October 9, 2009

Chinese Herbal Medicines to Prevent Diabetes?

A new Cochrane review of studies of the impact of Chinese herbal medicines on preventing prediabetes. It concludes that,
Meta-analysis of eight trials showed that those receiving Chinese herbal medicines combined with lifestyle modification were more than twice as likely to have their fasting plasma glucose levels return to normal levels (i.e. fasting plasma glucose <7.8 mmol/L and 2hr blood glucose <11.1 mmol/L) compared to lifestyle modification alone (RR 2.07; 95% confidence intervall (CI) 1.52 to 2.82). Those receiving Chinese herbs were less likely to progress to diabetes over the duration of the trial (RR 0.33; 95% CI 0.19 to 0.58)
You can find the abstract, here:

Chinese herbal medicines for people with impaired glucose tolerance or impaired fasting blood glucose Suzanne J Grant et al., Cochrane Database of Systematic Reviews, 2009, Issue 4. Art. No.: CD006690 DOI: 10.1002/14651858.CD006690.pub2

You are going to be hearing a lot about this from practitioners of alternative medicine so it is important to add the REST of what the researchers concluded, which was, "all trials had a considerable risk of bias and none of the specific herbal medicines comparison data was available from more than one study."

What this means is that the studies were done by people with a stake in the outcome--i.e. people selling the product. That's the "risk of bias"--and, in addition, that each study evaluated a different herb.

So what the review really found was this. Studies conducted by people selling particular herbs find them dramatically effective. With this in mind, the Cochrane researchers conclude more study is needed.

Let's assume for a moment that Chinese herbs do slow the progression from pre-diabetes to diabetes. What does this really mean?

It means that the researchers started with two groups of people whose fasting blood sugar at the beginning of the study was above 100 mg/dl or whose 2-hour Glucose Tolerance Test (GTT) result was over 140 mg/dl (7.7 mmol/L). At the end of the study one group had fewer people whose fasting blood sugar was now over 125 mg/dl or whose 2 hour GTT result was over 200 mg/dl (11 mmol/L).

However, these kinds of studies are always binary--a subject is judged to have diabetes or not. So if one group of pre-diabetics ends up with an average 2 hour GTT blood sugar of 198 mg/dl they are "not diabetic. If the other group ends up with an average GTT blood sugar of 201 mg/dl, they are diabetic.

In practice of course, the likelihood of complications is identical for both groups. The 3 mg/dl average difference may be statistically significant (i.e. not due to chance) but it is clinically meaningless.

This is the methodology used in every "diabetes prevention trial" I have ever read. What isn't measured is the extent to which blood sugar control deteriorates in each individual over the course of the trial. A person whose GTT result rises from 142 to 195 mg/dl is still considered "not diabetic" while one whose GTT blood sugar progresses from 190 to 201 is.

By manipulating the characteristics of the two groups it is possible to get better results in one group simply because that group started out with more people whose blood sugars were at the low end than was true in the other. The averages in both groups will be the same if the other group starts out with most people having individual sugars near the center. Since that group has more individuals with higher values, they will be more likely to progress no matter what treatment is used.

But that's not the only issue here. Let's say that the difference in the two groups is greater and they start out with the same average AND standard deviation (that's a measure of the distribution of values through the group.). One group has a mean GTT two hour test result of 201 mg/dl and the other has the average of 180 mg/dl.

The next question must be, what explains this difference?

In many cases the answer is that herb contains a natural form of a substance, like the active component in the sulfonylurea drugs, that stimulates insulin production. Is this good? Not necessarily. Drugs that stimulate insulin production also turn out to do several other things.

They produce significant weight gain, often because they stimulate insulin secretion in the absence of food, which causes swiftly dropping blood sugars which result in intense hunger.

They stimulate receptors on other organs besides the pancreas--most notably the heart. The first generation sulfonylurea drugs caused excess heart attacks for this reason and there is some evidence that Prandin and Starlix may do this, too. The evidence for the newer sulfonylurea drugs is missing--but there is a black box warning on those drugs citing heart attack risk as a possibility.

However, there's a further problem with the blood sugar-lowering herbs. When you are getting your "drug" from an herb you have the additional problem that you have no idea what else is in the herb or how toxic the substance lowering your blood sugar might be to you. There are plenty of drugs that lower blood sugar that fail in clinical trials because they also cause kidney damage, or liver damage, or cancer or other serious problems.

Since herbs are not subject to any oversight the way prescription drugs are, you have no idea what the active component of your herb is doing to the rest of your body.

