June 27, 2010

Friends of the Blog: Feedback Wanted!

My web stats tell me there are two different types of people who read this blog. One is people who find old posts thanks to Google Search. Google loves both this site and my main Blood Sugar 101 site, so even posts a few years old get a steady stream of visitors.

The other is blog subscribers--people who come in every time I post something new. A few of these regulars post comments. The rest just read and leave. But thanks to the magic of page stats I can see how many silent regulars we have here, too, and there are a lot of you.

As most of my regular readers know, this past year I haven't had the time I usually have to research and post about the latest diabetes news because, much to my amazement, last June I sold a novel and two sequels to a major publisher. The novel was finished, but the sequels weren't even begun,and because big publishers demand that their authors deliver new books very quickly, I have had to dig in this past year and work my butt off to meet my deadlines.

Since I have one more year to go on this current contract I'm not going to be able to post here three times a week for at least another year. That means that when I do post I want to give my devoted readers what they want the most. The question is, what? I hope you, who are reading this current post, can give me some feedback to help me do this.

Typically I do a couple different kinds of post. I comment on really important news about advances or new discoveries in the diabetes field. I warn you about the many highly publicized, poorly designed studies that come up with misleading and sometimes downright dangerous conclusions that result from poor study design or cynical manipulations on the part of the companies who fund them.

I also post about the tips and tricks that can help readers lower their blood sugar. Some of these posts may state things that are not news to those of you who have had diabetes but the mail this blog generates suggests that those simple posts are the ones that have the most impact on the many newly diagnosed people who find this site every week.

So tell me. Over the next year, what kinds of posts would you like to see when you find a new post on this blog? What do you find here that you find the most helpful in your ongoing struggle with diabetes?

I realize that readers will have different needs and that some of you might not agree with other's ideas of what is most important. That's good. I want to hear from as many of you as possible to get a feeling for what keeps you coming back and what helps you preserve your health.

Post your ideas in the comments section. What kinds of posts would you like to see here over the months ahead?


June 24, 2010

Timing Your Metformin Dose

The biggest problem many people have with Metformin is that it causes such misery when it hits their stomachs that they can't keep taking it even though they know it is the safest and most effective of all the oral diabetes drugs.

In many cases all that is needed is some patience. After a rocky first few days many people's bodies calm down and metformin becomes quite tolerable.

If you are taking the regular form of Metformin with meals and still having serious stomach issues after a week of taking metformin, ask your doctor to prescribe the extended release form--metformin ER or Glucophage XR. The extended release form is much gentler in its action.

If that still doesn't solve your problem, there is one last strategy that quite a few of us have found helpful. It is to take your metformin later in the day, after you have eaten a meal or two. My experience with metformin--and this has been confirmed by other people--is that it can irritate an empty stomach, but if you take it when the stomach contains food it will behave.

There are some drugs where it matters greatly what time of day you take the drug. Metformin in its extended release form is not one of them. As the name suggests, the ER version of the pill slowly releases the drug into your body over a period that, from my observations, appears to last 8 to 12 hours. Though it is supposed to release over a full 24 hours, this does not appear to be the case, at least not with the generic forms my insurer will pay for.

Because there seems to be a span of hours when these extended release forms of metformin release the most drug into your blood stream, when you take your dose may affect how much impact the drug has on your blood sugars after meals or when you wake up.

For example, the version I take, made by Teva, releases most strongly in a period that starts 2 hours after I take it and continues strong over the next 8 hours. If I take my full 1500 mg dose first thing in the morning, my blood sugars at lunch will show the impact of the drug most strongly. Dinner will be slightly less affected--i.e. if I ate the same lunch and dinner I'd see slightly better numbers at lunch and I see the least impact on my next mornings fasting blood sugars.

If I take the same full dose at 2 PM I will see the strongest effect on my blood sugar after dinner, but I will see a lower fasting blood sugar the next morning than I would if I took the drug first thing in the morning. The trade off is that my breakfast blood sugar will be higher on that schedule if I eat any carbs.

