Wednesday, October 18, 2017

Controlling Weight

Controlling weight is affected by so many physiological factors it's sometimes difficult to keep track. Before 1994, when leptin was discovered, people thought weight control was simply a matter of willpower. Now we know better.

Most of us know that leptin is secreted by fat cells when we have had enough to eat and the fat cells are full, and the leptin turns down our appetite. Children born without leptin have voracious appetites and become obese as toddlers; when given leptin, they slim down. People with no leptin are rare, but overweight people may have leptin resistance, just as people with type 2 diabetes have insulin resistance. In both cases, levels of the hormones can be high but the body doesn't respond to them properly.

On the other hand, the hormone ghrelin is produced by the stomach when we haven't eaten, and it makes us hungry.

Now a third hormone has been discovered that increases appetite during fasting and decreases it during feeding. It has been named neurosecretory protein GL, usually referred to simply as NPGL.
This hormone not only affects appetite, but it also increases the storage of fat, even on a low-calorie diet.

Another study found a gene with the snappy name GTRAP3-18 that helps to regulate both food intake and glucose levels. Mice without this gene were both lean and hypoglycemic, and this was due to neither less activity nor an increased metabolism, but rather to eating less. The authors suggested that the gene could be a target for drugs, saying, "Eating too much or too little could actually be a genetic problem," although we know that other factors such as emotions and the food environment can play a role as well.

A third study found yet-another protein with a snappy name, MKK6, that affects weight by stimulating the burning of fat to generate heat. Overweight people seem to have higher levels of MKK6, which hinders the conversion of white fat cells into brown fat cells. White fat cells store fat, and brown fat cells burn fat.

A fourth study described brain cells called tanycytes that detect nutrients and tell us when we've eaten enough. Foods high in certain amino acids (the building blocks of protein) activate the tanycytes and make us feel full sooner, which is consistent with the commonly stated fact that protein is satiating. Interestingly, the receptors in the tanycytes are the same as those in the tongue that detect the umami flavor of protein foods.

The two amino acids that react the most with the tanycytes are arginine and lysine. Foods rich in these amino acids include pork shoulder, beef sirloin, chicken, mackerel, plums, apricots, avocados, lentils and almonds.

Finally, a Swiss study showed that severely obese people release fewer satiety hormones than people of normal weight because they have fewer of the intestinal cells that produce the satiety hormones than normal-weight people. Weight-loss surgery seems to increase the number of these cells.

We all know that weight loss, and especially maintenance of weight loss, is difficult. One reason is that there are so many factors involved (and I'm sure even more will be found in the future), and different people may have deficits in different systems.

In fact, an Israeli study showed that the glycemic index of various foods could vary a lot between individuals. A food that was problematic for one person might be fine for another. And for some individuals, even white bread seems to be better for blood sugar levels than whole grain bread.

Even the bacteria in your gut may affect whether or not you will lose weight on a diet with a lot of fruits, vegetables, fiber, and whole grains, according to a Danish study. So if some recommended diet doesn't work for you, it may not be that you're "doing it wrong." It may be that the diet isn't the right one for you.

What this all means is that it's up to us to take charge and find out which diets are best for our personal physiology. It's a lot more work than simply following guidelines set by some "diet expert." But it's worth the effort.

And it's encouraging that so much research is going into what factors govern appetite and fat gain or loss. In the long run, this basic research should lead to real solutions. Let's hope funds for basic research aren't cut any more in a misguided effort to save money. In the long run, figuring out the best way for people to lose weight and keep it off will save even more money from health care expenses than the costs of the research.

Wednesday, August 30, 2017

Information overload

One of my favorite cartoons, which I have pasted on my desktop computer, shows a man with a little beach pail standing on a beach while a huge wave (which looks like the woodcut "Great Wave Of Kanagawa" by Katsushika Hokusa) is about to break over him. The man is saying, "Eureka! More information."

(I can't show the cartoon here because it's copyrighted. I was going to link to the author Ted Goff's page, but he's apparently updating his website and the links don't work for now.)

This cartoon illustrates how I feel about science news these days. I get about 150 Eurekalert science press releases every day, as well as the tables of contents from a lot of journals. And it seems as if just as some fact is generally accepted, a paper comes out refuting that fact.

