supposed to protect the heart and some seem to increase rates of heart disease. Some increase rates of pancreatitis. Other side effects include nausea, urinary tract infections, ketoacidosis, and even lower-limb amputation.

Clearly, deciding which medications are best for you depends on many factors, and different physicians have different preferences. However, today most agree that metformin is the best drug to start with unless you can't tolerate it because of GI side effects.

But despite all the new drugs, one treatment remains the same as when I was diagnosed: diet and exercise. At first, this treatment is the most difficult of all.

We'd all like to be able to take a pill and continue eating what we've always eaten, including, in almost all cases, more food than our body needs. This is not entirely our fault. Portions at restaurants are often huge, and tempting treats are offered everywhere. We've usually been raised to clean our plates and not waste food. But if we want to be healthy, we need a major brain reshuffle to reject old ideas and acquire new ones.

What works for me is a low-carb diet, and I think that's the best one to start with. If for some reason, it doesn't work for you, then you can try to find another diet that works for you. But controlling our food intake, no matter how, is essential. Exercise is good for the heart but usually has less effect on blood glucose levels than diet does.

The most difficult thing facing you when diagnosed, I think, is accepting the fact that you're going to have to revamp your eating habits, usually in a major way. You have diabetes, and it's not going to go away. It can be controlled, but not cured, at least not today. It's difficult to accept this at first, but it's necessary if you want to live a long and healthy life.

That's bad news, but here's some good news. One study showed that people with diabetes who take metformin actually live longer, on average, than people who don't have diabetes. This doesn't mean you can take metformin and not change your dietary habits. But it is consistent with the saying that the best way to stay healthy is to develop a chronic disease that forces you to take care of yourself.

So instead of raging against our fate, we should be grateful that fate has given us a second chance. Let's use it to stay healthy for many more years to come.




Tuesday, October 1, 2019

The Glimins

There's a new class of diabetes medications on the horizen, not yet approved by the FDA. They're called glimins, and the one that has had the most research is imeglimin. Results of Phase 3 trials in Japan were reported at the European Association for the Study of Diabetes annual meeting in Barcelona in September.

Phase 1 trials test the safety of a new drug in a small number of healthy volunteers. Phase 2 trials test the efficacy of the drug in more people. Phase 3 trials test even more people in what are usually blinded studies (meaning neither the patient nor the physicians know which patients got the drug and which got a placebo). Once a drug has passed Phase 3, the company can apply for FDA approval.

One problem with the glimin class is that there's already a generic drug on the market called Glimin. It seems to be a sulfonylurea or a sulfonylurea plus metformin. It's marketed in Asia, and perhaps the term glimin is used there to mean diabetes drug as there seem to be different formulations. As far as I know, none of these products are available in the United States. But there could still be confusion.

The drug imeglimin is reported to work via the mitochondria to affect several systems important for glucose control: decrease the release of glucose by the liver, increase the uptake of glucose by muscle, increase insulin secretion, and decrease the destruction of beta cells by apoptosis (a way the body gets rid of cells it thinks it doesn't need). It may also mobilize fat in the liver.

The exact mechanism by which imeglimin works is not yet known, but metformin was used for years before it was known how it worked, and the mechanism is still not completely understood.

The reports of imeglimin sound wonderful, but there's very little information about the new drug available yet. And side effects of new medications often don't emerge until thousands of people have taken the drugs. So this information doesn't have much immediate practical use. There were reports on its benefits in 2012 and it's still not on the market. However, knowing a little about it means that if there are news stories about it, you can understand their relevance.

Friday, September 27, 2019

Drunk Without Drinking

NAFLD, or nonacoholic fatty liver disease, is common in people with type 2 diabetes, especially when blood glucose levels aren't controlled. More than 50% may develop it.

And of course a high intake of alcohol can produce fatty liver disease.

Now researchers have discovered that more than half of patients with NAFLD have gut bacteria that produce alcohol from the sugar the people eat. There's apparently a specific bacterial strain of  Klebsiella pneumoniae that produces more alcohol than usual, and this strain was found in 61% of people with NAFLD, but only 6% of controls.

Mice fed these strains of K. pneumoniae developed signs of liver damage. When these mice got an antibiotic that killed K. pneumoniae, their condition was reversed.

One man studied had severe liver damage and a condition with the name Autobrewery Syndrome. It's normally caused by alcohol-producing yeast, but this man  had no signs of yeast infection. When tested on an alcohol-free high-carbohydrate diet, he had a very high blood alcohol concentration of 400 mg/L, or .04%. Legal intoxication is usually .08%.

Now, most people wouldn't produce as much alcohol as this man did on a high-carbohydrate diet. But the production of a smaller amount over a long period of time could damage the liver of a person who never drank alcohol.

This is another reason to avoid high carbohydrate diets. The bacteria seem to produce alcohol only when fed a lot of carbohydrates that can be broken down into glucose.

You can read the full study here.

They point out that endogenous alcohol production by particular bacteria is not the only cause of NAFLD: "It would be worth emphasizing that it has become clearer that NAFLD is a very heterogeneous disease and the findings here likely represent just one type of etiology."

But it's a fascinating finding and makes one wonder how many other unanticipated products of gut microbes contribute to disease.




Wednesday, September 25, 2019

YMMV

Here's a study confirming what most of us already know: YMMV, or Your Mileage May Vary. Some people prefer YDMV, or Your Diabetes May Vary.

Different people may have different reasons for getting diabetes. Some may have a lot of insulin resistance. Others may be pretty insulin sensitive but they just don't produce enough insulin. They do produce some, so unlike people with type 1, they can often get along without added insulin. And others may have a combination of these deficits.

In this study,  two groups were studied: Pima Indians from the Southwestern United States and Asian Indians from Chennai, India. They found that the Pima Indians tended to have a lot of insulin resistance (three times as much as the Asian Indians), but the Asian Indians, who were also older and thinner, tended to have defects in insulin secretion (three times less).

Unfortunately, when you're diagnosed, it's not common to have a lot of tests to find out exactly what is causing your diabetes. Most doctors tell you it doesn't matter, because they'd treat the disease the same way regardless of the cause. And a bunch of extra tests would be expensive.

However, if you come from an ethnic group that tends to have insulin resistance, that would probably be your major problem and you should focus on things like exercise and weight loss that can reduce insulin resistance. If you come from a group that tends to secrete too little insulin, it would make sense to focus on eating foods that don't require a lot of insulin, in other words, trying a low-carb diet.

Of course, many of us in the United States have a mixed heritage, so such studies would be less useful. Nevertheless, they might give hints about what kind of treatment to focus on.