There's been a huge outcry online now that Halle Berry, previously a poster girl for Type 1 diabetes, has told the press that she has been able to wean herself off insulin.
A lot of people with Type 1 diabetes are very upset with this for the very understandable reason that it is impossible to go insulin if you have Type 1 diabetes unless you get an experimental pancreas or beta cell transplant--and even those are iffy. So there are a lot of people with Type 1 who are feeling betrayed and that is making for a lot of anger.
In fact, what happened to Berry has happened to quite a few people who have emailed me over the years since I put up my web page about monogenic diabetes (MODY).
None of them are TV or movie stars, so their experiences didn't hit the media. But all of them were diagnosed with Type 1 diabetes in their late teens or early 20s only to find out years later that they actually had a genetic form of diabetes that keeps beta cells from secreting--a form of diabetes where it is possible to reestablish beta cell secretion using sulfonylurea drugs like Amaryl or, more recently, Byetta instead of, or in combination with, insulin.
While some forms of MODY, like the one I appear to have, are mild enough to be misdiagnosed as Type 2 diabetes, as mine was, others can be quite severe and easily confused with Type 1 diabetes. Here's a case history of just such a case:
Identification of MODY: the implications for Holly
Journal of Diabetes Nursing, Jan, 2004 by Jo Dalton, Maggie Shepherd
The main things hinting that MODY might be at fault here were that insulin doses remained in the "honeymoon" range, years after diagnosis and that the patient did not develop DKA. Note also that the patient's father was diagnosed with "Type 2" later in life, but actually had a much milder form of the same genetic diabetes. The virulence with which these gene express is modified by many environmental factors science does not yet understand.
Many doctors still believe, incorrectly, that a person cannot develop MODY unless one parent has been diagnosed with diabetes. But even though neither of Ms. Berry's parents was diagnosed with MODY it does not rule out that she might have inherited the gene from one of them. In addition, as in the case of Holly's father, the gene may spontaneously mutate and appear in a person with no relatives with diabetes.
That there are "silent" carriers of these genes scattered through the population was only realized recently when scientists started testing family members of people diagnosed with MODY via gene tests. They discovered that there were other people in the families who were carrying MODY genes but whose blood sugar abnormalities had escaped diagnosis--probably because, like mine, the gene defect affected only post-meal blood sugar levels and were not detectable using a fasting plasma glucose test.
It is also worth noting that scientists who study genetic diabetes believe there are many more genes out there causing insulin secretory disorders than the six that have been so far identified. So it is possible that there are a lot more people diagnosed as Type 1 diabetics who have one of these not yet diagnosed genes.
However, it is also very important to note that whatever the cause of the defect, these MODY forms of diabetes are every bit as capable of wreaking havoc on eyes, nerves, and kidneys as is Type 1.
As far as Ms. Berry's situation goes, I hope that she isn't settling for the 7%-8% A1c that so many doctors consider good enough for someone with Type 2. As exciting as it might be to be able to give up insulin, trading shots for blood sugars high enough to cause blindness, amputation, and dialysis is not such a smart idea.
Ms Berry still has diabetes, it still has the potential to ruin her life, and she still needs support from the rest of the diabetes community in learning how best to get her blood sugars down into the normal range so she can avoid developing complications.
And we all need to realize that Ms. Berry's situation points out how misleading are the current diagnostic criteria which lump hundreds of different genetic and metabolic disorders into one of two bins--Type 1 and Type 2.
November 8, 2007
November 7, 2007
"Overweight" is Healthiest Weight
This is not actually news, as there was a good study published some years ago that found the very same thing to be true, but a new study presented at this years American Heart Association meeting confirms the finding, and has led to some headlines on the topic.
The basic message here is that you are most likely to live a long and healthy life if your BMI is between 25 and 30, which for a 5' 4" woman means having a weight of 150-174 lbs and for a 5' 10" man is 175 - 208 lbs.
Here's a report on the finding from the New York Times.
Causes of Death are Linked to a Person's Weight
Here are some earlier large population-based studies that have found similar results:
From JAMA in 2005 based on NHANES III data
Here is a further review of the NHANES data that points out that over age 70, overweight AND obesity are more healthy than normal or underweight. Be sure to scroll down to Table 4.
Supplemental Analyses for Estimates of Excess Deaths Associated with Underweight, Overweight, and Obesity in the U.S. Population
by Katherine M. Flegal, Ph.D.
The current data does NOT break health down by decade, which is a shame, because the strongest signal in the NHANES study points to weight becoming increasingly healthful as we go through middle age. By not breaking mortality figures out by age, we may miss this vital point.
This data flies in the face of our society's obsession with thinness and its tendency to equate near-anorexia with moral superiority and overweight to sinfulness. However, as anyone who is over 50 knows, at middle age the body ramps up its weight gaining mechanisms to the point where it is almost impossible NOT to gain weight. Now this research suggests that there is a reason for it, and it is not that we suddenly become lazy, greedy slobs.
As we age, the metabolism slows down at a predictable rate. The result of this slowing is that at 59, I can now gain weight eating the same diet that I would have lost weight on at age 40. A diet, by the way that has the same number of calories used to induce starvation in men who averaged a weight only 10 lbs more what I now weigh during Ancel Keye's famous WWII Starvation Experiment.
This is not because I am less physically active than I was at 40, which is the usual excuse given for middle age weight gain. No, my body has clearly decided that I need an extra 20 lbs and the more I fight it the harder it fights back.
So what a sudden revelation it is to realize that maybe my body is doing this because it is trying to keep me alive!
