Before You Choose Weight Loss Surgery Read This

A new study confirms what quite a few other studies suggest. The reason that weight loss appears to "cure" diabetes has nothing to do with weight loss. It is because the surgery changes the way that gastric hormones, most notably GLP-1 are secreted.

The study is discussed here:

Science Daily: How weight loss surgery reverses Type 2 diabetes.

I've blogged before about the irresponsible way that stomach amputation is being promoted as a "cure" for diabetes when the promoters' own data show that it doesn't cure it, but merely slows it down for a few years. If you haven't read that post, I'd urge you to read it. You'll find it HERE.

But I bring up the topic again because this latest study--a rodent study--both confirms the temporary nature of the fix and suggests that many people could achieve the same effect without risking a surgery whose kill rate is so high that if it were associated with a drug, that drug would never have made it through the FDA approval process. (Surgery doesn't need to go through any approval process.)

The doctors who profit mightily from selling obesity surgery are NOT going to tell you that there is a drug which is far safer than the surgery and which controls blood sugar and provides dramatic weight loss to one third of those who take it: BYETTA.

Byetta is a synthetic form of GLP-1. It dramatically slows stomach emptying, making it very hard to overeat. For many people it changes the brain's way of processing hunger, making them not feel like eating. It may stimulate insulin release, too.

An FDA report found fewer than 100 cases of pancreatitis in the hundreds of thousands of people who had taken Byetta, which sparked a panic among doctors who stopped prescribing it. For some reason, the fact that 25 people out of every 10,000 who have weight loss surgery die shortly after having the surgery went unnoticed by these same doctors. That same statistic is rarely mentioned by the gastric surgeons they refer their patients to, either.

Further review has not conclusively linked Byetta with pancreatitis--the rate of pancreatitis in obese people who don't take Byetta is pretty much the same as the rate in obese people who do, and that rate is extremely low.

So before you amputate a big part of your stomach, rearrange your intestinal tract or have a band inserted that may cause severe scarring or infection, ask your doctor about Byetta. If he tries to scare you away from trying it, ask why he's not concerned about the far higher death rate from WLS. If he doesn't know the death rate from WLS, find a new doctor.

One huge advantage of Byetta is that if it doesn't work for you, you just stop taking it and any side effects go away. The surgery permanently modifies your digestive tract in a way that cannot be reversed.

It produces a shockingly high rate of complications, and those who have it often require subsequent surgeries when infections occur, stitches tear, and bands become embedded in tissue, These surgeries may also cause permanent malnutrition which puts you in danger of starving to death.

WARNING! There is a new drug similar to Byetta that is much less effective and more dangerous, VICTOZA. Your doctor may suggest you try it instead of Byetta because doctors inevitably put patients on new drugs in response to drug company marketing efforts which often include subtle bribes to the doctor. Don't let a doctor try to talk you into trying Victoza instead.

You can read about why Victoza is a bad substitute for Byetta HERE.

One last thing: If you're desperate enough to be considering weight loss surgery to "reverse" your diabetes, before you do something irreversible, spend a month trying out the drug-free technique that lowers blood sugars to the normal level for a very high proportion of people with Type 2 diabetes of those who try it--including those A1cs as high as 12%.

You'll find this extremely simple and dramatically effective technique described here:

How to Get Your Blood Sugar Under Control

The American Diabetes Association admits in its treatment guidelines that the approach sketched out here is both safe and effective.

It just doesn't pour profits into the pockets of surgeons and drug companies. Give it a try. If it doesn't work, you probably have something else going on besides garden variety Type 2 and need to see an endocrinologist not a gastric surgeon to find out what and get help with it.

The study referenced HERE makes it crystal clear that if your problem is insulin insufficiency or a serious endocrinological problem rather than high carb intake weight loss surgery will have no effect on your blood sugar.

 

Proof that the Diabetes Seen in the Young Is from Genetic Damage Not Lifestyle

I've been saying this for years, but finally someone has done the genetic work needed to prove it.