Metformin also builds up a cumulative effect on your fasting blood sugar after you take it for a week. This effect is not dependent on when you take it. If you miss a dose you will probably see a small but immediate difference in your post meal blood sugars. But if your stop taking it for a week you will not only see that effect the day after you you stop it, you will also see a second notable increase in your fasting blood sugar and pre-meal blood sugar about a week later.

If you are taking metformin primarily to lower high morning fasting blood sugars, it may make sense to take your full dose right before bed--but the trade off will be that this timing of your dose may give you the weakest coverage before lunch and dinner, which may leave you with higher sugars for many hours of the day which counteract any advantage you might get from having lowered your morning reading.

Some people take half their metformin in the morning and half at night. That might give a more even effect throughout the day but because you smoothe out any peak in the drug's effect, you might see slightly higher meal time sugars than you would if you took it all at once.

Personally, I have learned after a lot of experimentation that taking all my metformin ER in a single dose at 2 PM gives me the most benefits. First of all it keeps me from having stomach discomfort, secondly it gives me a little boost with my dinner numbers, and finally it knocks a little bit off my morning reading.

Your results might be different, but you won't know what works for you unless you test different schedules.

If you want to change the time when you take your metformin there is one rule you must follow: Don't ever take MORE than your full prescribed dose during a 24 hour period.

If you take all of your metformin at 6 AM don't take any more until 6 AM the next day. If you have been splitting your dose and taking half at 6AM and half at 6 PM don't take a full dose of metformin until 6 PM the day after your last 6 PM dose.

You do not want to overlap your doses because you do not want to give yourself an overdose. Overdoses of metformin are very rarely life threatening--there is a case on record of someone surviving an overdose of 63,000 mg--but from personal experience I can tell you they are unpleasant and can make you feel very sick indeed. My old family doctor prescribed me an overdose years ago after he confused the top dose for the regular with the ER form--the regular can be taken in larger doses. It made me very ill though I was fine the next day.

Also, if you are testing a new dosing schedule, give it at least a week before you decide if it is working for you. That will let the long term blood levels stabilize.

Another helpful thing to know about metformin is that unlike many medications, it is not one that will cause rebound problems if you stop it abruptly. If you stop metformin all that will happen is that your blood sugar response will gradually go back to whatever it was before you started taking it. And you can start it back up at any time after that without any problems save the usual side effects people experience the first few days on the drug.

If you are not seeing the expected results from metformin, you may be taking one of the weaker generic forms. My experience and that reported by Dr. Richard K. Bernstein is that various generic brands of metformin vary greatly in their impact.

Many pharmacies will let you try a different generic brand if you want to try it. Dr. Bernstein recommends Glucophage, which was the original patented form of metformin prescribed before the generics came on the market. I haven't tried it so I can't say how useful it is. But if you have a choice, you might ask for it.

One last issue I haven never seen reported before is this. If you have trouble sleeping at night because you frequently have to get up to pee, it might be better to take your metformin before 3 PM because metformin may increase your need to pee at night. This is probably because the kidneys help remove it from the body and work harder in the 8 hours after you take the dose.


June 22, 2010

Heat Harms Insulin, Meters, and Even Some Oral Drugs!

A recent article in Science Daily reports on a presentation given at this week's meeting of the Endocrine Society.

It's worth a look: Science Daily: Many People with Diabetes Do Not Know or Heed Dangers of Hot Weather

Unfortunately, while the points it makes are true, a much better title would have been Many doctors and pharmacies don't know or heed the dangers of hot weather.

Just this week I heard from someone whose insurance forces him to get his medications from a mail order service that refuses to ship insulin overnight or with any protection against temperature. This, even though the insulin manufacturer documented for this person that when insulin sits in a hot truck it dies.

Meters and test strips can also become unusable if left in a hot car. I've cooked a whole vial of strips by leaving them on a car seat when it was in the 90s outside.

The Science Daily article points out that even pills can be ruined by heat. That was new to me but I am no stranger to the phenomenon where one month's Metformin works a whole lot better than another's. Sadly, I am also no stranger to the phenomenon where when you complain to a pharmacy that your insulin is weak or there seems to be something wrong with your pills, they assure you it couldn't possibly be true and that no one else has complained about them.

