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.

Friday, June 9, 2017

Can Beta Cells Be Restored to Normal Function?

Is type 2 diabetes caused, in part, by beta cells that are dedifferentiated?

I say "in part" because type 2 is a complex disease and many things may contribute a little to its cause. Today more than 80 genes or parts of genes have been associated with type 2 risk. Each one may contribute only a little to that risk, but the additive effect of all those small effects can finally add up to a large effect that precipitates full-blown diabetes.

A recent article suggests that type 2 diabetes results in dedifferentiated beta cells that are like immature cells before they differentiate into their mature insulin-producing form. (You can see the full text of the article here.) Because they are immature, they don't produce insulin, and hence the number of insulin-producing beta cells in the pancreas is reduced and you have difficulty producing enough to keep blood glucose levels from rising, especially with a large carbohydrate load.

Most interesting, however, is that the researchers at the Sahlgrenska Academy in Sweden found that the product of a gene called SOX5 controls this process. When the researchers decreased the activity of SOX5, the cells become less mature and less insulin was produced. Conversely, increasing SOX5 increased the activity of 168 genes and the production of insulin was normalized.

The researchers say that eating "unhealthy foods" and exercising too little can decrease levels of SOX5. Of course different people have different ideas about what foods are healthy, but we probably all agree that a diet of potato chips and soda is not healthy.

The researchers also found that the drug valproic acid, which is used to treat epilepsy and bipolar disease, increases levels of SOX5. It is known that people given valproic acid sometimes develop hyperinsulinemia, but the drug has not been studied as a diabetes treatment. Like all drugs, valproic acid has side effects, sometimes serious, and only more study would determine if the benefits for type 2 diabetes exceed the risks .

This new discovery is not likely to lead to a cure for type 2 diabetes in the near future, but it's encouraging that the defective (dedifferentiated) beta cells can be restored to normal function and can produce normal amounts of insulin again. Wouldn't that be nice.

Friday, May 26, 2017

Genes and Health

One thing that we see a lot on the internet is the person who lost a ton of weight with some diet and saw their blood glucose levels revert to normal. Then they write about their diet and imply that it will work for everyone.

But it won't. We need to find the diet that works for us.

I remember long ago, when I thought I was fat because I weighed 110 pounds (I'm small, and in college I weighed between 100 and 105), so I went on the Weight Watchers diet, which at that time was low-carb. A Hungarian colleague who saw that I was dieting said to me, "I hate to tell you this, but you don't have to diet to lose weight." I asked what you had to do. "Just give up sour cream," she said. I told her I didn't eat sour cream. She was aghast, as she put sour cream on almost everything she ate.

But that's typical of the "It works for me, so it must work for you" attitude. But we can have different genes that affect how we react to different diets.

Here is an article about a population in a remote part of Greece who eat a very high animal fat diet but have low levels of triglycerides and LDL. Now, low-carb diets reduce triglyceride levels, but they don't usually reduce LDL and sometimes make it go up. And as this wasn't a diet study, they didn't describe the participants' diets, but most Greeks don't follow low-carb diets.

So people from this area of Greece could tell others that their diet (whatever it is) reduced LDL so it should work for everyone. But it's apparently their genes, not their diet, that is important. Anyone who wishes to read the full text of the article can see it here.

Another recent article, this one in the New York Times, describes a similar situation, but in an American woman: very low levels of LDL and triglycerides. Both the woman and some of her siblings were found to have a rare gene that caused a lack of plaque in their arteries. One sibling with the gene had been a heavy smoker and had high blood pressure and type 2 diabetes but still lacked plaque in his arteries.

Again, it was no particular lifestyle that resulted in low levels of some lipids. It was their genes.

So if some diet or some exercise program or some drug makes your blood glucose return to normal, of course that's wonderful. But before proselytizing on the internet, remember that our genes may affect how we respond to any regimen. By all means, let people know the wonderful results that you got. But don't expect the same regimen to work for everyone.

Nutrition Label Errors

Nutrition labels are good for knowing how much carbohydrate is in the processed food you eat, if you eat any. Unfortunately whole foods don't come with nutritional labels.

