December 13, 2010

Also of interest: End of Year Research Roundup

As I read the medical news, I bookmark many articles that aren't significant enough to form the basis of a blog post or which reinforce points I've already documented with quality research on the main Blood Sugar 101 web site. Many of these are discarded as time goes by, but when I went through the past year's accumulation, I ran into a few that I thought you might find interesting.

What I'm going to do here is give you the links to a dozen of the most interesting articles and studies I've collected over the past year, which didn't make the cut for a whole blog post but are still worth reading.

1. 90,000 years ago so called paleo humans were already eating grains. The quasi-religious belief that early humans ate a grain and starch free diet has never been well supported by actual research. Though there were a very few human societies that were eating animal-only diets in the 19th century, they lived in extreme environments with extenuating circumstances that made a broader diet impossible. This study pushes back the evidence that "hunter gatherers" ate grains and starches another 80,000 years. There are plenty of good reasons to cut down on carbs, but the diets of people living hundreds of generations before us are not among them.

2. Coronary Artery Calicification (CAC) scores explain the dismal results in the Veteran's study. The Veteran's study, which found no improvement in cardiovascular death rates with tight control and a higher level of hypos, has been used to argue that it is dangerous to lower blood sugar to normal levels. This study re-analyzed the data and found that that the lower a person's CAC score was, the more effective tight control was in preventing them from having heart attacks. It makes sense that if you wait until your arteries have mostly turned into rock, blood sugar control alone won't be be enough to save you.

3. Diabetic nerve damage in the bone marrow may be what causes diabetic retinopathy. This study suggests a fascinating new mechanism to explain how diabetic blood sugars damage organs. The bone marrow sends out stem cells to repair organs, but when the nerves in the bone marrow are damaged by blood sugar-caused neuropathy the feedback loop controlling this process breaks down. This may lead to tissue overgrowth elsewhere in the body as stem cells go where they aren't needed.

4. Bis-phenol A levels in human correlates to heart disease. This study looks at NHANES data, a lot of it, and finds the connection to be strong. Bis-phenol A is strongly associated with the risk of obesity in humans, too.

5. Bis-phenol A is found in high concentrations on retail receipts and most dollar bills. Other significant sources are canned food (which you eat any time you eat in a restaurant) because cans are lined with this plastic, too.

6. The most common Type 2 Diabetes gene TCF7L2 appears to lower the beta cell's sensitivity to normally secreted incretin hormones. This probably explains why incretin hormone drugs like Byetta work very well for some people, not at all for others.

7. The earlier metformin is started, the better off people with diabetes are. Taking metformin within 3 months of diagnosis doubled the length of time it was an effective method of controlling blood sugar. This data was gathered from a group of people eating high carb diets and maintaining blood sugar levels high enough to damage and kill their beta cells. (They had A1cs near 7%). Metformin taken with a lowered carb intake that normalizes blood sugar will stay effective even longer.

8. A disturbing round-up of neglected study data shows that statins not only are not effective for women but may increase cardiovascular risk in women. The author of this review points out that the FDA approves statins for women based on data from male-only studies and have not reviewed subsequent studies suggesting they raise cardiovascular risk for some women.

9. High maternal DDE blood levels lead to obesity in their babies after birth. DDE is another hormone-mimic organic chemical found in our environment. This is yet another explanation for the terrifying rise in childhood obesity and diabetes that has nothing to do with "lifestyle choices" unless you consider breathing and drinking polluted water "choices."

10. Metformin (in a mouse study) appears to block formation of the Tau protein associated with Alzheimers disease and several other forms of dementia. Though mouse studies are often misleading, because "diabetic" mice have a completely different genetic profile than humans with Type 2 diabetes and because mice are adapted to completely different diets than humans, we do know that people with Type 2 diabetes are less likely to get classical Alzheimer's disease than is the population at large. So it may be possible that their use of metformin may play a role. If you have a family history of classic Alzheimers (the kind characterized by amyloid deposits in the brain on autopsy) or Pick's disease, this may be another reason to take metformin. Unfortunately, people with diabetes get more vascular dementia than the population at large.

11. Hypothyroidism artificially raises A1c because of its effect on the blood cell, not necessarily because blood sugar is higher. This may explain why some people report their blood sugar improves after starting thyroid replacement therapy. If you are hypothyroid, this finding suggests you should trust your meter over your A1c.

12. More large-scale evidence that antidepressants are a significant factor causing Type 2 diabetes. The DPPT study found that over 10 years steady antidepressant use more than doubled the risk of developing diabetes except among those taking metformin.



Anonymous said...

re: the research on grains.