The epidemic of diabetes we are seeing among children and people in their teens is NOT caused by overeating and failure to exercise. It's caused by genetic damage to the mitochondria--the parts of the cell that burn glucose.

You can read the study that proved this here:

Subjects With Early-Onset Type 2 Diabetes Show Defective Activation of the Skeletal Muscle PGC-1α/Mitofusin-2 Regulatory Pathway in Response to Physical Activity. María Isabel Hernández-Alvarez et al. Diabetes Care March 2010 vol. 33 no. 3 645-651 doi: 10.2337/dc09-1305

You can read a report that gives slightly more information than the abstract in the Diabetes In Control report you'll find HERE.

Though it won't be, this should be front page news in every paper and headlining the TV Evening News, because what this study makes crystal clear is that cutting out sweets and lengthening recess is not going to be enough to keep children from developing both morbid obesity and Type 2 diabetes at tragically young ages.

Genetic damage like this occurs when children have been damaged in the womb by chemical exposures to substances ranging from pharmaceutical drugs the mother takes, to the herbicide atrazine in the water their mother drank, to pesticides in their food, to PCBs in dust, and to the plastics leaching into food from cans and containers. Once you damage a gene that occurs in every cell that burns glucose, the damage is not reversible.

The industry that has polluted our environment will fight to its last dollar to keep the public from realizing what is really causing the so-called diabetes epidemic. Twenty five years ago there was a much stronger public awareness of the dangers of this pollution, but since then it has been redirected into the Green movement, and the people who used to fight to keep herbicides out of your drinking water are now more obsessed with recycling their garbage and getting better mileage from their cars.

Meanwhile, a whole generation of children is turning out to have been as damaged by pollutants as the transgendered frogs found all over the world. The poisoning of our environment by industrialization may have grown to where it may be too late to reverse.

The drugs excreted into wastewater that are not filtered out in treatment plants, the chemicals in our air and water, and the plastics that surround us are taking a toll, and it will take a few more decades, and millions more permanently damaged babies until we know exactly which chemicals are causing it.

As you can see HERE, a map of the highest incidence of obesity in the US is very similar to the map of areas where Atrazine use is highest. We know that exposure in the womb to the plastic Bisphenol-A makes animal offspring dramatically obese. We know many of the powerful psychiatric pharmaceuticals,heavily overprescribed to people with normal emotional aches and pains, raise insulin resistance and cause weight gain--and then flush into the water that, when the solids and e coli are removed from it becomes municipal drinking water while still carrying the molecules of these drugs. We know the concentration of PCBs and arsenic in the blood stream correlate to the likelihood a person will develop diabetes. We even know that the fire retardants in a mother's couch or carpet enter her blood stream and may damage her baby as does the teflon on her frying pan.

All we don't know is how to make the public recognize the toll these environmental poisons are taking, so that the public realizes the rise in diabetes among our young is the result of poisoning, not personal weakness and the result of bad parenting.

Don't hold your breath. It's always easier to blame other people's lack of "personal responsibility"--which makes the blamer feel safe, than it is to admit we are all of us in a dangerous situation that may be difficult or even impossible to reverse.

 
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ADDED April 7, 2010:

Yet another study finds obesity can be diagnosed effectively in 6 month old babies and accurately predict weight at age two.

http://www.sciencedaily.com/releases/2010/04/100406093632.htm

No way obesity in infants can be from "lifestyle choices." It is impossible to overfeed a 6 month old with a normal metabolism. In fact, it can be frustratingly hard to FEED them as those of us with underweight children have learned. These are damaged babies, and blaming their mothers for introducing cereal at the age when almost all American mothers introduce cereal is ridiculous.

So is the idea that breastfeeding prevents weight gain. My breastfed-only 26 pound 4 month old boy proved that.

All Purpose Technique for Debunking Worthless Studies

Every time another study hits the news with a headline like, "Lowering blood sugar doesn't help diabetics" I get a slew of emails asking me what do I think of it? Unfortunately, what I think of most of them can't be printed here without the "adult content" warning popping up when you access the blog.

