Are you at risk for diabetes and obesity?

genes

This turned into a pretty long article, so I’m going to provide a summary up-front for those of you who are time-challenged:

  • Genetics play a significant role in type 2 diabetes and obesity;
  • but, recent evidence shows that genetics alone don’t cause diabetes without environmental triggers and a leaky gut.
  • The bad news is that almost everyone is exposed to these triggers and leaky guts are not uncommon;
  • but the good news is that a leaky gut can be healed, which may slow or even reverse the autoimmune process that causes type 2 diabetes.

So far in this series we’ve looked a model of understanding diabetes and obesity as autoimmune, inflammatory diseases. We’ve explored how obesity contributes to diabetes, and how insulin resistance contributes to obesity. And we’ve seen that, while diabetes and obesity often go hand in hand, that isn’t always the case; even skinny people get type 2 diabetes.

I hope you’re aware by now that obesity and diabetes are not simply diseases of sloth and gluttony. Nor are they caused by eating too many carbohydrates (more on this later). You’ve probably also noticed that some people get fat and stay fat despite exercising regularly and not eating much, while others can eat ridiculous quantities of food, never exercise and stay lean.

Obviously there are other factors at work here, and that’s what we’re going to talk about in this article. Specifically, I’m going to address the role of genetics as a risk factor for diabesity. There’s absolutely no question that genetics do play a significant role in both obesity and diabetes. To some extent genetics explain the apparent paradoxes I mentioned in the previous paragraph. But it’s equally important to understand that being genetically predisposed to develop diabesity doesn’t guarantee that you will. In fact, recent research suggests that other environmental and physiological factors must be present to activate the genetic patterns.

The triple whammy of genes, toxins and a leaky gut

In the second article in this series, I presented evidence that obesity and diabetes are autoimmune, inflammatory disorders. This is important to understand, because it suggests that we can learn more about what might cause these conditions by studying other autoimmune diseases. Autoimmunity is one of the hottest topics in the scientific literature. And although there’s still much we don’t understand, significant progress has been made over the past two decades in illuminating the mechanisms involved in autoimmune disease.

One of the heavyweights in the field is a researcher named Alessio Fasano. In 2009 he published an article in Scientific American called “Celiac Disease Insights: Clues to Solving Autoimmunity“. Fassano argues that all autoimmune diseases – not just celiac disease – involve a triad of factors: genetic susceptibility, an environmental trigger and a gut abnormality. Each of these is a risk factor for autoimmunity on its own, but Fassano’s work shows that those who go on to develop full-fledged autoimmune diseases (including diabesity) almost always have all three.

This theory – which is well supported by the evidence, as we’ll see – makes perfect sense when you understand the principles of epigenetics. Up until very recently, scientists believed that the affects of nurture (environment) on a species’ nature (genes) took generations to develop. Darwin’s Origin of Species taught us that evolutionary changes take place over millions of years of natural selection, not in a single lifetime. But recent work by pioneers like Dr. Lars Olov Bygren of the prestigious Karolinska Institute in Stockwholm has shown that powerful environmental triggers can bypass evolution and pass traits on in a single generation.

Epigenetics is the study of gene activity that doesn’t involve changes to the genetic code, but still gets passed down to at least one successive generation. These inherited patterns of gene expression (known as the “epigenome”) hover above the genome and are what determine whether your genes get switched on or off, and at what intensity. This epigenetic blueprint determines what effect environmental factors like diet, stress and toxins will have on genes passed from one generation to the next.

What this means is that, yes, genes are important. But it also means that the genes that might predispose us to develop conditions like diabesity may only be activated in the presence of environmental triggers like poor diet, toxic chemicals and a leaky gut. In the sections to follow we’ll look at each factor in the “genes-toxins-gut” triad in more detail.

Are there genes for diabesity?

There is no question that genes contribute to both obesity and diabetes. Studies on identical twins have shown an 80% concordance for type 2 diabetes (T2DM). That means that if one twin develops T2DM, there’s a 4 out of 5 chance the other one will too. And lest you think this might be described by something shared in the twins’ environment, there is no such concordance between fraternal twins.

That said, 1 in 5 of those identical twins carrying the same genes didn’t become diabetic, so there is clearly an environmental factor at work as well. This is exactly what you’d expect to see if you’re familiar with epigenetic principles.

There’s now a very long list of genes associated with T2DM and obesity, including TCF7L2, HNF4-a, PTPN, SHIP2, ENPP1, PPARG, FTO, KCNJ11, NOTCh3, WFS1, CDKAL1, IGF2BP2, SLC30A8, JAZF1, and HHEX. (I can’t understand how geneticist’s brains don’t explode from acronym overload.) And studies pretty clearly show that the more of these genes you have, the higher your risk of diabesity. With each abnormal gene, beta cell dysfunction (which in turn compromises insulin production) gets worse. If you’re unlucky enough to have five of them, your beta cell glucose sensitivity and insulin production is likely to be up to 40% lower than a person without those genes. That’s no small difference.