Also, science research is getting much more technical these days. Unless a study is commissioned by some commercial group like the the California Walnut Commission, which funds a lot of studies showing the health benefits of walnuts when some of those benefits might be found by eating similar nuts, people no longer tend to publish simple studies saying that factor X increases or decreases diabetes symptom Y. Instead the authors (often 20 or more) drill down to the molecular level and try to show that factor X increases or decreases the level of numerous cell factors that govern gene expression or hormone activity.

Unless the reader has a background in biochemistry or molecular biology, I figure the reader probably wouldn't understand these studies (sometimes I don't either), so there's no point in discussing them.

Also,  unless I think there's a major flaw in the evidence, I see no need to link to a study that has been picked up by all the news media, something like "Eating pickles and figs will make you lose 10 pounds in a week." You'll most likely see that study on the TV news anyway.

All this is a way of explaining why I'm not blogging much at the moment. But I haven't disappeared. I continue to try to keep up with new research developments, and when something both interesting and comprehensible by the average reader comes out, I'll let you know.

Hang in there. I'm trying to.

Tuesday, August 29, 2017

Is Childhood Obesity Psychological?

"Is Childhood Obesity a Psychological Disorder?" says a headline in a press release from Children's Hospital Los Angeles.

Now, many people get their information from headlines and don't read the articles. Also, a headline with a question mark suggests that the answer is Yes. If it were no, it wouldn't usually be newsworthy, akin to asking if childhood obesity were related to the name of the child's kindergarten teacher.

So this headline suggests that childhood obesity is a psychological disorder, and although there are many definitions of "psychological," a common one is "it's all in your head," meaning it's not a real disorder, and suggests that these kids are emotionally unstable and could become thin if they really wanted to.

In fact, the article focussed on brain scans of overweight or obese and normal-weight adolescents. They found that after showing the adolescents words describing various kinds of food, although the brains of all the participants were stimulated in areas that support reward and emotion, the overweight/obese ones had less activity in brain areas that support attention and self-regulation. I'd call this a brain disorder, not a psychological disorder.

As you might expect, when offered a buffet after the testing, the overweight/obese adolescents ate more than the lean ones.

This study is interesting, but I think the headline reflects an unconscious bias against fat people, suggesting that fat children have psychological problems. If the brains of overweight people are indeed different, we should try to figure out why they're different and then figure out how to normalize them.

I'm sure there are some overweight people who overeat because of psychological traumas. But there are others who overeat because they have differences in their hunger sensations, for example the rare children who lack leptin. And there are others who don't actually overeat but have metabolisms that are superefficient at converting food into fat.

It would be nice if all weight problems had only one cause so it would be easy to fix, but that's not the case. Until we have the solutions, we should at least stop stigmatizing overweight people and instead help them heal.





real. , and many

Monday, July 24, 2017

When to Measure Postmeal Glucose Levels

What's the best time to test your blood glucose (BG) after meals?

Of course that depends on what you want to learn from testing after meals. If you want to know the after-meal peak, then you should test about an hour after you eat. The peak will differ a bit with different foods; fats slow down gastric emptying, and liquids pass through faster than solids. It also can differ with different people.

So if you want to know where your own peaks are, you should test every 15 minutes or so starting about 45 minutes after eating and continuing until the numbers start coming down.

If you want to know if you're able to return to normal, or close to normal, BG levels within a few hours, then you should test at 2 or 3 hours.

"After eating" is also ambiguous. Should you test X minutes after you start to eat or after you stop eating? Again, it depends on your habits. If you wolf your meal down, it doesn't much matter. If you eat leisurely and take 30 minuts to finish a meal, then it does. What you really want to know is differences between different meals, so the important thing is to test about the same way every time. Don't compare one meal you ate in 4 minutes with another one that you took an hour to finish. Most people measure the time after starting to eat.

If you ask CDEs or your doctor when to test, they'll usually tell you to test at 2 hours. This is because most research papers about postprandial (after meal) BG numbers use the 2-hour reading. But this may not be the best.

