Friday, February 8, 2008

Insulin Insanity

The New York Times recently reported how a large study on the effects of lowering blood sugar in Type II diabetics had to be stopped due to ethical concerns, because a lot more people were dying in the treatment group. This was the ACCORD study run by the NHLBI and NIH, which enrolled over 10000 Type II diabetics. The treatment group received "intensive" therapy to control blood sugar, mainly in the form of insulin.

The increase in deaths seems to be a big surprise to most involved, eliciting a lot of handwaving explanations. But if you just think a little about the nature of Type II diabetes and the action of insulin in the body, I suspect the outcome makes perfect sense; worse, had anybody applied some logical thinking to well-established medical knowledge, the outcome would have seemed preordained. The problem here (which seems to be endemic in modern medicine) is that few people seem to be able to see the forest for the trees. Insulin and sugar have well-known physiological effects, and any hypothetical treatment for Type II diabetes should account for these. Of course, almost nobody does this, leading to the current mess.

Let's start by being clear on what Type II diabetes is. Diabetes is generally thought of as a condition where blood sugar is chronically too high; but is chronically high blood sugar the cause of the disease, or just a symptom? In Type I diabetics, the patient's immune system attacks the pancreas (the organ responsible for making insulin), destroying it's ability to secrete insulin. Insulin is one of the body's most powerful hormones, governing many aspects of metabolism, not least being blood sugar levels. Blood sugar is tightly regulated in the body, because sugar has several damaging toxic effects; but you need a little sugar in the blood to power certain cells, like red blood cells. So Type I diabetics, lacking insulin, suffer increasing blood sugar, and all of the attendant bad effects, on average having significantly shortened lives.

Type II diabetes is really the opposite condition: too much insulin. You still have the symptom of increased blood sugar, but now it occurs because your body's cells have a downgraded response to the insulin secreted by the pancreas. Since the cells don't respond as readily to the insulin signal, sugar tends to build up in the blood, so the pancreas cranks out more insulin, which further desensitizes the cellular insulin response, resulting in a vicious cycle where both insulin and blood glucose levels increase over time. Ultimately your pancreas reaches the limit of what it can do, blood sugar goes through the roof, and you're classified as a Type II diabetic.

Now it makes sense to treat a Type I diabetic with insulin, because they have a serious lack. Insulin does a lot of things besides regulate blood sugar, and if you don't have any, you're in big trouble. But insulin is a seriously powerful hormone. It has many effects beyond reducing blood sugar, and these are just as well-known as the effects of high blood sugar itself. There's a reason why, in the presence of a too much insulin, your cells lower their response: too much insulin is damaging. Insulin resistance is a protective mechanism, and in Type II diabetics, it's out of control. From an evolutionary standpoint, one could go so far as to argue that insulin is more toxic than high blood glucose, otherwise the mechanism for insulin resistance would not have evolved (but that's just speculation on my part).

Giving insulin to a Type II diabetic is like dumping water in a sinking boat. It just exacerbates the original problem by further increasing insulin resistance AND subjecting the body to further damaging effects of chronically elevated insulin levels.

Now, you might argue that the "experts" had more information, and that I am oversimplifying things. I probably am oversimplifying things, but not as much as the so-called experts. Check out these quotes from the NYT article:

“It’s confusing and disturbing that this happened,” said Dr. James Dove, president of the American College of Cardiology. “For 50 years, we’ve talked about getting blood sugar very low. Everything in the literature would suggest this is the right thing to do,” he added.

Dr. Irl Hirsch, a diabetes researcher at the University of Washington, said the study’s results would be hard to explain to some patients who have spent years and made an enormous effort, through diet and medication, getting and keeping their blood sugar down. They will not want to relax their vigilance, he said.

“It will be similar to what many women felt when they heard the news about estrogen,” Dr. Hirsch said. “Telling these patients to get their blood sugar up will be very difficult.”

Dr. Hirsch added that organizations like the American Diabetes Association would be in a quandary. Its guidelines call for blood sugar targets as close to normal as possible.

And some insurance companies pay doctors extra if their diabetic patients get their levels very low.

The low-blood sugar hypothesis was so entrenched that when the National Heart, Lung and Blood Institute and the National Institute of Diabetes and Digestive and Kidney Diseases proposed the study in the 1990s, they explained that it would be ethical. Even though most people assumed that lower blood sugar was better, no one had rigorously tested the idea. So the study would ask if very low blood sugar levels in people with Type 2 diabetes — the form that affects 95 percent of people with the disease — would protect against heart disease and save lives.

Not very scientific, wouldn't you say? Everybody just assumed that lowering blood sugar was "the right thing to do", come hell or high water. In a sense, that's true: high blood sugar definitely causes serious damage. The problem is that nobody gave any thought whatsoever to the potential downsides of the treatment, especially in light of the known cause and symptoms of Type II diabetes, and the known effects of high insulin. The result? Many people killed in an effort to prove the dogma, not to mention millions of dollars wasted. With even a little rational thinking based on well-established knowledge, those lives would have been spared, and those dollars put to much more productive use. And the scary thing is, they still don't get it:

Clearly, people without diabetes are different from people who have diabetes and get their blood sugar low.

