Wildly Fluctuating by Gretchen Becker
13 November 2019A diabetes blog with wildly fluctuating topics ranging from humor to serious stuff to miscellaneous musings on the diabetes news of the week by a type 2 diabetes patient/expert and author of The First Year: Type 2 Diabetes
I've had type 2 diabetes for 23 years now. When I was diagnosed, the only treatments available were sulfonylureas, metformin (which had only been approved here the year before), or insulin. And the cutoff for a diagnosis of diabetes was a fasting blood glucose (BG) level of 140 mg/dL.
Since then, myriad drugs have come on the market, including the glitazones, glutides, gliptins, gliflozins, and meglitinides. A real tongue-twister.
Examples of these newer drugs are Actos (glitazone, or thiazolidinedione); Victoza (glutide; GLP-1 agonist); Januvia (gliptin; DPP-4 inhibitor), Invokana; (gliflozin; SGLT-2 inhibitor), and Starlix (meglitinide; long-acting sulfonylurea). Some of them are available as combinations with other diabetes drugs. Some are injectable and others are pills. Some last a week and others just a day or less.
You can find a more complete list here.
Some of these drugs can cause weight gain and others can contribute to weight loss. Some are supposed to protect the heart and some seem to increase rates of heart disease. Some increase rates of pancreatitis. Other side effects include nausea, urinary tract infections, ketoacidosis, and even lower-limb amputation.
Clearly, deciding which medications are best for you depends on many factors, and different physicians have different preferences. However, today most agree that metformin is the best drug to start with unless you can't tolerate it because of GI side effects.
But despite all the new drugs, one treatment remains the same as when I was diagnosed: diet and exercise. At first, this treatment is the most difficult of all.
We'd all like to be able to take a pill and continue eating what we've always eaten, including, in almost all cases, more food than our body needs. This is not entirely our fault. Portions at restaurants are often huge, and tempting treats are offered everywhere. We've usually been raised to clean our plates and not waste food. But if we want to be healthy, we need a major brain reshuffle to reject old ideas and acquire new ones.
What works for me is a low-carb diet, and I think that's the best one to start with. If for some reason, it doesn't work for you, then you can try to find another diet that works for you. But controlling our food intake, no matter how, is essential. Exercise is good for the heart but usually has less effect on blood glucose levels than diet does.
The most difficult thing facing you when diagnosed, I think, is accepting the fact that you're going to have to revamp your eating habits, usually in a major way. You have diabetes, and it's not going to go away. It can be controlled, but not cured, at least not today. It's difficult to accept this at first, but it's necessary if you want to live a long and healthy life.
That's bad news, but here's some good news. One studyshowed that people with diabetes who take metformin actually live longer, on average, than people who don't have diabetes. This doesn't mean you can take metformin and not change your dietary habits. But it is consistent with the saying that the best way to stay healthy is to develop a chronic disease that forces you to take care of yourself.
So instead of raging against our fate, we should be grateful that fate has given us a second chance. Let's use it to stay healthy for many more years to come.
There's a new class of diabetes medications on the horizen, not yet approved by the FDA. They're called glimins,and the one that has had the most research is imeglimin. Results of Phase 3 trials in Japan were reported at the European Association for the Study of Diabetes annual meeting in Barcelona in September.
Phase 1 trials test the safety of a new drug in a small number of healthy volunteers. Phase 2 trials test the efficacy of the drug in more people. Phase 3 trials test even more people in what are usually blinded studies (meaning neither the patient nor the physicians know which patients got the drug and which got a placebo). Once a drug has passed Phase 3, the company can apply for FDA approval.
One problem with the glimin class is that there's already a generic drug on the market called Glimin. It seems to be a sulfonylurea or a sulfonylurea plus metformin. It's marketed in Asia, and perhaps the term glimin is used there to mean diabetes drug as there seem to be different formulations. As far as I know, none of these products are available in the United States. But there could still be confusion.
The drug imeglimin is reported to work via the mitochondria to affect several systems important for glucose control: decrease the release of glucose by the liver, increase the uptake of glucose by muscle, increase insulin secretion, and decrease the destruction of beta cells by apoptosis (a way the body gets rid of cells it thinks it doesn't need). It may also mobilize fat in the liver.
The exact mechanism by which imeglimin works is not yet known, but metformin was used for years before it was known how it worked, and the mechanism is still not completely understood.
The reports of imeglimin sound wonderful, but there's very little information about the new drugavailable yet. And side effects of new medications often don't emerge until thousands of people have taken the drugs. So this information doesn't have much immediate practical use. There were reports on its benefitsin 2012 and it's still not on the market. However, knowing a little about it means that if there are news stories about it, you can understand their relevance.
NAFLD, or nonacoholic fatty liver disease, is common in people with type 2 diabetes, especially when blood glucose levels aren't controlled. More than 50% may develop it.
