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."
Thursday, December 19, 2019
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.
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.
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.
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.
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.
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.
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.
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.
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.
Wednesday, September 4, 2019
Studying Rodents
Much diabetes research is done in rodents, mostly mice. But mice aren't humans, and they don't always react the same way as humans.
For example, mice have been cured of diabetes many times, but these cures don't translate into human cures. So should we abandon mouse research?
No. The mouse research makes suggestions for things that might work in humans, or in human cell cultures, and raising mice is a lot cheaper and faster than raising larger animals, so many more studies can be done.
However, more attention should be paid to how the mice are raised. Some people criticize mouse studies because they are not controlled for light intensity or electromagnetic fields, which can affect biochemical systems. Others criticize the standard mouse diets.
A recent editorial in the journal Nature discussed the problems with mouse diets. It focuses on obesity research, but obesity and type 2 diabetes are linked.
You can make mice obese pretty quickly by feeding them high-fat diets, which they love; their normal diet is relatively low in fat. Think of baiting a trap with cheese. But the Nature editorial asks if such high-fat diets have relevance to human obesity that usually develops at much lower dietary fat levels than the mouse obesity.
The editorial also asks if the metabolism of mice raised on a very high fat diet is different from that of mice raised on more normal diets. It also points out that the very high (60%) fat diets usually used to make mice obese quickly have a lot less sucrose than a lower-fat diet would, and sugar has metabolic consequences too.
So too, the types of fatty acids in a diet can affect the metabolism, and the fatty acids in the commercial mouse diets may not be similar to those in a typical (if any diet is typical) human diet.
One thing the editorial didn't address is the fact that many of these diets use the cheapest ingredients available and often satisfy the carbohydrate goal by adding sucrose instead of some kind of healthier carbohydrate like whole grains.
This editorial obviously raises questions rather than providing answers, and at the moment it has no practical value for most people.
However, the fact that people are drawing attention to the quality of the mouse diets used in so much research is a good thing. Maybe better mouse diets will result in better research results.
For example, mice have been cured of diabetes many times, but these cures don't translate into human cures. So should we abandon mouse research?
No. The mouse research makes suggestions for things that might work in humans, or in human cell cultures, and raising mice is a lot cheaper and faster than raising larger animals, so many more studies can be done.
However, more attention should be paid to how the mice are raised. Some people criticize mouse studies because they are not controlled for light intensity or electromagnetic fields, which can affect biochemical systems. Others criticize the standard mouse diets.
A recent editorial in the journal Nature discussed the problems with mouse diets. It focuses on obesity research, but obesity and type 2 diabetes are linked.
You can make mice obese pretty quickly by feeding them high-fat diets, which they love; their normal diet is relatively low in fat. Think of baiting a trap with cheese. But the Nature editorial asks if such high-fat diets have relevance to human obesity that usually develops at much lower dietary fat levels than the mouse obesity.
The editorial also asks if the metabolism of mice raised on a very high fat diet is different from that of mice raised on more normal diets. It also points out that the very high (60%) fat diets usually used to make mice obese quickly have a lot less sucrose than a lower-fat diet would, and sugar has metabolic consequences too.
So too, the types of fatty acids in a diet can affect the metabolism, and the fatty acids in the commercial mouse diets may not be similar to those in a typical (if any diet is typical) human diet.
One thing the editorial didn't address is the fact that many of these diets use the cheapest ingredients available and often satisfy the carbohydrate goal by adding sucrose instead of some kind of healthier carbohydrate like whole grains.
This editorial obviously raises questions rather than providing answers, and at the moment it has no practical value for most people.
However, the fact that people are drawing attention to the quality of the mouse diets used in so much research is a good thing. Maybe better mouse diets will result in better research results.
Thursday, August 22, 2019
New Hypotheses
Sometimes it seems as if almost everything I was taught in school is now considered wrong. Well, OK, not everything. The letter i still usually comes before e, except after c and a ton of other exceptions including neither leisured foreigner seized the heifer on the weird heights, and no one cares about spelling today anyway.
Of course in science, no theory is permanent. New evidence requires updating of current theories, somethings reversing them completely.
I just hope no one discovers that the universe isn't expanding, but imploding toward another Big Bang! And if it is, I hope it doesn't occur in my lifetime.
But on a more mundane level, three papers came in recently that are challenging accepted dogma.
The first suggests that lactate, a product of metabolizing glucose, isn't a dead-end molecule produced only when there isn't enough oxygen to metabolize it further, but rather is an important source of energy and a way to distribute this energy from one tissue to another. George Brooks of the University of California, Berkeley, has been proposing this idea for 40 years, but no one has been paying much attention, and most biochemistry sources still show it as a sort of waste product produced only in the absence of oxygen and causing pain after heavy exercise.
But the Brooks lab found that lactate is actually a preferred source of energy in some tissues like the brain and heart. Brooks calls the production, transport, and use in various tissues the lactose shuttle.
The whole review can be seen here.
A second paper suggests that it's not a lack of insulin but insulin hypersecretion that causes insulin resistance and type 2 diabetes. Australian researcher Christopher Nolan is one of the authors of this paper, and I've written about some of his ideas before, namely the idea that insulin resistance is protective for some tissues.
Nolan and his coauthor support the idea that there are five subtypes of diabetes and says that the type that causes insulin hypersecretion is severe insulin-resistant diabetes (SIRD). If someone has this kind of type 2 diabetes, then he says treating it with insulin injections or sulfonylureas would be counterproductive.
People with other subtypes might benefit from such treatments.
I suspect that researchers will eventually discover even more subtypes of diabetes, with some overlap, but for now we can stick to just five. Nolan says it's "time for a conceptual framework shift" to consider the main driver of type 2 diabetes to be not insulin resistance but insulin oversecretion. It's an interesting way of looking at the disease.
Finally, the third paper says that it isn't high glucose levels but defects in mitochondria and elevations in some fat derivatives and their processing in the defective mitochondria that cause inflammation. The senior author of the paper, Barbara Nikolajczyk, kindly sent me the full text, but the research is so complex I can't evaluate it and have to accept the summaries. There are 20 authors, and you can see the summary here.
In the past, there have been studies relating high blood glucose levels and inflammation, but as we all know, correlation is not causation, and it's not always clear if the high A1cs caused the inflammation or if inflammation caused the high A1cs, or if a third factor caused them both. One study even suggested that low blood glucose levels, but not high blood glucose levels, caused inflammation in monocytes (a type of white blood cell). The Nikolajczyk study used peripheral blood mononuclear cells, which include monocytes and a few other cell types.
New hypotheses usually stimulate new research and often result in significant advances. Maybe I should hypothesize e before i, don't ask me why, except for most words, that are known by all nerds and maybe I'd start a spelling revolution. At least no one would be hurt in such a revolution.
Of course in science, no theory is permanent. New evidence requires updating of current theories, somethings reversing them completely.
I just hope no one discovers that the universe isn't expanding, but imploding toward another Big Bang! And if it is, I hope it doesn't occur in my lifetime.
But on a more mundane level, three papers came in recently that are challenging accepted dogma.
The first suggests that lactate, a product of metabolizing glucose, isn't a dead-end molecule produced only when there isn't enough oxygen to metabolize it further, but rather is an important source of energy and a way to distribute this energy from one tissue to another. George Brooks of the University of California, Berkeley, has been proposing this idea for 40 years, but no one has been paying much attention, and most biochemistry sources still show it as a sort of waste product produced only in the absence of oxygen and causing pain after heavy exercise.
But the Brooks lab found that lactate is actually a preferred source of energy in some tissues like the brain and heart. Brooks calls the production, transport, and use in various tissues the lactose shuttle.
The whole review can be seen here.
A second paper suggests that it's not a lack of insulin but insulin hypersecretion that causes insulin resistance and type 2 diabetes. Australian researcher Christopher Nolan is one of the authors of this paper, and I've written about some of his ideas before, namely the idea that insulin resistance is protective for some tissues.
Nolan and his coauthor support the idea that there are five subtypes of diabetes and says that the type that causes insulin hypersecretion is severe insulin-resistant diabetes (SIRD). If someone has this kind of type 2 diabetes, then he says treating it with insulin injections or sulfonylureas would be counterproductive.
People with other subtypes might benefit from such treatments.
I suspect that researchers will eventually discover even more subtypes of diabetes, with some overlap, but for now we can stick to just five. Nolan says it's "time for a conceptual framework shift" to consider the main driver of type 2 diabetes to be not insulin resistance but insulin oversecretion. It's an interesting way of looking at the disease.
Finally, the third paper says that it isn't high glucose levels but defects in mitochondria and elevations in some fat derivatives and their processing in the defective mitochondria that cause inflammation. The senior author of the paper, Barbara Nikolajczyk, kindly sent me the full text, but the research is so complex I can't evaluate it and have to accept the summaries. There are 20 authors, and you can see the summary here.
In the past, there have been studies relating high blood glucose levels and inflammation, but as we all know, correlation is not causation, and it's not always clear if the high A1cs caused the inflammation or if inflammation caused the high A1cs, or if a third factor caused them both. One study even suggested that low blood glucose levels, but not high blood glucose levels, caused inflammation in monocytes (a type of white blood cell). The Nikolajczyk study used peripheral blood mononuclear cells, which include monocytes and a few other cell types.
New hypotheses usually stimulate new research and often result in significant advances. Maybe I should hypothesize e before i, don't ask me why, except for most words, that are known by all nerds and maybe I'd start a spelling revolution. At least no one would be hurt in such a revolution.
