Wildly Fluctuating by Gretchen Becker

18 April 2019

A 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
  • Prediabetes
    Sciencemagazine has a story suggesting that we retire the term prediabetes. They cite people who say the progression from prediabetes to diabetes is low (less than 2% per year or 10% in five years, rather than the 15% t0 30% that has been cited by the Centers for Disease Control and Prevention) and there are no drugs that specifically target prediabetes. So why worry people?

    The Diabetes Prevention Program study, which ended in 2001, showed that those who received intensive lifestyle changes reduced their development of type 2 diabetes by 58 percent. But those patients received intensive counseling and support, which is too expensive to offer to every person diagnosed with prediabetes.

    Metformin alone (850 mg twice a day) lowered diabetes incidence by 31 percent, but there was some disagreement over whether the drug really kept the patients from developing diabetes or whether the metformin simply masked any diabetes that developed.

    These opponents of the idea of prediabetes also claim that prediabetes doesn't increase the risk of heart disease and argue that the costs of treating patients with prediabetes outweigh the benefits.

    I understand their reservations, but I don't agree that we shouldn't warn people that they are on the track to diabetes. Patients are different, and there are always some who, when told they have prediabetes, will ask for a pill and not want to do anything about changing their habits. There are others who might like to eat a whole-food diet with lots of vegetables, but they can't afford it, or the stores in their area don't carry healthy foods.

    But there are also patients who, if warned, will take serious steps to improve their health. A fascinating exampleof this is geneticist Michael Snyder, who found out as a result of an exhaustive genome and metabolic analysis that his blood glucose (BG) went very high after a viral infection, and when a doctor later said he had type 2 diabetes, he worked hard on diet and exercise and brought things back to normal.

    Snyder recently published a paper on glucose spikes in nondiabetics. He says 70% of people with prediabetes will progress to overt diabetes.

    So should motivated patients be denied early warnings just because other people won't do anything about their health?

    And even if only 2% of patients per year progress to overt diabetes, if you're one of the 2%, wouldn't you want to be warned?

    I also don't agree that prediabetes doesn't increase the risk of heart disease. I've seen studies saying that even A1c's considered normal increase the risk, but I didn't save them as I thought that was generally accepted. Hereis one example.

    One problem is that definitions of things like prediabetesand diabetesdepend on where some group of physicians decide to put a cutoff point. It's not as if you're totally healthy until you reach that point and then suddenly you're sick. When I was diagnosed in 1996, the cutoff for diabetes was a fasting BG level of 140 mg/dL. Then that was reduced to 126. And fasting BG levels can change from day to day. Does that mean you can have diabetes on Wednesday when your fasting BG level was 127 but you were cured on Friday when it was 125?

    Today the A1c is often used for diagnosis, but that too is not an exact method. When I've had A1c tests at two different sites, they often don't agree.

     So should we retire the term prediabetes?

    When I was diagnosed, the term prediabetesdidn't exist. Instead you were said to have impaired glucose tolerance if your BG levels went higher than normal after meals and impaired fasting glucose if they were high when you got up. Both categories were combined into the prediabetesterm. I think it's less important what you call it than having a physician who will warn you if all is not well and then help you prevent diabetes, or who will refer you to someone else who can do this.

    I think the term prediabetesprobably has a bigger impact on the patient than something like impaired glucose tolerance so the patient will be motivated to do something about it. Most people who are diagnosed with diabetes are overweight, and most people who are overweight have been trying to lose weight off and on for years. A diagnosis of prediabetes can be the kick in the pants they need to take the weight loss seriously.

    Regardless of whether or not you agree about dumping the term prediabetes, the article in Science is a good summary of how professional organizations can disagree about diagnostic criteria, how those who specify those criteria often receive large amounts of money from drug companies, and how attitudes change through the years.


  • Me and NPH
    As everyone knows, insulin prices are now criminal. For a long time I was using Levemir, just once a day, in the morning. It worked fine, as I don't seem to need insulin overnight. If I just stopped eating, I could eliminate insulin altogether, but that doesn't seem like a likely scenario.

