Wednesday, February 22, 2017

Nutritional Information

I was at a local coop recently and saw a new brand of tortillas. They had only a few ingredients, mostly corn, so I looked at the nutritional information. It said they had only 1 gram of carbohydrate.

At first I was ecstatic. True, the tortillas were small, but if there was only 1 g of carbohydrate, it would be wonderful. Then I looked at the fiber content. It was 2 g. Huh? Fiber is indigestible carbohydrate, so how can you have more fiber than carbs?

If the product is made in Europe, this is possible. This is because the European system lists only digestible carbs as carbohydrate, so to get what we consider total carbs, you add the carbs to the fiber. In the American system, carbohydrate means total carbs, and to get digestible carbs you subtract the fiber.

This dual system can cause problems. The GG brand crispbread used to promote their product as having zero carbs because it was made in Europe and when you subtracted the listed fiber content from the listed carb content, you got zero. After many people complained, they fixed their label.

But these tortillas were made locally. That couldn't be the answer.

Back to the coop. I found someone in charge and asked about the label. I said regular tortillas that are about twice the size of the new ones have about 20 grams of carb, so I suspected this label was a typo and it should be 10. They went into the back room and stayed there for ages and then came out and gave some kind of an answer that made no sense, so I didn't buy the tortillas. When I got home, I emailed the company.

They replied that there was an error on the label, and the total carbs should be 11, not 1. They said they'd correct it, but the next week I found the same misinformation and no sign by the coop warning people that the label was wrong. In the meantime, were people on insulin injecting the wrong amount of insulin on the basis of incorrect information?

The tortillas I usually buy contain a mixture of grains and seeds, gluten (a protein), soy flour, and cornstarch. I get them because I think they have the best taste. The package used to claim 11 grams of carb and 6 grams of fiber, for 5 grams of digestible, or net, carbs. When I eat them (which isn't often), I eat only a half, which would be about 2.5 grams of net carbs. I can deal with that.

But when I recently bought a package, I noticed that they're now advertising 8 grams of net carbs, 12 grams of carbs and 5 grams of fiber. Of course 12 minus 5 is 7, not 8, but the difference probably has to do with rounding. So if I eat half of a tortilla, I'd be getting 4 grams of net carbs. Still not enough to send me into the stratosphere, but definitely higher.

When I scrutinize the label with a magnifying glass, I see that the order of the ingredients has been changed.  Have they changed their recipe? Or do they periodically test the product with slightly differing results each time? Or were the results falsified?

After the Dreamfields, and Julian Bakery scandals, one has to be cautious. When we find a product we like and buy it regularly, most of us don't scrutinize the label every time. But it's probably a good idea to double-check from time to time.

I've tested the tortillas I usually buy (Joseph's), and in small amounts they seem to be OK for me. That doesn't mean they'd work for you. We are fortunate in having meters to do tests of new foods. I tend to be lazy, and once I've tested something I don't keep retesting. This label snafu has reminded me that perhaps I should.




Thursday, December 22, 2016

On Science Research

Some people wonder why we haven't come up with a cure for type 2 diabetes yet. The paranoid among us often suggest that Big Pharma knows of a cure but is keeping it secret because type 2 diabetes is so profitable for them.

I acknowledge the flaws of Big Pharma, including huge salaries for those at the top and huge increases in the prices of life-saving drugs so that many people can't afford them. But I don't think there's a big conspiracy hiding a cure.

The fact is that the biochemistry underlying type 2 diabetes is complex, and adding to the complexity is individual variation.

For example, look at this figure printed in Nature. It's from a paper on mechanisms controlling insulin secretion. The figure shows the various pathways leading to or modifying to rate of insulin secretion. Each step had to be discovered through experimentation, often complex with the potential to give false results if something wasn't done correctly, or if some assumption proved later not to be true. If one group produced results that weren't accurate, those following up on that work would be basing their analyses on false results from the first group, so their analysis might be wrong too.

The New Yorker recently ran an interesting story about some stem cell research that was later questioned, and withdrawn, resulting in the suicide of the leader of the lab in which the research was done. He may have been innocent but couldn't deal with the stress of being associated with questionable research. The article illustrates how full of pitfalls this complex research can be.

Now look at the figure again and imagine different patients with defects in different parts of the scheme.

Seems almost impossible to understand in full, doesn't it.