There is a predictable backlash to this data from people who know it has to be wrong. But as the analysis of the NHANES research linked above shows, their belief that overweight is unhealthy may derive from studies that cherry-picked the data in such a way as to achieve the result that the researchers already believed to be true. Taubes' work has made it very easy to see how common this is in so-called scientific studies.
And it's also worth remembering many of the claims of excess mortality linked to weight, like Julie Gerberding of the CDC's famous discredited estimate of mortality due to overweight, were pulled from thin air.
Does this mean you should rush out and gain weight? Of course not. Does it mean that carrying an extra 100 lbs is good for you? Again, of course not. The health benefits of weight drop off significantly at a BMI of 35--204 lbs for a 5' 4" woman and 244 for a 5' 10" man.
In addition, the BMI as an index to health has to be taken with a grain of salt, because it completely the two Bs: boobs and brawn. I'm carrying 6 lbs of boob, which do not go away even if I weigh 108 (I've tried it.) That raises my BMI by 1.1. Does this mean I'm much less healthy than a completely flat chested woman of my size? I doubt it.
In a similar manner, when my son was playing on his college football team, he had a BMI well into the "obese" range, based on his height and weight, though he was measured as having a body fat percentage of 17% which is normal for a male. This discrepancy was because he was carrying an enormous muscle mass which the BMI calculations treat as if they were body fat.
One of the things doctors always tell people with diabetes is that if they could lose as little as ten pounds, they could lose the diabetes. Hundreds if not thousands of you reading this blog have probably tried this and found it to be nonsense. Some of us, like, say, me, have lost over 15% of our body weight and found it to have zero impact on our blood sugars.
Well, heave a sigh of relief. Your weight is not going to kill you. Then take another deep breath because no matter WHAT you weigh, your blood sugars might: the connection between blood sugars rising over 140 mg/dl after each meal and heart attack is very well documented with more research confirming it every year.
So concentrate on getting those blood sugars down. Get your A1c as close to 5% as you can, and once you do look forward to having long debates about "healthy eating" with your grandkids and great grandkids!
The basic message here is that you are most likely to live a long and healthy life if your BMI is between 25 and 30, which for a 5' 4" woman means having a weight of 150-174 lbs and for a 5' 10" man is 175 - 208 lbs.
Here's a report on the finding from the New York Times.
Causes of Death are Linked to a Person's Weight
Here are some earlier large population-based studies that have found similar results:
From JAMA in 2005 based on NHANES III data
Here is a further review of the NHANES data that points out that over age 70, overweight AND obesity are more healthy than normal or underweight. Be sure to scroll down to Table 4.
Supplemental Analyses for Estimates of Excess Deaths Associated with Underweight, Overweight, and Obesity in the U.S. Population
by Katherine M. Flegal, Ph.D.
The current data does NOT break health down by decade, which is a shame, because the strongest signal in the NHANES study points to weight becoming increasingly healthful as we go through middle age. By not breaking mortality figures out by age, we may miss this vital point.
This data flies in the face of our society's obsession with thinness and its tendency to equate near-anorexia with moral superiority and overweight to sinfulness. However, as anyone who is over 50 knows, at middle age the body ramps up its weight gaining mechanisms to the point where it is almost impossible NOT to gain weight. Now this research suggests that there is a reason for it, and it is not that we suddenly become lazy, greedy slobs.
As we age, the metabolism slows down at a predictable rate. The result of this slowing is that at 59, I can now gain weight eating the same diet that I would have lost weight on at age 40. A diet, by the way that has the same number of calories used to induce starvation in men who averaged a weight only 10 lbs more what I now weigh during Ancel Keye's famous WWII Starvation Experiment.
This is not because I am less physically active than I was at 40, which is the usual excuse given for middle age weight gain. No, my body has clearly decided that I need an extra 20 lbs and the more I fight it the harder it fights back.
So what a sudden revelation it is to realize that maybe my body is doing this because it is trying to keep me alive!
There is a predictable backlash to this data from people who know it has to be wrong. But as the analysis of the NHANES research linked above shows, their belief that overweight is unhealthy may derive from studies that cherry-picked the data in such a way as to achieve the result that the researchers already believed to be true. Taubes' work has made it very easy to see how common this is in so-called scientific studies.
And it's also worth remembering many of the claims of excess mortality linked to weight, like Julie Gerberding of the CDC's famous discredited estimate of mortality due to overweight, were pulled from thin air.
Does this mean you should rush out and gain weight? Of course not. Does it mean that carrying an extra 100 lbs is good for you? Again, of course not. The health benefits of weight drop off significantly at a BMI of 35--204 lbs for a 5' 4" woman and 244 for a 5' 10" man.
In addition, the BMI as an index to health has to be taken with a grain of salt, because it completely the two Bs: boobs and brawn. I'm carrying 6 lbs of boob, which do not go away even if I weigh 108 (I've tried it.) That raises my BMI by 1.1. Does this mean I'm much less healthy than a completely flat chested woman of my size? I doubt it.
In a similar manner, when my son was playing on his college football team, he had a BMI well into the "obese" range, based on his height and weight, though he was measured as having a body fat percentage of 17% which is normal for a male. This discrepancy was because he was carrying an enormous muscle mass which the BMI calculations treat as if they were body fat.
One of the things doctors always tell people with diabetes is that if they could lose as little as ten pounds, they could lose the diabetes. Hundreds if not thousands of you reading this blog have probably tried this and found it to be nonsense. Some of us, like, say, me, have lost over 15% of our body weight and found it to have zero impact on our blood sugars.
Well, heave a sigh of relief. Your weight is not going to kill you. Then take another deep breath because no matter WHAT you weigh, your blood sugars might: the connection between blood sugars rising over 140 mg/dl after each meal and heart attack is very well documented with more research confirming it every year.
