Sunday, January 23, 2022

Modifying the Gut through Diet

 Our gut is apparently modified by what we eat. This makes a lot of sense. If we usually eat a lot of some food and the body ramps up the enzymes that digest that food, then we should get more energy from that food, and until relatively recently, getting as much energy from our food as posible was the body's goal. It's only in the recent past that most of us have too much food available so that obesity and not starvation is the problem.

Here is a study showing that if you eat a lot of food, your gut expands so you can digest more food. It had previously been shown that cold does the same, which makes sense because you need to burn more calories to stay warm when it's cold. The interesting thing is that this process seems to be reversible, meaning that if you limit your food intake for a bit, your gut may change its structure again (reducing the number of absorptive villi and hence surface area) so that it absorbs fewer calories.

Interestingly, fructose seems to do the same thing, increasing the villus length: "the increase in villus length was associated with increased nutrient absorption, weight gain and fat accumulation in the animals" wrote the authors of this study. They note that this makes sense evolutionarily because fruit, which contains a lot of fructose ("fruit sugar"), is most available in the fall, when animals want to fatten up so they can survive the lean times of winter.

Eating a peach is not likely to fatten you up, but overeating fructose by drinking a lot of high-fructose corn syrup--sweetened sodas could.

The abstract of the paper can be found here. Note that the authors suggest that fructose also promotes tumor growth.

Of course, if you have diabetes, any sugars like glucose, sucrose, or fructose are not a great idea.

Tuesday, January 4, 2022

New Hormone Complex Affecting Diabetes

Sometimes it seems as if a new factor that affects diabetes is announced every week. The latest one is called fabkin, which sounds to me like a detergent or a new diet craze. And fabkin is not one factor but a complex of of several. The name comes from fatty-acid-binding protein 4 (FABP4), which forms a functional hormone complex with two kinases, adenosine kinase (ADK) and nucleoside diphosphate kinase (NDPK) to regulate extracellular ATP and ADP levels.

It's postulated that fabkin affects beta cells, blunting their effects. The interesting thing is that using antibodies to neutralize fabkin improves beta cell function in both type 2 and type 1 diabetes. In fact, it has been suggested that neutralizing fabkin could "spell the end of diabetes."

This is an exaggeration, although of course anything is possible. A lot more research needs to be done before fabkin wipes out diabetes.

But it's another factor to keep an eye on.



Sunday, January 2, 2022

The Demise of NuSI

 I don't know how many people have been following this, but NuSI (the Nutrition Science Initiative) was founded in 2011 with the goal of improving the quality of nutrition research, which would allow clarification of which diet was best for weight loss.

Gary Taubes, author of Good Calories and Bad Calories as well as many articles in various media supporting low-carb diets for weight loss, and Peter Attia, a physician interested in longevity, were the founders, and thanks to the John Arnold Foundation, they were able to throw a lot of money at studying the issue. They completed a few studies, but the results were not earth shaking.

 Unfortunately, like so much these days, the organization soon became embroiled in controversy and science politics, and Taubes has just announced its dissolution. 

This won't have much effect on most of us patients. What we want to do is find an eating plan that controls our blood glucose levels and lets us lose weight if we need to, or maintain our weight if we don't need to lose. Diet politics is of less importance to us.

If I were a physician prescribing diets to patients, I'd want to know the results of big controlled trials on many people, so I could first prescribe a diet with the greatest chance of succeeding and then if that didn't work, prescribe something else. But I'm not. So although it's too bad, the demise of NuSI doesn't have much effect on people like me. 

The success of any diet depends on many factors. No diet works well if the subject doesn't follow it, and different people have different tastes. A diet of 100% sea slugs might work 100% of the time, but how many people would be willing to eat nothing but sea slugs? A more reasonable diet might work most of the time if people adhered to it, but even then adherence would vary.

So although the demise of NuSI is sad, it won't have a huge effect on most of us patients. We'll just keep plugging away with the knowledge we have now.



Monday, November 29, 2021

New Drug Treatment

 I haven't seen a lot of new treatments for type 2 diabetes lately. Most research seems to concern refining current approaches, but here is a study about a drug, phenylbutyrate, commonly prescribed for urea cycle problems, that seems to help in type 2 diabetes.

I confess I'd never heard of phenylbutyrate, as I haven't had urea cycle problems, but the drug helps to remove urea from the blood. It also seems to improve insulin sensitivity and the oxidation of glucose. No adverse effects were found in the cited study, but the study was short term.

The idea that phenylbutyrate affects glucose metabolism is not new. For example, this 2011 study suggests that it helps reduce lipid-induced insulin resistance and improves beta cell function.

Phenylbutyrate works by breaking down branched-chain amino acids, which are amino acids that instead of having straight chains, have branched chains. They are leucine, isoleucine, and valine. How this affects glucose metabolism is not clear.

In other words, phenylbutyrate may help with glucose metabolism in type 2 diabetes, but it's not a miracle cure. Nevertheless, if you know it might be helpful, you can be alert to other news about this prescription drug.

Type 2 diabetes is such a complex disease, with genetics, lifestyle, and current food growing and processing all having effects. We will eventually figure it all out if we don't destroy the planet first. But it's going to take a long time.

Saturday, November 27, 2021

YMMV Again

 Another article highlighting the fact that we're not simple machines, that what works for one person may not work for another, has hit the popular press.

