Friday, November 27, 2020

New Satiety Hormone Described

I've often felt that people who have always had problems with weight have something wrong with their appetite control, so after a meal that would make most people feel full, they're still hungry. And if food is available, it's difficult not to eat it when you're hungy.

I gave an example of this in my book The First Year: Type 2 Diabetes. Someone described a time when a coworker brought some pastries into work and offered them to everyone. A thin person said, "Oh my those look good. I wish I were hungry so I could eat one." The overweight man said he was flabbergasted. He was hungry all the time and just assumed everyone else was too.

Now a new satiety hormone that decreases appetite after eating has been described. The interesting thing about this hormone, called lipocalin-2, is that it seems to work in people who are obese but not in those who are normal weight.

In mice, giving lipocalin-2 long term reduces their food intake and prevents weight gain, without leading to the slowdown in metabolism that is often seen when people try to lose weight by eating less. Studies to see if the mouse results could be replicated in humans showed that normal weight subjects showed an increase in lipocalin-2 after eating, and this coincided with how satisfied they felt after eating.

But in people who were obese, lipocalin-2 levels did not increase after a meal and in fact decreased. It's not clear if they became obese because of a defect in producing lipocalin-2, if they had lipocalin resistance, or if they became obese for other reasons and the obesity caused the defect in lipocalin-2 production. But those who lost weight after gastric bypass surgery (and presumably those who lost weight in other ways) had their lipocalin-2 levels restored to the levels seen in normal weight people, suggesting that the obesity came first.

This sounds like a miracle hormone, but we don't yet know a lot about it. The authors say "the hormone can curb appetite with negligible toxicity," but like most hormones, it does have other effects. For example, it sequesters iron and increases inflammation. and it also plays a role in the central nervous system.

This is not the only hormone that affects appetite; the incretin GLP-1 does the same about the same amount. The GLP-1 agonists like  Byetta and Victoza act in part by reducing appetite.

Time will tell if lipocalin-2 drugs, not yet available, have more benefits than drawbacks. You can read a little more about lipocalin here



Sunday, November 1, 2020

EMFs and Diabetes

 "Remote control of blood sugar: Electromagnetic fields (EMFs) treat diabetes in animal models" When I saw that headline, I thought, "Oh wow! Remote control of blood sugar. My doctor could sit in her office and dial up a good blood sugar level and send it, and I'd be cured."

Unfortunately, that's not what the story is about.

Rather, exposing diabetic mice to a combination of static electric and magnetic fields for a few hours per day normalizes blood sugar and insulin resistance. The fields used were approximately 100 times that of the Earth, and the researchers said they reversed the diabetes within three days of treatment.

Note that the study was done in mice, and human studies often don't replicate rodent studies. However, the researchers also treated human liver cells with EMFs for six hours and showed that a surrogate marker for insulin sensitivity improved significantly. So the EMFs might also work in humans.

Here is a link to the full article, which notes that "attempts to investigate the potential effects of EMFs on glucose metabolism have yielded conflicting findings with some studies demonstrating that EMFs raise fasting blood glucose and others suggesting that EMFs have no effect." But the authors criticize the methods of the earlier studies.

One researcher, Magda Havas, thinks that EMFs from electrical wiring (dirty electricity) may may elevate blood glucose and contribute to "brittle" diabetes.

Clearly, we have a lot to learn about EMFs and diabetes, but the current study is certainly interesting. Stay tuned for more developments.


Thursday, October 29, 2020

Potatoes: Another Stupid Study

"People with type 2 diabetes need not avoid eating potatoes based on glycemic index" is the title of a recent Eurekalert news release about potatoes. Now, most people seeing that would think "I don't need to avoid potatoes" and wouldn't read the rest of the story.

Note that the study was funded by the Alliance for Potato Research and Education (APRE), and although they say APRE had no role in designing or carrying out the study, one tends to be biased toward any group that is sponsoring one's work. APRE "is a not-for-profit organization 100% dedicated to expanding and translating scientific research into evidence-based policy and education initiatives that recognize the role of all forms of the potato—a nutritious vegetable—in promoting health for all age groups." That certainly doesn't sound unbiased.

However, even more important that the funder for this study is what they actually showed. They showed that participants had a better 'nocturnal' glycemic response when they ate a mixed meal with skinless white potatoes compared to an isoenergetic and macronutrient-matched mixed meal that included a low glycemic index carbohydrate food -- basmati rice. 

Note that they didn't compare potatoes with a no-starch meal, say substituting broccoli or spinach for the potatoes. They just say potatoes aren't worse than basmati rice. But I suspect some people, even dieticians, will remember "People with type 2 diabetes need not avoid eating potatoes" and eat baked potatoes or even french fries when they would have much better control if they ate green vegetables instead. 

Participants ate about 50 grams of carbohydrate per meal, the same amount that is used to measure glycemic index.

 I agree with the authors that the glycemic index alone isn't enough to predict the glycemic impact of a mixed meal. And even with the exact same meal, different people will have different responses. Even one person may have a different response on a different day. We have to test ourselves, preferably with a continuous glucose monitor, to find out how various foods and mixed meals affect us.