So concentrate on getting those blood sugars down. Get your A1c as close to 5% as you can, and once you do look forward to having long debates about "healthy eating" with your grandkids and great grandkids!
November 6, 2007
More Problems with Galvus the Other DPP-4 Inhibitor
UPDATE (April 2, 2013): Before you take Byetta, Victoza, Onglyza, or Januvia please read about the new research that shows that they, and probably all incretin drugs, cause severely abnormal cell growth in the pancreas and precancerous tumors. You'll find that information HERE.
Original Post:
There's a new and troubling problem connected with DPP-4 inhibition. Read about it here:
New Safety Warning Delays Norvartis Diabetes Drug
Galvus is the other drug that uses the same mechanism to lower blood sugars as Januvia does. It is a DPP-4 inhibitor which has been approved for use in Europe and Latin America, but so far, not in the U.S.. It came up for approval around the same time as Januvia, but the FDA refused to approve it citing vaguely described "skin-related findings."
The chances are very good that these skin related findings are the same ones that have recently been discovered to occur with Januvia, including the potentially fatal Stevens-Johnson syndrome, where your skin separates from your body, as well as other allergic skin reactions including severe rashes and swelling.
There's no mystery why Januvia and Galvus cause such problems. Both suppress DPP-4 which, besides having a role in eliminating GLP-1 from the body, are major players in the regulation of the immune system. Stop DPP-4 from doing its job, and the immune system will start displaying subtle changes like rises in some white blood cells and not so subtle changes, like major allergic skin reactions.
The recent discovery of these Januvia side effects is detailed in this Reuters news story:
(Merk's Januvia Wins New Uses but Risks Outlined.).
Now a new problem has emerged with Galvus. When prescribed in the dose needed to make it a once a day pill, like Januvia, it can elevate liver enzymes to an unacceptable level. Elevated liver enzymes tell you that liver cells are being damaged or killed. Kill enough of them and you are looking at a liver transplant or death.
It was high liver enzymes that first warned of the toxicity of an earlier diabetes drug, Rezulin. Unfortunately few doctors paid any attention to the warnings about elevated liver enzymes with Rezulin. So for several hundred patients on Rezulin, by the time they learned they had elevated liver enzymes it was too late and they died, several hundred of them.
The solution that Novartis has come up with to pretty up Galvus is to cut the recommended dose in half. Supposedly at the lower dose, taken twice a day, the liver enzymes signal disappears in the study pool. However, this does NOT mean that the drug isn't causing liver damage. Only that it may take longer for the tiny bits of damage to accumulate.
Galvus is a different molecule than Januvia, but we don't know whether the damage was caused by something specific to the Galvus molecule or by fiddling around with DPP-4 and GLP-1. There is no requirement for drug companies to study and explain WHY a certain dangeous side effect occurs with their drug.
Since the two drugs appear to be pretty similar in their effect on the body. It would probably be a very good idea to get your liver enzymes checked every year if you are taking Januvia and if you see any sign that your liver enzymes are rising, get off the drug.
If your doctor pooh-poohs your concern, remember that busy doctors are very unlikely to know about newly discovered side effects. Your doctor probably also doesn't know about the immune system and skin problems that FDA just discovered with Januvia and added to the prescribing information. The drug company reps who give doctors 99% of their "education" about new drugs are not legally required to inform doctors about new warnings put into the Prescribing Information doctors rarely read.
Original Post:
There's a new and troubling problem connected with DPP-4 inhibition. Read about it here:
New Safety Warning Delays Norvartis Diabetes Drug
Galvus is the other drug that uses the same mechanism to lower blood sugars as Januvia does. It is a DPP-4 inhibitor which has been approved for use in Europe and Latin America, but so far, not in the U.S.. It came up for approval around the same time as Januvia, but the FDA refused to approve it citing vaguely described "skin-related findings."
The chances are very good that these skin related findings are the same ones that have recently been discovered to occur with Januvia, including the potentially fatal Stevens-Johnson syndrome, where your skin separates from your body, as well as other allergic skin reactions including severe rashes and swelling.
There's no mystery why Januvia and Galvus cause such problems. Both suppress DPP-4 which, besides having a role in eliminating GLP-1 from the body, are major players in the regulation of the immune system. Stop DPP-4 from doing its job, and the immune system will start displaying subtle changes like rises in some white blood cells and not so subtle changes, like major allergic skin reactions.
The recent discovery of these Januvia side effects is detailed in this Reuters news story:
(Merk's Januvia Wins New Uses but Risks Outlined.).
Now a new problem has emerged with Galvus. When prescribed in the dose needed to make it a once a day pill, like Januvia, it can elevate liver enzymes to an unacceptable level. Elevated liver enzymes tell you that liver cells are being damaged or killed. Kill enough of them and you are looking at a liver transplant or death.
It was high liver enzymes that first warned of the toxicity of an earlier diabetes drug, Rezulin. Unfortunately few doctors paid any attention to the warnings about elevated liver enzymes with Rezulin. So for several hundred patients on Rezulin, by the time they learned they had elevated liver enzymes it was too late and they died, several hundred of them.
The solution that Novartis has come up with to pretty up Galvus is to cut the recommended dose in half. Supposedly at the lower dose, taken twice a day, the liver enzymes signal disappears in the study pool. However, this does NOT mean that the drug isn't causing liver damage. Only that it may take longer for the tiny bits of damage to accumulate.