Other studies have shown that genetic abnormalities predict T2DM independently of conventional risk factors, and that genetic defects in mitochondrial function cause insulin resistance in lean, otherwise healthy offspring of type 2 diabetics.

It’s not “nature versus nurture” – it’s “nature plus nurture”

We’ve seen so far that genes are a big factor in type 2 diabetes, but that not everyone with these genes develops diabetes. Environmental factors are the missing link that determine whether these bad genes get switched on and cause full-fledged diabesity.

So what might those environmental factors be? I’m just going to summarize them here, because many of them will be the subject of future articles in the series. They are:

It seems that at least one of these environmental factors must be present for the diabetes genes to be activated. Take a look at that list. Those aren’t exactly rare. They’re ubiquitous. I’d venture to say that all people living in the modern world are affected to some degree by at least one of them. Even those who eat a pristine diet and avoid pharmaceutical drugs can’t escape the toxins in our water, air and (even) organic food. This, my friends, is why we have a diabetes epidemic on our hands.

“All disease begins in the gut.” – Hippocrates

The phrase “leaky gut” used to be confined to the outer fringes of medicine, employed by alternative practitioners with letters like D.C., L.Ac and N.D. after their names. Researchers originally scoffed at the idea that a leaky gut contributes to autoimmune problems, but now they’re eating their words. It has been repeatedly shown in several well-designed studies that the integrity of the intestinal barrier is a major factor in autoimmune disease.

This new theory holds that the intestinal barrier in large part determines whether we tolerate or react to toxic substances we ingest from the environment. The breach of the intestinal barrier (which is only possible with a “leaky gut”) by food toxins like gluten and chemicals like arsenic or BPA cause an immune response which affects not only the gut itself, but also other organs and tissues. These include the skeletal system, the pancreas (hint: diabetes!), the kidney, the liver and the brain.

Researchers have identified a protein called zonulin that increases intestinal permeability in humans and other animals. This led to a search of the medical literature for illnesses characterized by increased intestinal permeability (leaky gut). Imagine their surprise when the researchers found that many, if not most, autoimmune diseases – including celiac disease, type 1 diabetes, multiple sclerosis, rheumatoid arthritis and inflammatory bowel disease – are characterized by abnormally high levels of zonulin and a leaky gut.

They also found that gluten causes excess production of zonulin in certain people with a genetic susceptibility. This could explain why gluten directly contributes to leaky gut in certain populations.

What these discoveries have shown us is that genetic susceptibility and environmental triggers alone may not be enough to explain autoimmune disease. In order for environmental triggers to damage or activate faulty genes, a third factor must be present: a leaky gut.

Recent evidence has also revealed that the gut flora play a significant role in determining the permeability of the gut, and that diabetics and healthy people have significantly different gut flora (suggesting that dysregulated gut flora plays a role in diabetes).

One study showed that showed that the overall number of colonic bacteria between diabetics and non-diabetics was similar, but that the proportion of species was different. Diabetics tended to have higher numbers of Bacteroidetes and Prevotella, which are gram negative bacteria that produce molecules called lipopolysaccharide (LPS). And guess what? LPS is known for its potent stimulation of the immune system.

Consider a hypothetical woman with a few genes that predispose her to diabetes. She eats a typical American diet, which is full of refined flour, industrial seed oils and fructose. Her mother had poor gut flora, and chose to bottle-feed her instead of breast-feed, both of which contribute to poor gut flora and intestinal permeability. This poor woman is now a walking diabetes time bomb. Anytime she ingests a toxin – whether it’s gluten or a chemical – it leaks through her gut and has the potential to activate her diabetic genes.

The bad news is that this is an incredibly common scenario. The good news, however, is that this new theory (that genetic and environmental factors are only problematic in the presence of a leaky gut) has an upside. According to Dr. Fasano:

…once the autoimmune process is activated, it is not self-perpetuating; rather, it can be modulated or even reversed by preventing the continuous interplay between genes and environment. As tight junction dysfunction allows this interaction, new therapeutic strategies aimed at re-establishing the intestinal barrier function offer innovative, unexplored approaches for the treatment of these devastating diseases.

In other words, it’s possible that you can’t get type 2 diabetes without a leaky gut, and that by healing your gut the autoimmune process driving T2DM may be slowed or even reversed.

Pretty cool, huh?

A final note: it’s not exactly true that improving metabolic health by repairing a leaky gut is an “unexplored” approach. Plenty of “alternative” practitioners have been doing this for years. In fact, they pioneered the techniques at a time when researchers were still snickering at the idea of “leaky gut”. Just another reminder of the danger of academic arrogance.