However, no one with type 2 diabetes should be eating 50 grams of carbohydrate per meal. Unless money is really tight and we need to fill up on cheap starches, when potatoes would be better than cake and cookies, I think the potatoes should remain at the grocery store. And people who write research press releases should be clearer about exactly what their research shows.

The full text of the study can be found here.


Tuesday, October 20, 2020

Short and Long-Term Effects

While looking for something or other, I recently came across this article saying that arginine has no long-term effect on heart health. Arginine is one source of nitric oxide, which dilates blood vessels. Nitroglycerin, used by heart patients for angina, also produces nitric oxide.

 The cited article was published in 2007 and took me back. At the time, arginine was hot stuff among some people concerned with heart disease. Author and blogger David Mendosa wrote about it in 2006, and it was strongly recommended by his endocrinologist, Dr. Joe Prendergast. Sadly, both David and Dr. Joe have since died. Here is a more recent article. 

I won't discuss here the merits of arginine or the arginine-containing Heart Bars (discontinued) that Dr. Joe was so enthusiastic about. What is interesting is the fact that according to the first article, arginine does improve heart health in the short term, but just not in the long term. 

This is true for other treatments and supplements as well. One good example is caffeine. Caffeine binds to a receptor for adenosine and blocks the adenosine from binding. When you need sleep, your levels of adenosine are high, and binding to that receptor makes you sleepy. When caffeine blocks the adenosine you're less sleepy.

Sounds great if you need to stay awake past your usual bedtime, but there's one problem. When you ingest caffeine on a regular basis, your body compensates by making more adenosine receptors. So now you need even more caffeine, and more, just to stay awake during the day. You're addicted.

Thus when you try anything new, you should be aware of the possibility that the short-term benefits, or side effects, may be different from the long-term effects. Metformin is a good example of the difference in negative effects. Many people can't tolerate metformin if they start it at the full dose, because of gastrointestinal problems like diarrhea. But if they start it slowly, it's fine. The body, which is generally smarter than we are, has figured out how to adapt.

I have personal experience with metformin side effects. I'd taken it for about 20 years with no problem, when it occurred to me that instead of taking 500 mg extended release (ER) twice a day, it would be easier to take 1000 mg once a day. My endocrinologist prescribed the 1000 mg without mentioning that it wasn't ER; the 1000 mg doesn't come in ER. I didn't notice that the bottle didn't mention ER, and because the pills were so large, I just assumed that's what it was. Dumb mistake.

After a while I started getting diarrhea. As my water supply isn't perfect (a spring with some surface water), I wondered if it was Giardia. We did tests and more tests. No clues. Finally, it occurred to me that it could just be the metformin, and sure enough, when I stopped taking it, the diarrhea went away.

A dosage that worked when spread out over the day didn't work without side effects when given at one time. I then returned to the 500 mg twice a day, introduced slowly, and had no more problems. 

Sometimes, especially if you find that a drug or supplement that worked wonderfully when you started taking it seems to have lost its oomph, it might make sense to take a vacation from it for a short time. Obviously this wouldn't be a good idea for a life-saving drug like insulin or medication for high blood pressure. But it might work for less essential supplements.

We don't know a lot more than we do know about how the body works, so any treatment is a work in progress. Stay alert to the effects of the drugs and supplements (and food) that you do take. Let your doctor know if prescription drugs seem to be working differently than when they were first prescribed. Maybe, like arginine, the differences are not in your imagination.



 


Sunday, August 16, 2020

CGM for Newbies

When I was diagnosed with type 2 diabetes in 1996, I lusted for affordable access to more test strips so I could learn more about which foods made my blood glucose (BG) levels go up.

My insurance would pay for only 3 strips a day, so if I wanted to do a detailed study of something, with a graph, I had to not test at all for several days or a week and stockpile the strips. I suppose I shouldn't complain. Previous generations didn't have BG meters at all; they had to test urine, which showed only what their glucose levels had been several hours earlier.

But now there are so many ways one can see what one's BG levels are, including continuous glucose monitors (CGMs), which measure BG every 5 minutes or so and even show the results as graphs.
But these gizmos aren't cheap. Most insurance plans will cover the CGMs for people with type 1 diabetes, but not for type 2 until your beta cells have degenerated to the point that your C-peptide levels indicate that you're producing almost no insulin.

 But it's now being discussed whether CGMs should be supported for type 2s. Some people think it's not cost-effective. But I've always thought people with type 2 should be given CGMs soon after diagnosis, as most people have no real understanding of what types of food make BGs go up. In fact, many don't even know what a carbohydrate is. Perhaps right away wouldn't make sense, as getting a diagnosis of type 2 is usually a shock, the patient's head is spinning, and learning to deal with a CGM might just be a burden. At first it might be better just to follow whatever the doctor or nurse or dietician suggests.

But after a few weeks, the patient should be ready to learn more. For example, the patient might learn that the "healthy" breakfast of cereal and skim milk suggested by a dietician still supporting low-fat diets for people with diabetes made the BG soar. Then the patient could try various other foods to look for something that kept BG steadier and was also tasty and satisfying for that patient.

Because of the cost, the CGM might not need to be a permanent part of the patient's regimen. As the patient learned what worked, finger-stick tests could be used to confirm what the patient had already learned.