Galvus is a different molecule than Januvia, but we don't know whether the damage was caused by something specific to the Galvus molecule or by fiddling around with DPP-4 and GLP-1. There is no requirement for drug companies to study and explain WHY a certain dangeous side effect occurs with their drug.
Since the two drugs appear to be pretty similar in their effect on the body. It would probably be a very good idea to get your liver enzymes checked every year if you are taking Januvia and if you see any sign that your liver enzymes are rising, get off the drug.
If your doctor pooh-poohs your concern, remember that busy doctors are very unlikely to know about newly discovered side effects. Your doctor probably also doesn't know about the immune system and skin problems that FDA just discovered with Januvia and added to the prescribing information. The drug company reps who give doctors 99% of their "education" about new drugs are not legally required to inform doctors about new warnings put into the Prescribing Information doctors rarely read.
November 4, 2007
Debugging Unexpected Blood Sugar Highs
Every time I get things working, as far as balancing food and insulin, something changes and I get knocked back to square one. And, surprise, surprise, it has happened again.
Out of the blue, last week, I started seeing highs after meals using doses of insulin that up until then had matched specific food inputs perfectly. Over the week they've gotten worse until yesterday I spent most of the day well over 150 mg/dl and partly over 200, though I used more insulin yesterday than I've ever before used in one day.
I checked the Usual Suspects that I always consider when my blood sugar goes blooey on insulin, which I'll list here:
1. Meter problem: I tested highs on two different meters with strips from two batches and they matched within 4 mg/dl. No meter problem. (Of course, I washed my hands after seeing the first high, to make sure I didn't have sugary fingers.)
2. Insulin problem: Because I use very small doses of insulin, one vial or pen can last me a very long time. But over the past two years I've learned that any vial of insulin that gets used 3 times a day can deteriorate after six weeks, even if I've only used 100 units out of the 300 in the bottle. Sometimes I can see tiny crystals in the previously clear insulin. Sometimes I can't see anything, but replacing the vial or pen solves the problem of mysterious highs.
I replaced both my R and my Novolog pen with new ones. The problem did not go away.
3. Getting Sick? Sometimes we see rises in blood sugar days before we get sick.
I did end up developing a nasty viral outbreak in my mouth this past week, which is something I get from time to time. But I'm not sure that would be enough to cause the dramatic deterioration I'm seeing. I've had it before without seeing highs. And the outbreak is clearing up while the blood sugars are getting worse.
4. Carb Creep/Wrong Carb Insulin Ratio: Is that 30 grams of carbs really 60? Sometimes we get sloppy with our carb counting.
I thought that might be the problem, but yesterday I weighed portions and had a very good idea of what I was eating and saw crazy high numbers. More importantly, the timing of the highs was really strange--with the highest reading almost 3 hours after eating and injecting Novolog. When I did a Novolog correction at 3 hours, I ended up with a wicked low an hour later. This is NOT the usual pattern I see at all, but it does require further investigation.
5. A Change in Meds or Supplements: Any medication or supplement we take, whether for diabetes or not, can impact on our blood sugar.
In this case there were two obvious suspects. The high blood sugars started before I stopped taking Metformin again, and ideally I should have NOT stopped taking metformin when I developed highs, because my blood sugar will go up a bit without metformin, though not a lot. But I had no choice, as the Metformin was giving me continual burning stomach pain and I was also feeling very exhausted after taking it, which is something that had gone away when I stopped taking it before. So I decided that I had to stop taking it, because it was clearly not helping me out anymore.
But that said, I had stopped taking Metformin for several months only a few months ago without seeing dramatic highs. Usually I see a rise of about 10 mg/dl in fasting blood sugar and maybe of 20 mg/dl after eating when I am not taking Metformin. In the past, to correct for this I had only had to add another unit or so to my dose at meals, and 1.5 unit of NPH at night to knock down the fasting blood sugar. This was nothing like the 50-70 mg/dl rise I have been seeing this past week.
A I blogged earlier, I have also recently started taking 1000 IU of Vitamin E, which initially was causing lows which stopped after a week or so. Then after reading up about Vitamin E I added 2 Calcium/Magnesium supplement pills to my daily regimen, since it turns out that without available Cal/Mag Vitamin D may store metals in your bones. Hmmmmm. Needs further investigation!
6. Too Much Insulin Causing IR? It's one of the ironies of insulin use that if you use too much insulin the body may get into a counter-regulatory mode where surges fight and flight hormones push blood sugar up out of the low range and the body becomes more insulin resistant out of self-protection. I have always had a huge problem with unwanted counter-regulation in the past, which is characteristic of MODY-2, the kind of genetic diabetes I'm currently being tested for.
So this idea isn't so far fetched. When I figured out the right dose of Lantus to use to avoid hypos last year, I saw very high post-prandial numbers--and that was why I stopped the Lantus. I have been using increasing doses of NPH for the past month to try to get my always high fasting bg down and had added a unit or two every morning, too. Requires investigation.
7. Deteriorating Beta Cells: While this is not a likely explanation, we can't rule out that something may have caused my beta cells to shut down or otherwise misbehave. I don't think this is likely, because the last time I stopped using insulin (with a very low carb diet) my post-prandial control was a lot better than it had been 2 years ago when I started insulin, suggesting that beta cell rest had given me more function in my beta cells, not less.
Into Debugging Mode!
Since I come from a computer engineering background, I'm familiar with the techniques used to debug problems that develop in large, complex, poorly documented systems. So now it's time to sort out what might be causing these highs.
Key to doing this is the basic debugging concept: When there are multiple possible causes for a poorly understood problem, go back to something that works (if possible) and then change one thing at a time and see if you can reproduce the problem. Start with the most likely and work back to the least likely.