I think you are right that many people are "quasi-religious" about this issue. And the results presented in the article make more sense to me than the idea that humans 90,000 ago ate no grains.

That said, I think your statement "There are plenty of good reasons to cut down on carbs, but the diets of people living hundreds of generations before us are not among them" doesn't make sense. If you had said "cut out carbs" or "eliminate carbs", I would agree. Even though these humans were consuming grains, it would seem to me that they likely ate much less of them than we do today, and therefore an excellent reason for us to "cut down on carbs".

Chris Kresser said...

Re: grains. In that paper (or one similar) the speculation was that they weren't eating the grains but fermenting them into an alcoholic beverage. In addition, the grain found in that study was sorghum, which is non-gluten grain and thus free of gliadorphins, opioids and wheat germ agglutinin - three of the most harmful substances in gluten-containing grains.

The weight of the evidence still suggests that grains were not a significant part of humans' diet until relatively recently on the evolutionary scale. And they certainly weren't eating white flour, which now constitutes a large percentage of calories for modern people.

Simon said...


I want to take this end of the year round up as an opportunity to thank you for your work. I think I can say with confidence that you are one of the most rigorous, objective researchers out there, and do us all a great service with your work. Your equal skepticism of alternative medicine and mainstream medicine proves that you have no interests besides the well being of your fellow citizens (wow that sounds cheesy). Thanks and Happy Holidays.


Jenny said...

Simon, Thanks!

Chuck said...

whether our ancestors ate cereal grains or not doesn't matter much to me anymore. i think everyone should try cutting them out of their diet for a month and see if it affects their health in any way. what are the negatives of eliminating cereal grains? maybe for the poor it would lead low caloric intake.

Jenny said...

Plenty of people can eat all the grain they want. It's only people who can't metabolize carbohydrates properly who have to worry about them. The biggest problem I see in the online health community is the failure to accept the huge range of differences in people's metabolisms and the insistence that everyone should be eating the same foods and pursuing the same health strategies.

Some people live into their 90s with no heart disease eating whatever they want. Why should they have to eat what we people with diabetes do?

That's why it is essential to know your own metabolic status, your own blood sugar control, and make your decisions based on what you find when you have looked at the evidence.

Chris Kresser said...

Jenny: for the record, I agree with you. There is obviously a huge variation in carbohydrate and food tolerance in people who are generally healthy. Some people do all the "wrong" things and live a long time; others to all the "right" things and die young. There are countless variables involved in health and disease, and it's impossible to make blanket statements for this reason.

That said, I see many people in my practice that can't tolerate grains and do far better without them. This isn't because of the carbohydrate content, necessarily, but because of certain phytotoxins present in the grains and their effect on intestinal permeability. This is not "alternative" thinking in any way. Just look at the recent scientific literature on autoimmunity, and you'll see several papers clearly establishing the link between intestinal permeability and autoimmunity, as well as papers showing a link between compounds found in (primarily) gluten-containing grains and intestinal permeability. This is not imaginary. It's real.

Does that mean everyone is negatively affected by grains in this way? Obviously not. Certain traditional cultures appear to be very health eating traditionally-prepared (i.e. soaked/fermented/sprouted) grains. But it does mean that removing grains from the diet is a viable and sensible experiment for someone experiencing autoimmune disease or other health problems to try. It's harmless and far safer than any pharmaceutical alternative.

I also think the weight of evidence suggests that widespread grain consumption is a relatively new phenomenon. How significant that is is still up for debate, but a few studies finding grains at paleo dig sites doesn't convince me that they were a staple in the diet at that time - especially in light of some evidence that the grains were used to make alcoholic beverages, rather than eaten.

I'm not a zealot about this stuff. But nor do I like to see grain-free diets dismissed as some kind of fad, when in all likelihood a grain-free diet is what humans evolved on and ate exclusively for a couple of million years.

Debbie Cusick said...

I enjoy the grain comments, as I also agree that any grains eaten by paleolithic man would hardly have constituted a major part of the diet, and would hardly have been the same as the mutant-strain high-gluten white flour that most people eat in this day and age. I have been gluten-free for two years now and the improvement in my health is immeasureable.

But the article that really caught my eye was the one on A1C and hypothyroidism. I've been really shocked and bummed with high A1C readings this year - 6.8 in the spring and then 6.7 in the fall. The chart I found online equates 6.8 to an *average* blood glucose reading of 165, and 6.7 to an average of 161. Yet in an entire year of checking my blood glucose religiously I have only *twice* in almost 12 month's time seen readings that exceeded 160 - a reading of 169 and one of 179, both times after eating something I knew I shouldn't have.