One program, United Health Group's Level2, is offering CGMs to patients enrolled in a United Health insurance. They say that "Level2 is provided at no additional cost to eligible members as part of their covered health insurance plan." The program also includes personal coaching and a Fitbit to track activity. But you have to have been diagosed in the previous 24 months to be eligible. There are also some other restrictions.

I would have killed (well, maybe not literally) for a program like that when I was diagnosed.

Other diabetes programs offer not CGMs but unlimited test strips along with coaching. Examples are Virta Health, which promotes low-carb diets, OneDrop, and Livongo. They all charge monthly fees, sometimes considerable, but employers or health insurance will sometimes pay those fees. Other sites like MySugr and Dario offer unlimited strips with or without coaching.

Today, on Medicare I don't qualify for a free CGM because I don't use mealtime insulin, and I no longer lust after unlimited strips. I test fasting BG just to make sure I'm not totally out of control, but otherwise I test only if I have a new food or some unusual exercise or get sick. But I occasionally buy a Libre CGM for $63 for two weeks as a spot check in case some food I thought was fine and so didn't think to test actually sends me way up, or if there's something I want to test.

The technology has certainly improved since I was diagnosed, and I'm pleased that newbies have a lot of support if they know where to get it. I hope they do get this support. Good control from the beginning reduces the probability of complications, and that reduces the overall cost of treatment. A CGM is a lot cheaper than new legs or a kidney transplant.

I wonder what's next.




Thursday, July 30, 2020

New Type of Diabetes Medication

 A new type of diabetes medication is being developed, and it sounds great. However, although it works in rodents, human cells, and dogs, there has not yet been a clinical trial of the drug, so it won't be available for some time.

The drug has the decidedly unmemorable name SRI-37330, and it works in part by decreasing glucose output from the liver. Glucose levels are controlled primarily by two hormones: insulin, which lowers blood glucose (BG) levels, and glucagon, which raises them. When you have type 2 diabetes, you not only don't produce enough insulin, but you produce too much glucagon. The glucagon stimulates the liver to produce glucose (gluconeogenesis) and release it into the bloodstream, even if your BG level isn't low.

SRI-37330 inhibits glucagon secretion and function, reduces glucose production in the liver, lowers serum triglyceride levels, and also reduces fatty liver. It does this by inhibiting a protein called TXNIP (thioredoxin-inhibiting protein), which has been shown to be elevated in people with diabetes and to have detrimental effects on islet function. The islets in the pancreas are where the beta cells produce insulin.

The drug has no effect on insulin secretion or function. It has no effect on glucose uptake by muscle or white adipose tissue. It has no effect on the secretion of glucose in urine.

SRI-37330 has no effect on glucagon secretion when BG levels are low, which reduces the chance that it could cause hypoglycemia. And it has no effect on body weight. But in obese, diabetic mice, it reduced BG levels significantly within 3 days, and they eventually returned to normal.

All these effects sound wonderful, and even if they don't turn out to be as dramatic in humans as in animals, it would be nice to have another drug with a different mechanism of action, as we're all different, and a drug that works wonderfully for one person might not be so great for another.

The lead author of this paper, Anath Salev, kindly sent me a copy of the full text. An interview with her can be seen here.


















Saturday, July 18, 2020

Metformin and Energy

If you're trying to lose weight, there's a good chance that medical people will tell you that the important factor is that energy coming in is less than energy going out.

This is true.

But most people equate "energy out" with exercise. If you want to lose weight, they suggest that you exercise more. One problem with this advice is that for a lot of people, exercising just increases their appetite and makes them eat more, and so "energy in" goes up along with "energy out" and there's no loss of weight.

But exercise isn't the only part of "energy out." Any physiological process that wastes energy and converts it to heat will mean less energy is available to create fat. One example of this is the so-called biochemical futile cycles in which a chemical reaction converts A to B but then the body just converts B back to A. Because no reaction in the body is 100% efficient, each time the cycle occurs, a little bit of energy is lost as heat.

There are substances called uncoupling agents that increase the wasting of energy, and they were used by patients some years ago. The only problem is that one side effect of these compounds is death, so they weren't very popular.

Another part of "energy out" is any food lost in feces.  For example, if you eat a food that is poorly digested, much of the energy in the food is lost. An example of this is fiber. There's energy in fiber, and some microorganisms can digest it and convert it to useful substances. Humans can't. But sometimes bacteria in the lower bowel digest the fiber and produce substances like butyrate that we can digest.

So just measuring what you eat isn't enough. You need to know how much of what you eat is digested. In animal nutrition this is known as TDN, or total digestible nutrients.

Recently, research has shown that the diabetes drug metformin can increase the amount of sugar that is secreted in feces. This would both lower blood glucose levels and mean fewer calories were metabolized so they couldn't contribute to weight. (In animal nutrition, the goal is usually to get the animal to put on weight as quickly as possible, but the principles are the same.)

When I was diagnosed with type 2 in 1996, no one knew how metformin worked, but I was told it was better than the sulfonylureas (they didn't say why), which were the only other oral drugs available at the time, so I chose it and have been taking it ever since.