But I've always considered the labels as approximations rather than exact numbers. They'll tell you, for example, that there's more protein than fat or whatever in some food, but they won't really tell you the exact amounts.

There are several reasons for this. First, they round the numbers off. So 3.49 grams would be listed as 3 grams and 3.5 grams would be listed as 4.

Second, they don't have to include anything with less than 5 calories or 0.5 grams. And this pertains to the serving size. So if you ate 4 servings, you could have a lot more of something than you thought.

Third, the manufacturers don't analyze every package they sell. One estimate was $750 per analysis in 1997, a lot for a loaf of bread, although they can also us nutritional tables to estimate the totals.

Finally, the nutritional content of the ingredients used to make the product can change from batch to batch and the manufacturer can't control that.

So overall, the labels are useful but not exact.

I recently came across a label that was just plain wrong. It was a sausage product and listed the ingredients as pork, water, wheat rusk, and salt and spices. So pork was the first ingredient (manufacturers are required to list ingredients according to amounts) but the label said it had no protein, as well as no carbohydrate. Huh? Pork is mostly protein and fat and rusk is mostly carbohydrate.

I telephoned the company and asked if maybe they just used pork fat and was told yes. Then I went back to the label and saw that it said one link had 150 calories, of which 50 calories were from fat. So what were the other 100 calories from. The water?

I called the company back, and now they admitted that the label was wrong. The sausage contained 4 g of carbohydrate and 19 g of protein. That totaled 146 calories, or 150 rounded up.

But what if someone used the carbohydrate and protein content to calculate bolus insulin. The calculated insulin would be incorrect, and they'd go higher than expected.

So that's yet-another reason it's so difficult for people who inject bolus insulin to keep their blood glucose levels level. I wonder how many other labels contain similar errors.

What this means is if you see a label that seems odd, don't assume it's correct. First check the numbers. Multiply grams of carbohydrate and protein by 4 and grams of fat by 9 to get calories. If they don't add up, call the company to find out. In someone without diabetes, thinking you were eating a little less carbohydrate and protein would not cause much harm. But when you're injecting bolus insulin, it could.

And because of rounding off, always take labels with a grain of salt.

Furthermore, remember that you can't always believe what someone who answers the telephone tells you. They could know about the issue, or they might not. In a large company, it sometimes pays to call twice to see if two different people have the same response.

Good control requires constant vigilance, but it's worth it in the long run.

Friday, May 12, 2017

Honoring David Mendosa

Diabetes writer David Mendosa died on May 8, only about a month after he was diagnosed with angiosarcoma in the liver. The diabetes community is mourning, with tributes at all the major diabetes sites in the United States and Europe as well as personal blogs.

David didn't want any kind of services. I was thinking of a fitting memorial for him, and I thought of this. He told me that he hoped his legacy would be his promotion of low-carbohydrate diets. He had been following one since 2007, with excellent results.

So one way to honor David would be to follow a low-carb diet for a month, or a couple of weeks, or just a week, if you haven't already been doing so. If you're already on a low-carb diet, you could make sure you're strict with the diet for a period of time to honor David. Let's face it, most of us do fall off the wagon from time to time.

Then, if you find the low-carb diet works for you, if you have better blood glucose levels and you discover that a low-carb diet doesn't mean deprivation, tell your diabetic friends. Ask them to tell their friends. Wouldn't it be wonderful if we could see an explosion in the number of diabetic people following low-carb diets in honor of David Mendosa?

A couple of caveats: if  you go suddenly from a high-carb to a low-carb diet, a period of adaptation is needed as your body builds up the enzymes needed to metabolize fat, and some people lack energy for a week or two. It's called the low-carb flu. If that happens to you, don't despair. It's temporary. Also, low-carb diets act like diuretics, so make sure you eat enough salt to retain some water.

Of course not everyone may be able to honor David in this way. For those who would prefer some other kind of donation, Caring Bridge, on which David, and then his friends and relatives, posted about his final journey is accepting donations in his memory, as is Tru Hospice Care Center, the hospice where he spent his final days.

Wednesday, May 3, 2017

David Mendosa

Many have heard already, but for those who haven't, David Mendosa, diabetes journalist, blogger, hiker, photographer, and so much more, has incurable cancer, angioscarcoma in the liver. He has recently been moved to a respite place with 24-hour care but may be able to return to his apartment if he can gain back some strength.