It is getting to where I have two choices. I can spend my very limited research time reading and debunking bad studies or I can spend it looking for information that might help people.

With this in mind, this post gives you the tools you need to do your own debunking.

WHEN YOU READ A STUDY THAT SEEMS TO PROVE SOMETHING YOU SUSPECT IS FALSE ASK:

1. What was the real question being asked by the researchers?

Most of the time studies reported with the headline "Lowering blood sugar doesn't prevent X in diabetics" are studies that asked, "Does using very expensive new drug Y that lowers blood sugar a very small amount prevent heart attacks?" This is a very different question but you wouldn't know it from the way the studies are reported.

To find out what a study really asked--and what it really found--look up the abstract of the study as displayed by the research journal that published it. You can usually find this abstract by googling the name of the researcher cited in the news releases along with a keyword.

Sometimes you have to see the whole article to understand what was really discovered. The journals Diabetes Care and Diabetes and many others make their full content available to the public six months after publication.

2. Who were the subjects in the study?

There is a huge difference between the health outcomes you will see when you impose tight control on a newly diagnosed 50 year old person with Type 2 diabetes compared with attempting it in a 70 year old who was diagnosed 20 years before and has been running a fasting blood sugar of 195 mg/dl for 20 years.

Often the real headline should be, "People whose bodies are severely damaged by years of incompetent medical treatment respond poorly to drug cocktails that include drugs known to cause dangerous side effects."

3. How many subjects were in the study--and was it really a study?

Study size matters. A study of 150 people is easily skewed to produce the result a sponsor wants to see. A study with 20,000 people is not. Sponsors play a lot of statistical games with data from small studies because when a study is small you can coax just about any result you want to see out of the data if you use techniques that amplify numbers like using "risk" instead of "incidence." This is harder (though not impossible) to do with large sample sizes.

But when you see a large sample size, make sure that sample size reflects a single study. Metastudies that combine data from many studies to come up with total number of subjects are highly unreliable as the methodology in the individual studies and even the lab reference ranges used are usually very different. Mixing apples and oranges makes for a delicious, though high carb, fruit salad. It's not so good for research conclusions.

4. What was the blood sugar of the study subjects like at the beginning and the end of the study?

Too many studies that prove some drug or interventions "doesn't work" will start out with patients whose average A1c is 9% and at the end of the study the average A1c will be 8%. This is way over the level now known to cause complications and heart attack.

Lowering blood sugar WON'T prevent complications if blood sugar isn't lowered enough to prevent complications. That sounds self-evident, but researchers do not seem aware of what other researchers--usually not in the employ of drug companies--have found to be the level at which complications occur.

That level for heart disease appears to be a level where one hour readings after meals do not exceed 155 mg/dl (8.6 mmol/L). (Details HERE.) The research studies that identified toxic blood sugar levels for other complications are described HERE.

5. Was it a human study?

Shocking amounts of what doctors think they know about diabetes and diabetes dietary treatments come from rodent studies. Rodents have very different genomes from people, very different pancreases, and extremely different lipid metabolism.

6. If it was a diet study, what was the actual diet composition?

Many "low carb" studies involve people eating over 150 g of carb a day. Even some "Atkins" diet studies involve people eating over 100 g of carb a day.

Many diet studies purporting to find meat toxic are questionnaire studies where people are asked questions like "How many servings of meat did you eat in the last month." These questionnaires are standardized and do not include the question, "Did you eat fries with that?" Meat eaten with fries, bread, and a soda registers as "meat" or a "high protein diet" when these studies are reported.

7. Who sponsored the study?

If a study is paid for by a drug company independent research confirms it is likely to come up with a positive finding. Often the study itself comes up with negative findings for the original question the study was run to test but the media will report the drug company spin. This means the headline "Drug X lowers Y" often turns out to ignore the rest: "In a statistically insignificant manner indistinguishable from chance."

By the same token, the headline "Drug X prevents hangnails!" ignores that the study was conducted to see if Drug X prevented heart attack, which it did not, and which, in fact, it increases.