Eventually they discovered that metformin causes an increase in a molecule called AMPK, which is an energy sensor, and the recently discovered increased glucose excretion is a second mechanism. I suspect there are others that haven't yet been discovered.

The increased secretion of glucose into stool is analogous to the increased secretion of glucose into urine caused by the drugs called SGLT-2 inhibitors, for example, Invokana and Jardiance. In both cases, you're wasting calories by excreting them rather than converting them to heat.

There's still a lot we don't know about how metformin works, but we do know that it helps a lot of people with type 2 diabetes, and it's relatively inexpensive. On some drug plans, it's free.

Recently, the slow-release form of metformin was shown to contain a substance that increases rates of cancer. So far, only some brands have found this contaminant, but it's possible more will be added to the list when they are tested. If you want to see if your metformin is on the list, you can check here. This list was compiled on July 15, and there might be others added later.


Sunday, July 5, 2020

YMMV revisited

Some time ago, I wrote about "YMMV," or "your mileage may vary," the concept that sometimes what works well for one person doesn't work for another. The diabetes community was aware of that variation, but the evidence was annectotal and no one had studied it formally until a study in an Israeli cohort.

Now someone has done a similar study in mostly midwestern Americans without diabetes. The results are similar. Look at Figure 2A to see how people's blood glucose can vary after the same meal, in this case a bagel with cream cheese. One person's glucose levels went up to 190 and another to only 110. Note that these are people who haven't been diagnosed with diabetes. Whether they're on their way to diabetes is not known.

The researchers took 72 parameters into account in developing their model, which is designed to predict  how someone will react to a particular meal. You'll have to go to the Supplemental Content section to see these parameters, which I won't try to list here. They include species of 23 bacteria in the microbiome as well as usual things like nutrients, BMI, age, and CGM results.

The model is not yet available to the general public.


Tuesday, June 9, 2020

Toxins and Obesity

Some of us have long felt that toxins in our environment, our food as well as chemicals in cleaning products and chemicals used to control pests, could contribute to the obesity epidemic. Many of these chemicals were not available in previous times when very few people were obese.

A recent paper reports a study that so-called obesogens do indeed disrupt normal metabolic processes and cause lipid profiles in the liver to be abnormal. These changes increased susceptibility to weight gain, especially when they occurred early in life.

This is not the first time chemicals have been related to obesity and diabetes. For example, here is a study linking endocrine-disrupting chemicals like bisphenol A, found in tin can linings and cash register receipts; phalates, found in plastics and cosmetics; flame retardants; and pesticides with insulin resistance as well as other health problems including cancer. The effect seems to be greater early in life.

Interestingly, the authors of the recent paper said that rosiglitazone, a drug that used to be used to control diabetes, is among the obesogens,  and it was known to cause weight gain. I took it for a short time as part of a clinical study, and the doctor in charge warned me about weight gain, although she said it was mostly water weight and would go away when I stopped taking it, and the weight did reverse when the study was over.

The authors of the current study tried to find out how the obesogens work, and said they caused an increase in various fats in the liver when the liver cells were exposed to concentrations of obesogens often seen in today's environment.

One thing I found interesting in the current paper is that the authors said that today there are approximately 350,000 chemicals commercially available, compared with 100,000 in 2000, a huge increase in just 20 years. And with so many chemicals available, many of them are undoubtedly getting into our environment, including our food. Even monarch butterflies are threatened by toxins in their only food, milkweed.

So even if we try very hard to eat healthy food and we still gain weight, or can't lose weight, it might be more than genetics and food choices. We may be getting too many obesogens.

So what can we do? In today's world, it's impossible to avoid them completely, but we can try to minimize our exposure. If we can afford to, we can eat mostly organic foods, although they probably also contain some obesogens. We can avoid processed foods, which often contain additives. And we can mostly cook our own food at home, because who knows what restaurant food contains.

I realize that's difficult for many people, when trends are to eat more and more foods in restaurants or get them from takeout.

But we can try.

Saturday, April 25, 2020

Insulin Sensitivity in the Brain

We all know people who go on a diet, lose weight, and manage to keep it off. Others go on a similar diet, lose a little weight, and then regain it all, often ending up heavier than when they started.

Many people would say the latter group probably didn't follow the diet carefully and gradually ate more and more of the things they shouldn't eat.

But now there's some evidence that insulin resistance in the brain can predict weight-loss and weight-gain patterns. A German research group showed that people with insulin resistance in the brain lost less weight than people who were insulin sensitive and then regained the weight, whereas the insulin-sensitive ones were able to keep the weight off.

Apparently, the insulin sensitivity in the brain also determines where fat will be deposited. Those with brain insulin resistance deposited more fat in the visceral area, and this fat is supposed to be more detrimental than subcutaneous fat.

So what can we do with this information? At this time, not much. I don't know about you, but I'm not keen on injecting insulin into my brain.

However, knowing about this effect may help if you're one of the people who doesn't lose much weight even though you're following a diet strictly. When that happens, many health people probably blame you, assuming you're cheating on the diet even though you say you're not.

I know that kind of disbelief by medical people. My endo put me on an ACE inhibitor, which is usually used to lower blood pressure, because she said it would protect the kidneys, and people with diabetes are at risk of kidney disease. When other medical people see I'm on an ACE inhibitor, they ask how long I've had high blood pressure. I say I don't have high blood pressure, and they give me a patronizing look. At that point, I probably do have high blood pressure because I don't like not being believed.