So here's what I'm gong to do:
1. Cut out everything that looks like it might be causing the problem: the Vitamin E/Cal/Mag supplementation, carbs, and NPH. I can do this because I am fortunate to still have some natural insulin production left. A Type 1 could not cut out a basal insulin, because cutting out the basal could make them very, very sick.
2. Cut carbs way, way down and stick to foods where I'm certain about the carb count. My most recent stint of low carbing wasn't that long ago. I was able to stay between 95-120 most of the time if I kept my carbs under 12 grams per meal and 6 at breakfast, a la Bernstein diabetes diet. I have some other problems that this diet makes worse, but for now I'm going to eat that way to get to an acceptable baseline. It mostly eliminates the problems caused by mismatching insulin to meals.
3. Add back one suspicious element at a time to see if I can determine what is causing the problem. Here's my thinking:
a. Add nighttime NPH. I started using NPH at night when I was off Metformin before because without Metformin my fasting blood sugar is always around 100 or more. It did not seem to cause a rise in my day time blood sugars. Because my fasting bg on a Bernstein diet will quickly go up to 110-120 mg/dl I want to address the high fasting value first before doing anything else.
If after doing this I don't see daytime highs:
b. Raise the number of carbs I eat in each meal gradually using my old reliable R insulin and my usual Non-Met carb/insulin ratio (1:10-1:12). Use measured portions of foods I'm familiar with. This should quickly tell me if using the wrong carb/insulin ratio was the problem.
If this solves the problem of daytime highs:
c. Add back the Vitamin D and Calcium/Magnesium.
If this doesn't cause daytime highs:
d. Add back the morning NPH dose.
Obviously, if one of these elements DOES cause the daytime highs, I'll have to stop using it.
I should wait a couple days before introducing each element.
Obviously, this is all a pain in the neck, but when I'm done, I should have a better idea of what is going on. I hope! If the problem was that I'm really about to come down with a cold, I might add everything back in and not reproduce the problem, but that works too.
Any other debugging suggestions from you folks who live with this crap day in and day out?
Out of the blue, last week, I started seeing highs after meals using doses of insulin that up until then had matched specific food inputs perfectly. Over the week they've gotten worse until yesterday I spent most of the day well over 150 mg/dl and partly over 200, though I used more insulin yesterday than I've ever before used in one day.
I checked the Usual Suspects that I always consider when my blood sugar goes blooey on insulin, which I'll list here:
1. Meter problem: I tested highs on two different meters with strips from two batches and they matched within 4 mg/dl. No meter problem. (Of course, I washed my hands after seeing the first high, to make sure I didn't have sugary fingers.)
2. Insulin problem: Because I use very small doses of insulin, one vial or pen can last me a very long time. But over the past two years I've learned that any vial of insulin that gets used 3 times a day can deteriorate after six weeks, even if I've only used 100 units out of the 300 in the bottle. Sometimes I can see tiny crystals in the previously clear insulin. Sometimes I can't see anything, but replacing the vial or pen solves the problem of mysterious highs.
I replaced both my R and my Novolog pen with new ones. The problem did not go away.
3. Getting Sick? Sometimes we see rises in blood sugar days before we get sick.
I did end up developing a nasty viral outbreak in my mouth this past week, which is something I get from time to time. But I'm not sure that would be enough to cause the dramatic deterioration I'm seeing. I've had it before without seeing highs. And the outbreak is clearing up while the blood sugars are getting worse.
4. Carb Creep/Wrong Carb Insulin Ratio: Is that 30 grams of carbs really 60? Sometimes we get sloppy with our carb counting.
I thought that might be the problem, but yesterday I weighed portions and had a very good idea of what I was eating and saw crazy high numbers. More importantly, the timing of the highs was really strange--with the highest reading almost 3 hours after eating and injecting Novolog. When I did a Novolog correction at 3 hours, I ended up with a wicked low an hour later. This is NOT the usual pattern I see at all, but it does require further investigation.
5. A Change in Meds or Supplements: Any medication or supplement we take, whether for diabetes or not, can impact on our blood sugar.
In this case there were two obvious suspects. The high blood sugars started before I stopped taking Metformin again, and ideally I should have NOT stopped taking metformin when I developed highs, because my blood sugar will go up a bit without metformin, though not a lot. But I had no choice, as the Metformin was giving me continual burning stomach pain and I was also feeling very exhausted after taking it, which is something that had gone away when I stopped taking it before. So I decided that I had to stop taking it, because it was clearly not helping me out anymore.
But that said, I had stopped taking Metformin for several months only a few months ago without seeing dramatic highs. Usually I see a rise of about 10 mg/dl in fasting blood sugar and maybe of 20 mg/dl after eating when I am not taking Metformin. In the past, to correct for this I had only had to add another unit or so to my dose at meals, and 1.5 unit of NPH at night to knock down the fasting blood sugar. This was nothing like the 50-70 mg/dl rise I have been seeing this past week.
A I blogged earlier, I have also recently started taking 1000 IU of Vitamin E, which initially was causing lows which stopped after a week or so. Then after reading up about Vitamin E I added 2 Calcium/Magnesium supplement pills to my daily regimen, since it turns out that without available Cal/Mag Vitamin D may store metals in your bones. Hmmmmm. Needs further investigation!
6. Too Much Insulin Causing IR? It's one of the ironies of insulin use that if you use too much insulin the body may get into a counter-regulatory mode where surges fight and flight hormones push blood sugar up out of the low range and the body becomes more insulin resistant out of self-protection. I have always had a huge problem with unwanted counter-regulation in the past, which is characteristic of MODY-2, the kind of genetic diabetes I'm currently being tested for.