    For more than a year, I've been on Tresiba as part of a clinical study, which meant the insulin was free. That was nice. The Tresiba worked OK, but because it lasts for 24 hours, it meant I couldn't use as high a dose as I used for Levemir. I was on 20 units of Levemir but only 12 units of Tresiba. Any more and I'd go low overnight. In fact, even on the 12 units, I was going slightly low at night for long periods, according to the Freestyle Libre continuous glucose monitor (CGM) I was trying at my own expense.

    When the Tresiba trial was over, I still had two Levemir pens that hadn't quite expired, so I used them. But when I found out that refilling my 3-month prescription would cost about $1000, I figured no way and  decided to try NPH. For the last week of the Tresiba trial, we'd been put on NPH, and it seemed to work OK, but my CGM stopped working after only a day on the NPH, so I was curious to give it a longer trial.

    NPH is about $24 for a 10-mL vial of 100 units/mL at Walmart. So at 20 U/day, a vial should last me about 50 days, or 48 cents a day, $43 for three months.

    On my Plan D, I actually pay only $30 for a 3-month supply of Levemir, but my plan pays $1359.40, and because the infamous doughnut hole is based on total drug costs, not what the patient pays, with those prices plus another expensive drug, I'd reach the doughnut hole for sure.

    Other than expense, an important factor is how well it works. Two endocrinologists warned me that NPH is  unpredictable, that the same dose might work one way on one day and another on another. But I find that diabetes is unpredictable anyway. You can eat exactly the same thing and get the same amount of exercise on two days and get different results, so it's difficult to know which of the myriad factors that affect blood glucose (BG) levels is responsible.

    Dr. Richard Bernstein, low-carbohydrate diet proponent and author of The Diabetes Solution,warns about using NPH because it contains protamine, which can interfere with the reversal of the anticoagulant heparin. But an endocrinologist I asked about this said he used NPH for years before the modern insulins were available and he'd never seen this problem, and besides, people these days tend to use other anticoagulants, so I decided not to worry about it. Anyway, I'd already used it in the clinical study.

    Bernstein also says one reason the cloudy insulins seem unpredictable is that people don't shake the vials enough so the insulin isn't distributed evenly.

    So what did I find?

    NPH is definitely peakier than Levemir. Some sources say it peaks 4 to 8 hours after you inject, others say 4 to 6 hours, and the Joslin Diabetes Center says 4 to 12 hours (at least they're consistent with the 4). So there's obviously a lot of individual variation. I find it peaks about 7 hours after I inject. I get up early, usually around 5 am, and inject then, so my NPH peaks at lunchtime. This is handy, and I try to eat my big meal of the day at noon. If I don't have lunch, I might go low.

    This is, of course, not the way you're supposed to use a basal insulin. You're supposed to inject just enough to keep your BG at a good level when you don't eat and then use a bolus insulin to cover meals. I'm too lazy to do that. And as a type 2 I have a bit of a buffer because I'm still producing small amounts of insulin, just not enough to cover meals.

    Some people take a second shot just before going to bed to use the NPH peak to cover the dawn phenomenon. However, although my BG goes up a little in the morning, starting when I wake up, the rise is not large.

    After the Tresiba study was over, I went back to Levemir until those pens were finished. Then, wearing the CGM,  I tried NPH, 5 units in the morning and 5 in the evening. Then I tried 10 in the morning. Then I tried 15 and then 20 in the morning. The 20 didn't make me go low except for once, and that was about an hour after I injected so it was probably not a result of too much insulin. Maybe I injected too close to a blood vessel. That happened with Lantus once, and I went down to 25.

    Then for two days I tried no insulin, but the CGM gave out after just one day.

    Then I got a new sensor and tried a few different concentrations.

    The program you can use with the CGM calculates average BG each day. Here are what I got. When there's only one dosage listed, I took it first thing in the morning.