Friday, August 2, 2019
Does Paleo Diet Increase Risk for Heart Disease?
A recent flurry of articles in the popular press claim that following the Paleo diet causes an increase in your risk of heart disease, primarily because of a molecule called TMAO (trimethylamine N-oxide).
Most people agree that the bacteria in your colon convert carnitine, found in red meat, to TMAO. How dangerous this is, however, is not as clear, and several bloggers have detailed why they don't think we should lose sleep about TMAO, so I won't repeat their analyses.
Two things I think should be emphasized: (1) resistant starch increases TMAO and (2) some fish increase TMAO.
The author of the recent study emphasized the lack of whole grains in Paleo diets, saying, "We know that whole grains are a fantastic source of resistant starch." But wait! Resistant starch increases TMAO levels.
Another study even suggests that vegetables can increase TMAO levels and increased TMAO levels are helpful in heart failure.
I think we don't know enough about the relation between TMAO and heart disease to make any dietary changes according to what increases or decreases its levels. Fish and resistant starch are supposed to be healthy but they both can increase TMAO. Some people think red meat is unhealthy, but it can increase TMAO.
I think the publicity about the Paleo diet and TMAO is an example of some people thinking that any diet that doesn't follow the recommendations of the Dietary Guidelines for Americans is a fad diet and then looking for reasons to avoid it.
I remember one nutritionist criticizing low-carb diets because "They don't provide the 60% carbohydrate content recommended by the DGA." Um, isn't that what "low-carb" means? Sometimes I wonder where such people learned to think. . . if they ever did.
So I'd say one shouldn't lose sleep over TMAO. Eat what works for you to keep your blood glucose levels as close to normal as you can, keep an eye on your blood pressure and blood lipid levels, and don't panic over every flashy headline that appears in the popular press.
Most people agree that the bacteria in your colon convert carnitine, found in red meat, to TMAO. How dangerous this is, however, is not as clear, and several bloggers have detailed why they don't think we should lose sleep about TMAO, so I won't repeat their analyses.
Two things I think should be emphasized: (1) resistant starch increases TMAO and (2) some fish increase TMAO.
The author of the recent study emphasized the lack of whole grains in Paleo diets, saying, "We know that whole grains are a fantastic source of resistant starch." But wait! Resistant starch increases TMAO levels.
Another study even suggests that vegetables can increase TMAO levels and increased TMAO levels are helpful in heart failure.
I think we don't know enough about the relation between TMAO and heart disease to make any dietary changes according to what increases or decreases its levels. Fish and resistant starch are supposed to be healthy but they both can increase TMAO. Some people think red meat is unhealthy, but it can increase TMAO.
I think the publicity about the Paleo diet and TMAO is an example of some people thinking that any diet that doesn't follow the recommendations of the Dietary Guidelines for Americans is a fad diet and then looking for reasons to avoid it.
I remember one nutritionist criticizing low-carb diets because "They don't provide the 60% carbohydrate content recommended by the DGA." Um, isn't that what "low-carb" means? Sometimes I wonder where such people learned to think. . . if they ever did.
So I'd say one shouldn't lose sleep over TMAO. Eat what works for you to keep your blood glucose levels as close to normal as you can, keep an eye on your blood pressure and blood lipid levels, and don't panic over every flashy headline that appears in the popular press.
Tuesday, July 16, 2019
Diagnosing diabetes risk early
I've been following the saga of Michael Snyder, a geneticist at Stanford, for some time. Snyder participated in a genetic study in which his own DNA was analyzed, and in the process he discovered that he had a gene linked with increased risk of type 2 diabetes. Then a viral infection made his blood glucose (BG) levels soar high enough that he was told he had type 2 diabetes.
Snyder modified his diet and increased his exercise and slowly brought his BG levels back to normal ranges within 6 months. When I mentioned this in a blogpost, I wrote as if bringing his BG levels back to normal meant that he could escape chronic type 2 diabetes as long as he maintained his diet and exercise regimen.
I was wrong. A recent story in the New York Times states that although he was able to maintain normal BG levels for three years after the initial diagnosis, they eventually increased enough that he was again told he was diabetic. He said it seems he's slow to release insulin.
In fact, almost everyone with type 2 diabetes lacks the rapid phase 1 insulin release that knocks down BG levels quickly, but we still have the slower phase 2 insulin release. When I was in a clinical study at the Joslin Diabetes Center, I showed almost zero phase 1 insulin release. Interestingly, when I took high-dose aspirin (actually an aspirin-like drug used in the study), my phase 1 insulin response increased to almost 70% of normal.
The classic description of type 2 diabetes is that it's caused by insulin resistance, but more and more research is showing that different people get type 2 diabetes (perhaps better called non-autoimmune diabetes) for different reasons. For some, the insulin resistance may be the strongest factor, but for others, factors like poor insulin secretion may be more important. Not all people with type 2 are overweight and some overweight people are insulin sensitive.
“We learned that people are Type 2 diabetic in very different ways,” said Snyder in the New York Times article.
In one study, "nine of the cohort members developed diabetes during the study. But it appears their health followed different paths to reach that state. Two people gained weight before their diagnosis, but seven developed the condition without substantial weight gain. The subjects also showed differences in how much insulin they produced. Some made very little insulin, while others produced enough insulin, but not sufficient to lower their glucose levels and forestall diabetes."
So a treatment that is best for people with one subtype of type 2 may not be best for people with another. This is not big news, but it's always nice to see some scientific validation of what we've observed.
Snyder is still trying to control his BG levels without drugs, and he's still getting a lot of lab tests. Perhaps this intense scrutiny of the physiology of one type 2 diabetes patient will give hints about the process that will help us all.
And what Snyder's story means for you is that if your diabetes progresses even though you are doing all you can to control it, don't blame yourself. Your genes may be responsible
Snyder modified his diet and increased his exercise and slowly brought his BG levels back to normal ranges within 6 months. When I mentioned this in a blogpost, I wrote as if bringing his BG levels back to normal meant that he could escape chronic type 2 diabetes as long as he maintained his diet and exercise regimen.
I was wrong. A recent story in the New York Times states that although he was able to maintain normal BG levels for three years after the initial diagnosis, they eventually increased enough that he was again told he was diabetic. He said it seems he's slow to release insulin.
In fact, almost everyone with type 2 diabetes lacks the rapid phase 1 insulin release that knocks down BG levels quickly, but we still have the slower phase 2 insulin release. When I was in a clinical study at the Joslin Diabetes Center, I showed almost zero phase 1 insulin release. Interestingly, when I took high-dose aspirin (actually an aspirin-like drug used in the study), my phase 1 insulin response increased to almost 70% of normal.
The classic description of type 2 diabetes is that it's caused by insulin resistance, but more and more research is showing that different people get type 2 diabetes (perhaps better called non-autoimmune diabetes) for different reasons. For some, the insulin resistance may be the strongest factor, but for others, factors like poor insulin secretion may be more important. Not all people with type 2 are overweight and some overweight people are insulin sensitive.
“We learned that people are Type 2 diabetic in very different ways,” said Snyder in the New York Times article.
In one study, "nine of the cohort members developed diabetes during the study. But it appears their health followed different paths to reach that state. Two people gained weight before their diagnosis, but seven developed the condition without substantial weight gain. The subjects also showed differences in how much insulin they produced. Some made very little insulin, while others produced enough insulin, but not sufficient to lower their glucose levels and forestall diabetes."
So a treatment that is best for people with one subtype of type 2 may not be best for people with another. This is not big news, but it's always nice to see some scientific validation of what we've observed.
Snyder is still trying to control his BG levels without drugs, and he's still getting a lot of lab tests. Perhaps this intense scrutiny of the physiology of one type 2 diabetes patient will give hints about the process that will help us all.
And what Snyder's story means for you is that if your diabetes progresses even though you are doing all you can to control it, don't blame yourself. Your genes may be responsible
Sunday, June 30, 2019
On Illustrations
I don't know about other people, but I'm getting really, really, really tired of seeing popular press articles about type 2 diabetes illustrated with photos of people pricking their fingers to get blood.
I mean, I know that unless you use a continuous glucose monitor, pricking your fingers is part of having diabetes. But it's not the only part. In fact, it's a very minor part. Controlling your diet is much more important.
But the finger jabbing seems to be a cliche for type 2 diabetes.
Another cliche I hate is that of a man and a woman, usually about 40 or 50 and trim, running along a deserted beach, intended to illustrate exercise.
I mean, I know running along a beach would be good exercise, but how many people live near a beach, especially a deserted beach like the ones always shown? And if they were just diagnosed with type 2 diabetes, how many would be slim and trim like the models? Maybe some, but not the majority.
Finally, the last cliche is the same attractive couple that was running along the beach preparing a salad in a perfectly appointed kitchen while grinning from ear to ear. "Diabetes is such fun! We can't wait to finish this delicious salad so we can go out to the beach again for some more running. If it's rainng, we can stay home and do some finger-pricking to prove we're really diabetic."
OK. I'm in a bad mood. I couldn't find a deserted beach and I ran out of salad fixings. Maybe tomorrow someone will come up with some more interesting popular-press illustrations.
I mean, I know that unless you use a continuous glucose monitor, pricking your fingers is part of having diabetes. But it's not the only part. In fact, it's a very minor part. Controlling your diet is much more important.
But the finger jabbing seems to be a cliche for type 2 diabetes.
Another cliche I hate is that of a man and a woman, usually about 40 or 50 and trim, running along a deserted beach, intended to illustrate exercise.