So this idea isn't so far fetched. When I figured out the right dose of Lantus to use to avoid hypos last year, I saw very high post-prandial numbers--and that was why I stopped the Lantus. I have been using increasing doses of NPH for the past month to try to get my always high fasting bg down and had added a unit or two every morning, too. Requires investigation.
7. Deteriorating Beta Cells: While this is not a likely explanation, we can't rule out that something may have caused my beta cells to shut down or otherwise misbehave. I don't think this is likely, because the last time I stopped using insulin (with a very low carb diet) my post-prandial control was a lot better than it had been 2 years ago when I started insulin, suggesting that beta cell rest had given me more function in my beta cells, not less.
Into Debugging Mode!
Since I come from a computer engineering background, I'm familiar with the techniques used to debug problems that develop in large, complex, poorly documented systems. So now it's time to sort out what might be causing these highs.
Key to doing this is the basic debugging concept: When there are multiple possible causes for a poorly understood problem, go back to something that works (if possible) and then change one thing at a time and see if you can reproduce the problem. Start with the most likely and work back to the least likely.
So here's what I'm gong to do:
1. Cut out everything that looks like it might be causing the problem: the Vitamin E/Cal/Mag supplementation, carbs, and NPH. I can do this because I am fortunate to still have some natural insulin production left. A Type 1 could not cut out a basal insulin, because cutting out the basal could make them very, very sick.
2. Cut carbs way, way down and stick to foods where I'm certain about the carb count. My most recent stint of low carbing wasn't that long ago. I was able to stay between 95-120 most of the time if I kept my carbs under 12 grams per meal and 6 at breakfast, a la Bernstein diabetes diet. I have some other problems that this diet makes worse, but for now I'm going to eat that way to get to an acceptable baseline. It mostly eliminates the problems caused by mismatching insulin to meals.
3. Add back one suspicious element at a time to see if I can determine what is causing the problem. Here's my thinking:
a. Add nighttime NPH. I started using NPH at night when I was off Metformin before because without Metformin my fasting blood sugar is always around 100 or more. It did not seem to cause a rise in my day time blood sugars. Because my fasting bg on a Bernstein diet will quickly go up to 110-120 mg/dl I want to address the high fasting value first before doing anything else.
If after doing this I don't see daytime highs:
b. Raise the number of carbs I eat in each meal gradually using my old reliable R insulin and my usual Non-Met carb/insulin ratio (1:10-1:12). Use measured portions of foods I'm familiar with. This should quickly tell me if using the wrong carb/insulin ratio was the problem.
If this solves the problem of daytime highs:
c. Add back the Vitamin D and Calcium/Magnesium.
If this doesn't cause daytime highs:
d. Add back the morning NPH dose.
Obviously, if one of these elements DOES cause the daytime highs, I'll have to stop using it.
I should wait a couple days before introducing each element.
Obviously, this is all a pain in the neck, but when I'm done, I should have a better idea of what is going on. I hope! If the problem was that I'm really about to come down with a cold, I might add everything back in and not reproduce the problem, but that works too.
Any other debugging suggestions from you folks who live with this crap day in and day out?
November 1, 2007
Good Germs, Bad Germs
No, this is not a pun on the title of Gary Taubes' new book. It's the name of a completely different book which should be of great interest to anyone whose diabetes is autoimmune in origin.
Good Germs, Bad Germs: Health and Survival in a Bacterial World
by Jessica Snyder Sachs, is an up-to-date summary of what we know about how bacteria interact with humans.
It's a fascinating story, because after a lifetime of "fighting germs" it seems that scientists are coming to learn that the interaction between bacteria and our bodies is far more complex than was ever realized and we have to work with germs and make alliances with "good germs" in order to survive.
Why this relates to diabetes is that the book starts out with several chapters that explore in greater detail than I've seen elsewhere, the research that has been establishing "The Hygiene Hypothesis." This is the idea that the huge rise in autoimmune disease we are currently experiencing is being caused by too much cleanliness.
It is starting to look like we are not being exposed to enough of the right bacteria very early in life or as we go through our daily lives, thanks to changes in water treatment, how we get our food, how we medicate illness, and how we clean our homes.
It turns out that our bodies are complex ecosystems in which maintaining populations of billions of bacteria of various kinds is essential for preserving our health, particularly in the digestive system, where, if our population of bacteria are killed off, the digestive system fails to function properly. Children absorb the good bacteria they need to have populating their own digestive tract from birth on. A caesarian birth, for example, results in a baby who is not exposed to the bacteria found in the mother's perineal area, which raises the risk of developing autoimmune problems like asthma and Type 1 diabetes.
Children who are given antibiotics early in life which kill off the developing populations of healthful bacteria also develop more autoimmune diseases, particularly asthma.
And all of us who drink filtered water (which the book mentions was not common until the last 25 years of the 20th century) and eat packaged, preservative-filled foods, may not be maintaining the colonies of soil and fecal bacteria which our bodies depend on to regulate our immune systems and fend off dangerous bacterial invaders.
An important point that Sach's raises in Good Germs, Bad Germs, is that while in the past many people, including those opposed to vaccination, have argued that exposure to disease is required for the development of a healthy immune systems this is not, in fact, true. More recent research suggests that it is not infection with disease that protects children. Disease, is NOT good for people.
What is good for people is acquiring populations of benign non-disease causing bacteria that live on skin, on mucous membranes, and within the digestive tract. This is because these populations of benign bacteria do two things. One is that they fill up the ecological niche your body represents, making no room for the more dangerous bacteria which cause disease to move in.