No one else probably has complained, because they probably assumed it was something in their own physiology that made their blood sugars suddenly shoot up. Given the vague way that most people with Type 2 are prescribed insulin and their lack of understanding of how insulin doses should correlate tightly with blood sugars, it is no surprise that customers pay for their insulin and accept whatever they're given, even if it barely works.

Sadly, the problems caused by temperature are not limited to heat. I took an insulin pen with me, in my purse, when I dined at a restaurant last December when outside temperatures dropped to a low in the very low 20s. Even though I was only outside for maybe ten minutes, that was enough to freeze the pen. A faulty fridge can do the same thing. If you see ice crystals in your milk or vegetables, chances are any insulin you had in the fridge is toast, too.

But just try getting a replacement from your health insurance when your insulin pen dies. Good luck!

Because pharmacies get their insulin from wholesalers who won't ship it overnight or with temperature buffering anymore, there is no easy solution to this problem. The insulin you buy from the pharmacies is just as likely to have sat in a hot truck for three days as the mail order stuff.

Doctors aren't aware of this problem, and neither, based on my experience, are pharmacists. That means if you suddenly see unexplained high blood sugars after using a vial of bad insulin, the doctor may just raise your dose rather than insist that your pharmacy replace the vial.

What makes it more of a problem is that this issue is fairly. Five years ago mail order pharmacies always shipped insulin overnight with cold packs. The switch to sending it in hot slow trucks is a recent, cost cutting move--one that is going to result in more blindness, amputation and death for those who use dead insulin and more hypos for those who get used to weakened insulin and then get a vial of full strength.

I wish I had some sage words of advice to offer about how to deal with this. About all I can do is assure you that if you are experiencing major fluctuations in blood sugar response from vial to vial or pen to pen it might not be your physiology at fault.

If you use small doses, it is also a good idea to remember that some insulins weaken over time no matter what you do. I found Levemir very prone to weaken. On the other hand when I used Apidra it stayed potent for many months even though it was not refrigerated. The Apidra I used was a sample my doctor gave me since my insurance wouldn't pay for it. When the doctor got another batch, mailed to her in the summer, it arrived dead. No insulin can survive temperatures in the very high 90s for very long.

If you have a good vial or pen, protect it from heat and cold. A Frio pack works well for this. Don't leave your meter in a hot or cold car, either. And remember that even ten minutes of exposure, as you walk to a restaurant on a very hot or very cold day may be enough to weaken your insulin or render it useless.

Post your experiences with this issue in the comments, along with any solutions you might have found!

June 13, 2010

Too Much Vitamin D and Calcium ==> Trouble

I've been struggling with a very tough to diagnose blood pressure problem for the past six months. A lot of expensive tests came up with nothing that would explain why my blood pressure was randomly surging well into the danger zone (168/110) and refusing to respond to the medications that had always worked for me in the past.

To make it more confusing every so often my blood pressure would randomly drop back to normal and stay there for a few days so it was clear that my high blood pressure was not due to obstructed arteries or kidneys.

As so often happens, my family doctor did one round of tests and then sent me to a nephrologist who was supposed to be an expert in blood pressure. The nephrologist did another round of tests and sent me to my endocrinologist. The endo did yet another round of tests that came up blank and then told me that such cases were extremely difficult to diagnose and that my insurer would not pay for the next step which involved going to an expert at a major hospital outside of our rural region.

Fortunately, a health news item came across my screen that gave me some insight into what was going on. It described a condition called "Milk Alkali Syndrome" which after many years of nonexistence had come roaring back. The syndrome causes high blood pressure and kidney problems.

You can read about Milk Alkali Syndrome in this summary posted on Diabetes in Control:

Calcium Supplements Can Increase Risk of Kidney Failure

Though the study makes it sound as if the problem is caused by calcium supplements, close reading reveals that it caused by the combination of high calcium and high Vitamin D and that the recent spike in cases has been caused by the recent fad of people supplementing with high levels of Vitamin D.