8. What was actually measured?

Conclusions are often drawn by measuring something that isn't as closely connected to the result as the reporting of the study would have you believe.

Studies of lipid lowering drugs may report only the LDL level attained by subjects, not whether lowering LDL decreased the incidence of heart attack. (It rarely does.) This is an example of using a "surrogate marker." Surrogate markers are factors believed to be connected to an outcome, but which often aren't.

Measuring A1c instead of incidence of complications when studying a drug's effectiveness is another example of using a surrogate marker.

Studies that tell you that food X lowers blood sugar often actually measure the level of some micronutrient in the food which resembles some pharamaceutical that lowers blood sugar or which has an impact in a test tube but the study does not ot measure whether people who eat the food experience lower blood sugars.

9. Is the finding an average and if so, what was the standard deviation?

Drug X lowers blood sugar of one third of those who take it by 120 mg/dl of another third by 100 mg/dl and of the last third by 90 mg/dl. Drug Y lowers blood sugar of one third of those who take it 300 mg/dl of all the rest by 0. The studies on both these drugs reports that Drug X and Y lower blood sugar by a mean of 100 mg/dl.

These drugs report the same statistic, but the first drug is moderately helpful to everyone who takes it, the second drug is useless for two thirds of those who take it.

This is why you can't tell much about any research finding by looking at means (averages). Unfortunately averages are the statistic used in most medical research.

If there is a standard deviation (SD) given, that helps, though you will never see it discussed in the study or the reporting. The SD shows you the size of the spread around the average. The SD would be much greater for the second study than the first.

Medians are a much better measure, too. But you never see them used. In the case above, the median for Drug X is 100 mg/dl and for Drug Y it is 0 mg/dl.

When studying the impact of anything on blood sugar, it's also worth remembering that the higher the starting blood sugar, the more dramatic a statistical outcome the sponsor can achieve. This is why drug studies are always done with a population of people who start out with very poorly controlled diabetes. You can drop someone from an 11% A1c to a 9% A1c a lot easier with any intervention than you can drop someone from 8% to 6%.

10. Be alert for the tell tales signs of statistically massaged results

There are many dodgy statistical techniques that can turn a very small number into a larger number. Use the "risk" of some condition rather than "incidence" of that condition in the same population and you get a number 10 to 100 times bigger than you started with.

Even dodgier, if your original result is statistically insignificant, you can measure something like "percent of change" rather than risk or incidence. The percent of change between two numbers that vary by a statistically insignificant amount may be reported as statistically significant. I have seen this done more than once. This secondary measurement is meaningless to anyone who understands statistics, but unfortunately, my years of reading studies have convinced me that peers who review medical studies flunked statistics. More than once.

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When you see criminally inept research getting play in the media write letters to your newspaper, TV channel, or the publisher who printed it. They will pay the same attention to your letters than they do to mine--none. I've been writing them for years and have never received anything more than an automatically generated form. But perhaps if three thousand people sent in the same letter, it would have more impact. This blog gets a whole lot more than three thousand readers each month. Let the health media hear from you!

 
If you have more suggestions, please post them in the comments.

One Hour Blood Sugar Test is Best Predictor of Future Diabetes Risk

A study just published in the journal Diabetes Care confirms what I have suspected for a long time. The one test that gives the best indication of whether a person is in the process of developing diabetes is not the fasting glucose test used by 99% of family doctors. Nor is it the two hour value found on an oral glucose tolerance test--which has long been the gold standard endorsed by the American Diabetes Association.

What best predicts diabetes in people who are in that middle ground of not normal but not frankly diabetic is the result seen on a blood sugar test taken one hour after a glucose challenge--i.e. after eating a significant amount of carbohydrate.

You can read this study here:

Minimal Contribution of Fasting Hyperglycemia to the Incidence of Type 2 Diabetes in Subjects With Normal 2-h Plasma Glucose. Muhammad A. Abdul-Ghani. Diabetes Care March 2010 vol. 33 no. 3 557-561. doi: 10.2337/dc09-1145

In this study the researchers looked at the records of 3,450 subjects who started out with 2-hour plasma glucose concentration <140 mg/dl.[7.7 mmol/L] These subjects were participants in the San Antonio Heart Study (SAHS) and the Botnia Study for 7–8 years.