And of course a high intake of alcohol can produce fatty liver disease.
Now researchers have discovered that more than half of patients with NAFLD have gut bacteria that produce alcoholfrom the sugar the people eat. There's apparently a specific bacterial strain of Klebsiella pneumoniaethat produces more alcohol than usual, and this strain was found in 61% of people with NAFLD, but only 6% of controls.
Mice fed these strains of K. pneumoniae developed signs of liver damage. When these mice got an antibiotic that killed K. pneumoniae,their condition was reversed.
One man studied had severe liver damage and a condition with the name Autobrewery Syndrome.It's normally caused by alcohol-producing yeast, but this man had no signs of yeast infection. When tested on an alcohol-free high-carbohydrate diet, he had a very high blood alcohol concentration of 400 mg/L, or .04%. Legal intoxication is usually .08%.
Now, most people wouldn't produce as much alcohol as this man did on a high-carbohydrate diet. But the production of a smaller amount over a long period of time could damage the liver of a person who never drank alcohol.
This is another reason to avoid high carbohydrate diets. The bacteria seem to produce alcohol only when fed a lot of carbohydrates that can be broken down into glucose.
You can read the full study here.
They point out that endogenous alcohol production by particular bacteria is not the only cause of NAFLD: "It would be worth emphasizing that it has become clearer that NAFLD is a very heterogeneous disease and the findings here likely represent just one type of etiology."
But it's a fascinating finding and makes one wonder how many other unanticipated products of gut microbes contribute to disease.
Here's a study confirming what most of us already know: YMMV, or Your Mileage May Vary. Some people prefer YDMV, or Your Diabetes May Vary.
Different people may have different reasons for getting diabetes. Some may have a lot of insulin resistance. Others may be pretty insulin sensitive but they just don't produce enough insulin. They do produce some, so unlike people with type 1, they can often get along without added insulin. And others may have a combination of these deficits.
In this study, two groups were studied: Pima Indians from the Southwestern United States and Asian Indians from Chennai, India. They found that the Pima Indians tended to have a lot of insulin resistance (three times as much as the Asian Indians), but the Asian Indians, who were also older and thinner, tended to have defects in insulin secretion (three times less).
Unfortunately, when you're diagnosed, it's not common to have a lot of tests to find out exactly what is causing your diabetes. Most doctors tell you it doesn't matter, because they'd treat the disease the same way regardless of the cause. And a bunch of extra tests would be expensive.
However, if you come from an ethnic group that tends to have insulin resistance, that would probably be your major problem and you should focus on things like exercise and weight loss that can reduce insulin resistance. If you come from a group that tends to secrete too little insulin, it would make sense to focus on eating foods that don't require a lot of insulin, in other words, trying a low-carb diet.
Of course, many of us in the United States have a mixed heritage, so such studies would be less useful. Nevertheless, they might give hints about what kind of treatment to focus on.
Much diabetes research is done in rodents, mostly mice. But mice aren't humans, and they don't always react the same way as humans.
For example, mice have been cured of diabetes many times, but these cures don't translate into human cures. So should we abandon mouse research?
No. The mouse research makes suggestions for things that might work in humans, or in human cell cultures, and raising mice is a lot cheaper and faster than raising larger animals, so many more studies can be done.
However, more attention should be paid to how the mice are raised. Some people criticize mouse studies because they are not controlled for light intensity or electromagnetic fields, which can affect biochemical systems. Others criticize the standard mouse diets.
A recent editorial in the journal Nature discussed the problems with mouse diets. It focuses on obesity research, but obesity and type 2 diabetes are linked.
You can make mice obese pretty quickly by feeding them high-fat diets, which they love; their normal diet is relatively low in fat. Think of baiting a trap with cheese. But the Nature editorial asks if such high-fat diets have relevance to human obesity that usually develops at much lower dietary fat levels than the mouse obesity.
The editorial also asks if the metabolism of mice raised on a very high fat diet is different from that of mice raised on more normal diets. It also points out that the very high (60%) fat diets usually used to make mice obese quickly have a lot less sucrose than a lower-fat diet would, and sugar has metabolic consequences too.
So too, the types of fatty acids in a diet can affect the metabolism, and the fatty acids in the commercial mouse diets may not be similar to those in a typical (if any diet is typical) human diet.
One thing the editorial didn't address is the fact that many of these diets use the cheapest ingredients available and often satisfy the carbohydrate goal by adding sucrose instead of some kind of healthier carbohydrate like whole grains.
This editorial obviously raises questions rather than providing answers, and at the moment it has no practical value for most people.
However, the fact that people are drawing attention to the quality of the mouse diets used in so much research is a good thing. Maybe better mouse diets will result in better research results.