 This time it's not diet but exercise they're speaking of. Some people, despite sticking closely to an exercise program, see no improvement in their fitness. They're called nonresponders.

 Unfortunately, most health care providers don't have the time to investigate your lifestyle closely, so if you are supposed to go on an exercise program but fail to improve your fitness, they probably think you're "cheating," and not exercising as much as you're supposed to. In some cases, that's probably true, but in others not. I wish I'd be prescribed a napping program, which I'm sure I'd follow religiously, but that has yet to happen.

 The results described in the cited article at first sound depressing. Who wants to lift weights for an hour if it doesn't do anything beneficial. But then, if you read the whole thing, you see that when one type of exercise doesn't work for a person, another type will. "No one had failed to respond at all. Every man and woman had measurably improved his or her fitness in some way after one of the sessions, if not the other."

So the secret is to try different types of exercise to see which seems to work best for you, and also to see which types you enjoy enough to keep doing. I hate running, because I have the wrong build for that, but I enjoy walking, and I don't mind lifting weights. So I never plan to run.

One problem with various studies is that their conclusions are usually based on the average results. A group does X and 90% of them improve factor Y. The headlines will all say something like "X improves Y," but you might be in the 10% who don't improve. Keep that in mind if you try it.

The chances are good that you will improve factor Y, so it's certainly worth trying. But if it doesn't improve, don't despair. Try something else.


Sunday, November 7, 2021

Obesity as a Disease

 Many people think of obesity as a moral failing. They think that obese people simply have no self-control, and if they did they would be slim.

But that doesn't explain why you can have two people who eat exactly the same things and one is skinny and one is fat. I once read of a mother who had two daughters, one fat and one thin. She told her doctor that one daughter loved vegetables and the other one loved doughnuts and pizza. The veggie lover was the one with the weight problem.

Many of us already know that obesity isn't a moral failing, but sadly some health care practioners do not, and blaming their patients for their weight problems can cause even more harm. Luckily, they do not all think this way. Here is a practitioner, Dr. Lee M Kaplan, who told healthcare professionals at a recent virtual meeting that obesity isn't a moral failing but a disease caused by dysfunction of the metabolic system that regulates body fat, in the same way that immune dysregulation can lead to asthma.

Now, if you're thinking of mildly overweight, for example the "freshman 10" or "freshman 15," the amount of weight that some college freshmen are said put on in their first year, that's not apt to be a disease but stress or a more fattening diet than they had at home. If it were a disease, they would have arrived fat.

We're talking about real obesity, a BMI (body mass index) of 30 or more, the kind that really doesn't want to leave no matter how much the person diets. Or if they starve themselves into losing, the weight just returns with time.

No one really understands what causes this metabolic dysfunction. When the hormone leptin was discovered in 1994, some people thought the problem was solved. But it wasn't. Obesity, like type 2 diabetes, is undoubtedly multifactorial, and because of this, different people have different reasons for the problem and different responses to treatment.

A few people who lack leptin can transform from obese ravenously hungry constant eaters to slim normal eaters when given leptin. But those cases aren't common. Most of us will have to find a way of eating that lets us slowly lose the excess weight or resort to weight-loss surgery.

There is no one perfect weight-loss diet. If you're diabetic, I think the best place to start is with a low-carb diet, as this controls blood sugar levels as well as weight. Then you can tinker with the diet to get something you enjoy and you can follow for years. 

On your journey it's important to realize that your obesity is not your fault. You have a disease. Try to find a health care team that understands this and is willing to work with you to find the best treatment for your particular physiology.

It is good that Dr. Kaplan is trying to educate health care professionals. Let's hope that in the future we will all be educated about the complex factors controlling weight.

Friday, October 22, 2021

Too Many Carbohydrates

 Most of us with type 2 diabetes don't stuff ourselves with huge plates of spaghetti, but some nondiabetics and even some people with diabetes do, sometimes because they're still brainwashed by the low-fat diet fad of the 1990s. And when you limit fat, you eat more of other things, especially carbohydrates, which are both cheap and filling, at least for a short time.

 When I was diagnosed with type 2 in 1996, I started off following the ADA-recommended low-fat diet. I did lose weight on this diet, which limited calories as well as fat, but I was ravenously hungry 24 hours a day. I finally decided I didn't want to live if I was hungry all the time, so I switched to a low-carb diet, even though the traditional dieticians said the diet would kill me. My hunger immediately went away. The weight loss also slowed down.

The dieticians also said no one could stick with this diet long term. I don't know if 25 years qualifies as long term, but so far the diet hasn't killed me.

Some people continue to criticize low-carb diets, but a recent study showed the dangers of high consumption of carbohydrates. They found that high consumption of carbohydrates reduces the level of antioxidants in the body, especially in those who are overweight. The study was done in nondiabetics.

Here is the journal article. You can download a 52-page full text if you like.

Now, there are populations that have always had high-carb diets, like the Kitavans, who eat lots of yams, not lots of croissants, and they're pretty healthy. Have their bodies adapted to their diet to produce more antioxidants? No one has studied this, but the body is often able to adapt to dietary changes.

Also notice that the article refers to overconsuming carbohydrates, not just having the occasional piece of bread. So the research probably doesn't have much practical application for now. But it's interesting. And it's another small piece of evidence showing the advantages of low-carb diets, which are demonized by some.