I mean, I know running along a beach would be good exercise, but how many people live near a beach, especially a deserted beach like the ones always shown? And if they were just diagnosed with type 2 diabetes, how many would be slim and trim like the models? Maybe some, but not the majority.
Finally, the last cliche is the same attractive couple that was running along the beach preparing a salad in a perfectly appointed kitchen while grinning from ear to ear. "Diabetes is such fun! We can't wait to finish this delicious salad so we can go out to the beach again for some more running. If it's rainng, we can stay home and do some finger-pricking to prove we're really diabetic."
OK. I'm in a bad mood. I couldn't find a deserted beach and I ran out of salad fixings. Maybe tomorrow someone will come up with some more interesting popular-press illustrations.
Thursday, June 27, 2019
Pancreatic Islet "Leader" Cells
No one understands yet exactly what regulates the release of insulin from the beta cells in the pancreas. We just know that the process is disrupted when you have diabetes, almost completely in the case of type 1 diabetes and partially when you have type 2.
Now researchers in several countries, including Germany, Great Britain, Canada, and Italy, have discovered a new clue. It seems that certain beta cells are "leader" cells or "hub" cells, and they control the other beta cells. This is like the heart's sinoatrial node (called the "pacemaker of the heart"), which controls the beating of other heart cells. And some researchers refer to the leader cells in the pancreas as pacemakers.
The studies show that if you selectively delete the leader cells in animal models of diabetes, the response to glucose becomes disrupted. It is known that in type 2 diabetes, the normally regular pulses of insulin that occur even when fasting are lost. Could this be because the leader cells are damaged? If so, why are they damaged? Are they more sensitive to high glucose and other toxins than the other beta cells?
The researchers found that the coordination of responses controlled by the leader cells was impaired in human islets taken from subjects with diabetes.
This is all fascinating albeit early days. This new study doesn't have any practical utility yet, but it could lead to more research that would have practical application.
If the heart's pacemaker isn't working well, they can give you an artificial pacemaker. The beta cell pacemakers wouldn't be as easy to replace. But perhaps now that it's known that there are such pancreas pacemakers, someone will figure out how to rejuvenate them.
Now researchers in several countries, including Germany, Great Britain, Canada, and Italy, have discovered a new clue. It seems that certain beta cells are "leader" cells or "hub" cells, and they control the other beta cells. This is like the heart's sinoatrial node (called the "pacemaker of the heart"), which controls the beating of other heart cells. And some researchers refer to the leader cells in the pancreas as pacemakers.
The studies show that if you selectively delete the leader cells in animal models of diabetes, the response to glucose becomes disrupted. It is known that in type 2 diabetes, the normally regular pulses of insulin that occur even when fasting are lost. Could this be because the leader cells are damaged? If so, why are they damaged? Are they more sensitive to high glucose and other toxins than the other beta cells?
The researchers found that the coordination of responses controlled by the leader cells was impaired in human islets taken from subjects with diabetes.
This is all fascinating albeit early days. This new study doesn't have any practical utility yet, but it could lead to more research that would have practical application.
If the heart's pacemaker isn't working well, they can give you an artificial pacemaker. The beta cell pacemakers wouldn't be as easy to replace. But perhaps now that it's known that there are such pancreas pacemakers, someone will figure out how to rejuvenate them.
Monday, June 3, 2019
Helping Beta Cells
Two recent research reports concern helping beta cells produce more insulin. Interestingly, they both involve inhibiting something rather than trying to stimulate the beta cells, as the sulfonylurea drugs do.
People think of type 2 diabetes as being caused by insulin resistance and some wonder why you would want to produce more insulin if you have type 2. But in fact, type 2 is often caused by insulin deficiency. That is, you're producing insulin, often more than normal, but it's not enough to overcome your insulin resistance. So more insulin can help.
The first study involves deleting senescent, or old, beta cells from the pancreas. When the Joslin Diabetes Center researchers did this in mice, they found that the remaining beta cells were rejuvenated and started producing enough insulin to keep blood glucose (BG) levels in the normal range.
How did they do this? One approach was genetic modification, which is fine in mice but unlikely to be practical in humans. The other approach was with senolytic drugs, drugs that remove senescent cells. Although you can buy drugs claiming to be senolytics from companies that market supplements, this field is relatively new and large-scale controlled trials have not yet been done. Pilot studies show promise.
The authors of this paper think that diabetes is caused by stress: in type 2 the stress of insulin resistance and in type 1 the stress of an autoimmune attack. Of course this doesn't explain what causes insulin resistance or an autoimmune attack, and these are the underlying problems.
The second study involved removing two signaling molecules that dampen the insulin response. This is the opposite of most approaches, which try to stimulate the insulin response directly instead of inhibiting inhibitors. The sulfonylureas stimulate insulin release, even when a person is not eating carbohydrate, which means your blood glucose can go low when you're not eating.
These studies were done in mice, and oddly, removing the inhibitors worked only when the mice were on a high-fat diet. The reason for this is not yet known.
The inhibitors are TLR2 and TLR4. TLR stands for toll-like receptor, and normally, TLR2 and TLR4 stimulate the immune system when they detect invadors. But they also work together to block beta cell proliferation, so when you remove them, the beta cells multiply like mad, so much that they can be seen with the naked eye.
There are in fact drugs that inhibit TLR2 and TLR4, but inhibiting them would not only stimulate beta cell growth, but it would inhibit the immune system and make a person susceptible to infection.
Nevertheless these new approaches are interesting and may result in methods to rejuvenate beta cells in people with both types of diabetes (most people with type 1 do have a few beta cells remaining despite the autoimmune attack). How wonderful that would be.
a
People think of type 2 diabetes as being caused by insulin resistance and some wonder why you would want to produce more insulin if you have type 2. But in fact, type 2 is often caused by insulin deficiency. That is, you're producing insulin, often more than normal, but it's not enough to overcome your insulin resistance. So more insulin can help.
The first study involves deleting senescent, or old, beta cells from the pancreas. When the Joslin Diabetes Center researchers did this in mice, they found that the remaining beta cells were rejuvenated and started producing enough insulin to keep blood glucose (BG) levels in the normal range.
How did they do this? One approach was genetic modification, which is fine in mice but unlikely to be practical in humans. The other approach was with senolytic drugs, drugs that remove senescent cells. Although you can buy drugs claiming to be senolytics from companies that market supplements, this field is relatively new and large-scale controlled trials have not yet been done. Pilot studies show promise.
The authors of this paper think that diabetes is caused by stress: in type 2 the stress of insulin resistance and in type 1 the stress of an autoimmune attack. Of course this doesn't explain what causes insulin resistance or an autoimmune attack, and these are the underlying problems.
The second study involved removing two signaling molecules that dampen the insulin response. This is the opposite of most approaches, which try to stimulate the insulin response directly instead of inhibiting inhibitors. The sulfonylureas stimulate insulin release, even when a person is not eating carbohydrate, which means your blood glucose can go low when you're not eating.
These studies were done in mice, and oddly, removing the inhibitors worked only when the mice were on a high-fat diet. The reason for this is not yet known.
The inhibitors are TLR2 and TLR4. TLR stands for toll-like receptor, and normally, TLR2 and TLR4 stimulate the immune system when they detect invadors. But they also work together to block beta cell proliferation, so when you remove them, the beta cells multiply like mad, so much that they can be seen with the naked eye.
There are in fact drugs that inhibit TLR2 and TLR4, but inhibiting them would not only stimulate beta cell growth, but it would inhibit the immune system and make a person susceptible to infection.
Nevertheless these new approaches are interesting and may result in methods to rejuvenate beta cells in people with both types of diabetes (most people with type 1 do have a few beta cells remaining despite the autoimmune attack). How wonderful that would be.
a
Monday, April 29, 2019
Is Type 2 Diabetes Autoimmune?
Is type 2 diabetes as well as type 1 diabetes autoimmune?
The classic description of type 1 diabetes is that it's an autoimmune disease. Normally, control mechanisms make sure that the body doesn't attack itself, but in type 1 diabetes, something has gone wrong with this process and the immune system does attack the beta cells, eventually almost totally wiping them out, so people have to inject insulin.
Type 2 diabetes, on the other hand, is described as a disease of insulin resistance. The beta cells can still produce insulin, but not enough to overcome the insulin resistance, and as time goes on and the beta cells deteriorate, type 2 patients may need insulin as well.
But researchers at the Stanford University School of Medicine and the University of Toronto say their research suggests that type 2 diabetes is also an autoimmune disease.
This makes sense to me. I've always felt that the two types of diabetes have a similar underlying cause and secondary effects that modulate this response. Also, studies show that people with type 1 diabetes can have some insulin resistance but not usually as much as in people with type 2, and people with type 2 diabetes can produce some autoantibodies but not usually as much as people with type 1.
In other words, there may not be a sharp line between the two versions of the disease but a continuum, with some people having more of one type of defect and others more of another.
But because of the classic understanding of the two types of diabetes, doctors don't usually test for antibodies in patients with typical signs of type 2, those who are overweight and don't get much exercise, and they don't test for insulin resistance in thin patients who have autoimmune antibodies.
Of course, this new theory wouldn't mean that classic approaches to type 2 diabetes such as weight loss and increased exercise wouldn't help. When such approaches reduce insulin resistance enough, then the defective beta cells may be able to produce enough insulin to keep blood glucose normal, depending on how damaged the beta cells are by the time of diagnosis.