I have been supplementing with Vitamin D for three years at my doctor's suggestion because I am a melanoma survivor and there's some data suggesting Vitamin D fights melanoma. I had achieved a level of 39 ng/ml a year ago, taking 1000 IU a day so I had raised the dose to 2000 IU because I'd been influenced by some vocal online doctors to believe that higher was better.

When I dug out my many recent lab tests I found that my family doctor had tested my calcium level. It was NOT flagged as abnormal. The range for blood calcium went up to 10.3. But even so, My blood calcium was 10.3. So while my calcium level was normal, it was just barely normal.

Further research revealed that taking diuretics (which I was doing in an attempt to lower my very high blood pressure )lowers blood calcium. So that "normal" reading was almost certainly lower than the blood calcium level I'd had a few weeks before.

Hunting for previous values I found one from before I supplemented with Vitamin D which was in the 8s. Much more normal.

I do not supplement with calcium. I stopped after reading about the Aukland Study described further on in this post). But I do eat a lot of cheese. I had already noticed that there seemed to be some link between my blood pressure and my cheese intake, but I had thought this might have something to do with a factor found in aged cheese that has also been associated with elevated blood pressure. As a result, I'd cut back on aged cheese, but not all cheese.

When I looked at my latest Vitamin D test I found it showed my Vitamin D to be 55.8 ng/dl. The test a year and a half earlier when I'd been taking only 1000 IU a day had been 39 ng/dl. My doctor had thought 55.8 an excellent level, but recent research suggests that more is not necessarily better when it comes to Vitamin D levels.

All of a sudden, my mysterious symptoms started to come into focus. I had two "normal" lab results that were no more "normal" than a 2 hour glucose tolerance test result of 139 mg/dl (a result that often ignores a one hour value well over the 200 mg/dl level diagnostic for full fledged diabetes).

When I read on further, I learned that the safe ranges for Vitamin D were drawn from studies done on White males of European ancestry--and that some data suggests that people from Non-Northern European ethnic heritages have adapted to lower Vitamin D levels and that they do poorly when they attain the high blood levels suggested for White males.

More interestingly, a decently conducted three year study of older women given high dose injections of Vitamin D to avoid osteoporosis discovered that levels of blood Vitamin D corresponding to mine correlated with more not less bone fractures. You can read that study here:

Annual High-Dose Oral Vitamin D and Falls and Fractures in Older Women: A Randomized Controlled Trial. Kerrie M. Sanders. JAMA. 2010;303(18):1815-1822.

(Note that the units used in this study were nmol/L not the ng/dl labs use in the United States. Converting the units shows that these women started out deficient with average Vitamin D levels of 19.63 ng/dl, but after the Vitamin D shots their levels went up to an average 48.08 ng/dl.) We know that too much blood calcium is linked with bone brittleness, too.)

Another recent study, The Aukland Study, had found that women supplementing with calcium had more heart disease (presumably linked to calcification in their arteries) than women who didn't.

Vascular events in healthy older women receiving calcium supplementation: randomised controlled trial. Mark J Bolland. BMJ. 2008;336:262-266 (2 February), doi:10.1136/bmj.39440.525752.BE (published 15 January 2008)

And a disturbing comment in yet a brand new study commenting on the Aukland Study really got me thinking.

It said:
there is substantial epidemiological evidence that serum calcium levels in the upper part of the normal range are a risk factor for vascular disease
The combination of this information with the information that Milk Alkali syndrome (high blood calcium caused by high calcium and Vitamin D intake) caused high blood pressure suggested to me that I might have found the explanation for my blood pressure problems--and that I had been, once again, the victim of another doctor-caused medical disaster!

Once I had sorted this out, I stopped taking the 2000 IU a day of Vitamin D I had been taking for the past year. I cut out all cheese from my diet--which made me realize just how much cheese I'd been eating--much more than I thought!

I had read it takes about 2 weeks to eliminate HALF the excess vitamin D in the blood and that more Vitamin D is stored in fat and slowly released, so I figured it would take a while to restore truly normal calcium levels. Even so, after ten days it looks like I might be onto something. My blood pressure has already come down--it's in the 120s over 80s rather than the 140s over 90s when I wake up and has been staying in that range most of the day instead of spiking higher.