But nothing is impossible. Eventually we'll sort it all out. We'll do genetic studies on all patients to find out where their metabolism is faulty and hence what sort of treatment would be the best. This won't happen next week. Maybe not in this century. But it will happen if we don't wipe out life on Earth before we get a chance to cure type 2.

In the meantime, our best approach is not to accept a one-size-fits-all approach to controlling diabetes but to find what works for us, including careful attention to diet, experimenting to find out which diet works best for each of us so our need for drugs is minimal. Then we need to work with our doctors to figure out which drug is best for us. Being active also helps. I think low-carb diets are best for most people and should be where they start on diagnosis. But some patients may have better success with other approaches. The important thing is to find out what works for you. You might have a defect that is slightly different from another person's and so you might need treatment that is slightly different.

For example, a recent study showed that some patients with glioblastoma (a brain tumor) benefit from a treatment that was shown in clinical trials not to work. That's because results of clinical trials are reported as averages. Some treatment may harm some patients, help some patients, and have no effect on some patients. If the harm canceled out the benefit, then the researchers would say the treatment was ineffective. But if you were in the small group that was helped, it would be worthwhile for  you.

 Until we know everything, which is unlikely ever to happen, I think we should support, at least emotionally, the efforts of the scientists who are trying to puzzle this all out. It's true that many are more concerned with their own careers than they are with helping patients, but the world isn't perfect. And I don't think it helps to rant that all doctors are money-grubbing opportunists, all drug companies are hiding cures so they can sell us expensive drugs, and all researchers are just trying to justify their next big research grant so they can fly to conferences at scenic beach resorts.

These accusations do apply to some people.  And I think we sometimes do need to rant, especially when we've just been diagnosed and have been given bad advice, or no advice at all, by the medical people we trusted to take care of our health. Or if we're shamed by medical people who think excess weight is our fault and is easy to lose. The internet gives us a chance to share our rants with other people who can understand where we're coming from.

But the internet also gives us a chance to share our successes and the results of any N = 1 experiments we've done. For example, an engineer has done some fascinating experiments correlating his fat intake with his lipid results from standard tests. The results are not what you'd expect, and maybe they'll lead to research in formal clinical studies with lots of people. Once we've gone beyond the ranting stage, the internet gives us a chance to contribute to the knowledge base that will eventually help others control this disease.

In the meantime, we need to understand that biochemical and biomedical research is complex and open to error, but headline writers want simplistic conclusions, like "Eating Food X Prevents Diabetes," when in fact some study showed that eating Food X was associated with a tiny reduction in diabetes rates in a specific population.

So hang in there. Keep testing. Keep an open mind. Be sceptical of popular press articles about diabetes. Don't expect perfection, but control as well as you can.

And enjoy the holiday season, which involves more than just food: the music, the companionship, the beautiful lights. The days are getting longer. Soon it will be spring (well, first we have to survive February, but at least it's short). Maybe this year someone will make a type 2 diabetes breakthrough. We can always hope.


Wednesday, November 30, 2016

Restoring Insulin Secretion

Can nonfunctioning beta cells be rejuvenated? Researchers from Florida State University think they can.

In a paper published in PLOS Computational Biology, the researchers, led by Richard Bertram, postulate that it's oscillating pulses of glucose that cause the oscillating pulses of insulin that are seen in healthy people. In nondiabetics, insulin isn't secreted continuously but in pulses, and it's been known for some time that this pulsatile insulin release is lost in people with type 2 diabetes. But no one knew why.

These researchers used sophisticated technology and mathematical modeling to come up with a new model, a Dual Oscillator Model (this type of model has been used in other research, for example, in understanding circadian rhythms here and here). They first put beta cells from mice in a high-glucose environment and found that they lost the pulsatile insulin secretion. Then by using their techniques to manipulate the glucose levels in ways suggested by the mathematical modeling, they were able to resuscitate the beta cells so that they produced insulin again in a healthy pulsatile way.

This technique is nowhere near the stage at which it could be used clinically to cure type 2 diabetes. But it's exciting because it suggests that a type 2 cure is possible, at least in those with viable beta cells. Those cells apparently aren't dead; they're just not functioning properly.