But if these new ideas are confirmed with more research, it would open the door to new treatments for patients with type 2, focussing on the autoimmune aspects of the disease.
The researchers say that immune cells cause inflammation in fat when the fat cells are growing so fast that new blood vessels to support the fat cells can't keep up. Some of the fat cells die as a result and spill their contents into the fat, causing inflammation. This is seen in mice on a high-fat, high-calorie diet and in humans with type 2 diabetes.
The inflammation then causes insulin resistance, according to the researchers. And mice genetically engineered so they didn't produce antibody-producing B cells did not become insulin restant when they became fat. Injecting such mice with B cells or antibodies from obese insulin-resistant mice made the mice insulin resistant. So the immune system clearly plays a role in this.
In humans, “We were able to show that people with insulin resistance make antibodies to a select group of their own proteins,” said Edgar Engleman, senior author of the paper. “In contrast, equally overweight people who are not insulin-resistant do not express these antibodies.”
This line of investigation is in early stages, but it suggests new avenues of research. And new ways of looking at a problem often lead to new solutions.
The classic description of type 1 diabetes is that it's an autoimmune disease. Normally, control mechanisms make sure that the body doesn't attack itself, but in type 1 diabetes, something has gone wrong with this process and the immune system does attack the beta cells, eventually almost totally wiping them out, so people have to inject insulin.
Type 2 diabetes, on the other hand, is described as a disease of insulin resistance. The beta cells can still produce insulin, but not enough to overcome the insulin resistance, and as time goes on and the beta cells deteriorate, type 2 patients may need insulin as well.
But researchers at the Stanford University School of Medicine and the University of Toronto say their research suggests that type 2 diabetes is also an autoimmune disease.
This makes sense to me. I've always felt that the two types of diabetes have a similar underlying cause and secondary effects that modulate this response. Also, studies show that people with type 1 diabetes can have some insulin resistance but not usually as much as in people with type 2, and people with type 2 diabetes can produce some autoantibodies but not usually as much as people with type 1.
In other words, there may not be a sharp line between the two versions of the disease but a continuum, with some people having more of one type of defect and others more of another.
But because of the classic understanding of the two types of diabetes, doctors don't usually test for antibodies in patients with typical signs of type 2, those who are overweight and don't get much exercise, and they don't test for insulin resistance in thin patients who have autoimmune antibodies.
Of course, this new theory wouldn't mean that classic approaches to type 2 diabetes such as weight loss and increased exercise wouldn't help. When such approaches reduce insulin resistance enough, then the defective beta cells may be able to produce enough insulin to keep blood glucose normal, depending on how damaged the beta cells are by the time of diagnosis.
But if these new ideas are confirmed with more research, it would open the door to new treatments for patients with type 2, focussing on the autoimmune aspects of the disease.
The researchers say that immune cells cause inflammation in fat when the fat cells are growing so fast that new blood vessels to support the fat cells can't keep up. Some of the fat cells die as a result and spill their contents into the fat, causing inflammation. This is seen in mice on a high-fat, high-calorie diet and in humans with type 2 diabetes.
The inflammation then causes insulin resistance, according to the researchers. And mice genetically engineered so they didn't produce antibody-producing B cells did not become insulin restant when they became fat. Injecting such mice with B cells or antibodies from obese insulin-resistant mice made the mice insulin resistant. So the immune system clearly plays a role in this.
In humans, “We were able to show that people with insulin resistance make antibodies to a select group of their own proteins,” said Edgar Engleman, senior author of the paper. “In contrast, equally overweight people who are not insulin-resistant do not express these antibodies.”
This line of investigation is in early stages, but it suggests new avenues of research. And new ways of looking at a problem often lead to new solutions.
Tuesday, April 23, 2019
On Eggs and Press Releases
I've written before about the egg trampoline: stories saying eggs are good and then eggs are bad, seeming to bounce from one extreme to the other.
But part of the problem is not the research but the way the popular press deals with that research, writing sensational headlines to capture the interest of the public.
Most popular science sites like Eurekalert and Science Daily don't research stories they post to their sites but simply print press releases sent out by the public relations departments of the universities and research centers where the research was done, including the headlines. The goal of the PR people is to call attention to their institutions, so, as often occurs these days, if the research was done at several different instutions, each one may send out press releases with a slightly different spin.
You might see one saying "X University Scientists Discover New Hormone" and another saying "Y Institute Researchers Find Hormone to Cure Halitosis." Same research, different slant. But both tend to inflate the impact of the hormone that was discovered and the importance of the researchers at their institution.
The problem is that the average reader won't track down the original research to see if it did, indeed, cure halitosis. They'll just remember the headlines.
Two examples related to eggs are "UBC Researchers Say Eggs for Breakfast Benefits Those With Diabetes, and "Bad News For Egg Lovers."
I won't critique these stories because frankly I'm tired of this egg controversy and I'm especially tired of observational studies that don't really show much of anything. And then I came across a blogpost that analyzes the problem with nutritional studies. It's worth reading if you read or listen to news stories about nutrition. Enjoy.
But part of the problem is not the research but the way the popular press deals with that research, writing sensational headlines to capture the interest of the public.
Most popular science sites like Eurekalert and Science Daily don't research stories they post to their sites but simply print press releases sent out by the public relations departments of the universities and research centers where the research was done, including the headlines. The goal of the PR people is to call attention to their institutions, so, as often occurs these days, if the research was done at several different instutions, each one may send out press releases with a slightly different spin.
You might see one saying "X University Scientists Discover New Hormone" and another saying "Y Institute Researchers Find Hormone to Cure Halitosis." Same research, different slant. But both tend to inflate the impact of the hormone that was discovered and the importance of the researchers at their institution.
The problem is that the average reader won't track down the original research to see if it did, indeed, cure halitosis. They'll just remember the headlines.
Two examples related to eggs are "UBC Researchers Say Eggs for Breakfast Benefits Those With Diabetes, and "Bad News For Egg Lovers."
I won't critique these stories because frankly I'm tired of this egg controversy and I'm especially tired of observational studies that don't really show much of anything. And then I came across a blogpost that analyzes the problem with nutritional studies. It's worth reading if you read or listen to news stories about nutrition. Enjoy.
Sunday, April 21, 2019
Appetite and Genetics
Are thin people thin because they have incredible self-control whereas overweight people have very little? Or could their genetics play a large role?
A story in the New York Times suggests the latter. They describe people with a version of a particular gene, MCR4, who are simply almost never hungry. Self-control has little to do with it. Conversely, people with another version of the gene are constantly hungry. In other words, it's appetite that controls how much people eat in an environment in which food is plentiful, and some people are hungrier than others.
Overweight people often think that, but no one believes them and people tell them (or at least believe) they have no self-control.
I've always thought genes play a large role in controlling appetite. A good example is in my book The First Year: Type 2 Diabetes:
"Having diabetes genes may affect the appetite. Alex E. described the time someone brought some scrumptious pastries to work. A thin person walked in, looked at the pastries, and said, "Oh my, those look good. I wish I were hungry so I could try one." Alex was flabbergasted. He was hungry all the time and thought everyone else was too."
Of course, genes are not the only factors affecting appetite. Hormones such as leptin and ghrelin and fluctuating blood glucose levels can affect hunger, as can habit, for example always eating lunch at a certain time. If you always have lunch at noon, you're likely to get hungry around noon. Other psychological triggers can affect appetite too. And one can change habits. But genes are important.
The researchers note that the MCR4 genes don't affect metabolism but affect appetite. In other words, if a thin person and an obese person eat the same meal, they'll burn about the same number of calories, but the thin person often eats less of the meal.
Researchers have found at least 300 mutations in the MCR4, and it's likely that mutations in different parts of the gene would have slightly different effects. It had been shown previously that mutations in the MCR4 gene increase the risk of obesity, but the recent study was the first time it has been shown that other mutations in the MCR4 make people feel full even when they haven't eaten.
Unfortunately efforts to develop drugs to increase activity of the MCR4 gene to decrease appetite were halted when the drugs were found to decrease appetite but also to increase blood pressure. Other efforts produced other unacceptable side effects. Clearly, tweaking this gene is possible but not easy. But as more is learned about the gene's effects, useful drugs without side effects might be developed.
And it's important to understand that it's unlikely that dealing with just one gene that affects obesity is unlikely to solve the growing problem of obesity. Many genes are involved, as illustrated by this study.
As the authors note: "Finally, a clear understanding of the genetic predisposition to obesity may help to destigmatize obesity among patients, their health care providers, and the general public."
So how does this all affect you? Well, if you're very overweight and feeling guilty about it, understand that it may not be your fault. It could be your genes.
However, that doesn't mean you shouldn't try to do something about it if the excess weight is contributing to other problems like high blood pressure or type 2 diabetes. The fact that weight loss will be more difficult for you than for some other people doesn't mean it's impossible. Dump the guilt and get to work.
You can succeed.
A story in the New York Times suggests the latter. They describe people with a version of a particular gene, MCR4, who are simply almost never hungry. Self-control has little to do with it. Conversely, people with another version of the gene are constantly hungry. In other words, it's appetite that controls how much people eat in an environment in which food is plentiful, and some people are hungrier than others.
Overweight people often think that, but no one believes them and people tell them (or at least believe) they have no self-control.
I've always thought genes play a large role in controlling appetite. A good example is in my book The First Year: Type 2 Diabetes:
"Having diabetes genes may affect the appetite. Alex E. described the time someone brought some scrumptious pastries to work. A thin person walked in, looked at the pastries, and said, "Oh my, those look good. I wish I were hungry so I could try one." Alex was flabbergasted. He was hungry all the time and thought everyone else was too."