The researchers found that while incidence of type 2 diabetes at follow-up was related to the fasting, 1-h, and 2-h plasma glucose concentrations,

... when the 1-h plasma glucose, but not 2-h plasma glucose, concentration was added to the model, FPG [fasting plasma glucose] concentration was no longer a significant predictor of type 2 diabetes in both studies (NS).

When subjects were matched for the level of 1-h plasma glucose concentration, the incidence of type 2 diabetes markedly increased with the increase in 1-h plasma glucose, but the increase in FPG was not associated with a significant increase in the incidence of type 2 diabetes.

I get a lot of mail from people whose home testing is showing blood sugars well over 140 mg/dl (7.7 mmol/L) but whose doctors insist they are "fine" based on their fasting glucose readings.

If you fall into that category, and are having trouble getting your doctor to take your concerns about your blood sugar seriously, track your one hour blood sugar test results and if they are routinely over 140 mg/dl, print out this abstract and take it with you to your appointment.

You can learn how to use a blood sugar meter to test your blood here:

Am I diabetic? How to test your blood sugar to find out.

There is a less common variant of diabetes usually seen in males where the fasting blood sugar is very high but post meal blood sugar is not. If you have normal post-meal blood sugar, but see fasting blood sugars heading towards 120 mg/dl (6.7 mmol/L) you might be developing diabetes in this manner. Over time it may proceed to full fledged diabetes. Because most family doctors diagnose diabetes based on fasting tests people who develop diabetes in this pattern are more likely to have their diabetes diagnosed early.

You can read about what research has revealed about the different patterns in which diabetes develops and the likelihood of having your blood sugar dysfunction progress to diabetes HERE .

But what if your blood sugar is not going over 140 mg/dl when you eat carbohydrates? Unless your fasting blood sugar is near 120 mg/dl, you are fine. This sounds obvious, but I get a surprising amount of mail from people who have normal fasting blood sugar and normal one hour readings who are convinced there is something wrong with them. There may be, but it is usually not because they are developing diabetes.

That's because normal people's blood sugar fluctuates and may reach the upper 130s an hour after eating and then drop back to normal. The only time you might have a valid concern if your blood sugar at one hour is spiking into the 130s is if it is still in the 130s two hours after eating and even three hours after eating.

This would suggest that your body is having trouble with its second phase insulin response, which you can read about HERE. But this is rare. The most common progression to diabetes begins with one hour readings over 140 mg/dl that resolve or even produce reactive hypoglycemia. This then proceeds to readings over 140 mg/dl that stay over 140 mg/dl for another hour or two.

Though this is technically the "prediabetic range" researchers now know that the incidence of neuropathy, heart attack, and diabetic retinopathy all start to rise as one hour blood sugar goes into the range over 140 mg/dl. (More about that HERE and HERE)

If steps aren't taken to lower blood sugar when it is in the prediabetic range it may rise eventually into the official diabetic range--over 200 mg/dl. But it is very foolish to do what too many family doctors do--ignore oncoming diabetes until a person has an official diagnosis.

That's because the interventions that lower blood sugar are so much easier and more effective when you begin them when blood sugar is only modestly abnormal. When you are only seeing spikes slightly above 140 mg/dl at one hour, usually all it takes to lower blood sugar is to cut down on the amount of carbohydrate you eat at each meal.

Because blood sugars over 140 mg/dl are toxic to the beta cells that produce insulin and can, over time, kill enough of them to make you permanently diabetic, taking steps early can keep your diabetes from progressing, whatever your family history might be.

And because the most effective intervention is one that requires no prescription or help from a doctor, there is nothing to keep you from embarking on a program of healing whether or not your doctor takes your mildly abnormal blood sugars seriously.

You'll find detailed instructions for how to lower your blood sugar safely on your own here:

How to Get Your Blood Sugar Under Control

Does the Low Carb Diet Raise Cholesterol?