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Comments Join the Conversation

  1. says

    The less a food is processed and cooked the better it should be for gut flora. So I would rate fruit as the best food, followed by salads, greens, raw nuts, steamed vegetables, and at the bottom of the gut-flora list would be cooked whole grain cereals and cooked meats. Of course wholesome fats like coconut oil, butter, ghee, olive oil are welcome, though sparingly in the diet and in proper combination.

    That being the case it is high time that we turned the present meat-starch food pyramid upside down if we hope to at least improve the dietary habits of future generations

  2. Chris Kresser says

    Yes, I think infections also play a role.  Though my sense is that they’re not as significant as dietary toxins and stress.

  3. Jesse says

    Sure, but in children who are breastfed, diet still has a role in determining their community structure. Actually in the study I linked, the two groups of infants had similar bacteria while they were breastfeeding, but diverged greatly after they started eating other food. I’m not sure which factor has the biggest effect.

  4. Chris Kresser says

    Jesse:

    As I said, there are studies showing that the mother’s gut flora and whether or not the child is breastfed plays a large role in determining the child’s gut flora.  That has nothing to do with diet, because we’re talking about newborn infants.

  5. Chris Kresser says

    Anna,

    Yes, it goes both ways.  But there are studies showing that kids with bad gut flora are more likely to become obese and develop diabetes later on.  The gut flora of the mother and whether the child is breastfed plays a large role in how the child’s gut flora develops.

  6. Anna Delin says

    Very interesting blog! Regarding this particular post, I was wondering a bit about the connection between gut flora and diabetics. It is quite possible that certain species thrive on the repeatedly high blood sugars so that the gut flora is a consequence of diabetes and not the other way around.

  7. Jean Folon says

    Jesse, you now you understand enough about what the linked material suggests to know that if it indeed offers the correct interpretation about vaccines, you and those close to you have been and might yet be at great risk. You can choose to go with the soothing tales offered by the main stream media, and risk dying for a lie. Or you can take charge and research the veracity of the proffered thesis yourself.
    In particular the presentation given in the first video is well-referenced. Your could chose to follow its excerpts to the original source material, for example. You have the means, so I’ll leave it at that.

  8. Jesse says

    Jean, most of what I quoted was from links you provided. The citation in the second video transcript says “Baxter denied that the contaminated product were to manufacture vaccines for human use and called it ‘experimental virus material’. Baxter failed to reveal for what use it was because doing so would give away proprietary information about Baxter’s production process.” I don’t know where Teresa Forcades got the “72 kg” number, because the citation given doesn’t say anything about it, nor do any other links I have found, and Forcades seems to have been wrong about some other things, so I won’t take her word for it.
     
    Even if she was right about the number, though, I don’t see why it might not have been for testing. Since the contamination was discovered in January 2009, the vaccines must not have been for the 2009 H1N1 flu, and it seems like it was rather late to be distributing seasonal vaccines for the 2008-2009 flu season, so it seems likely that they were testing some sort of new vaccine. I don’t know much about how vaccines are produced or tested, so I don’t know whether 72kg seems like a lot of material for a new vaccine that may need extensive testing. Details just seem too sparse to suggest that there was some kind of plot going on.

  9. Jean Folon says

    Jesse, I was referring to the second video and its transcript, as I thought you were discussing the “second one”. I suggest you read section two of the transcript: it is talking about vaccines and vaccine material, and what might have happened had the contamination not been detected.
    Of course, the event had to be spun once it gained some exposure, so I am sure it is possible to find plenty of articles claiming it was an accident (no way, see my prior post), was intended for tests only (72 kg of it to 16 labs in 4 countries for testing? nonsense: a typical vaccination dose is 0.5 mL, that makes for 144.000 doses), and so on.

  10. Carroll says

    “In other words, it’s possible that you can’t get type 2 diabetes without a leaky gut, and that by healing your gut the autoimmune process driving T2DM may be slowed or even reversed.”

    I thought the caeliac research had implication for autoimmune diseases (ie T1DM, not type 2).

  11. Jesse says

    Jean, I can’t find anything in the links you provided or in those I found on my own that suggests the material was intended for inoculating the public. On the contrary, it “was supplied to an Austrian research company,” “used in laboratories,” “was intended for use in laboratories,” and was supplied to a company that “was conducting research…using materials supplied by Baxter.” The transcript of the video says “Baxter delivered 72 kilos of vaccine material to 16 laboratories in Austria, Germany, the Czech Republic and Slovenia.” Laboratories, not health clinics or something like that. Can you show me why you think the material was supposedly ready for public use?