One researcher, Antonio Ceriello, recently published a paper proposing that it's time to switch to a one-hour postprandial measurement. He kindly sent me a copy of the full text of the paper.

Ceriello says that there's evidence that the one-hour measurement has even stronger power than the two-hour measurement for identifying impaired glucose tolerance. He said this number is also related to the risk for cardiovascular complications. In vitro experiments have shown that just one hour of high BG levels is enough to cause endothelial dysfunction that can then lead to coronary vascular disease, as well as reactive oxygen species (strong oxidants), he said.

Endothelial function is worse at one hour than at two hours both during oral glucose tolerance tests and after meals, he said.

If all this isn't enough, Ceriello said short-term high BG levels can impair beta-cell function.

When I've measured BG levels in nondiabetic friends and relatives, I've sometimes found one-hour readings of 160 or so, but the numbers come down to baseline by two hours. Testing only at two hours wouldn't identify these people, who might be at risk of developing diabetes in the future.

Ceriello's recommendations apply to clinical studies, but there's no reason you couldn't measure at one hour if you so chose. The best, of course, would be to measure at both one hour and two hours if you could afford enough strips. Then you'd know which time made most sense for you.

Even if most clinicians accept Ceriello's recommendations, it will take time before they become standard. So for now most studies will continue to use the two-hour numbers. But when  you see a study mentioning postprandial (or postmeal) numbers in the future, you should check to see what they mean, if you can (abstracts may not specify).

If anyone wants references to the studies Ceriello was citing, let me know and I'll send them to you. If I get tons of requests, I'll just edit this post to put the links in.

Saturday, July 8, 2017

Of Mice and Humans

"New Research Describes the Differences Between Mice and Humans" screams a headline of an article in Eurekalert. 

Golly. I guess I'm ahead of my time because I've known the differences between mice and humans for decades. The mice are the furry ones with long tails, and the humans are the larger ones who fight and kill each other because they don't agree on politics or religion.

But once you get past the headline on Eurekalert, you find that researchers are finally accepting that mouse research often doesn't translate into human treatments. Mice have been cured of diabetes hundreds of time, but the drugs the researchers used just don't seem to work when they try them on humans. 

The problem is that it would be unethical to try new drugs on humans without some evidence that they might do something beneficial. Mice are relatively cheap to maintain, and we already know a lot about them. If we used only larger animals like pigs or dogs or monkeys, the cost of research would be even higher than it is now, and animal rights groups would protest. Very few people object to mistreating rodents.

Now researchers are beginning to find out why mouse research doesn't always translate into human cures. These researchers looked into a class of receptors found on beta cells in both mice and humans. They are called G-protein-coupled receptors (GPCRs), but the names don't matter.

What they found was that some of these receptors are found in both mice and humans, but others are not. Some are found only in mice, and others are found only in humans. If they know which ones are found in both mice and humans, future researchers can limit their research to those receptors. There's no point in spending millions of dollars on some drug that affects a receptor found only in mice! That money could instead be used to study drugs that affect both species.

Of course not all drugs target GPCRs. But a large number do. Let's hope these findings channel research into fruitful drugs, and not duds.

Thursday, July 6, 2017

Hunger

I know what ravenous hunger is.

More than 20  years before I was Dx'd with type 2 diabetes, I used to get reactive hypoglycemia, although I didn't realize that's what it was. At the time, I was working at a daily newspaper, and I occasionally did the wire desk, which mean I had to arrive at work at 7 a.m.

I normally didn't eat breakfast, and I wasn't especially hungry for lunch. But because I was a night owl and hated getting up early enough to get to work by 7, I'd reward myself with a chocolate doughnut, in addition to the strong black coffee I usually had.

Then, almost exactly 4 hours later, I'd get the shakes and a feeling that if I didn't eat something immediately, I was going to die. So I'd rush to the candy machine and get a candy bar, and that got rid of the shakes and the feelings of doom.

Now if I go low, which doesn't happen often but it does happen, I have that same feeling that if I don't eat I'm a goner. And because I want to get rid of that feeling that I'm doomed, I sometimes overtreat and then go high for hours.