The authors' model is described in detail in their paper, the full text of which is free online. It's fairly dense and mathematical. They found that in response to glucose, some beta cells produce electrically driven fast oscillations in calcium levels, and other produce metabolically driven slow oscillations. They suggest that these two types of cells cooperate to produce pulsatile insulin secretion.

Clearly, creating conditions in vivo that would replicate the results found in their "microfluidic device" would not be simple. But the more we understand about how beta cells operate, the better. And their finding that continuously high glucose levels caused the beta cells to lose their oscillating insulin pulses is another indication that the standard Western lifestyle with too many calories as well as too many carbohydrate foods is not a good idea. Many close relatives of people with type 2 diabetes lack oscillating insulin pulses, suggesting a high risk of progressing to full-blown diabetes.

Maybe this new way of looking things will help us to find at-risk people in the very early stages, when their condition can be truly reversed.

Monday, November 28, 2016

Adolescent weight gain

An interesting study has shown that resting energy expenditure in adolescents is lower than in older or younger people. This means that they'll burn fewer calories when resting, leaving more available for growth and weight gain.

I found this fascinating because I was a normal-weight child but became "chubby" at about 11 or 12 and then lost weight with no change in lifestyle when I was about 16. Other family members showed the same pattern.

I'm always interested in why something happens, and in this case the authors hypothesize that because growth requires a lot of energy, the body tackles the problem of rapid growth in adolescence by making adolescents be more energy efficient, so they get more calories from the same amount of food.  In a society in which food was scarce, this would be the only way those rapidly growing bodies could get enough calories to build the new tissues they needed.

When growth is complete, the body stops being so efficient with its digestion as the extra calories are no longer needed, and the metabolism increases again. 

However, in our world, where food is usually easily available, turning down the metabolism during adolescence may lead to obesity that doesn't reverse when growth is complete.

This pattern of decreased metabolism only during adolescence is obviously not universal. Some people were chubby children and others don't slim down in their late teens when growth is complete.

However, it's an example of the fact that weight gain and loss are not always a result of voluntary food choices. Sometimes Mother Nature is nudging us in one direction or the other.

Wednesday, November 9, 2016

Trump and Diabetes

One of Donald Trump's goals as President is to repeal the Affordable Care Act, often referred to as "Obamacare."

I can understand why many are upset about the fact that it's expensive. Good health care is expensive, and Medicare isn't free either.

But one of the mandates in Obamacare is that insurers can't penalize people for having preexisting conditions. Before that, it was almost impossible for people without health insurance who had already been diagnosed with diabetes to get any health insurance at all.

If Obamacare is repealed, does this mean millions of people with diabetes will suddenly find themselves with no insurance and no possibility of getting replacement insurance?

It's a scary thought.


Wednesday, October 5, 2016

Quantum Leap in Diabetes Treatment


 I recently attended a talk on diabetes at Harvard, led by Doug Melton of the Harvard Stem Cell Institute. It was inspiring because they were talking about a cure, not just about some new drug or some new type of pump.

Melton has two children with type 1 diabetes, and after the talk, when I went up to thank him for his work, he said he's really driven to find a cure because of his kids.

The talk was titled A Quantum Leap in Diabetes Treatment, and Melton described how they can now take induced pluripotent stem cells (iPSCs) and transform them into beta cells. They use iPSCs instead of regular stem cells isolated from aborted embryos because President Bush restricted funding for stem cell research in 2001. One speaker said that move set back the research by about 10 years.

However, in the long run it turns out that using iPSCs instead of cells from aborted embryos has the advantage that you can use cells from your own body, which would be less likely to be destroyed by your immune system, although autoimunity can destroy your own tissues.

Melton said it's taken about 10 years to work out how to make beta cells from the iPSCs. First you have to tell the cells to differentiate into gut cells. Then into pancreatic cells. Then into hormone-producing pancreas cells. Then into beta cells. Each step in the process requires different chemicals, some small molecules and some proteins. Complex thought it is, they can now quickly make a lot of functioning beta cells in a test tube. Well, actually in flasks.

You can see the process here. Semma Therapeutics, which this links to, is named for Melton's two children Sam and Emma.

One thing emphasized at the talk was that this type of research requires cooperation among different specialists. Melton and his lab do the basic research, but they're not physicians and require the help of transplant surgeons like Sayeed Malek, of Harvard Medical School and Brigham & Women's Hospital. They also need engineers to scale up production of beta cells and pharmaceutical companies to produce large amounts of the substances used to transform the stem cells. They said that only in the Boston area can one find so many different specialists, so the cure is likely to be found there.