Of course, genes are not the only factors affecting appetite. Hormones such as leptin and ghrelin and fluctuating blood glucose levels can affect hunger, as can habit, for example always eating lunch at a certain time. If you always have lunch at noon, you're likely to get hungry around noon. Other psychological triggers can affect appetite too. And one can change habits. But genes are important.
The researchers note that the MCR4 genes don't affect metabolism but affect appetite. In other words, if a thin person and an obese person eat the same meal, they'll burn about the same number of calories, but the thin person often eats less of the meal.
Researchers have found at least 300 mutations in the MCR4, and it's likely that mutations in different parts of the gene would have slightly different effects. It had been shown previously that mutations in the MCR4 gene increase the risk of obesity, but the recent study was the first time it has been shown that other mutations in the MCR4 make people feel full even when they haven't eaten.
Unfortunately efforts to develop drugs to increase activity of the MCR4 gene to decrease appetite were halted when the drugs were found to decrease appetite but also to increase blood pressure. Other efforts produced other unacceptable side effects. Clearly, tweaking this gene is possible but not easy. But as more is learned about the gene's effects, useful drugs without side effects might be developed.
And it's important to understand that it's unlikely that dealing with just one gene that affects obesity is unlikely to solve the growing problem of obesity. Many genes are involved, as illustrated by this study.
As the authors note: "Finally, a clear understanding of the genetic predisposition to obesity may help to destigmatize obesity among patients, their health care providers, and the general public."
So how does this all affect you? Well, if you're very overweight and feeling guilty about it, understand that it may not be your fault. It could be your genes.
However, that doesn't mean you shouldn't try to do something about it if the excess weight is contributing to other problems like high blood pressure or type 2 diabetes. The fact that weight loss will be more difficult for you than for some other people doesn't mean it's impossible. Dump the guilt and get to work.
You can succeed.
Saturday, April 20, 2019
Tagatose Again
Tagatose is a sugar with a glycemic index of 3, and it's also 92% as sweet as sucrose (table sugar). Like sucrose, it's crystalline, and you can pretty much substitute it for sucrose tablespoon for tablespoon. Also, it browns like sugar.
I wrote more about tagatose and a related sugar called allulose here and here.
Thus tagatose has many appealing characteristics except that it's expensive. When it first became available in the early 2000s, mostly in Europe, I was thrilled. But the availability didn't last, and in 2006, the only company making it decided it wasn't economically feasible.
Now researchers have reported that they could engineer yeast to produce tagatose with much greater efficiency than the traditional methods. Chemists might enjoy the original article, which has more details.
"For example, rare sugars such as tagatose and allulose are currently produced by enzymatic reactions followed by complicated separation processes. As a result, the production costs of rare sugars are significantly higher than HFCS, which does not require additional separation. Due to this high production cost, introduction of rare sugars into foods and beverages has been hampered in spite of potential benefits of rare sugars."
It will be interesting to see if this new method makes it into commercial production.
I wrote more about tagatose and a related sugar called allulose here and here.
Thus tagatose has many appealing characteristics except that it's expensive. When it first became available in the early 2000s, mostly in Europe, I was thrilled. But the availability didn't last, and in 2006, the only company making it decided it wasn't economically feasible.
Now researchers have reported that they could engineer yeast to produce tagatose with much greater efficiency than the traditional methods. Chemists might enjoy the original article, which has more details.
"For example, rare sugars such as tagatose and allulose are currently produced by enzymatic reactions followed by complicated separation processes. As a result, the production costs of rare sugars are significantly higher than HFCS, which does not require additional separation. Due to this high production cost, introduction of rare sugars into foods and beverages has been hampered in spite of potential benefits of rare sugars."
It will be interesting to see if this new method makes it into commercial production.
Monday, March 18, 2019
Prediabetes
Science magazine has a story suggesting that we retire the term prediabetes. They cite people who say the progression from prediabetes to diabetes is low (less than 2% per year or 10% in five years, rather than the 15% t0 30% that has been cited by the Centers for Disease Control and Prevention) and there are no drugs that specifically target prediabetes. So why worry people?
The Diabetes Prevention Program study, which ended in 2001, showed that those who received intensive lifestyle changes reduced their development of type 2 diabetes by 58 percent. But those patients received intensive counseling and support, which is too expensive to offer to every person diagnosed with prediabetes.
Metformin alone (850 mg twice a day) lowered diabetes incidence by 31 percent, but there was some disagreement over whether the drug really kept the patients from developing diabetes or whether the metformin simply masked any diabetes that developed.
These opponents of the idea of prediabetes also claim that prediabetes doesn't increase the risk of heart disease and argue that the costs of treating patients with prediabetes outweigh the benefits.
I understand their reservations, but I don't agree that we shouldn't warn people that they are on the track to diabetes. Patients are different, and there are always some who, when told they have prediabetes, will ask for a pill and not want to do anything about changing their habits. There are others who might like to eat a whole-food diet with lots of vegetables, but they can't afford it, or the stores in their area don't carry healthy foods.
But there are also patients who, if warned, will take serious steps to improve their health. A fascinating example of this is geneticist Michael Snyder, who found out as a result of an exhaustive genome and metabolic analysis that his blood glucose (BG) went very high after a viral infection, and when a doctor later said he had type 2 diabetes, he worked hard on diet and exercise and brought things back to normal.
Snyder recently published a paper on glucose spikes in nondiabetics. He says 70% of people with prediabetes will progress to overt diabetes.
So should motivated patients be denied early warnings just because other people won't do anything about their health?
And even if only 2% of patients per year progress to overt diabetes, if you're one of the 2%, wouldn't you want to be warned?
I also don't agree that prediabetes doesn't increase the risk of heart disease. I've seen studies saying that even A1c's considered normal increase the risk, but I didn't save them as I thought that was generally accepted. Here is one example.
One problem is that definitions of things like prediabetes and diabetes depend on where some group of physicians decide to put a cutoff point. It's not as if you're totally healthy until you reach that point and then suddenly you're sick. When I was diagnosed in 1996, the cutoff for diabetes was a fasting BG level of 140 mg/dL. Then that was reduced to 126. And fasting BG levels can change from day to day. Does that mean you can have diabetes on Wednesday when your fasting BG level was 127 but you were cured on Friday when it was 125?
Today the A1c is often used for diagnosis, but that too is not an exact method. When I've had A1c tests at two different sites, they often don't agree.
So should we retire the term prediabetes?
When I was diagnosed, the term prediabetes didn't exist. Instead you were said to have impaired glucose tolerance if your BG levels went higher than normal after meals and impaired fasting glucose if they were high when you got up. Both categories were combined into the prediabetes term. I think it's less important what you call it than having a physician who will warn you if all is not well and then help you prevent diabetes, or who will refer you to someone else who can do this.
I think the term prediabetes probably has a bigger impact on the patient than something like impaired glucose tolerance so the patient will be motivated to do something about it. Most people who are diagnosed with diabetes are overweight, and most people who are overweight have been trying to lose weight off and on for years. A diagnosis of prediabetes can be the kick in the pants they need to take the weight loss seriously.
Regardless of whether or not you agree about dumping the term prediabetes, the article in Science is a good summary of how professional organizations can disagree about diagnostic criteria, how those who specify those criteria often receive large amounts of money from drug companies, and how attitudes change through the years.
The Diabetes Prevention Program study, which ended in 2001, showed that those who received intensive lifestyle changes reduced their development of type 2 diabetes by 58 percent. But those patients received intensive counseling and support, which is too expensive to offer to every person diagnosed with prediabetes.
Metformin alone (850 mg twice a day) lowered diabetes incidence by 31 percent, but there was some disagreement over whether the drug really kept the patients from developing diabetes or whether the metformin simply masked any diabetes that developed.
These opponents of the idea of prediabetes also claim that prediabetes doesn't increase the risk of heart disease and argue that the costs of treating patients with prediabetes outweigh the benefits.
I understand their reservations, but I don't agree that we shouldn't warn people that they are on the track to diabetes. Patients are different, and there are always some who, when told they have prediabetes, will ask for a pill and not want to do anything about changing their habits. There are others who might like to eat a whole-food diet with lots of vegetables, but they can't afford it, or the stores in their area don't carry healthy foods.
But there are also patients who, if warned, will take serious steps to improve their health. A fascinating example of this is geneticist Michael Snyder, who found out as a result of an exhaustive genome and metabolic analysis that his blood glucose (BG) went very high after a viral infection, and when a doctor later said he had type 2 diabetes, he worked hard on diet and exercise and brought things back to normal.
Snyder recently published a paper on glucose spikes in nondiabetics. He says 70% of people with prediabetes will progress to overt diabetes.
So should motivated patients be denied early warnings just because other people won't do anything about their health?
And even if only 2% of patients per year progress to overt diabetes, if you're one of the 2%, wouldn't you want to be warned?
I also don't agree that prediabetes doesn't increase the risk of heart disease. I've seen studies saying that even A1c's considered normal increase the risk, but I didn't save them as I thought that was generally accepted. Here is one example.
One problem is that definitions of things like prediabetes and diabetes depend on where some group of physicians decide to put a cutoff point. It's not as if you're totally healthy until you reach that point and then suddenly you're sick. When I was diagnosed in 1996, the cutoff for diabetes was a fasting BG level of 140 mg/dL. Then that was reduced to 126. And fasting BG levels can change from day to day. Does that mean you can have diabetes on Wednesday when your fasting BG level was 127 but you were cured on Friday when it was 125?