I will be avoiding cheese for another month and tracking how my blood pressure does. When I see my endo for my regular appointment in October I'll ask for repeat Calcium and Vitamin D tests. Since I did well at the 39 ng/ml Vitamin level I'll shoot for that--but only if I can sustain that level without elevated calcium. Meanwhile, I hope I haven't inadvertantly deposited damaging amounts of calcium in my arteries and kidneys.


For those of you reading this who have been supplementing with Vitamin D thanks reading all the doctor-inspired hype, my message here is NOT that you should not take Vitamin D.

Instead, what I'm saying is that if you are supplementing Vitamin D you need to get your blood levels of both Vitamin D and Calcium tested periodically so you can avoid dangerous Calcium levels. 1000 IU appears to be a safer level for supplementation than anything higher, and if you don't know what your levels are you should not supplement with more until you can check those levels out.

My other point is this: if you are eating a low carb diet and also taking white, chalky pills--prescription or other supplements), be aware that you may be getting much more dietary calcium than you realize.

Since it is looking like high normal calcium levels damage both your arteries and kidneys maintaining truly normal calcium levels is probably most important than obsessing about cholesterol.

UPDATE 8/5/10: Two months after stopping ALL Vitamin D supplementation and avoiding cheese my calcium levels are back to normal and my blood pressure is far more stable. I'm gong to stick with this regimen for a few more months and only supplement D in the fall after I stop gardening each day. I'll stick with the 1000 IU level which worked well for me in the past.


June 9, 2010

Yet More Good News About Metformin

Sometimes it seems like every day brings us new bad news about the side effects associated with the expensive, new heavily promoted diabetes drugs that most doctors push on patients.

And then there's metformin. We keep getting news about metformin's side effects, but for the past year every single on of those side effects has been something good, for example, we now know metformin decreases the risk heart attack and also of contracting several important cancers.

Now scientists have found that metformin has yet another positive side effect: it blocks the reproduction of the Hepatitis C virus which allows people infected with it to recover from this dreadful disease.

You can read the details here: Science Daily: New Use for Old Drugs in Treating Hepatitis C

Given that you can buy a month's worth of generic Metformin for $4 at many pharmacies you won't hear much about this. No one gets rich selling you generic metformin so no one sends out the press releases. Your doctor may not hear about this either.

But if you are someone who, like me, thinks long and hard before popping a pill because you know how dangerous so many pharmaceuticals have turned out to be, this latest piece of news should reassure you that metformin--which lowers blood sugar, stops the liver from dumping glucose, and helps muscles and liver burn fat--is one drug you can take knowing that its side effects make it fight other dangerous diseases and keep you living a longer and healthier life.

June 3, 2010

The Latest Avandia Outrage: A Shockingly Bad Study Promotes It for Prediabetes

The slimy weasels who profit from selling the dangerous drug Avandia don't give up easily. Though there is incontrovertible evidence that their drug causes heart failure in people who did not have it before starting the drug, as well as ostoporosis and an increased risk of heart attack, they keep sending the health media carefully doctored press releases touting new and marvelous features of their drug.

The latest is the claim that Avandia does a humdinger of a job at preventing diabetes, reducing it by two thirds. The study is a triumph of sleazy research technique, but because the drug reps will be hard at work "teaching" your doctor of this wonderful new feature of their dreadful drug, you need to understand what the study actually did and what it learned.

The study abstract can be found here:

Low-dose combination therapy with rosiglitazone and metformin to prevent type 2 diabetes mellitus (CANOE trial): a double-blind randomised controlled study. Prof Bernard Zinman. The Lancet. June 3, doi:10.1016/S0140-6736(10)60746-5

As you can see by looking at the title, this study combined Avandia with Metformin. Because we know that Metformin delays the diagnosis of Type 2 diabetes (by lowering blood sugar, not by correcting underlying flaws) you'd assume that any trial of metformin with another added drug would compare the combination with metformin alone.

But since the point of this study was to breath life into the decaying corpse of Avandia, that comparison was omitted. There are only two groups in this study, those on the Avandia metformin combo and those on a placebo.