Determining whether or not you have insulin resistance in the brain is not simple. The researchers used magnetoencephalography and functional MRI, techniques not available at your doctor's office.

Presumably, anything that reduces insulin resistance elsewhere in the body should also reduce it in the brain, and that would include exercising and losing weight, things we mostly likely already know we should do.

But if you're still having trouble losing weight, it could be it's not a lack of willpower. It could be insulin resistance in your brain.

Sunday, April 12, 2020

Comments

I tried to reply to a Comment yesterday, and it wouldn't post.

After trying this and that and searching the internet for help, I concluded that the problem is Firefox, which is my standard browser. With Chrome, I was able to post.

Computers can be very helpful, but they can also be very time-consuming when things don't go well. I sometimes wonder about returning to paper and pencil. No, I'll be more up to date than that. How about paper and ballpoint pen.

I still remember the time my father, a lawyer, came home with an amazing device to show us all. He had a client who was developing a special pen that wasn't yet for sale, but he had one. It was called a ballpoint. We were awed.

But I digress. I just wanted to give a heads up if anyone else is having problems posting. Try another browser.

I do moderate the Comments. If it's clear that the point of the Comment is to provide a link to someone's website, I don't approve it. So if you've sent such a Comment and it didn't appear, it's the moderation not the browser that is the cause.

Saturday, April 11, 2020

"Pumping" with Regular Insulin

When you use a pump, you fill it with fast-acting insulin like Humalog or Novolog. All day and night, the pump dispenses small amounts of the fast insulin, called basal insulin, and allows you to dispense larger amounts with meals, called bolus insulin.

Now a nonelectronic simple type of insulin pump can be used with regular insulin (R). Because the device is simpler than a regular pump and because R insulin is cheaper than newer insulins, the overall cost could be lower, especially for someone with no insurance.

The basal insulins use chemistry to modify R insulin so it forms depots in the fat that then release slowly. This device uses mechanics to release the R insulin slowly.

The device is called V-Go. It is designed for people with type 2 diabetes who still produce some insulin and thus don't need such exact amounts to be injected.

You fill a reservoir with R insulin and the device releases 20, 30, or 40 units a day as a steady infusion and can also release bolus insulin in increments of 2 units, up to 36 units a day when you press a button. The device has to be filled and placed on the body once a day and then is removed and thrown out after 24 hours. You can see detailed instructions here.

The V-Go had been approved for fast-acting insulins some time ago. But recently the device was shown to be effective with R.

The V-Go is nowhere as sophisticated as a regular pump. For example, it can release insulin at only one rate, whereas pumps can be programmed to release insulin at different rates at different times of day. And if you need less than 20 units or more than 40 a day, it wouldn't work. However, it's also much less expensive.

The device costs about $75 a month if you have no insurance. This would give you enough to use one a day. And you also have to buy insulin: 2 vials for 20 units a month and 3 vials for 30 or 40 units a month. You can get R insulin at Walmart for about $25, so the total cost would be about $125 a month for the 20 and $150 for the 30 or 40. Insurance could bring the price down.

The V-Go requires a prescription; Walmart insulin does not.

And someone with good insurance might find a regular pump at a lower out-of-pocket cost, although insurance, including Medicare, won't usually cover regular pumps for type 2 patients.

If you use only basal insulin, for example, Lantus, Levemir, or Tresiba, and inject only once a day, it might not be worth the extra trouble to set up the V-Go, but if you're doing basal/bolus multiple daily injections, it could be handy, especially if you wanted to bolus at work without hauling out a pen or syringe.

If you're on a low-carbohydrate diet, R insulin actually matches the increases in blood glucose after a meal better than the faster bolus insulins because it starts slowly and lasts longer. When you're eating protein and fat and fiber, your blood glucose also goes up slowly and but stays higher for a longer time, as the fat slows gastric emptying. When you're eating mostly carbohydrate, you get spikes in blood glucose that go up quickly and come down quickly, so the faster bolus insulins are a better match for that type of diet.

Because the insulin release from the V-Go is preset (20, 30, or 40 units for the basal and multiples of 2 for the bolus), you don't have as much flexibility as you do with a regular pump. You might need a bolus of 5 units but you could get only 4 or 6. You might need 25 units a day for the basal but you could use only 20 or 30. For a type 1 patient who produces no insulin of their own, this could be a big drawback. But type 2 patients have a bit of a buffer with their own insulin production.

One caveat: the studies I found had researchers with connections to or stock in Valeritas, Inc., the maker of the device, and some of their press releases are linked to reports on the value of their stock. This doesn't mean the studies are flawed, but it's sometimes a red flag.

Nevertheless, this is an interesting addition to the armamentarium we have to control type 2 diabetes.



Saturday, April 4, 2020

Support Groups, Good or Bad?

This article recently appeared on Eurekalert. The title, "Patients with type 2 diabetes belonging to online support groups have poorer health" makes it sound as if belonging to an online support group causes you to have poorer health, which doesn't make sense.