Today the A1c is often used for diagnosis, but that too is not an exact method. When I've had A1c tests at two different sites, they often don't agree.
So should we retire the term prediabetes?
When I was diagnosed, the term prediabetes didn't exist. Instead you were said to have impaired glucose tolerance if your BG levels went higher than normal after meals and impaired fasting glucose if they were high when you got up. Both categories were combined into the prediabetes term. I think it's less important what you call it than having a physician who will warn you if all is not well and then help you prevent diabetes, or who will refer you to someone else who can do this.
I think the term prediabetes probably has a bigger impact on the patient than something like impaired glucose tolerance so the patient will be motivated to do something about it. Most people who are diagnosed with diabetes are overweight, and most people who are overweight have been trying to lose weight off and on for years. A diagnosis of prediabetes can be the kick in the pants they need to take the weight loss seriously.
Regardless of whether or not you agree about dumping the term prediabetes, the article in Science is a good summary of how professional organizations can disagree about diagnostic criteria, how those who specify those criteria often receive large amounts of money from drug companies, and how attitudes change through the years.
Monday, February 18, 2019
Me and NPH
As everyone knows, insulin prices are now criminal. For a long time I was using Levemir, just once a day, in the morning. It worked fine, as I don't seem to need insulin overnight. If I just stopped eating, I could eliminate insulin altogether, but that doesn't seem like a likely scenario.
For more than a year, I've been on Tresiba as part of a clinical study, which meant the insulin was free. That was nice. The Tresiba worked OK, but because it lasts for 24 hours, it meant I couldn't use as high a dose as I used for Levemir. I was on 20 units of Levemir but only 12 units of Tresiba. Any more and I'd go low overnight. In fact, even on the 12 units, I was going slightly low at night for long periods, according to the Freestyle Libre continuous glucose monitor (CGM) I was trying at my own expense.
When the Tresiba trial was over, I still had two Levemir pens that hadn't quite expired, so I used them. But when I found out that refilling my 3-month prescription would cost about $1000, I figured no way and decided to try NPH. For the last week of the Tresiba trial, we'd been put on NPH, and it seemed to work OK, but my CGM stopped working after only a day on the NPH, so I was curious to give it a longer trial.
NPH is about $24 for a 10-mL vial of 100 units/mL at Walmart. So at 20 U/day, a vial should last me about 50 days, or 48 cents a day, $43 for three months.
On my Plan D, I actually pay only $30 for a 3-month supply of Levemir, but my plan pays $1359.40, and because the infamous doughnut hole is based on total drug costs, not what the patient pays, with those prices plus another expensive drug, I'd reach the doughnut hole for sure.
Other than expense, an important factor is how well it works. Two endocrinologists warned me that NPH is unpredictable, that the same dose might work one way on one day and another on another. But I find that diabetes is unpredictable anyway. You can eat exactly the same thing and get the same amount of exercise on two days and get different results, so it's difficult to know which of the myriad factors that affect blood glucose (BG) levels is responsible.
Dr. Richard Bernstein, low-carbohydrate diet proponent and author of The Diabetes Solution, warns about using NPH because it contains protamine, which can interfere with the reversal of the anticoagulant heparin. But an endocrinologist I asked about this said he used NPH for years before the modern insulins were available and he'd never seen this problem, and besides, people these days tend to use other anticoagulants, so I decided not to worry about it. Anyway, I'd already used it in the clinical study.
Bernstein also says one reason the cloudy insulins seem unpredictable is that people don't shake the vials enough so the insulin isn't distributed evenly.
So what did I find?
NPH is definitely peakier than Levemir. Some sources say it peaks 4 to 8 hours after you inject, others say 4 to 6 hours, and the Joslin Diabetes Center says 4 to 12 hours (at least they're consistent with the 4). So there's obviously a lot of individual variation. I find it peaks about 7 hours after I inject. I get up early, usually around 5 am, and inject then, so my NPH peaks at lunchtime. This is handy, and I try to eat my big meal of the day at noon. If I don't have lunch, I might go low.
This is, of course, not the way you're supposed to use a basal insulin. You're supposed to inject just enough to keep your BG at a good level when you don't eat and then use a bolus insulin to cover meals. I'm too lazy to do that. And as a type 2 I have a bit of a buffer because I'm still producing small amounts of insulin, just not enough to cover meals.
Some people take a second shot just before going to bed to use the NPH peak to cover the dawn phenomenon. However, although my BG goes up a little in the morning, starting when I wake up, the rise is not large.
After the Tresiba study was over, I went back to Levemir until those pens were finished. Then, wearing the CGM, I tried NPH, 5 units in the morning and 5 in the evening. Then I tried 10 in the morning. Then I tried 15 and then 20 in the morning. The 20 didn't make me go low except for once, and that was about an hour after I injected so it was probably not a result of too much insulin. Maybe I injected too close to a blood vessel. That happened with Lantus once, and I went down to 25.
Then for two days I tried no insulin, but the CGM gave out after just one day.
Then I got a new sensor and tried a few different concentrations.
The program you can use with the CGM calculates average BG each day. Here are what I got. When there's only one dosage listed, I took it first thing in the morning.
12 units Tresiba: 98, 105, 96, 91, 92, 103, 99, 96, 92, 89 (96.1 average with overnight lows )
15 units Levemir: 98, 104 (101 av)
20 units Levemir: 107, 89, 103, 104, 82, 94, 93, 100, 106, 110 (98.8 av)
10 +10 units Levemir (10 units in moring and 10 in evening): 90, 93 (91.5 av)
0 insulin: 114
5 + 5 units NPH: (5 in morning and 5 in evening: 118, 109, 103 (110 av)
10 units NPH: 102, 106 (104 av)
15 units NPH:109, 101, 96, 101, 109 (103.2 av)
20 units NPH: 101, 100, 109, 101, 99, 95, 97, 96, 86, 103, 93 (98.1 av)
Note: One problem is that the Libre is that every sensor can read slightly differently, and I find that they read high on the first day after insertion, so I don't use that day.
Thus the Levemir given twice a day gave the lowest average BG, but that was only two days and might not be reliable. Not surprisingly, the highest average was with no insulin, but that was only one day. The sensors and then the receiver kept not working at important times.
12 units of Tresiba gave the next lowest average BGs, but there were also a lot of overnight lows.
The 20 units of Levemir given in the morning, with lots of data points, and the 20 units of NPH given in the morning, with lots of data points, gave about the same averages, 98.8 and 98.1, respectively, and the NPH readings were with a sensor that read about 10 points high.
So FOR ME, it seems as if NPH works just as well as Levemir. Whether or not I'll continue with it permanently depends on how close to the doughnut hole I seem to be getting. It is a lot more convenient to use a pen. I think NPH comes in a pen, but that's more expensive.
And my feeling is that Big Pharma won't reduce insulin prices unless people stop buying their product when it costs too much.
My experience suggests that patients with no insurance and low incomes might find that they were better off with the old-fashioned bottled NPH, with regular (R) for meals if they use a bolus insulin. They're not as convenient as the newer insulins, or the pens, but no one should die because they can't afford modern insulins. Low carbohydrate intakes require less insulin, and R actually covers low-carb meals better than the faster bolus insulins.
I plan to do more experimenting with the CGM in the future. If I have any interesting results, I'll post them.
For more than a year, I've been on Tresiba as part of a clinical study, which meant the insulin was free. That was nice. The Tresiba worked OK, but because it lasts for 24 hours, it meant I couldn't use as high a dose as I used for Levemir. I was on 20 units of Levemir but only 12 units of Tresiba. Any more and I'd go low overnight. In fact, even on the 12 units, I was going slightly low at night for long periods, according to the Freestyle Libre continuous glucose monitor (CGM) I was trying at my own expense.
When the Tresiba trial was over, I still had two Levemir pens that hadn't quite expired, so I used them. But when I found out that refilling my 3-month prescription would cost about $1000, I figured no way and decided to try NPH. For the last week of the Tresiba trial, we'd been put on NPH, and it seemed to work OK, but my CGM stopped working after only a day on the NPH, so I was curious to give it a longer trial.
NPH is about $24 for a 10-mL vial of 100 units/mL at Walmart. So at 20 U/day, a vial should last me about 50 days, or 48 cents a day, $43 for three months.
On my Plan D, I actually pay only $30 for a 3-month supply of Levemir, but my plan pays $1359.40, and because the infamous doughnut hole is based on total drug costs, not what the patient pays, with those prices plus another expensive drug, I'd reach the doughnut hole for sure.
Other than expense, an important factor is how well it works. Two endocrinologists warned me that NPH is unpredictable, that the same dose might work one way on one day and another on another. But I find that diabetes is unpredictable anyway. You can eat exactly the same thing and get the same amount of exercise on two days and get different results, so it's difficult to know which of the myriad factors that affect blood glucose (BG) levels is responsible.
Dr. Richard Bernstein, low-carbohydrate diet proponent and author of The Diabetes Solution, warns about using NPH because it contains protamine, which can interfere with the reversal of the anticoagulant heparin. But an endocrinologist I asked about this said he used NPH for years before the modern insulins were available and he'd never seen this problem, and besides, people these days tend to use other anticoagulants, so I decided not to worry about it. Anyway, I'd already used it in the clinical study.
Bernstein also says one reason the cloudy insulins seem unpredictable is that people don't shake the vials enough so the insulin isn't distributed evenly.
So what did I find?