    Actually, some vaccines do use live attenuated viruses: FluMist, for example. Minor correction, perhaps.
     
    If I get the right drift, the first video is suggesting that there is a conspiracy to control developing countries’ populations by using vaccines to make people sick?

  12. Jean Folon says

    Jesse, not quite: it says that a big batch of vaccine material was delivered by Baxter to four countries. No, it is not mentioned that it was for testing. The large quantity means it was to be used for what vaccine material is normally used for: innoculating the populace. An unscheduled and fortuitous test by a diligent lab technician in the Czech republic found the material to be deadly to ferrets. Further testing found the material to contain two types of live viruses: a bird flu virus (virus A/H5N1) and a seasonal flu virus (virus A/H3N2).
    Note that flu vaccines are not supposed to contain a live virus. The viruses in question are biohazard level 4 viruses, and as such are obliged to be handled handled in biosafety level 4 biolab facilities with corresponding elaborate safety procedures. These viruses are not being handled callously in a normal biolabs, ready to cause accidental contamination.
    That makes the chance that vaccine material, which is produced in biolabs, is accidentally contaminated with one such type of live virus exceedingly small. It follows that it is infinitesimally improbable that an accidental contamination with two biohazard level 4 live viruses occurs in a biolab setting.
    As to the first one: just browse the slides, I’m sure you’ll catch the drift of it.

  13. Jesse says

    I didn’t really understand the first one, but the second one seems to say that some flu vaccines that were sent for testing were found to be contaminated with H5N1 viruses. Is that right?

  14. Jesse says

    I’m sorry, Jean, I don’t really have time to watch such long videos… is there a place I could read the same info?
     
    Hm, I thought vaccines and their components had to be shown to be safe before they could be sold. Even if squalene and tween can cause problems, is there really enough present in the vaccines to do any harm? I mean, I like cooking with vinegar, but too much of it can be painful, I think… Isn’t squalene present naturally in plants and animals, anyway?

  15. Jean Folon says

    Jesse, it varies. Since people tend to believe myths sold with a veneer of authority, anything goes. Hence the composition is mostly a function of the agenda:
    http://video.google.com/videoplay?docid=6890106663412840646
    No big surprise that compounds like squalene and polysorbate 80 (aka tween 80), get added to the mix:
    http://www.ncbi.nlm.nih.gov/pubmed/8473002?dopt=Abstract
    Sometimes the composition is very different from what is advertised:
    http://www.globalresearch.ca/PrintArticle.php?articleId=14709
    For more background on that, see here:
    http://www.youtube.com/watch?v=A0JqQyl09zQ
     

  16. Jean Folon says

    Not just heavy metals. Some vaccines contain squalene which is directly implicated in causing auto-immune disease:
    http://ajp.amjpathol.org/cgi/content/short/156/6/2057
    Then there is the tissue the virus or bacterium used for the vaccine is cultured in. Not easy to separate and purify a mush of proteins, so some of that makes it into the vaccine as well and causes its own immune response.
    Some tissues used for culturing (e.g. monkey kidney cells, aborted fetal tissue) contain proteins close to or identical to human native ones, and as such might well cause an auto-immune response.

  17. Chris Kresser says

    Thanks for the suggestion, Jesse.  It’s on my list, but unfortunately my list is very long right now.  I hope to get to it eventually.

  18. Chris Kresser says

    Vaccines have heavy metals in them (some do, at least).  Heavy metals damage the gut and make it permeable, among other things.  Vaccines also dysregulate the immune system, and 70% of the immune system is in the gut.  This is all connected, Jean.

  19. Jean Folon says

    The intestinal barrier a major factor in auto-immune disease? I’d figure that vaccines are the major factor. But that is taboo, of course. I’ve seen several examples of Sci Am selling lies by giving bogus science broad exposure. Are you sure this leaky gut cause is not put out there with superficially convincing science as a convenient patsy for the real culprit?

  20. Jesse says

    Yeah, many bacteria are coated with LPS. It’s part of their cell wall.
     
    “He also said LPS is so toxic that if it were injected into a vein, it could be lethal.”
     
    The same could be said about air… But it is true that it’s not a good thing to have in your blood.

  21. says

    i asked my husband (a research biochemist) about lipopolysaccharide (LPS).  He also mentioned e. coli gut bacteria and said LPS is found in the coating on it’s exterior.  He also said LPS is so toxic that if it were injected into a vein, it could be lethal.

  22. Jesse says

    Now that I think about it, also references for the claim that “Plenty of “alternative” practitioners have been doing this for years.” Unless that will be included in a follow-up post.

  23. Jesse says

    Minor complaint: Lipopolysaccharide is almost everything but a protein.
     
    Also, do you have some references for the claim that refined grains and seed oils contribute to this stuff?

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