David wrote a chapter on Searching the Internet for my book, and it was a needed addition, as it wasn't something I had a lot of expertise with. David has been using computers since the early days and has a lot more experience with them than I do.

He was also one of the first people to have a diabetes webpage on the internet, and it has grown into a gigantic site. A friend will continue to maintain that.

He also has a blog describing various hikes, illustrated with photographs of birds and other wildlife. Many of his wildlife photos can also be found here.

David is a Buddhist and is very accepting of his situation. He has medication to control his pain. Some of his many friends in Boulder, and a niece, are supervising his care. He has become too weak to type, and telephone calls tire him out, but any who wish can follow his final journey on Caring Bridge. He has already received thousands of messages of thanks and love from all over the world.

David has said that he hopes his legacy will be his promotion of low-carb diets for people with diabetes. Even at the end, he is thinking of the well-being of fellow patients with diabetes.

Thursday, March 30, 2017

Can a Drug Reverse Insulin Resistance?

A new drug seems to reverse insulin resistance in fat mice, who have normal blood glucose (BG) levels when taking the drug. Of course, we've all seen mice cured of diabetes kazillion times, but I find the approach in this case interesting.

To understand what the drug does, you have to understand a little about what causes insulin resistance, which I'll try to outline. When insulin binds to the insulin receptors on target cells, for example muscle cells, the insulin receptor phosphorylates itself. This means it adds phosphate groups. As a result, a complex chain of reactions is triggered, culminating with glucose transporters called GLUT-4 moving to the cell membrane. This allows glucose to get into the cell.

In general in the body, when something triggers a reaction, something else then slows down or stops the reaction so it won't get out of hand. For example, if you eat carbohydrate, which stimulates insulin secretion, BG falls, and that stimulates glucagon secretion, which keeps the BG from falling too low. If you get an infection, you produce chemicals that cause inflammation. But then if things are working properly, you produce chemicals that stop the inflammation when its job is done.

In the case of the insulin receptor, another enzyme called a phosphatase removes the phosphate groups that the insulin receptor added, and this slows the action down. So it made sense to look for compounds that would inhibit the phosphatase so that a little insulin would have a longer effect.

In the last half of the 20th century, scientists were investigating the effect of vanadium compounds on people with diabetes, as there were reports that it lowered BG levels. The vanadium seemed to inhibit a phosphatase. Unfortunately, because phosphatases are involved with many systems in the body and the vanadium wasn't specific to the insulin receptor, giving people enough of the vanadium compounds to be effective caused too many side effects, and interest waned.

There are many different phosphatases in the body, and what is new about this recent study is that they targeted on specific phosphatase, called LMPTP for low molecular weight protein tyrosine phosphatase. Then they looked for a small molecule that would inhibit LMPTP, and they found one. Giving this drug to the mice, they found no side effects.

One interesting thing is that blocking LMPTP only in the liver, via genetic studies, improved BG control. When one has type 2 diabetes, the liver seems to be insensitive to insulin. When BG levels are low, the liver produces glucose. When BG levels go up, insulin is supposed to stop the liver from producing glucose. But that doesn't happen in type 2. So a drug that could make the liver more sensitive to insulin sounds promising.

In fact, as I noted here, insulin resistance might be protective for the heart. So increasing insulin sensitivity in the liver while retaining it in heart muscle might be just what we need.

Science magazines have been describing this research as if the cure for type 2 diabetes has been found. Far from it.

Reversing insulin resistance might "cure" diabetes in people whose primary defect was insulin resistance, as is often the case in obese people. The studies were done in diet-induced obese mice. But it takes at least two defects to produce type 2 diabetes: insulin resistance and a defect in beta cells that makes them unable to produce the extra insulin needed to overcome that insulin resistance. In people with very little insulin production left, even reducing the insulin resistance might not be enough.

Also, as noted before, these studies are in mice, and often mouse studies don't translate into human treatments. Taking a drug from "proof of concept" to a safe drug for humans is a long process.

Nevertheless, I think this approach is interesting enough to be aware of. Perhaps it will develop into something very useful for type 2.