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Tags: diabetes, fat, inflammation, obesity, type 2
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I believe the inflammation hypothesis is in some ways meant to supersede the insulin hypothesis, however, it’s quite possible that excess insulin is a significant contributor to inflammation, by both inhibiting prostaglandin production, and by activating delta 5 desaturase, which would increase the proportion of inflammation-causing prostaglandins — at least that’s how I understand it.
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Amber: did you read the article? I discuss a few mechanisms by which insulin and leptin resistance contribute to inflammation. There are several I didn’t mention in the interest of keeping it from becoming a book. I think the upregulation of delta-5 desaturase is important, but probably not the primary one.
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Of course I read it. I ought to have started my comment with more acknowledgement. Your analysis and insights, as I have come to expect from you, are careful, relevant, and reflect the most recent advances in our knowledge. You did discuss insulin resistance as both a cause and effect of diabesity. I was just mentioning another possible mechanism, that comes from the prolonged presence of insulin itself. It may be a minor point.
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Forgive me. I wasn’t sure if you had read the article, or were just asking a question about that particular mechanism. In any event, this is a fascinating subject and could easily be the target of an entire series. Maybe someday…
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Chris,
I definately think that there is something to the Inflamation and insulin resistance connection. But I wonder if there is even more.
I would love to know how to reverse insulin resistence. I know what most recommendations are….exercise. But if exercise was the key to reversing it then why isn’t it the key to preventing it. What does one do when one reaches a pain threshold that prevents them from exercise? Particularly when it affects every major muscle group and every major joint.
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Chris, I see now how my comment looks like I am asserting they work together as if you hadn’t already asserted it, and could even be construed as implying you are proposing inflammation as an alternative mechanism to insulin, which you are obviously not. Sorry for the sloppiness.
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We’ll be talking about how to prevent and, when possible, reverse insulin resistance at length in this series. Stay tuned.
As for exercise, we’ll also discuss that. But the short answer is that high-intensity strength training is far more effective for improving insulin sensitivity than steady state cardio, because it more fully depletes glycogen stores in the liver and muscle.
The other keys (which should reduce inflammation and pain) are removing dietary toxins (wheat, fructose & seed oils), fixing the gut (addressing chronic infections, intestinal permeability, and dysbiosis), managing stress and restoring proper adrenal function, balancing blood sugar and addressing essential fatty acid (EFA) imbalances.
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Yippee skippy!! Finally seems as if, after searching everywhere on the web, there might, just might be a ray of hope and answers to “questions no one wants to hear” – never mind find a solution to — like: why do my joints hurt? why can’t I eat wheat without getting sick? why do I have little patches of eczema? whence the peripheral neuropathy? and are all these ailments related?” Most are greeted with the equaivalent of <SHRUG>.
Thanks, Chris.
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Great post. Has some ideas in common with some other blog posts I’ve come across recently on Carb-Sane Asylum and Adipo Insights and maybe a few others that have overturned my previous notions on insulin resistance. The idea that was overturned is that obesity results from insulin resistance of muscle cells. The idea was that muscle cells become insulin resistant which forces blood glucose to be taken up by fat cells and then converted to fat. Now this blog post reinforces the new interpretation that it is only after the fat cells are overfilled and hence insulin-resistant (not accepting any more glucose) that blood sugar can no longer be adequately controlled and diabetes develops. In other words the fat cells protect against diabetes up until they can’t accept enough glucose anymore. What the heck is my point?
Well considering all this, it seems to me that insulin resistance is in large part due to over-consumption of calories. Even of fat calories. Excess fat is taken up by fat cells which can fill them up and lead to the point where they won’t accept any more glucose. So I really believe that overeating is one of the main contributors to insulin resistance and that is regardless of the macro-nutrient composition of the diet and regardless of the quality of the diet. I’m just wondering what you think Chris. -
I don’t think excess SFA or MUFA can cause insulin resistance, except in the presence of excess glucose. If one limits glucose calories to 400-600 per day, they can eat all the SFA and MUFA they want. Insulin and leptin resistance is cause, on the other hand, by excessive intake of highly refined carbs and by excess PUFA intake (primarily n-6). So I don’t agree that macronutrient composition doesn’t matter – it’s the crucial element.
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@Taylor - Your theory that IR is due to over consumption of calories doesn’t explain all of the skinny T2 diabetics out there. Like one of my grandmothers. She was always tiny and yet lost her eyesight and legs to a raging case of T2.
Regarding inflammation – mine is sky high and I’m always looking for supplements to help bring it down. I’m taking a baby aspirin every day along with krill oil and turmeric. Anything else that would help?
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Laurel,
The most important thing is to identify the cause of the inflammation. Have you done that yet? Have you removed wheat, fructose (except small amounts of fruit) and industrial seed oils? Have you tried going without legumes, nightshades and other grains? Have you balanced your omega-6:omega-3 ratio?
In terms of supplements, I like Meriva-SP. A detox program using an anti-inflammatory diet and nutritional products would also be helpful.
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@Chris - My omega-6 consumption is very low for past couple years, I eat grass-fed beef, take fermented cod liver oil, drink raw milk from pastured cows. Only oils at home are olive & coconut.
I do have some tomato and potato, but I can eliminate them. Also, legumes I eat rarely. Wheat I do have small amounts of daily. I’ll eliminate them, too.
However I have a lot of weight to lose, but could that cause my C-reactive protein to be 20+ instead of 2? Oh, also my fasting insulin is always high and insulin is inflammatory, yes? Recently started on Metformin. Thanks!