It might be that patients suffered unintended consequences from taking so many drugs, which might interact in unexpected ways, said Dr. Steven E. Nissen, chairman of the department of cardiovascular medicine at the Cleveland Clinic.

"Clearly", Type II diabetics with low blood sugar are different from non-diabetics: they have high insulin. They knew that before the study, but chose to ignore it, and blindly continue to do so. Apparently most of the deaths in the study were from heart attacks. Should we be surprised? Below is an excerpt from an excellent article about insulin (go down to the section "Insulin and Cardiovascular Disease"):

But there are certain tissues that aren't becoming resistant such as your endothelium; the lining of the arteries doesn’t become resistant very readily, so all that insulin is affecting the lining of your arteries.

If you drip insulin into the femoral artery of a dog, there was a Dr. Cruz who did this in the early 70s by accident, the artery will become almost totally occluded with plaque after about three months.

The contra lateral side was totally clear, just contact of insulin in the artery caused it to fill up with plaque. That has been known since the 70s and has been repeated in chickens and in dogs; it is really a well-known fact that insulin floating around in the blood causes a plaque build-up. They didn't know why, but we know that insulin causes endothelial proliferation. This is the first step as it causes a tumor, an endothelial tumor.

Insulin also causes the blood to clot too readily and causes the conversion of macrophages into foam cells, which are the cells that accumulate the fatty deposits. Every step of the way, insulin is causing cardiovascular disease. It fills the body with plaque, it constricts the arteries, it stimulates the sympathetic nervous system, it increases platelet adhesiveness and coaguability of the blood.

Insulin is a part of any known cause of cardiovascular disease. It influences nitric oxide synthase; you produce less nitric oxide in the endothelium. We know that helps mediate vasodilatation and constriction, i.e. angina.

So it would seem that, given what is known about the effects of insulin on arteries, an increase in deaths from heart attack should have been the expected outcome.

Once again, do you want these people making decisions about your health? If you are a Type II diabetic, the outcome of this study should serve as motivation to find out for yourself what is known about the cause of the disease, and the treatment options available. Don't blindly follow the brain-dead dogma espoused by most physicians and scientists, apparently blind themselves to long-established knowledge about the effects of insulin. Get the information for yourself, and ask your doctor hard questions about WHY you should do what he/she recommends. If the best answer they can give is "because I said so", you might consider looking for another doctor.


Anonymous said...

As a type II diabetic diagnosed 3 years ago, the first thing I did when tests confirmed I had T2 was reduce my carbohydrates. Quite predictably, my BG dropped to near normal levels in about 6 weeks. This is what I expected to happen. Since I can not read my insulin levels I have to assume that they also dropped which woukd be a very good thing. I did this when I didn't know squat about diabetes. It just seemed like a logical approach. What I didn't do what was allow my MD to get me started on medication(s).

A few years later I have learned quite a bit about diabetes. I am now following a very low carbohydrate, no grain diet with intermittment fasting (1-2 meals per day with no snacks). And I have never felt better in my life. What I discovered after testing the effect many times is that I react very strongly to grains such as wheat. It does not matter whether it is refined or wholegrain. It makes no difference.

I am currently researching phase 1 insulin response (a.k.a 'the insulin dump'). I am speculating that IF eating provides the cycle time needed for the insulin dump to replenish where multiple meals per day don't allow this to happenn in T2 diabetics, especially closely spaced meals. This is an issue that you might consider looking into. Interestingly, (maybe not)I can not find much research on the subject.

I assume you saw the new research study that indicates that treating heart attack patients aggressively with insulin saves their lives. In the short term this may be the case. But I doubt many MDs will pay attention to the long term effects. As with other drugs such as statins, they will simply rationalize that insulin has so many positive benefits a few deaths are acceptable.

Dave said...

Yes, it's amazing how often the "logical approach" is actually the best one. Modern medicine too often eschews logic in favor of maximum intervention - and as with giving insulin to Type II diabetics, maximally illogical intervention at that. Hopefully more people will follow your example and think for themselves, rather than putting all of their faith in modern medicine.

That said, modern medicine does do some things well, namely dealing with problems that really do require maximum intervention, like a heart attack. One of the actions of insulin is to dilate blood vessels, so it is not surprising that it is effective in reducing damage from heart attacks. It may save your life in the short term, but as you note, the long term effects are probably negative. But at least it improves your chances of living long enough to experience the long-term negative effects :-)

OhYeahBabe said...

Great post, thank you! I hope appropriate conclusions are drawn when the study data is released. I'm not optimistic, though, because the conclusions will follow the money. :-(
My blog: Kimorexia

Anonymous said...

If the point you are trying to make is that reducing blood glucose in Type 2 diabetics is a non-worthy goal I'm afraid I am going to have to disagree!

