Monday, January 11, 2021

Subtypes of Type 2 and Prediabetes

 A recent study has suggested that there are six subtypes of prediabetes, with each subtype having different risks of progressing to type 2 diabetes and different risks of various side effects. The study, which was begun 25 years ago, grouped people into clusters depending on factors like blood glucose levels, liver fat, body fat distribution, blood lipid levels, and genetic risks.

They found that people in different clusters differed in insulin secretion and insulin action in addition to the factors listed above.

People in three of the clusters have a low risk of diabetes. People in another cluster produce too little insulin. Those in another cluster have kidney damage even before overt diabetes is diagnosed.

It would be nice to know what cluster a newly diagnosed patent was in, but many patients today have difficulty getting even basic tests, and its unlikely they could get all the tests required to classify them. Even the authors concede that "our clustering aproach is not designed to provide definitive subphenotypes for individual patients in a clinical seting." However it would be useful for researchers.

I suspect that in the future they'll find even more subtypes, but for now this is a start.

Patients can differ a lot in both physical characteristics and economic and emotional ones. One patient might be willing to go on a strict low-carb diet, and another couldn't tolerate that, or couldn't afford it. Treatment may depend on a particular patient's situation, and good doctors take that into account agaialready, rather than relying on a cookie cutter approach.

The full text of this study, in preprint form, can be found here

This is not the first time researchers have tried grouping patients into clusters. Other researchers have grouped people with type 2 diabetes into five subgroups, using GAD autoantibodies, age at diabetes onset, HbA1c, BMI, and measures of insulin resistance and insulin secretion.

They found that the group with severe insulin-deficient diabetes had increased risk of retinopathy and neuropathy, whereas the severe insulin-resistant diabetes group had the highest risk for diabetic kidney disease and fatty liver

Again, most physicians will probably not have the resources to measure all these parameters for every patient, but again, it's a start.


Thursday, December 17, 2020

Does Control Get Easier as We Age?

 Someone recently mentioned to me that their control had gotten easier as they got older. I'm not talking about going from 20 to 30 years old. By older I mean senior citizen status.

This is the second person who has told me that. The first one was a type 1 on basal/bolus insulin. She was on a low-carb diet and didn't need much insulin to cover meals, but she needed some. When she reached her mid-80s, however, she found she sometimes didn't need mealtime insulin at all. And she could again eat peaches, which she adored.

She said her doctor, a GP, said that sometimes happens.

"I'm cured," she often said.

One thing that can make blood glucose (BG) go up is gluconeogenesis in the liver, where glucose is formed from other things. Insulin is supposed to turn the gluconeogenesis off, but when you have insulin resistance, that doesn't happen, and the gluconeogenesis is one reason for high fasting BG levels.

Both these reports are, of course, annecdotal, but when I heard this a second time, I decided to look into it.

Here is a study in rats that says, "It is concluded that the gluconeogenic capacity of liver declines with age regardless of the gluconeogenic regulator." So the concept may have some merit.

Long ago I read somewhere that I unfortunately can no longer find that an Indian doctor said some of the Indian herbs that seemed to work to keep BG levels down did so by damaging the liver, which would reduce gluconeogenesis.

So liver function might be key.

 I was wondering if any others had noticed improved BG control with aging, meaning 70 years old or older.

Of course, there are other reasons control might improve. With time we get accustomed to whatever diet works for us. We usually get less exercise than when we were younger and playing several sets of tennis before lunch. Well, OK, I never did that, but some people did. And we often eat less because with less exercise we're not as hungry.

But if you're doing pretty much the same thing you've been doing for some time and you find your control improving with age, I'd be interested in hearing about it.

Sunday, November 29, 2020

Chocolate Cake Again

 A few years ago, I posted a recipe for a quick low-carb chocolate cake. Well, OK, I see it's from 2009, which is more than a few years, but time passes so quickly, it seems as if it were just a couple of years ago.

As often happens, I made this cake a few times and then forgot all about it. Recently, retrieving the recipe from behind a cabinet (don't ask), I decided to try it again. This time, I didn't cook it long enough, so the center was rather liquid, but I thought that made it even better, like a lava cake, although if you're worried about eating raw eggs you wouldn't want to undercook it.

Today, there are a zillion recipes for mug cakes like this that are cooked in minutes in the microwave, so if you want another flavor, just do a search on "mug cake" and modify for low carb if needed.

What I like about these cakes is that if you get a sudden need for some cake, you can make one in a few minutes if you keep flour alternatives around. I keep almond flour and coconut flour in the freezer as well as protein powder on the shelf.

Happy Holidays.

 


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.