NPH is definitely peakier than Levemir. Some sources say it peaks 4 to 8 hours after you inject, others say 4 to 6 hours, and the Joslin Diabetes Center says 4 to 12 hours (at least they're consistent with the 4). So there's obviously a lot of individual variation. I find it peaks about 7 hours after I inject. I get up early, usually around 5 am, and inject then, so my NPH peaks at lunchtime. This is handy, and I try to eat my big meal of the day at noon. If I don't have lunch, I might go low.
This is, of course, not the way you're supposed to use a basal insulin. You're supposed to inject just enough to keep your BG at a good level when you don't eat and then use a bolus insulin to cover meals. I'm too lazy to do that. And as a type 2 I have a bit of a buffer because I'm still producing small amounts of insulin, just not enough to cover meals.
Some people take a second shot just before going to bed to use the NPH peak to cover the dawn phenomenon. However, although my BG goes up a little in the morning, starting when I wake up, the rise is not large.
After the Tresiba study was over, I went back to Levemir until those pens were finished. Then, wearing the CGM, I tried NPH, 5 units in the morning and 5 in the evening. Then I tried 10 in the morning. Then I tried 15 and then 20 in the morning. The 20 didn't make me go low except for once, and that was about an hour after I injected so it was probably not a result of too much insulin. Maybe I injected too close to a blood vessel. That happened with Lantus once, and I went down to 25.
Then for two days I tried no insulin, but the CGM gave out after just one day.
Then I got a new sensor and tried a few different concentrations.
The program you can use with the CGM calculates average BG each day. Here are what I got. When there's only one dosage listed, I took it first thing in the morning.
12 units Tresiba: 98, 105, 96, 91, 92, 103, 99, 96, 92, 89 (96.1 average with overnight lows )
15 units Levemir: 98, 104 (101 av)
20 units Levemir: 107, 89, 103, 104, 82, 94, 93, 100, 106, 110 (98.8 av)
10 +10 units Levemir (10 units in moring and 10 in evening): 90, 93 (91.5 av)
0 insulin: 114
5 + 5 units NPH: (5 in morning and 5 in evening: 118, 109, 103 (110 av)
10 units NPH: 102, 106 (104 av)
15 units NPH:109, 101, 96, 101, 109 (103.2 av)
20 units NPH: 101, 100, 109, 101, 99, 95, 97, 96, 86, 103, 93 (98.1 av)
Note: One problem is that the Libre is that every sensor can read slightly differently, and I find that they read high on the first day after insertion, so I don't use that day.
Thus the Levemir given twice a day gave the lowest average BG, but that was only two days and might not be reliable. Not surprisingly, the highest average was with no insulin, but that was only one day. The sensors and then the receiver kept not working at important times.
12 units of Tresiba gave the next lowest average BGs, but there were also a lot of overnight lows.
The 20 units of Levemir given in the morning, with lots of data points, and the 20 units of NPH given in the morning, with lots of data points, gave about the same averages, 98.8 and 98.1, respectively, and the NPH readings were with a sensor that read about 10 points high.
So FOR ME, it seems as if NPH works just as well as Levemir. Whether or not I'll continue with it permanently depends on how close to the doughnut hole I seem to be getting. It is a lot more convenient to use a pen. I think NPH comes in a pen, but that's more expensive.
And my feeling is that Big Pharma won't reduce insulin prices unless people stop buying their product when it costs too much.
My experience suggests that patients with no insurance and low incomes might find that they were better off with the old-fashioned bottled NPH, with regular (R) for meals if they use a bolus insulin. They're not as convenient as the newer insulins, or the pens, but no one should die because they can't afford modern insulins. Low carbohydrate intakes require less insulin, and R actually covers low-carb meals better than the faster bolus insulins.
I plan to do more experimenting with the CGM in the future. If I have any interesting results, I'll post them.
Sunday, February 10, 2019
Would this "Make Diabetics Happy"?
A new invention that put little syringes loaded with insulin into capsules has riveted the popular press.
Here is one story that shows how the things work. And this story says they'll "make diabetics happy." Even the New York Times did a story on it.
As usual, the people designing new drugs and gizmos don't really understand diabetes. The biggest problem facing people with diabetes is not "painful insulin injections." It's figuring out what you can eat and, if you take insulin, how to match the insulin you inject to the food you eat.
One can also inhale insulin. But one problem with that, in addition to the problem of lung damage although the supporters of inhaled insulin say the risk is minimal, is that the amounts you can inhale are limited. With a pen or a syringe, you can inject any amount you want, not just 4 or 8 or 12 units (the choices available with the inhaled insulin Afrezza). Would these little encapsulated syringes offer a similar benefit? I doubt it.
Another problem is that although the inventors say these things work in pigs, that's only when they have empty stomachs. One might have an empty stomach first thing in the morning, but probably not before meals, so the injections couldn't be used for bolus (premeal) insulins.
If inventors want to "make diabetics happy" they should listen to people with diabetes and see what they really want. There are probably a few people who would love to use tiny syringes in capsules, but I suspect not a lot. Inhaled insulin hasn't caught on, and I suspect encapsulated syringes would have a similar fate in the marketplace even if the cost was low.
Sure, it's fun for the scientists and engineers to come up with gizmos like this, but let's hope they come up with more useful gadgets. Continuous glucose monitors became popular when they became more affordable than some of the older CGMs. Patients are reporting major reductions in their hemoglobin A1c when they use the CGMs and find out what makes their blood glucose go up.
So I'd be happy if the engineers developed cheap CGMs that everyone could use.
Here is one story that shows how the things work. And this story says they'll "make diabetics happy." Even the New York Times did a story on it.
As usual, the people designing new drugs and gizmos don't really understand diabetes. The biggest problem facing people with diabetes is not "painful insulin injections." It's figuring out what you can eat and, if you take insulin, how to match the insulin you inject to the food you eat.
One can also inhale insulin. But one problem with that, in addition to the problem of lung damage although the supporters of inhaled insulin say the risk is minimal, is that the amounts you can inhale are limited. With a pen or a syringe, you can inject any amount you want, not just 4 or 8 or 12 units (the choices available with the inhaled insulin Afrezza). Would these little encapsulated syringes offer a similar benefit? I doubt it.
Another problem is that although the inventors say these things work in pigs, that's only when they have empty stomachs. One might have an empty stomach first thing in the morning, but probably not before meals, so the injections couldn't be used for bolus (premeal) insulins.
If inventors want to "make diabetics happy" they should listen to people with diabetes and see what they really want. There are probably a few people who would love to use tiny syringes in capsules, but I suspect not a lot. Inhaled insulin hasn't caught on, and I suspect encapsulated syringes would have a similar fate in the marketplace even if the cost was low.
Sure, it's fun for the scientists and engineers to come up with gizmos like this, but let's hope they come up with more useful gadgets. Continuous glucose monitors became popular when they became more affordable than some of the older CGMs. Patients are reporting major reductions in their hemoglobin A1c when they use the CGMs and find out what makes their blood glucose go up.
So I'd be happy if the engineers developed cheap CGMs that everyone could use.
Thursday, January 17, 2019
Measuring Metabolism
I don't usually write about commercial products, but this one seems interesting . . . if it fulfils its promise. It's a way of determining whether you're burning primarily carbohydrate or fat.
This is done by calculating something called the respiratory quotient (RQ), which is the ratio of carbon dioxide production to oxygen consumption. An RQ of 1 means you're metabolizing mostly carbohydrate, and an RQ of 0.7 means you're burning mostly fat. Obviously, numbers between these extremes indicate you're burning both. Protein has a small effect on the RQ.
When I was in a clinical study at the Joslin Diabetes Center some years ago, they measured my RQ. I had a big hood over my head for what seemed like a long time, and it was horrid when my nose started to itch but I couldn't scratch it.
Now an Israeli company has produced a little gizmo into which you breathe, and they say it will give you an RQ. It's not cheap (about $300), and it won't be available until next August, although you can order it now for $249. Last summer, articles were saying it would ship in February 2019 and preorder price was $179. I've seen a lot of gizmos being announced that never come to market, so I'll believe this one when I see it. Nevertheless, it's interesting.
So why would you care what your RQ was? Well, we can all be a little different, and some people may be better at burning carbohydrates or burning fats. Let's say you want to lose fat. When your carbohydrate intake, and hence your insulin level, is low, your hormones can help you break down the fat in your fat cells and ship fatty acids out into the circulation to be taken up and burned by tissues that need energy.
But if you don't burn the fatty acids very efficiently they'll just stay around and eventually may get taken up by the fat cells for storage as (ugh) fat.
It would be interesting to measure the RQ of someone just starting a low-carb diet and then keep measuring as the person became adapted to the diet. Would the RQ show more fat oxidation as time went by and the body became accustomed to using fat for energy? Could the RQ be shown to be related to the fatigue some people feel when going on a low-carb diet?
Some people are more efficient at fat burning than others. Could they determine this by measuring the RQ with this gizmo
If despite limiting carbohydrate in your diet, the gizmo showed that you were still getting a lot of your energy from carbohydrate, you would know that you had to limit carbohydrate more than some other people.
Of course the gizmo could also be used by people who wanted to burn a lot of carbohydrate.
I look forward to the day when this is actually available to see how people are using it.
This is done by calculating something called the respiratory quotient (RQ), which is the ratio of carbon dioxide production to oxygen consumption. An RQ of 1 means you're metabolizing mostly carbohydrate, and an RQ of 0.7 means you're burning mostly fat. Obviously, numbers between these extremes indicate you're burning both. Protein has a small effect on the RQ.