Beyond that, the study involved only about 200 people, divided into two groups. This means that if one out of every two hundred people taking Avandia developed a severe or even fatal complication, the study group is too small to detect it. Since the problem with Avandia is that it has been shown in large studies to cause severe and sometimes fatal complications the study design used here is worthless and very clearly designed only to squeeze more profit out of GlaxoSmithKline's dangerous drug.

The next problem with the study is that it lasted only a median of 3.4 years. Why is this a problem? Because even if the study size had been big enough to make the severe side effects evident, the most serious of the Avandia side effects may take up to a decade to become evident. That is because Avandia works by transforming bone stem cells into baby fat cells into which glucose gets pushed. (That is why Avandia causes permanent weight gain.) This means that over time bones are weakened because they don't get new bone cells coming in to reinforce them. Eventually they start to crack and by then it is too late to fix the problem. But you won't see this effect over 4 years. So again, this study was designed to avoid highlighting a known damaging side effect of Avandia.

But setting aside the fact that it is impossible to know from this study whether Avandia is safe in this context, the actual finding of the study was another blow to Avandia's claims, and makes it crystal clear why there was no "metformin only" group included in the study--though you wouldn't know this from the press coverage.

The study claims,
70 (80%) patients in the treatment group regressed to normal glucose tolerance compared with 52 (53%) in the placebo group (p=0·0002).
Note that the study is reported as claiming that two thirds of those who took Avandia (with metformin, though the headlines miss that) did not progress to diabetes. But at the same time, more than one half of those who did not take any drug also reverted to normal blood sugar status. So in fact, the drug combo only kept an additional 27% of participants from being diagnosed with diabetic blood sugars.

Note that DPPT--a far more robust study of 3234 people with pre-diabetes found that Metformin alone decreased the progression to diabetes by 31% over an average of 2.8 years.

Reduction in the Incidence of Type 2 Diabetes with Lifestyle Intervention or Metformin:Diabetes Prevention Program Research Group NEJMVolume 346:393-403, February 7, 2002, Number 6

So there is basically no significant difference in effect between the use of metformin alone and metformin combined with dangerous drug Avandia even allowing for the extra couple months in the Avandia study.

All this seems to have eluded the peer reviewers who approved this study for publication.

Okay, that's bad enough, but there's one last point. The makers of Avandia promote it to doctors with the claim--unsupported by evidence--that members of the TZD drug class to which it belongs rejuvenate beta function. This study, like every other study of the subject finds that isn't true. The Lancet study states,
The change in β-cell function, as measured by the insulin secretion-sensitivity index-2, did not differ between groups (placebo −252·3, −382·2 to −58·0 vs rosiglitazone and metformin −221·8, −330·4 to −87·8; p=0·28)
So the improvement achieved in the drug group (most likely from taking the metformin) did not occur because the beta cells were functioning better, but only because blood sugar was lowered. Whether this was because the metformin blocked liver dumps, or because it promoted glucose uptake at the muscles by revving up AMP-Kinase, or because Avandia pushed excess glucose into brand new baby fat cells is unknown.

So that's the story that the folks at The Lancet somehow missed. And because they missed it, you can be sure some percentage of boneheaded doctors will read this new study and put patients who don't have diabetes on Avandia. After all, why prescribe an effective, safe, generic drug that can be bought for $4 a month--Metformin--when you can prescribe one that does nothing but harm and costs up to $100 a month? The answer has a lot to do with the subtle incentives drug companies still provide doctors, but that's the subject for another blog post.

Unfortunately, even doctors who are gun shy about Avandia still believe that its evil twin Actos is safe. It isn't. Actos also causes heart failure and works by changing bone baby cells into baby fat cells causing permanent weight gain and, long term, damaged and broken bones. Actos may not cause heart attack, but that information won't mean much if you develop heart failure, which over time is just as fatal. It's also worth noting both drugs raise the risk of retinal edema which means that if you are particularly unlucky, both Avandia and Actos can seriously damage your vision.

Bottom line: If you have pre-diabetes can't get your blood sugar back to normal by cutting carbs (which has been proven far more effective than any drug) stick with metformin. It's safe, it works, and its side effects include things like weight loss and a lower incidence of cancer.