You may see studies that purport to prove that eating a low carb diet raises cholesterol. There was one reported in the latest edition of Diabetes in Control which you can see HERE. You may even see your cholesterol go up when you start to eat a low carb diet.

Is this reason for concern?

No. And here's why. The studies that show a rise in cholesterol are always studies of very short duration. The study reported in Diabetes in Control lasted six week. If you look at long term studies, you will see the exact opposite occur. Over time people eating low carb diets develop more favorable cholesterol profiles than those eating high carb/low fat diets.

You can see this finding documented in this metastudy published in the Nature journal, Obesity:

Cardiovascular and Hormonal Aspects of Very-Low-Carbohydrate Ketogenic Diets. Jeff S. Volek* and Matthew J. Sharman. Obesity Research (2004) 12, 115S–123S; doi: 10.1038/oby.2004.276

The very slight and short-lived rise in LDL--and it is very slight--12 mg/dl in the study described by Diabetes in control--is nothing to be afraid of. By six months into the diet it will be gone in most people, replaced by a better cholesterol profile.

The only people who may not experience this improvement are the very small number of people with diabetes who, because of some specific genetic issue, are very fat sensitive. You can tell if you are one of them because if you are, when you eat a low carb diet for six weeks your blood sugar will go up, not down. This is very rare. I have heard from two people over the past five years who experienced it.

No research has ever shown an increase in any negative health outcome from long-term adherence to a truly low carb diet--one that does not exceed 100 g per day--and trust me, they have looked for them. Because these diets are so effective in lowering blood sugar, they lower the incidence of new diabetic complications.

You can find links to many more studies proving the safety and efficacy of the low carb diet HERE. You'll also find the huge, multi-million dollar, multi-year study that proved beyond a doubt that the low fat diet, whatever its short term effect on cholesterol might be, has no effect at all on the incidence of heart disease or cancer.

Analyzing Your Cholesterol Results

If your cholesterol goes up after you start a low carb diet, it is important to understand that cholesterol is only very weakly associated with the incidence of heart disease--despite the myth promoted by the companies that sell drugs that lower total cholesterol.

Here are the measurements that actually map down to a slight rise in heart disease. To find more discussion of the studies that document this, with links, visit THIS PAGE:

1. High fasting triglycerides. If your triglycerides are over 150 mg/dl, your risk of heart disease may rise. Triglycerides are blood fats, but they rise in response to carbohydrate consumption.

2. Low HDL cholesterol. HDL the so called "good cholesterol" is protective for most people, especially when it rises to levels above 60 mg/dl. However total cholesterol is computed by adding in HDL, so it is possible to see your total cholesterol rise because your HDL has moved from a low, dangerous level to a high protective level. It is not uncommon to see people who eat long-term low carb diets develop HDL that ranges from 80 to over 100 mg/dl. This is not a problem.

3. Apo(a). This is a factor family doctors rarely measure, but it is a much more sensitive indicator of heart attack risk than cholesterol measures. If you have a family history of early heart attack, it would be a good idea to get it measured.

4. Cardiac Specific CRP. Heart disease is now understood to be an inflammatory disease that affects the arteries. The Cardiac specific CRP (C-Reactive Protein) test will tell you if your arteries are inflamed. High levels on this test suggest that you would benefit from a statin drug, because what statins actually do that prevents heart attack is NOT lower cholesterol but lower inflammation.

5. A1C Rising over 5% and Post-Meal Sugars over 153 mg/dl at 1 Hour. This is starting to look like the single strongest predictor of heart attack. Details HERE. Since lowering your carbohydrate intake is the single most powerful tool you have to lower A1c, the long term benefit of cutting carbs becomes very clear.

One Last Thing: You Don't Have to Lose Weight to Get The Benefits

Doctors often tell you that you have to lose weight to improve blood sugar and heart attack risk. While losing weight takes strain off your heart, you will get significant benefits from a diet that cuts carbohydrate even if you don't lose a single pound. That's because that kind of diet lowers blood sugar, and it is high blood sugar that is so damaging to your capillaries, nerves, retinas, and kidneys.