Of course the official recommendation is to eat 15 grams of carbs, wait 15 minutes and retest, then eat a little more if you're still low. But one thing I really miss on my low-carb diet is fruit. When I was a kid I remember telling my mother, "What I really like is meat and fruit." So I keep canned sugarfree peaches in the cupboard to eat if I go low. They have about 6 grams of carbs in a cup, which is often just right when I'm not very low, and I wolf them down.

So I was wondering if this same 15/15 approach would work not just for lows but for weight loss.

I suspect that many people who have weight problems have something wrong with their appetite controls. When everyone else is feeling just hungry before a meal, they may feel ravenous. And when you're ravenous you tend to wolf down whatever you can reach. It takes about 20 minutes before your body lets you know you've had enough, and if you eat fast, by that time you've eaten a lot more than you need.

It's not enough to tell people to eat slowly. What exactly does that mean? Would it work better to measure out a small amount of food, eat it, and then wait 15 minutes? If you were still hungry, you could eat a second small amount of food. You'd keep doing this until you were no longer hungry.

Of course, if you have only 30 minutes for lunch, this would be difficult. Even with an hour it might be hard if it took four small portions and until you felt full. If so, you could increase the portions until you found an amount that filled you up with one or two servings.

So would this work? I really don't know. I'd try it myself but I no longer get ravenously hungry except when I'm very low, and that doesn't happen very often. I've always had a big appetite. One time a waiter at a Chinese restaurant remembered me two years later. He said they'd all been talking about me, "Because we'd never seen anyone so small eat so much." (This was in the days before they let you take extra food home and I hated to waste food, so I ate my whole meal, including the rice, and then finished what my brother couldn't eat.)

But as I get older my appetite seems to have abated, and "normal" portions now seem dauntingly large. So I no longer have that urge to stuff myself. I sometimes even stop eating when there's still food on my plate and heat it up and eat it at the next meal. So my weight has been steady for a long time.

It's nice to have a normal appetite after all these years, but I do understand what it's like to feel ravenous. I wish we could figure out how to fix that.

Sunday, June 11, 2017

Is Blood Glucose Testing Worthwhile?

Here we go again: Another study  claiming that self-monitoring of blood glucose levels (SMBG) doesn't help patients with type 2 diabetes. You can see the full text here.

Some previous studies have claimed the same thing, and some even claimed harm from SMBG, namely increased rates of depression or decreased "quality of life," although others claimed benefit.  Most informed patients agree that in order to be effective, patients must be trained in how to interpret the results and take action as a result. If you eat doughnuts and see a high number on your meter after a couple of hours, don't eat doughnuts. Just measuring without using the results to take some kind of action is, most agree, pretty useless and a waste of money.

The authors of the recent study agree: ". . . for SMBG to be an effective self-management tool in non–insulin-treated T2DM, the patient and physician must actively engage in performing, interpreting, and acting on the SMBG values."

In this study, patients were randomly assigned to one of three groups: no testing, testing, or testing with feedback. In the latter group, the feedback was computer-generated, not actual conversations with a human being. Here are examples of the feedback:

Sample Messages for Blood Glucose Values at Goal

• You are right on target. Remember to check your blood sugar tomorrow morning.”
• “Keep up the good work.”
• “Outstanding!”
• “Way to go. Keep checking every morning before breakfast!”
• “Your blood glucose goal is between 70-130 in the morning before you eat. You are doing marvelously.”

Sample Messages for Blood Glucose Values that are Mildly Elevated
 
• “Keeping track of the foods you are eating and the physical activity you are doing may help you pinpoint reasons why your blood sugars are running high.”
• “This number is a bit off target. Remember to check again tomorrow morning before eating.”
• “Your target in the morning before eating is 70-130.”
• “Staying on track with your diabetes can be tough at times. You can do this! Aim for a target fasting blood glucose value in the morning between 70-130.”

Sample Messages for Blood Glucose Values that are Very Elevated
 
• “Please discuss with your health care provider to talk about ways to get your blood sugars down to a more healthy range.”
• “Please consider making an appointment with your doctor. Your blood sugars have been too high lately. Your target before breakfast is 70-130.”
• “Time to check in with your primary care provider about these blood sugar numbers. They have been running too high.”