The other, which is just starting to be understood, is that by their very presence, these benign bacteria send out biochemical signals that cause the immune system to respond by developing what is called "tolerance"--i.e. turning down the immune system. It is this tolerance that turns off the inappropriate immune attacks that cause asthma, diabetes, multiple sclerosis, etc. When the body is not populated by the bacteria it expects to meet, it does not develop tolerance, and instead seems to go on high alert, and unfortunately, this leads it to attack things like peanuts and pancreases.
Another interesting finding is that having the right bacteria established in your body causes changes in the cytokine mix which affect your mood. Sachs describes some research that finds that when levels of Interleukin-10, a cytokine that is secreted when tolerance develops, rise, serotonin levels surge too. The implication here is that the depression that is associated with autoimmune disease may not be psychological. Yes, it is a bummer having to deal with diabetes, but it may FEEL like a bummer because of the lack of calming chemicals in the brain.
This reminded me of one of the oddities of tuberculosis in the 19th century, which is that its victims were always described as being bizarrely cheerful especially as their condition worsened. One wonders if perhaps this had something to do with their immune systems having developed too much tolerance and pumping out serotonin happy juice. The book mentions that this kind of inappropriate tolerance can develop in the presence of some kinds of chronic infections that the immune system cannot take care of.
The good news reported in this book is that there are people working on using carefully cultured populations of benign bacteria to modulate the immune system. The bad news is that it turns out that bacteria can trade just about any trait you can think of with each other, particularly resistance to any antibiotic ever made, and they do it across species lines and very, very fast. A bad bug you pick up on your spinach can pick up a drug resistance gene from a "good" bacteria in your gut in the 3 hours it takes to hit your lower intestine.
This means that the most "healthful" bacteria in the world can go bad if you already have drug resistant bacteria haunting your gut. And unfortunately, most of us do. Much of the rest of the book is taken up with discussing the problems caused by the drug resistant bacteria that now fill our world.
One huge reason for the unstoppable growth of MRSA and other bacteria that do not respond to antibiotics is the overuse of antibiotics in animal feed. It turns out that the problem is not just residues that you might eat. The problem is that resistance genes that develop in livestock pass into the ground and get out into the world where the promiscuous bacteria trade them around continually. You don't need to eat meat to get bacteria in your gut that are resistant to antibiotics used only in cattle.
Another problem is the use of antibacterial soaps which kill off the friendly bacteria in our homes and leave a nice, big empty place for baddies to grow. Sachs compares cleaning your cutting board with antibiotic soap to nuking your lawn with Roundup without reseeding it, which ensures that you will end up ONLY with clumps of crabgrass and weeds.
There's lots more in this book that you should read if you are concerned about MRSA or worry about infection--a huge issue for anyone whose diabetes is not in excellent control.
For those of you who won't get around to reading it, here are a few "takeaway messages."
1. If you are serious about preventing autoimmune disease don't overprotect your baby from dirt. Throw out the antibacterial soaps. Let your kids get dirty. Let them play with the dog. Let them help diaper the baby. Eat fresh vegetables from local farms where possible.
2. Do not give your children antibiotics for viral diseases. If you do need an antibiotic, try to get the doctor to do a culture first so that the doctor prescribes a drug that is limited to attacking the kind of infection you have, rather than the "broad spectrum" antibiotics that also wipe out the bugs that are teaching your kids' immune system how to play nice.
3. Some autoimmune disease is caused by genetic flaws in the mechanisms that the body uses to develop tolerance. If that is the case, no amount of exposure to healthful bacteria will help. This may be what is going on in families that have long histories of autoimmune disease going back generations.
4. MRSA (antibiotic resistant staph) is probably the biggest health risk we all face. It is a direct result of the overuse of antibiotics in both hospitals and in animal feed. There is no easy solution to this problem. It is a huge killer of people who go to hospitals for other causes. It also produces a pneumonia that can be fatal very quickly, often in young people. Unfortunately, the U.S., alone in the Western World has no organized system for tracking hospital borne infections. So you will not know when there is an epidemic of MRSA in your local hospital. In fact, doctors at the hospital across town may not know about it.
5. If you have diabetes, the best thing you can do is avoid getting infections by keeping your blood sugar normal. People with diabetes who have high blood sugars are more prone to drug resistant infections than the rest of the population. These infections are a huge cause of amputation. Because drug resistant infections once established can be impossible to fight, take any infection no matter how small very seriously. If you are a diabetic with an A1c over 6.5% and your doctor does not treat a foot infection as an emergency, find another doctor who will.
Good Germs, Bad Germs: Health and Survival in a Bacterial World
by Jessica Snyder Sachs, is an up-to-date summary of what we know about how bacteria interact with humans. It's a fascinating story, because after a lifetime of "fighting germs" it seems that scientists are coming to learn that the interaction between bacteria and our bodies is far more complex than was ever realized and we have to work with germs and make alliances with "good germs" in order to survive.
Why this relates to diabetes is that the book starts out with several chapters that explore in greater detail than I've seen elsewhere, the research that has been establishing "The Hygiene Hypothesis." This is the idea that the huge rise in autoimmune disease we are currently experiencing is being caused by too much cleanliness.
It is starting to look like we are not being exposed to enough of the right bacteria very early in life or as we go through our daily lives, thanks to changes in water treatment, how we get our food, how we medicate illness, and how we clean our homes.
It turns out that our bodies are complex ecosystems in which maintaining populations of billions of bacteria of various kinds is essential for preserving our health, particularly in the digestive system, where, if our population of bacteria are killed off, the digestive system fails to function properly. Children absorb the good bacteria they need to have populating their own digestive tract from birth on. A caesarian birth, for example, results in a baby who is not exposed to the bacteria found in the mother's perineal area, which raises the risk of developing autoimmune problems like asthma and Type 1 diabetes.