    12 units Tresiba:  98, 105, 96, 91, 92, 103, 99, 96, 92, 89 (96.1 average with overnight lows )
    15 units Levemir: 98, 104 (101 av)
    20 units Levemir: 107, 89, 103, 104, 82, 94, 93, 100, 106, 110 (98.8 av)
    10 +10 units Levemir (10 units in moring and 10 in evening):  90, 93 (91.5 av)
    0 insulin: 114
    5 + 5 units NPH: (5 in morning and 5 in evening: 118, 109, 103 (110 av)
    10 units NPH: 102, 106 (104 av)
    15 units NPH:109, 101, 96, 101, 109 (103.2 av)
    20 units NPH: 101, 100, 109, 101, 99, 95, 97, 96, 86, 103, 93 (98.1 av)

    Note: One problem is that the Libre is that every sensor can read slightly differently, and I find that they read high on the first day after insertion, so I don't use that day.

    Thus the Levemir given twice a day gave the lowest average BG, but that was only two days and might not be reliable. Not surprisingly, the highest average was with no insulin, but that was only one day. The sensors and then the receiver kept not working at important times.

    12 units of Tresiba gave the next lowest average BGs, but there were also a lot of overnight lows.

    The 20 units of Levemir given in the morning, with lots of data points, and the 20 units of NPH given in the morning, with lots of data points, gave about the same averages, 98.8 and 98.1, respectively, and the NPH readings were with a sensor that read about 10 points high.

    So FOR ME, it seems as if NPH works just as well as Levemir. Whether or not I'll continue with it permanently depends on how close to the doughnut hole I seem to be getting. It is a lot more convenient to use a pen. I think NPH comes in a pen, but that's more expensive.

    And my feeling is that Big Pharma won't reduce insulin prices unless people stop buying their product when it costs too much.

    My experience suggests that patients with no insurance and low incomes might find that they were better off with the old-fashioned bottled NPH, with regular (R) for meals if they use a bolus insulin. They're not as convenient as the newer insulins, or the pens, but no one should die because they can't afford modern insulins. Low carbohydrate intakes require less insulin, and R actually covers low-carb meals better than the faster bolus insulins.

    I plan to do more experimenting with the CGM in the future. If I have any interesting results, I'll post them.
  • Would this "Make Diabetics Happy"?
    A new invention that put little syringes loaded with insulin into capsules has riveted the popular press.

    Hereis one story that shows how the things work. And this story says they'll "make diabetics happy." Even the New York Times did a storyon it.

    As usual, the people designing new drugs and gizmos don't really understand diabetes. The biggest problem facing people with diabetes is not "painful insulin injections." It's figuring out what you can eat and, if you take insulin, how to match the insulin you inject to the food you eat.

    One can also inhale insulin. But one problem with that, in addition to the problem of lung damage although the supporters of inhaled insulin say the risk is minimal, is that the amounts you  can inhale are limited. With a pen or a syringe, you can inject any amount you want, not just 4 or 8 or 12 units (the choices available with the inhaled insulin Afrezza). Would these little encapsulated syringes offer a similar benefit? I doubt it.

    Another problem is that although the inventors say these things work in pigs, that's only when they have empty stomachs. One might have an empty stomach first thing in the morning, but probably not before meals, so the injections couldn't be used for bolus (premeal) insulins.

    If inventors want to "make diabetics happy" they should listen to people with diabetes and see what they really want. There are probably a few people who would love to use tiny syringes in capsules, but I suspect not a lot. Inhaled insulin hasn't caught on, and I suspect encapsulated syringes would have a similar fate in the marketplace even if the cost was low.

    Sure, it's fun for the scientists and engineers to come up with gizmos like this, but let's hope they come up with more useful gadgets. Continuous glucose monitors became popular when they became more affordable than some of the older CGMs. Patients are reporting major reductions in their hemoglobin A1c when they use the CGMs and find out what makes their blood glucose go up.

    So I'd be happy if the engineers developed cheap CGMs that everyone could use.

  • Measuring Metabolism
    I don't usually write about commercial products, but this oneseems interesting . . . if it fulfils its promise. It's a way of determining whether you're burning primarily carbohydrate or fat.

    This is done by calculating something called the respiratory quotient (RQ),which is the ratio of carbon dioxide production to oxygen consumption. An RQ of 1 means you're metabolizing mostly carbohydrate, and an RQ of 0.7 means you're burning mostly fat. Obviously, numbers between these extremes indicate you're burning both. Protein has a small effect on the RQ.

    When I was in a clinical study at the Joslin Diabetes Center some years ago, they measured my RQ. I had a big hood over my head for what seemed like a long time, and it was horrid when my nose started to itch but I couldn't scratch it.