When I was in a clinical study at the Joslin Diabetes Center some years ago, they measured my RQ. I had a big hood over my head for what seemed like a long time, and it was horrid when my nose started to itch but I couldn't scratch it.
Now an Israeli company has produced a little gizmo into which you breathe, and they say it will give you an RQ. It's not cheap (about $300), and it won't be available until next August, although you can order it now for $249. Last summer, articles were saying it would ship in February 2019 and preorder price was $179. I've seen a lot of gizmos being announced that never come to market, so I'll believe this one when I see it. Nevertheless, it's interesting.
So why would you care what your RQ was? Well, we can all be a little different, and some people may be better at burning carbohydrates or burning fats. Let's say you want to lose fat. When your carbohydrate intake, and hence your insulin level, is low, your hormones can help you break down the fat in your fat cells and ship fatty acids out into the circulation to be taken up and burned by tissues that need energy.
But if you don't burn the fatty acids very efficiently they'll just stay around and eventually may get taken up by the fat cells for storage as (ugh) fat.
It would be interesting to measure the RQ of someone just starting a low-carb diet and then keep measuring as the person became adapted to the diet. Would the RQ show more fat oxidation as time went by and the body became accustomed to using fat for energy? Could the RQ be shown to be related to the fatigue some people feel when going on a low-carb diet?
Some people are more efficient at fat burning than others. Could they determine this by measuring the RQ with this gizmo
If despite limiting carbohydrate in your diet, the gizmo showed that you were still getting a lot of your energy from carbohydrate, you would know that you had to limit carbohydrate more than some other people.
Of course the gizmo could also be used by people who wanted to burn a lot of carbohydrate.
I look forward to the day when this is actually available to see how people are using it.
Friday, January 11, 2019
Connected Systems
Everything is connected.
No, this won't be a New Age rant on oneness with the universe. I'm speaking of the various systems in the body, which used to be put into boxes as if they operated on their own. There was the circulatory system, the nervous system, the respiratory system, the digestive system, and so forth, and many doctors specialized in one system or another.
Different processes were thought to take place in different systems. For example, gluconeogenesis (the formation of glucose from other compounds) was said to take place in the liver, and although it was mentioned that the kidney also performed some gluconeogenesis, this was mostly ignored. This approach made sense in the past, when measurement techniques were relatively crude, but today techniques have improved and it's even possible in some cases to measure what's going on in single cells.
So now, more and more, we're learning that the various organs have roles other than the main roles that have been known for decades, and the various systems are interconnected, sometimes in surprising ways. For example, not long ago, fat was considered just a way to store extra energy. It's now well known to secrete hormones too.
One recent study showed that a gut hormone interacts with brown fat to tell the brain that it's time to stop eating. The hormone, secretin, has been known since 1902, but its role was said to be to stimulate the pancreas to release bicarbonate to neutralize the acids coming from the stomach. Now it seems it has at least one other role. Mice injected with secretin had less appetite and increased the amount of heat the brown fat produced. Unless you're cold, heat is "wasted" energy, so increasing the amount of heat produced would mean they would gain less weight from the food they ate.
And a study of mast cells also revealed unexpected effects. Mast cells produce histamine, which is important in causing allergic symptoms, so many allergy sufferers take antihistamines. This study showed that histamine that goes to the liver, not the lungs or nose, also helps regulate ketogenesis (the production of ketone bodies from fatty acids).
It does this via a molecule called OEA (oleoylethanolamide). Previously, researchers thought OEA's role was to block hunger pangs. It does, but it also stimulates ketogenesis.
These complex interactions are one reason different people can react differently to various medications and diets. One person might have a difference in the mast cells and another might have a difference in the sensitivity of the liver to histamine and another might have a difference in some related but as-yet-unknown reaction in the same system. (I'm using the term "difference" rather than "defect" because sometimes a metabolic difference that is detrimental in one environment turns out to be beneficial in another.)
Hence we should never assume that what works for one person will work for us. Today we have so many tools to measure the various aspects of our diabetes that we can try something and then if it doesn't work try something else. No one diet or one drug or one exercise regime is best for everyone.
And we should remember that everything is connected. We shouldn't focus on just one system in our body and ignore the rest. They all talk to each other, and maybe healing an ingrown toenail will help our diabetes.
No, this won't be a New Age rant on oneness with the universe. I'm speaking of the various systems in the body, which used to be put into boxes as if they operated on their own. There was the circulatory system, the nervous system, the respiratory system, the digestive system, and so forth, and many doctors specialized in one system or another.
Different processes were thought to take place in different systems. For example, gluconeogenesis (the formation of glucose from other compounds) was said to take place in the liver, and although it was mentioned that the kidney also performed some gluconeogenesis, this was mostly ignored. This approach made sense in the past, when measurement techniques were relatively crude, but today techniques have improved and it's even possible in some cases to measure what's going on in single cells.
So now, more and more, we're learning that the various organs have roles other than the main roles that have been known for decades, and the various systems are interconnected, sometimes in surprising ways. For example, not long ago, fat was considered just a way to store extra energy. It's now well known to secrete hormones too.
One recent study showed that a gut hormone interacts with brown fat to tell the brain that it's time to stop eating. The hormone, secretin, has been known since 1902, but its role was said to be to stimulate the pancreas to release bicarbonate to neutralize the acids coming from the stomach. Now it seems it has at least one other role. Mice injected with secretin had less appetite and increased the amount of heat the brown fat produced. Unless you're cold, heat is "wasted" energy, so increasing the amount of heat produced would mean they would gain less weight from the food they ate.
And a study of mast cells also revealed unexpected effects. Mast cells produce histamine, which is important in causing allergic symptoms, so many allergy sufferers take antihistamines. This study showed that histamine that goes to the liver, not the lungs or nose, also helps regulate ketogenesis (the production of ketone bodies from fatty acids).
It does this via a molecule called OEA (oleoylethanolamide). Previously, researchers thought OEA's role was to block hunger pangs. It does, but it also stimulates ketogenesis.
These complex interactions are one reason different people can react differently to various medications and diets. One person might have a difference in the mast cells and another might have a difference in the sensitivity of the liver to histamine and another might have a difference in some related but as-yet-unknown reaction in the same system. (I'm using the term "difference" rather than "defect" because sometimes a metabolic difference that is detrimental in one environment turns out to be beneficial in another.)
Hence we should never assume that what works for one person will work for us. Today we have so many tools to measure the various aspects of our diabetes that we can try something and then if it doesn't work try something else. No one diet or one drug or one exercise regime is best for everyone.
And we should remember that everything is connected. We shouldn't focus on just one system in our body and ignore the rest. They all talk to each other, and maybe healing an ingrown toenail will help our diabetes.
Tuesday, January 8, 2019
On Eggs
Recommendations on eggs seem to go from one extreme to the other, or "yo-yo egg advice."
In the 1950s and 1960s, eggs were considered healthy. Adele Davis, a popular health food guru in those days, had a chapter in her book Let's Cook it Right titled "Serve Eggs and Cheese Daily." She went on to note that in addition to their protein content, eggs contain a lot of vitamins and minerals, which she discussed.
Then came the low-fat fad, in which any kind of fat was considered poisonous. Egg yolks, which contain a lot of fat as well as a lot of cholesterol, were banned from many tables, and Egg Beaters were used to make egg white omelets and other low-fat egg dishes.
Then the tide turned, and we were told one or two eggs a week, or even one a day (gasp), were OK unless we were diabetic, in which case we should stick to those tasteless egg white omelets. But then the experts changed their minds again and said eggs were OK even for people with diabetes.
And Harvard's Walter Willet said, “There was never any data that showed that people who ate more eggs had higher risk of heart attacks.”
Now comes a study from Finland that says that egg metabolites in blood are related to a lower risk of type 2 diabetes. Note that risk factors in the blood are not the same as actual mortality rates in egg eaters. But they're consistent with the idea that eggs aren't poison, and a previous study had linked egg eating with a lower risk of type 2. This new study was designed to help figure out how the egg consumption affected diabetes risk.
Have we yo-yo'd back to the 1950s and 1960s in terms of egg advice? I suspect we have.
In the 1950s and 1960s, eggs were considered healthy. Adele Davis, a popular health food guru in those days, had a chapter in her book Let's Cook it Right titled "Serve Eggs and Cheese Daily." She went on to note that in addition to their protein content, eggs contain a lot of vitamins and minerals, which she discussed.
Then came the low-fat fad, in which any kind of fat was considered poisonous. Egg yolks, which contain a lot of fat as well as a lot of cholesterol, were banned from many tables, and Egg Beaters were used to make egg white omelets and other low-fat egg dishes.
Then the tide turned, and we were told one or two eggs a week, or even one a day (gasp), were OK unless we were diabetic, in which case we should stick to those tasteless egg white omelets. But then the experts changed their minds again and said eggs were OK even for people with diabetes.
And Harvard's Walter Willet said, “There was never any data that showed that people who ate more eggs had higher risk of heart attacks.”
Now comes a study from Finland that says that egg metabolites in blood are related to a lower risk of type 2 diabetes. Note that risk factors in the blood are not the same as actual mortality rates in egg eaters. But they're consistent with the idea that eggs aren't poison, and a previous study had linked egg eating with a lower risk of type 2. This new study was designed to help figure out how the egg consumption affected diabetes risk.
Have we yo-yo'd back to the 1950s and 1960s in terms of egg advice? I suspect we have.
Subscribe to:
Posts (Atom)
Posts