It also contradicts other studies like this one, titled "Joining a Support Group Improves Diabetes Treatment." The authors of this study wrote that "men and women who were enrolled in an online support program were nearly twice as likely to take their medication as prescribed and less likely to discontinue it."

So what's going on here? To try to figure it out, I read the full text of the article, "Participation of Patients With Type 2 Diabetes in Online Support Groups is Correlated to Lower Levels of Diabetes Self-Managemen."

In this study, 307 patients were recruited through an online survey. Then they were asked about their diabetes self-care management (glucose management, healthcare, dietary restrictions, and physical activity) and complications related to the disease, as well as their participation in online social groups and forums (duration, time, and intensity).

The researchers found that type 2 participants involved in online support groups had lower scores in "healthcare and self-management of diabetes." They also reported more diabetes complications.

I can think of several reasons for these results.

First, we know that correlation doesn't mean causation. A patient who follows medical advice and has wonderful control would be less apt to scour the internet looking for information about diabetes. But a patient who follows medical advice and is having problems controlling blood glucose might go online seeking more information. So the online support groups wouldn't be causing the lower scores for diabetes control, but the lower scores for diabetes control would be causing the people to join online support groups.

The authors also mention this, saying, "We cannot predict the direction of effects between using online support groups and the disease’s self-management, that is, we do not know whether the self-management complications are the cause or the consequence of such a type of online support group."

But many readers would just read the headline and conclude that participation in a support group caused the poor control.

Second, the study relied on self-reports, which may not be accurate. I might think my self-management was wonderful when it wasn't or vice versa.

Throughout the article, it's clear that the authors think patients need to have medical professionals in charge of information. For example, "it is likely that intervention or assistance is required for those patients to select and critically analyze the information they encounter in online support groups,"  "Hence, misinformation about diabetes, including its “cure”, has been found" [in the online support groups], and "information shared and consumed in online support groups may not be 100% rigorous and veracious."

It is true that online support groups can contain misinformation. But so can professional advice. The members of various groups must decide which information is credible and which is snake oil. When I was diagnosed almost 25 years ago, the professional view (with a few exceptions like Dr Richard Bernstein) was that low-carb diets are dangerous and one should follow a Food Pyramid that prescribed a lot of white bread and rice. Since then, the tide has turned, and now many, if not most, professionals are supporting low-carb diets.

But the point of this blog is not to criticize medical professionals. Rather, the point is that the headlines describing diabetes research, written by journalists trained to find interesting stories, not physicians, may be misleading.

So if you see a headline that sounds too good to be true ("Eating food X will cure your diabetes") or unlikely ("Just 30 minutes of exercise a day will make your diabetes go away"), make sure you read as much of the article as you have access to and decided if the headline is really supported by the evidence.

Monday, March 9, 2020

Coronavirus

Diabetes Daily has a blogpost on coronavirus as it relates to people with diabetes.

There's no reason to panic. But this is a good time to be extra careful with your blood glucose levels, as high levels increase the risk of various infections.

One benefit of having diabetes is that it almost forces you to eat a healthy diet. I'm sure that someone who eats a whole-foods diet for diabetes is in better shape to fight off infections than a nondiabetic who lives off fast food and boxed dinners.






Friday, March 6, 2020

More Reasons to Eat Low Carb

Several recent studies have supported the consumption of low-carbohydrate diets, especially, of course for people with diabetes but also for people without the disease.

The first study showed that although artificial sweeteners by themselves don't affect metabolism or the brain's sensing of a sweet taste, when these sweeteners are eaten along with carbs, they do, causing insulin resistance and a decrease in the brain's response to a sweet taste. These changes increase the risk of obesity.

In other words, it's OK to drink a diet soda with some steak, but not with french fries.

The mechanism of this effect is not clear, but it could explain seemingly contradictory results of studies of artificial sweeteners. Some studies may have given the sweeteners along with carbs, say adding them to yogurt, whereas others did not.

The full text of the study is available. I found it a bit confusing. For example, they say, ". . . in healthy human adults we observed reduced insulin sensitivity and blunted brain response to sucrose following consumption of seven 355 mL beverages over 2 weeks," but they don't say what the beverages contained.

Nevertheless, the overall conclusions are interesting: "consuming sucralose with, but not without, a carbohydrate rapidly impairs glucose metabolism." Of course, if you're on a low-carb diet, you're less apt to be using a sweetener with significant amounts of carbohydrate.

Another study suggests that low-carb diets may help prevent age-related changes in the brain. The authors say that communication between brain regions destabilizes with age, starting in the late 40s, and destabilization correlates with poorer cognition and accelerates with insulin resistance.

The researchers found that glucose decreases, and ketones (which are formed when glucose ingestion is low) increase, the stability of brain networks. 

The authors say that as people get older, "their brains start to lose the ability to metabolize glucose efficiently, causing neurons to slowly starve, and brain networks to destabilize." Hence a ketone-producing low-carb diet could provide the energy the brains need.

They used functional MRI to image the brains of 1000 people aged 18 to 88 and found that destabilization was associated with impaired cognition and was accelerated with type 2 diabetes, which affects the neurons' ability to metabolize glucose. They found that either a low-carb diet or a ketone-rich drink stabilized the networks.