Children who are given antibiotics early in life which kill off the developing populations of healthful bacteria also develop more autoimmune diseases, particularly asthma.
And all of us who drink filtered water (which the book mentions was not common until the last 25 years of the 20th century) and eat packaged, preservative-filled foods, may not be maintaining the colonies of soil and fecal bacteria which our bodies depend on to regulate our immune systems and fend off dangerous bacterial invaders.
An important point that Sach's raises in Good Germs, Bad Germs, is that while in the past many people, including those opposed to vaccination, have argued that exposure to disease is required for the development of a healthy immune systems this is not, in fact, true. More recent research suggests that it is not infection with disease that protects children. Disease, is NOT good for people.
What is good for people is acquiring populations of benign non-disease causing bacteria that live on skin, on mucous membranes, and within the digestive tract. This is because these populations of benign bacteria do two things. One is that they fill up the ecological niche your body represents, making no room for the more dangerous bacteria which cause disease to move in.
The other, which is just starting to be understood, is that by their very presence, these benign bacteria send out biochemical signals that cause the immune system to respond by developing what is called "tolerance"--i.e. turning down the immune system. It is this tolerance that turns off the inappropriate immune attacks that cause asthma, diabetes, multiple sclerosis, etc. When the body is not populated by the bacteria it expects to meet, it does not develop tolerance, and instead seems to go on high alert, and unfortunately, this leads it to attack things like peanuts and pancreases.
Another interesting finding is that having the right bacteria established in your body causes changes in the cytokine mix which affect your mood. Sachs describes some research that finds that when levels of Interleukin-10, a cytokine that is secreted when tolerance develops, rise, serotonin levels surge too. The implication here is that the depression that is associated with autoimmune disease may not be psychological. Yes, it is a bummer having to deal with diabetes, but it may FEEL like a bummer because of the lack of calming chemicals in the brain.
This reminded me of one of the oddities of tuberculosis in the 19th century, which is that its victims were always described as being bizarrely cheerful especially as their condition worsened. One wonders if perhaps this had something to do with their immune systems having developed too much tolerance and pumping out serotonin happy juice. The book mentions that this kind of inappropriate tolerance can develop in the presence of some kinds of chronic infections that the immune system cannot take care of.
The good news reported in this book is that there are people working on using carefully cultured populations of benign bacteria to modulate the immune system. The bad news is that it turns out that bacteria can trade just about any trait you can think of with each other, particularly resistance to any antibiotic ever made, and they do it across species lines and very, very fast. A bad bug you pick up on your spinach can pick up a drug resistance gene from a "good" bacteria in your gut in the 3 hours it takes to hit your lower intestine.
This means that the most "healthful" bacteria in the world can go bad if you already have drug resistant bacteria haunting your gut. And unfortunately, most of us do. Much of the rest of the book is taken up with discussing the problems caused by the drug resistant bacteria that now fill our world.
One huge reason for the unstoppable growth of MRSA and other bacteria that do not respond to antibiotics is the overuse of antibiotics in animal feed. It turns out that the problem is not just residues that you might eat. The problem is that resistance genes that develop in livestock pass into the ground and get out into the world where the promiscuous bacteria trade them around continually. You don't need to eat meat to get bacteria in your gut that are resistant to antibiotics used only in cattle.
Another problem is the use of antibacterial soaps which kill off the friendly bacteria in our homes and leave a nice, big empty place for baddies to grow. Sachs compares cleaning your cutting board with antibiotic soap to nuking your lawn with Roundup without reseeding it, which ensures that you will end up ONLY with clumps of crabgrass and weeds.
There's lots more in this book that you should read if you are concerned about MRSA or worry about infection--a huge issue for anyone whose diabetes is not in excellent control.
For those of you who won't get around to reading it, here are a few "takeaway messages."
1. If you are serious about preventing autoimmune disease don't overprotect your baby from dirt. Throw out the antibacterial soaps. Let your kids get dirty. Let them play with the dog. Let them help diaper the baby. Eat fresh vegetables from local farms where possible.
2. Do not give your children antibiotics for viral diseases. If you do need an antibiotic, try to get the doctor to do a culture first so that the doctor prescribes a drug that is limited to attacking the kind of infection you have, rather than the "broad spectrum" antibiotics that also wipe out the bugs that are teaching your kids' immune system how to play nice.
3. Some autoimmune disease is caused by genetic flaws in the mechanisms that the body uses to develop tolerance. If that is the case, no amount of exposure to healthful bacteria will help. This may be what is going on in families that have long histories of autoimmune disease going back generations.
4. MRSA (antibiotic resistant staph) is probably the biggest health risk we all face. It is a direct result of the overuse of antibiotics in both hospitals and in animal feed. There is no easy solution to this problem. It is a huge killer of people who go to hospitals for other causes. It also produces a pneumonia that can be fatal very quickly, often in young people. Unfortunately, the U.S., alone in the Western World has no organized system for tracking hospital borne infections. So you will not know when there is an epidemic of MRSA in your local hospital. In fact, doctors at the hospital across town may not know about it.
5. If you have diabetes, the best thing you can do is avoid getting infections by keeping your blood sugar normal. People with diabetes who have high blood sugars are more prone to drug resistant infections than the rest of the population. These infections are a huge cause of amputation. Because drug resistant infections once established can be impossible to fight, take any infection no matter how small very seriously. If you are a diabetic with an A1c over 6.5% and your doctor does not treat a foot infection as an emergency, find another doctor who will.
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