The first patients to get the new beta cells will be those who have had a pancreatectomy and who have very labile diabetes as a result, they said. This is because such people lack the autoimmune attack that is part of type 1 diabetes, so they can investigate one half of the puzzle without the other. This will be done next year, with only 10 patients.

The next step will involve patients who are already taking immune-suppression drugs, for example those who have had a kidney transplant.

Finally, patients with type 1 will get the cells, and eventually even those with type 2 whose beta cells can't produce enough insulin to overcome their insulin resistance. Clearly the cure will take time, but Melton said he's really optimistic about it.

Others who spoke and answered questions were Gordon Weir of the Joslin Diabetes Center, who was a teacher and mentor of Melton, Robert Millman of Semma Therapeutics, and Peter Amenta of the Joslin Diabetes Center.

Weir said this field is really accelerating. They're starting trials for spinal transplants and retinitis pigmentosa.

Someone said that cancer cells resist immune attack, and they're trying to find out how they do it, so this could be used with autoimmune diseases.

They're also trying to find a universal donor cell that would lack the triggers for autoimmune attack.

They said it will cost $1 million per patient to do the stem cell implants, so until they reduce the cost, they're probably not going to implant many patients.  However, they also noted that T1 is also very expensive, and will get even more so, and if you spent $1 million on a 6-year-old, you might recoup the cost through the kid's lifetime.

They noted that beta cells replicate very slowly, like brain cells. So each beta cell normally divides only 5 or 10 times in a lifetime, or 1/10,000 cells dividing per day. So just eliminating the autoimmune attack without beefing up the replication wouldn't help.
 
Again, I found it inspiring to hear people who know what they're talking about instead of the opinionated views one hears on the internet and the paranoid idea that big pharma will never contribute to a cure because producing the relevant drugs is so profitable. These people really want to find a cure.

I want that too.



Tuesday, August 16, 2016

Diet and Cholesterol

Most of us with type 2 diabetes also have problems with lipid levels, both cholesterol and triglycerides. So the following blogposts about diet and lipid levels, written by a nondiabetic/prediabetic software engineer, are relevant to us.

Because the author, Dave Feldman, is a software engineer,  his blog is a bit geeky (understatement of the year), and it will probably tell some of you more about diet and cholesterol than you wanted to know. But he's done an incredible number of N=1 experiments on himself, and the results are fascinating.

He's on a low-carb diet, and in a nutshell, he's shown that at least in his case:

1. Cholesterol levels change quickly, in about 3 days, not very slowly as most people will tell you.
2. Counterintuitively, the more fat he eats, the lower his total cholesterol levels go. Also lower triglycerides, LDL cholesterol, and LDL particle number, which some people think is a better marker of cardiovascular risk than LDL cholesterol. HDL levels increase.
3. It's his diet in the 3 days preceding the test that affect the cholesterol levels. Diet on other days doesn't seem to matter.

Note that some people argue that cholesterol levels don't matter. Whether they do or don't, it's interesting to see how quickly they change with the fat content of the diet, which suggests that unless you eat the same thing every day, the lipid values you get with standard testing don't mean a lot.

After testing himself rigorously, Feldman also tested his sister. He says he's a "hyper-responder" to a low-carb ketogenic diet, meaning that when he went low-carb, his cholesterol levels skyrocketed. Although most people see cholesterol levels fall when they go low-carb, Atkins Diet author Robert Atkins had noted that in about 25% of people, cholesterol levels do go up on such a diet.

Feldman's sister, also on a low-carb ketogenic diet, is not a hyper-responder, and he wanted to see if she'd react the same way he did, so they both ate the exact same food at the exact same time of day for a few days. It turned out that although her cholesterol levels were lower, they followed the same pattern: more fat in the three days preceding the test resulted in lower cholesterol levels.

If you want the details, you can find them here:

Part I
Part II
Part III
Part IV
Part V
with more undoubtedly to come.

Feldman says he's planning to write something for the nonengineer. 

In the meantime, this suggests that if you're concerned about cholesterol levels that have changed from your last test, it might be worthwhile to see what you were eating in the three days before each of the tests, to see if that could have been a factor.