The last study found that mice fed a ketogenic diet were better able to fight off the influenza virus than mice on high-carbohydrate diet. The authors said that the diet enhances the production of a certain type of T cell that produces mucus in the lungs that helps to trap the virus.

This study was done with the flu virus, and there is no evidence that a ketogenic diet would protect against coronavirus. But perhaps it could. We know that high blood glucose levels weaken your immune system, and people on low-carb diets tend to have lower glucose levels, so it could help in that way as well as possibly triggering lung changes.

Not everyone is happy on a low-carb diet long term, but it's certainly worth trying.


Sunday, February 23, 2020

More Misleading Headlines

A recent article in Eurekalert says in the headline, "University of Minnesota researchers discover Mediterranean diet ingredient may extend life." This illustrates two problems with popular science articles.

First, the authors emphasize the university where the research was done more than the research itself. Of course, this is the job of the PR people who write press releases, as sites like Eurekalert and Science Daily simply print the press releases as they come in, without editing them.

Second, and more important, the headline mentions "Mediterranean diet ingredient," which turns out to be olive oil. If they mean olive oil, why don't they say olive oil. People on a lot of different diets use olive oil. But seeing something in a headline tends to make people remember it. So many will see this headline and think, "Oh yes. If I follow a Mediterranean diet, I'll live longer."

That might be true if they're currently on a fast-food diet or a diet with lots of processed foods. For someone without diabetes, I think the so-called Mediterranean diet is healthy, even though it doesn't represent what many people in that part of the world actually eat. But the diet emphasizes whole grains, which make blood glucose (BG) go up in people with diabetes. Of course, whole grains are better than highly processed grains, but better doesn't mean best. And many people don't really understand what a whole grain is.

Corn and rice are whole grains, but in people with diabetes they'll make BG levels soar.

Health writers, and even some researchers, tend to get on the Diet du Jour bandwagon. You're more apt to get funding if you're researching the popular Mediterranean diet, looking at it from some new angle, than if you're researching the Blubber and Kale diet, which no one eats.

I'm all for informing nonscientists about research results. But not if the publicity is misleading. In this case, the original article was titled "Lipid Droplet-Derived Monounsaturated Fatty Acids Traffic via PLIN5 to Allosterically Activate SIRT1," and although it mentioned that the Mediterranean diet is high in monounsaturated fats (olive oil is monounsaturated), the focus of the research was on how olive oil helps, not on any life extension of that diet.

They write, "While undoubtedly a plethora of components in the Mediterranean Diet contribute to its positive effects on health, the data presented herein provide at least one feasible biological mechanism that may underlie these well-established benefits."

Almost any whole-food diet will show benefits when compared to the Standard American Diet. Maybe the mechanism of the benefits of the Mediterranean diet is simply eliminating chicken nuggets, cheeseburgers, french fries, and doughnuts rather than using more olive oil.




Thursday, February 20, 2020

Physician Reviews

The internet allows us to see reviews of our physicians, or of physicians we're thinking of seeing.

However, we're all aware of the dangers of believing online reviews of anything. It's very easy for people to hire people to write positive reviews. Or a disgruntled reader can write negative things. When the book The Four Corners Diet," which advocated low-carb eating, came out, someone didn't like something I said online (I think it was a suggestion that they should count the carbs in coffee) and proceeded to write negative reviews of the book, for which I was a coauthor.

The same applies to online reviews of physicians. Irl Hirsch, an endocrinologist who has had type 1 diabetes for most of his life, wrote this in an article titled "Ranting in 2020: Reflecting About the Past and the Future (with Concerns About the Present)":

"There are other frequent venues to evaluate physicians, particularly on the Internet. I was not even aware of physician evaluations on Yelp until I was emailed that I received a low grade (1 star out of 5) from a dissatisfied patient. I went to the site and indeed, I was a horrible disrespectful man, saying derogatory things about a woman's weight. Not only that, I had horrible body odor (at least no mention was made of my bad breath). In the email I received, I was told the poor review could be removed from the website for $3000. After checking with a few people, I learned this is a common scam and many of these evaluations are posted by swindlers looking to make a quick dollar."

I knew about negative reviews by disgruntled patients. But I'd never heard of review scams.

One more reason to not trust online reviews. If you do read them, see if there are at least several reviews that make similar points, but not so similar that they're probably written by the same person. Then if you decide to try that physician, keep the criticisms in mind and see if they seem to be valid.

The internet offers us a chance to get a lot of information with very little effort. It also offers us a chance to read lies.

Caveat emptor, buyer beware.

Thursday, February 13, 2020

Big Pharma and Research

I'm hardly a big fan of big pharma (understatement). But I think we sometimes don't think of how difficult it is to develop an effective drug that is also safe. Derek Lowe is a chemist who used to work in drug development, and I follow him to see how such people think. I found this recent blog interesting.

Management puts pressure on their chemists to develop profitable drugs in a minimum amount of time. But that means they sometimes don't have time for rigorous testing. He cites a trial in France in which 2 of 9 patients in a phase 1 trial (which is supposed to test safety) died.

PK = pharmacokinetic, and PD = pharmacodynamic.

Sunday, February 9, 2020

Is Dietary Protein Dangerous?