This is certainly better than nothing, but the messages are too general to be of much use and focus on fasting levels. I don't see anything like "Oops. Your numbers were high after this meal. See if you can figure out what it was in the meal that made your numbers go too high."

In fact, I couldn't find in the paper or even supplementary material anything about when patients were told to test, so I asked the corresponding author, Katrina Donahue. It turns out it was not simple. She said,

"The testing was based on once daily testing, but would vary depending on the patient’s blood sugar levels. First, they were instructed to test a.m. fasting blood sugars. When at goal, they were instructed to test a.m. fasting 3-4 times per week and pre bed 3-4 times per week. If still at goal, they were instructed to test a.m. fasting 1-2 times per week and 2 hour post prandial 5-6 times per week."

So only those patients who reached their fasting goals (7-130 mg/dL) were told to test after meals, and it's testing after meals that really tells you how different foods affect your blood sugar numbers, although your fasting levels may give a general idea of your overall control.


One interesting thing in this paper is the graphs showing hemoglobin A1c levels with time and the proportion of patients actually testing when assigned to the testing group. The A1c levels over 12 months are very similar to the results we usually see in diet studies. Initially the intervention is successful, but then, usually after about 6 months, the results slowly revert to baseline.

A similar pattern was seen with the proportion of patients told to test who were actually testing: High compliance at first dropping to about 60% by the end of the year.

I think these graphs show something important. People who are diagnosed with diabetes are at first really upset and are willing to follow some lifestyle change, be it eating less, eating fewer carbohydrates, exercising more, taking expensive drugs, or whatever. But then, with time, the enthusiasm for major changes begins to pall. Temptations seem greater.

The same is often seen with people who diet simply for weight loss. Each new diet promises that they'll look like movie stars, so they're very compliant at first, but then the cheesecake seems more important than fitting into smaller clothing and gradually they revert to former habits and then try some other diet that has the same unrealistic promises.

So the really important question is: How can we deal with this loss of enthusiasm for a new, healthier lifestyle? I don't think getting text messages from faceless health care people will have a tremendous impact long term, although as a non-texter maybe I'm wrong.

I think we need intensive education with real human beings and contact with other people who have diabetes. We don't need individual instruction; classes should work and also let people meet fellow patients they can keep in touch with. Of course, diabetes classes already exist, but too many people have complained that they were pretty useless and focussed on cutting out fat.

We need to study what kind of diabetes education works best. We need to teach people that it's not enough to "watch your diet." As patients, we have to accept that our diet must change in major ways, and that these changes are not short term but for the rest of our lives. I think accepting that is one of the most difficult aspects of having diabetes. Years ago, when I went on a diet to lose weight, I thought that when I reached my goal weight I could then eat like everyone else. Of course if one has a tendency to gain weight, one can't.

In order for dietary changes to  have a major impact, we must accept that we can no longer revert to eating the huge amounts of food usually served at restaurants, and we can no longer eat a lot of cake and cookies. Even "healthy" fruit makes my blood glucose go too high, although I do eat limited amounts of berries. Yes, it's inconvenient, but so is losing your feet or going blind.

We need to teach people that that for most (there are always exceptions) fingerpricks really don't hurt very much. I always laugh when I read popular press articles about some new treatment that they claim will eliminate "painful insulin injections." Insulin injections are even less painful than fingersticks because you inject into areas that aren't very sensitive. The popular press probably doesn't realize that neuropathy is a lot more painful than insulin injections or fingersticks.

The key is real education. Maybe not in the first weeks or so, when most patients are still in shock, but as soon as possible. With real education, we can live a long time with this disease, maybe even longer than we would have lived had we maintained our old habits.

So the health care system should figure out how to teach patients how to test productively rather than just testing. Productive testing is a lot cheaper than treating complications.

With time, the frequency of testing can decrease as we learn what we can eat and what we should avoid. I've had type 2 for more than 20 years, and I had a continuous glucose monitor for about a year (thanks to a generous friend), so I have a pretty good idea of what works and what doesn't and now do only spot checks to make sure my control hasn't deteriorated. Without all this information I might now have serious complications that would be expensive to treat.

Testing works when done correctly. Let's find out the best way to teach it.