    Now an Israeli company has produced a little gizmo into which you breathe, and they say it will give you an RQ. It's not cheap (about $300), and it won't be available until next August, although you can order it now for $249. Last summer, articles were saying it would ship in February 2019 and preorder price was $179. I've seen a lot of gizmos being announced that never come to market, so I'll believe this one when I see it. Nevertheless, it's interesting.

    So why would you care what your RQ was? Well, we can all be a little different, and some people may be better at burning carbohydrates or burning fats. Let's say you want to lose fat. When your carbohydrate intake, and hence your insulin level, is low, your hormones can help you break down the fat in your fat cells and ship fatty acids out into the circulation to be taken up and burned by tissues that need energy.

    But if you don't burn the fatty acids very efficiently they'll just stay around and eventually may get taken up by the fat cells for storage as (ugh) fat.

    It would be interesting to measure the RQ of someone just starting a low-carb diet and then keep measuring as the person became adapted to the diet. Would the RQ show more fat oxidation as time went by and the body became accustomed to using fat for energy? Could the RQ be shown to be related to the fatigue some people feel when going on a low-carb diet?

    Some people are more efficient at fat burning than others. Could they determine this by measuring the RQ with this gizmo

    If despite limiting carbohydrate in your diet, the gizmo showed that you were still getting a lot of your energy from carbohydrate, you would know that you had to limit carbohydrate more than some other people.

    Of course the gizmo could also be used by people who wanted to burn a lot of carbohydrate.

    I look forward to the day when this is actually available to see how people are using it.
  • Connected Systems
    Everything is connected.

    No, this won't be a New Age rant on oneness with the universe. I'm speaking of the various systems in the body, which used to be put into boxes as if they operated on their own. There was the circulatory system, the nervous system, the respiratory system, the digestive system, and so forth, and many doctors specialized in one system or another.

    Different processes were thought to take place in different systems. For example, gluconeogenesis (the formation of glucose from other compounds) was said to take place in the liver, and although it was mentioned that the kidney also performed some gluconeogenesis, this was mostly ignored. This approach made sense in the past, when measurement techniques were relatively crude, but today techniques have improved and it's even possible in some cases to measure what's going on in single cells.

    So now, more and more, we're learning that the various organs have roles other than the main roles that have been known for decades, and the various systems are interconnected, sometimes in surprising ways. For example, not long ago, fat was considered just a way to store extra energy. It's now well known to secrete hormones too.

    One recent studyshowed that a gut hormone interacts with brown fat to tell the brain that it's time to stop eating. The hormone, secretin, has been known since 1902, but its role was said to be to stimulate the pancreas to release bicarbonate to neutralize the acids coming from the stomach. Now it seems it has at least one other role. Mice injected with secretin had less appetite and increased the amount of heat the brown fat produced. Unless you're cold, heat is "wasted" energy, so increasing the amount of heat produced would mean they would gain less weight from the food they ate.

    And a study of mast cells also revealed unexpected effects. Mast cells produce histamine, which is important in causing allergic symptoms, so many allergy sufferers take antihistamines. This study showed that histamine that goes to the liver, not the lungs or nose, also helps regulate ketogenesis (the production of ketone bodies from fatty acids).

    It does this via a molecule called OEA (oleoylethanolamide). Previously, researchers thought OEA's role was to block hunger pangs. It does, but it also stimulates ketogenesis.

    These complex interactions are one reason different people can react differently to various medications and diets. One person might have a difference in the mast cells and another might have a difference in the sensitivity of the liver to histamine and another might have a difference in some related but as-yet-unknown reaction in the same system. (I'm using the term "difference" rather than "defect" because sometimes a metabolic difference that is detrimental in one environment turns out to be beneficial in another.)

    Hence we should never assume that what works for one person will work for us. Today we have so many tools to measure the various aspects of our diabetes that we can try something and then if it doesn't work try something else. No one diet or one drug or one exercise regime is best for everyone.

    And we should remember that everything is connected. We shouldn't focus on just one system in our body and ignore the rest. They all talk to each other, and maybe healing an ingrown toenail will help our diabetes.