Many people think that to get the benefits of a low carb diet they have to eat at extremely low levels--ones many people find difficult if not impossible to sustain. However, this is not true. Many people can see impressive improvements in their health by eating at higher levels of carbohydrate intake--closer to 100 g a day, with no meal exceeding 35 g, rather than 20 g a day.

The key to health is to eat at a level that keeps your blood sugar below the levels that cause damage to your organs. Using the strategy you'll find described here, you can determine what carbohydrate intake level normalizes your blood sugar. It is different for every person:

How To Get Your Blood Sugar Under Control

If diet alone can't give you normal blood sugars, carefully chosen, safe drugs plus lowered carbohydrate intake will.

 

AMP-Kinase, Metformin and Resveratrol

AMP-kinase (AMP-k) is an enzyme which is involved in many of the processes that break down in people with Type 2 diabetes.

Wikipedia has this to say about it:

Activated by muscle contractions... It is expressed in a number of tissues, including the liver, brain, and skeletal muscle.

The net effect of AMPK activation is stimulation of hepatic fatty acid oxidation and ketogenesis, inhibition of cholesterol synthesis, lipogenesis, and triglyceride synthesis, inhibition of adipocyte lipolysis and lipogenesis, stimulation of skeletal muscle fatty acid oxidation and muscle glucose uptake, and modulation of insulin secretion by pancreatic beta-cells.

Translated into English this means that AMP-k turns on the liver's ability to burn fat and create ketones, that it lowers cholesterol and blocks the creation of fats (triglyceride) from carbohydrates, that it gets muscles burning fat and taking up glucose, and cuts back on insulin secretion.

AMP-k is partially regulated by the fat governing hormones leptin and adiponectin, hormones that are often out of control in people with Type 2 Diabetes. It has an effect on the hypothalamus which is the part of the brain that regulates appetite.

AMP-k is even more interesting when you learn that, as summarized in Wikipedia,

Under conditions of exercise, however, blood sugar levels are not necessarily high, and insulin is not necessarily activated, yet muscles are still able to bring in glucose. AMPK seems to be responsible in part for this exercise-induced glucose uptake.

Wikipedia points to THIS CITE to support that statement.

But interestingly, AMP-k expresses the most in muscles when people are not in good shape. The better trained a person is, the less AMP-k is produced.

MPK activation also produces physiological effects that appear to prevent myocardial injury during ischemia--i.e. it prevents damage to the heart muscle during a heart attack.You can read more about the technical details of how AMP-k protects the heart from heart attack in this review:

AMP-Activated Protein Kinase Conducts the Ischemic Stress Response Orchestra. Lawrence H. Young, et al. Circulation. 2008;117:832-840. doi: 10.1161/CIRCULATIONAHA.107.713115

What makes all this very relevant to people with Type 2 diabetes is this: There is evidence that what the diabetes drug metformin really does is that it activates AMP-k. This would explain many of its known effects: that it stops weight gain and can help with weight loss, that it lowers blood sugar, that it stops the liver from dumping glucose, that it lowers cholesterol and triglyceride levels, and that it appears to lower the risk of heart attack.

Role of AMP-activated protein kinase in mechanism of metformin action Gaochao Zhou et al., J. Clin. Invest. 108(8): 1167-1174 (2001). doi:10.1172/JCI13505.

Even more insight into how metformin works is given by this review:

AMPK: Lessons from transgenic and knockout animals. Benoit Viollet et al. Front Biosci. 2009; 14: 19–44.

It is important to note that the lab findings suggest that because metformin's impact is related to its ability to raise AMP-k it does not really "reduce insulin resistance," if by that we mean that it makes cell receptors more sensitive to insulin. Instead, what it seems to do to lower blood sugars--besides keeping the liver from dumping extra glucose inappropriately--is increase the ability of the muscles to take up glucose without the need for insulin.