If, on the other hand, you are trying to indicate that dosing a patient with extra insulin or insulin sensitizing agents while still allowing them to consume unhealthy amounts of carbohydrate is only going to make things worse I am in agreement.

Simply put, and without resorting to completly falacious interpretations of the effects that natural selection might have upon all this, diabetes (whether Type 1 or 2) is a disorder virtually defined by the patient's reduced or totally absent ability to process carbohydrate. Thus it would only make sense that the first and most important step to take would be to greatly reduce the amount of carbohydrate in the diabetic patient's diet.

In many type 2 patients that is all that is required to puts things on the right track. Others are of necessity forced to add either insulin sensitzing agents or insulin to their regimen.

This riduculous "study" however followed the Silver Bullet approach pushed by the drug companines. Thus with little or no dietary/behavior modification the protocol utilized just pumped in pills or injections in an ill informed effort to get that bG down.

The rest, as you have quite rightly pointed out, is an inevitable consequence.

Once again the so-called Best & Brightest turn out to be more than a bit slow and dim...

Dave said...

I absolutely think reducing blood glucose in Type II diabetics is a worthy goal. I just don't think the way to do it is by reinforcing the original disease process.

I agree with you. Type II diabetes is characterized by poor glucose metabolism and hyperinsulinemia. Telling Type II diabetics to eat more carbohydrates (which they can't process) and take insulin (which they already have too much of) is just about as poor a strategy as one could possibly conceive.

Anonymous said...

Hi Dave,
the question that arises having read most of Gary Taubes book is;

Whats worse for long term health
a) slightly elevated blood sugars?
b) elevated insulin levels?

Given that the two usually go hand in hand in people sliding towards type II diabetes, I do wonder if the harm attributed to mild hyperglycaemia should be laid at the door of hyperinsulinaemia?

Michael Eades points out that the normal resting level of glucose equates to a rounded teaspoon of sugar dissolved in the complete blood volume. Increase this by 50% and I presume you have fasting BG readings of 7 and higher, in the region where damage is likely. But I find it hard to believe that this extra half teaspoon of sugar is the culprit, and perhaps its the associated higher insulin that is the problem. The higher BG then become an innocent bystander. Further, given that low GI eating spreads the BG and insulin peaks over a longer period of time, then a short sharp high GI meal with the same amount of carbs might actually be less harmful. I've no idea what the answers are, or how you do any single variable research? Is there anyone with high BG yet low insulin?

Neil Wilkinson

Dave said...

Hi Neil. Type I diabetics have high blood glucose and low insulin. But again, it's difficult to separate the effects, because lack of insulin causes a whole range of metabolic problems (like starvation).

I suspect it would be very difficult to answer questions of elevated blood glucose vs. elevated insulin. You might get some info from animal studies, but human studies would be require tightly controlled conditions over long times.

Personally, it wouldn't surprise me at all if an extra half-teaspoon of glucose in the blood caused significant problems, if maintained over time. See e.g. this article on advanced glycation endproducts (AGE), the end result of chemical reactions where sugar binds with proteins. AGE increase oxidative stress, interfere with protein function, and induce inflammation. That the body responds aggressively to even small elevations in blood sugar is a strong hint that evolution has "discovered" that elevated blood sugar will decrease your life span. There's also a special receptor for AGE (called RAGE) which, amongst other things, induces inflammatory reactions, probably in an effort to clear AGE from the body before they can do too much damage.

Insulin has many effects beyond controlling blood sugar. Insulin is an anabolic hormone, meaning that it tends to "create new stuff". Glucose turns into glycogen or fat, amino acids to proteins, etc. Insulin is popular amongst bodybuilders, because it is difficult to detect, and produces definite "results". There is growing evidence that insulin is involved in cell differentiation, i.e. making brain cells vs. liver cells, and more importantly vs. "undifferentiated cells", which are potentially cancerous. For instance, it is well known that Type II diabetes is strongly correlated with risk for many types of cancer. Data is apparently sparser for Type I diabetic cancer risk, but I found this study which would indicate considerably less correlation between cancer risk and incidence of Type I diabetes. That certainly raises the question as to the potential role of insulin in the development of cancer. More study is needed, particularly in defining the role of insulin and insulin-like hormones on cell differentiation and division.

In the end, I would think the best course of action is to get both insulin AND blood glucose under control, which means not using exogenous insulin to lower blood sugar in Type II diabetics. I'll be posting more information about insulin in the future.

Anonymous said...

Thanks for your speedy reply Dave.
I am attempting to reduce my blood glucose, (fasting was 7.3 - hospital lab test - in November,) principally by a big reduction in refined carbs. I don't appear to go very high, between 8 and 9 after an experimentally.
moderately carby meal, so I hope that long term, my presumed IR will decrease. (I haven't had a fasting insulin done)
I do want to avoid another fasting BG over 7, and I don't want the label of 'diabetes' on my medical record, that would ensue!
Looking forward to future posts on your blog.

Neil Wilkinson