A currently popular diet is a low-carbohydrate diet, often high fat with normal amounts of protein. But some people call low-carb diets high-protein diets. So recent headlines disparaging high-protein diets may cause worry to people on low-carb diets even if they're not eating an especially high amount of protein.

Two examples of such headlines are

High-protein diets boost artery-clogging plaque, mouse study shows.

And Lower-protein diet may lessen risk for cardiovascular disease.

If you just read headlines like this, you might worry that you're eating too much protein.

But we need protein. And as we get older, we need more protein because our muscles tend to lose strength and the dietary protein helps to slow this decline.

So how much protein do we need? A rule of thumb is 0.8 grams of protein per kilogram of body weight, or 0.36 grams per pound. An ounce of meat has about 7 grams of protein.

If you're math-phobic, Jenny Ruhl has a calculator that will estimate how much protein you need on the basis of size and age, and you can find other calculators online. Some use lean body mass, rather than weight, for the calculations because it's muscle mass, not fat, that determines how much protein  you need.

Note that all these calculations refer to a minimum amount needed for good health. Especially if you're getting older, you should eat a little more than the minimum, and recommendations increase to 1.2 to 1.5 grams per kilogram weight or lean body mass. I weigh about 50 kg, and different calculators say I need from 31 to 71 grams of protein a day, so don't take the results as totally accurate.

When I was first diagnosed in 1996, I was told to follow the ADA low-fat diet, which prescribed an average of less than 2 ounces of meat per meal. I felt very deprived and not satisfied. I now try to eat 3 or 4 ounces of meat or other protein per meal, and that satisfies me.

But the real question here is what the authors of the papers I've cited mean by "high protein" or "low protein." The mice in the first study were fed 46% protein. This is indeed high. Normal protein intake in humans is 12% to 20% of calories from protein. And except for people on the Carnivore Diet (nothing but meat), I doubt that many people, even those on low-carb diets, are eating 46% of calories as protein. 

However, with protein, the amounts rather than the percentages are the important factors, because as you reduce one nutrient, like carbohydrate, the percentages of the other nutrients go up even if the amounts stay the same.


In addition, this study was done in mice, and mouse results often don't translate to  human results. In the wild mice eat mostly seeds, grains, and small fruit, although they'll eat almost anything they can get their paws on.

However, people seeing "high protein" and "artery clogging" linked in the headline might cut back on their protein intake and end up protein deficient.

The second study, citing "lower protein diet," focussed on sulfur-containing proteins, and their intake is difficult for the average person to estimate. But again, the headline is misleading. It doesn't refer to sulfur-containing proteins but proteins in general.

And just to confuse patients even more, a 2015 study was titled "High protein foods boost cardiovascular health, as much as quitting smoking or getting exercise."


Nutrition is a very fuzzy science. Many studies are done with food-frequency questionnaires. I sometimes can't remember what I had for lunch, much less how many chicken legs I ate last month. Sometimes people don't mention foods they think are unhealthy. Or they'll overestimate or underestimate the amounts they ate.

So when you see headlines like the ones cited here, take them with a grain of salt (unless, of course, you're on a low-salt diet). If they worry you, try to read the papers themselves to find out what they mean by fuzzy terms like "high protein," and ask your doctor for another opinion.

If you eat real foods, not fast foods or boxed foods, in reasonable portions, you probably have a healthy diet. If your blood glucose and hemoglobin A1c levels are good, you're following a diet that is good for your diabetes. Keep it up and don't obsess about sensational headlines.


Sunday, January 26, 2020

Drug Costs

We're all aware of the obscene increases in the price of insulin and the Epipen. But it's not just those drugs. All drugs are fast getting more expensive.

I'm doing bookkeeping in preparation for taxes, and I could see how the prices are going up. I have Plan D, which means I don't pay the full costs of the drug, but in the following I'll use the full cost so the results won't be affected by the rules of the plan. Here are some examples, all in 2019. I get drugs mail-order and each order is for 3 months.

Ezetimibe (generic Zetia) increased by 2.56 times

    April, $24.50
    July, $36.75
    October, $44.88
    December, $62.83

Omeprazole (generic Prilosec)  increased by 4.8 times
    January, $5.89 
    April, $10.59
    July, $19.38
    October, $28.42
    December, $28.42

Lisinopril (went up then down; maybe they negotiated a new contract)
    January, $2.20
    April, $5.54
    September, $10.48
    December, $6.05

Pravastatin doubled
    April, $21.06
    July, $36.16
    October, $45.97
    December, $43.53   

Some drugs did stay the same, including Levemir, $926, but I paid only $30.

What will we do if the drug costs double, or more, every year? Will it come to choosing between food and shelter and drugs? Some people are already doing that with insulin, and some deaths have resulted from people with type 1 reducing their insulin doses to save money. That's criminal in a country whose president has spent more than $13 million on golfing trips. Where are our priorities? Does golf for some matter more than lives of others?

We must figure out a fair way to provide life-saving drugs to those who need them.


   




Thursday, January 2, 2020

Insulin Clearance

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

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

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

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

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

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

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


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


Wednesday, January 1, 2020

Helping Obese Mice (humor)

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

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

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

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

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

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

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

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