Because metformin is easily available and cheap, doctors tend to ignore it in favor of newer, more hyped medications. This is a shame, especially since new and highly hyped substances may turn out to merely be repeating what metformin already does. For example, a study just published this month came up with compelling evidence that the health impacts of resveratrol, the substance found in red wine that is currently the subject of much hype and misleading supplement marketing is not due to resveratrol's impact on SIRT1, as was initially speculated. Instead resveratrol's effects appear to be caused by its ability to activate AMP-k. You can read about that finding here:

AMP-Activated Protein Kinase–Deficient Mice Are Resistant to the Metabolic Effects of Resveratrol. Jee-Hyun Um et al. Diabetes March 2010 vol. 59 no. 3 554-563. doi: 10.2337/db09-0482.

Since metformin is available as a cheap generic drug and the bogus resveratrol supplements and upcoming resveratrol-derived drugs are, or will be, extremely expensive, all this suggests metformin is probably an excellent, safe way to get whatever benefits are attributed to resveratrol.

However, in the course of my reading about AMP-k I learned a few other things which may point to some additional strategies that could help those of us who take metformin. One major finding is that in a natural state AMP-k gets produced in response to various stresses. It is not normally at high levels all the time which may be what happens when we take a drug that keeps it activated.

When AMP-k is kept "on" continuously, there are subtle hints that it may cause some bad things may happen. These studies point to this possibility--though I caution you not to overreact to these findings:

Diverse Cytopathologies in Mitochondrial Disease Are Caused by AMP-activated Protein Kinase Signaling Paul B. Bokko et al. MBoC March 1, 2007. doi/10.1091/mbc.E06-09-0881

Over-expression of AMP-activated protein kinase impairs pancreatic ß-cell function in vivo S K Richards, et al. Journal of Endocrinology (2005) 187, 225-235 DOI: 10.1677/joe.1.06413

Fortunately, another study suggests that the concentrations of metformin achieved by people who take the drug are "suboptimal" as far as raising AMP-k which might help prevent negative outcomes from taking it.

The Antidiabetic Drug Metformin Activates the AMP-Activated Protein Kinase Cascade via an Adenine Nucleotide-Independent Mechanism Simon A. Hawley et al. Diabetes August 2002 vol. 51 no. 8 2420-2425.doi: 10.2337/diabetes.51.8.2420

The long term data on the health of people taking metformin which has been in use for many decades is very good. They appear to have lower rates of heart attack and less cancer as well as slightly better blood sugars and better weight than those taking other competing drugs for insulin resistance or insulin deficiency.

However, the fact that AMP-k levels drop in people as they become more physically trained and hints that there may be problems with keeping an enzyme that naturally fluctuates at higher levels all the time got me thinking. I have found that with some other drugs, that taking a "drug holiday" now and then, which means stopping the drug for a week and then going back on it, gives me much better results than taking the drug all the time. This is particularly true for hormone supplements like estrogen which fluctuate in a natural state.

I had also noticed that metformin seemed to have much more impact on weight and even blood sugar the first few months after it is started. So for the past few months I have been experimenting with cycling off Metformin for a week every month and then going back on it. My doctor had assured me years ago that metformin is a drug that can be started and stopped without any negative effect.

Since I am a sample of one and have some very odd metabolic issues not common to most people with diabetes, my experience probably isn't relevant to others, though subjectively I do seem to be getting more impact out of metformin taking this way. It is worth experimenting with this if you are a person who had a strong response to metformin when you started it, only to see it wear off. In that case, it might be worth trying a cycling approach for a month or two to see if it helps.

My personal experience is that when I start metformin again I also get day or two of gastrointestinal symptoms characteristic of the drug. If this is a problem for you, you might not want to try the experiment.

Note: There are SOME drugs that are dangerous if you start them and then stop them without a doctor's help. Do not take a drug holiday from any drug without discussing the issue with a registered pharmacist. Pharmacists are much better informed about drug behavior and safety than are most doctors. Just make sure if you are in a pharmacy that you speak to a registered pharmacist, not an assistant, as the assistants do not have the training you need to get a good answer to this kind of question.