And that's just looking at the active component! Other substances may be contaminating your herb and they too may be dangerous. If the herb was grown using dangerous neurotoxic pesticides (illegal in the US but used elsewhere) it may be harming your nerves while it lowers your blood sugar. If it was grown using polluted water, you might be getting arsenic or any number of other dangerous chemicals with your "natural" herb.

Since herbs are completely unregulated, you have no way of knowing what you are actually getting. Unscrupulous sellers have been known to doctor "natural" supplements with cheap first generation sulfonylureas to make them "effective." Those are, you remember, the drugs that lower blood sugar while increasing the risk of heart attack.

There's one last problem with any strategy to "prevent diabetes." In every well conducted, double blinded clinical trial, as soon as people are taken off of the drug or treatment that "prevents" progression, many people's blood sugar goes right back up, and the same proportion turn out to be diabetic (i.e. they test with blood sugars over the cut off number on the glucose lab test) as were found in the other group.

That's probably because none of the drugs or treatments tested lower blood sugar low enough to avoid glucose toxicity. "Glucose toxicity" is the term for what happens when blood sugar gets so high, it starts poisoning beta cells.

If your blood sugar is over 160 mg/dl for hours at a time, you may be officially "pre-diabetic" but your blood sugars are high enough to kill beta cells. (Details on this phenomenon are discussed HERE.) People who develop diabetes have underlying genetic conditions where a) they start out with less effective beta cells than normal people and b) they are unable to grow new beta cells to take up the slack when their existing ones are stressed. If they lose a beta cell from glucose toxicity, it's gone, and because they started out with already marginal glucose control, it doesn't take much to kill off enough beta cells to render them fully diabetic.

One last issue here is that there is ANOTHER reason some people don't progress from pre- to full fledged diabetes. That is that many people who do NOT have family histories of diabetes and lack the genes associated with diabetes will become "pre-diabetic" entirely due to insulin resistance but, because they have the ability to grew new, healthy beta cells, they respond to rising blood sugars by growing new beta cells and never become diabetic. There are a lot more of these people than those who become diabetic, because it almost always takes the existance of the underlying genetic flaw to produce diabetes.

So a well-conducted study should only look at people who have family histories of diabetes, not at a population with "pre-diabetes" many of whom are not capable of developing diabetes because their genes are normal.

With this in mind, it's worth noting that there is NO data available to answer the question, "Does lowering blood sugar to normal levels that avoid beta cell death from glucose toxicity really prevent progression?"

It's worth attempting the experiment with a study group of one--i.e. yourself. If you have been diagnosed with pre-diabetes, cut back on your carbohydrates until your blood sugar is always under 140 mg/dl at 1 hour after eating and 100 at 2 hours (if possible) and see what happens over the next decade.

Many of us who have tried this experiment find that our blood sugars do not deteriorate significantly after we get blood sugars down to normal.

This approach is not going to bring back dead or dying beta cells, but it can keep you from damaging more of those that are left.

Don't expect anyone to fund that research, though. It doesn't sell product.

And do expect those who are selling product to keep showing you poorly conducted studies run by people who profit from the herb involved that "prove" that this or that ancient remedy from [insert distant land or exotic culture here] "reverses" or prevents diabetes.

NOTE: If your beta cells are dying from an autoimmune attack as happens in about 8% of those diagnosed with Type 2 who really have a slow form of Type 1, you will probably not be able to stop the attack. Nothing yet has been shown to stop autoimmune diabetes from progressing though interesting research is going on in this area.

 

4 comments:

Jim Purdy said...

Jenny, I love your persistent skepticism about everything.

I wish you were the editor of JAMA or NEJM.

Better yet, I wish you were FDA Commissioner.

Susan said...

It would behoove you to post this info on a certain board where Chinese herbs tend to dominate the diabetes discussion in lieu of common sense.

trinkwasser said...

It's not impossible that some herbs. supplements, etc. actually do have an effect, but as you say it may be dwarfed by the effect of a suitable diet.

For example I find Alpha Lipoic Acid reduces my BG on average by around 10 - 20 points. Not eating breakfast cereal drops my BG by 100 points.

Similar to that cinnamon study where researchers found adding cinnamon to breakfast porridge oats reduced BG slightly. NOT eating the porridge would have blown the results out of the water.

On the one hand if these things didn't work they would probably not have been used for generations: on the other hand if they DID work they'd probably be developed into a patented drug and marketed. Your choice . . .

Cristina Ungstad said...
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