Yet my normal readings, even when checking 6 times a day at all hours of the day, are always *well* below those numbers. I just tested right now, 1 hour PP, and got a reading of 127, which is not untypical. I've had fasting numbers as low as 77, though that is not usual, alas. But numbers in the 90s are not uncommon, and my 1-hour PP reading rarely go above the 130s, and 2-hour PP is typically in the 110s. So I could never make sense out of why my A1C was so high.

But I have also been diagnosed with hasimoto's in the past year, and am definitely hypothryoid, and still struggling to find a doctor who will treat me properly for it - as most doctors seem to be as ignorant about thyroid treatment as the ADA is about diabetes treatment.

Jenny said...

I agree that thyroid finding is very interesting. One has to wonder how it dovetails with other research showing that individual's reading may often be consistently higher than predicted.

The health implications are not known. Whether a lot of glycosylated hemoglobin harms us, or is just a marker for the high glucose levels that do the harm has never been made clear. My guess is that it isn't the hemoglobin, just the blood sugar highs.

Chris Kresser said...

I suspect Jenny might be right about glycosylated hemoglobin being more of a canary in a coal mine than a problem in itself. In my practice I see a lot of weird A1c results that don't make sense according to conventional wisdom. I test A1c, fasting glucose and post-meal blood sugars (they do it with a glucometer) on every patient. Last week I had one with FGB of 83, post-meals never going above 120, and an A1c of 6.3. Out of curiosity I also ran fructosamine, another measure of glycosylation, and it was normal.

This patient was mildly anemic, which could have been skewing the results. He also had borderline low T4/T3 levels, although his TSH was normal.

I suspect there's a lot more to this than we currently understand.

Scall0way: you're correct about widespread ignorance about how to treat Hashimoto's. Most docs ignore the fact that it's an autoimmune disease, and only focus on replacement (which is important, but not at all the end of the story).

Jenny said...

Anemia supposedly will make the A1c lower than predicted, not higher. But genetic variations in the hemoglobin can also make for results that don't reflect blood sugar control.

There really is little reason to use it with patients who are keeping blood sugar logs.

Helen said...

Posting in two parts because my original comment was too long.


Re: A1c's - I'm still kind of a newbie to this, but I'd also worry about relying on A1c's because they can skew low. I still wonder if I was falsely reassured by a low (<5.0) A1c six years ago when I had a high (101) fasting blood sugar and an odd spot reading (146) around the same time. I was taking a fair amount of vitamin C, which can lower A1c results.

My A1c now does seem to correlate with my glucose readings. I wish it were elevated for some other reason.

re: Grains. I couldn't agree with Chris more. About 30-40% of the U.S. population carries genes making them susceptible to gluten sensitivity, celiac disease, and a host of autoimmune diseases (like Hashimoto's thyroiditis, alopecia areata, and Type 1 diabetes, and primary biliary cirrhosis) that are known to be correlated with anti-gluten antibodies (even if celiac is not present).

A PubMed search will turn up lots of articles on gluten-related ailments other than celiac disease per se (which itself is grossly underdiagnosed and can lead to all sorts of problems, including neuropathy), including gluten ataxia, gluten psychosis, seizures, increased gallbladder disease, and even pancreatic insufficiency. The gluten-sensitive tribe really shouldn't eat gluten-containing grains, even if they test negative for celiac.

Helen said...


Gluten causes leaky gut to some degree in all people, by stimulating the release of zonulin, but in people with a celiac-susceptible genetic profile, the effect is a lot stronger and much longer-lasting. Zonulin opens the tight junctions in the gut, allowing large particles of food, endotoxins, and pathogens into the blood that otherwise wouldn't. This may be the smoking gun in the development of autoimmunity and food allergies. Other things may cause leaky gut, too, but gluten is a ringer.

I heard on the radio recently about genetic research showing a 300-fold increase in genes allowing for lactose digestion in a European group since Roman times. This shows that people can adapt to neolithic foodstuffs, and maybe the 60-70% of the population without gluten-sensitive genes already has. As for me, I don't want to be one of the casualties in the natural-selection process: I'm passing on my gluten-sensitive genes and gluten-free recipes to the next generation.

PJNOIR said...

Paleo has been the best diet style I have tried and stuck with. I feel 15 yrs younger, 70 lbs lighter.And been 70 lbs lighter for several years now.
As a diabetic I can't even look at oatmeal or any of the so-called good carbs or grains without my numbers blasting thru the roof. Unlike vegetarians, Paleo should not be stuck in a dogma but used as a solid foundation to good health.