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Laurel: may be worth a try to eliminate all grains, nightshades and legumes for a 3-4 week trial. I don’t think raw dairy is a problem for most people, but some do have issues with caesin so I’d eliminate that too. This isn’t forever – you’re just trying to figure out if there are any dietary triggers. If the inflammation improves, you’ll know something in your diet was contributing. Add one food back in at a time, every 3 days. Watch for symptoms.
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Thanks for informative post, Chris. You took quite a big bite with this one. I totally agree with importance of the inflammation in the diabesity. Couple of things I’d like to comment.
You wrote that expanding of the fat cells leads to the inflammation of the adipose tissue. I have to disagree with that. It seems that the size of the fat cells is a driving force for adipose tissue inflammation not the fat mass. PPARg agonists are meds that are used against the malfunction of the fat storage seen in diabesity or metabolic syndrome.
Another thing is that inflammation is something that is made by our own cells. It is highly dependent on the state of our immune cells. The responce to the inflammatory stimuli like LPS can differ markedly in different situations. High omega-6 for example blunts the immune responce and that leads to higher mortality for infections and cancer. Dietary saturated fatty acids have opposite effect on immune system. -
Westie,
I agree that the size of the adipocytes may be more significant than fat mass, but there’s plenty of evidence that expanding fat mass alone can cause lipotoxicity. Plasma free fatty acid (FFA) levels are increased in obese patients. FFAs activate macrophage-like cells via the LPS receptor Toll-like receptor (TLR)4. Also, FFAs can undergo phosphorlyation to ceramide, which has been shown to promote inflammation and originate secondary metabolites with the same effect.
Both adipocyte hypertrophy and hyperplasia activate inflammatory pathways and stimulate FFA release, which in turn stimulates macrophages through TLR4, which in turn causes increased expression of TNF-a, MCP-1 and other pro-inflammatory cytokines.
I agree that n-6 PUFA is pro-inflammatory, whereas SAFA and MUFA are not. I’ve argued this elsewhere on the blog at length.
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I have to ask because I don’t understand what you just wrote. If serum FFA (which are mainly SAFA) increase the macrophage related inflammation through TLR-4 why it is opposite with dietary SAFA? Saturated FFA directly bond and activate TLRs and/or they increase the responce of macrophages to acivation made by LPS.
In either way SAFA seems to increase inflammation. -
Lipotoxicity is the result of metabolic derangements caused by high-carb diets and food toxicities from grains, vegetable oils, and fructose. In a healthy person, SAFA are readily burned in the mitochondria for calories with no toxic byproducts. Also, SAFA can be elongated and desaturated in the liver to transform 16-carbon SaFAs created from carbs into SaFA or MUFA that are relatively deficient. So lipotoxicity isn’t evidence for the dietary toxicity of SAFA, and high SAFA diets – by removing toxins – are essential to healing the metabolism and eliminating lipotoxicity.
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I ment something like this:
http://www.ncbi.nlm.nih.gov/pubmed/20067961
A high fat meal (even dairy fat) can increase inflammation like high BS. Also SOCS-3 is increased and that is related to leptin resistance:
http://www.ncbi.nlm.nih.gov/pubmed/18560028 -
I’ll comment more on this later, when I have a chance to read more carefully, but I’m wary of drawing any conclusions from studying the effects of foods on individual markers that we don’t fully understand. This comment in the text raises a huge red flag:
In this context, it is important to state that our recent data demonstrate that the consumption of orange juice with an HFHC meal prevents not only oxidative stress and inflammation but also the increase in LPS concentrations and the increase in the expression of TLR-4 and SOCS3 observed after ingestion of the HFHC meal alone (20).
And again in the conclusion:
In contrast, orange juice intake does not induce oxidative stress, inflammation, SOCS3, TLR-4, or an increase in plasma LPS concentrations.
So, to prevent diabetes we should be eating a low-saturated fat diet and drinking plenty of orange juice. Wait a second, I think that’s already been tried – and it failed miserably. We know that excess fructose intake is one of the primary contributing factors to an increase in obesity, T2DM, metabolic syndrome and NAFLD. We also know that traditional peoples who eat high amounts of saturated fat (without dietary toxins like wheat, liquid fructose and omega-6 PUFA) don’t develop T2DM or CVD. The Inuit got up to 80% of calories from fat – a lot of it saturated – and were free from chronic diseases like T2DM & CVD.
Also, studies have shown that SAFA does not decrease insulin sensitivity.
When all of this is taken together, I am very skeptical of interpreting the data from this study as evidence that SAFA contributes to or worsens T2DM (in the absence of high carbohydrate intake and/or insulin resistance).
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westie,
I read through the study and I’m still not impressed – largely for the reasons I mentioned above. It highlights the problem with drawing conclusions from single-meal studies, which are useful in identifying avenues for exploration but don’t tell us anything about the long-term effects of that particular macro/micronutrient composition.
See this article on Hyperlipid for more on why this type of thinking isn’t sound.
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I mentioned this researsch because this kind of research is growing atleast in Europe. We have to know how to deal with it. For example this type single high fat meal worsens the symptoms of asthma. I think these results fit to the picture but I think we have to be more clever than those low fat high fibre proponents. We do have advantage because we know that for example dairy fat is very good in healing or atleast relieving inflammatory diseases like asthma.
I think this all is understandable if we truly understand how innate immunity works and how its responce can be modified towards more tolerant phenotype. If you have no idea what I mean I think there could be much more interesting reading. Problem is that I don’t think that answer can be found in any written book so far. It hasn’t been done yet. -
westie,
I understand. Thanks for the interesting dialogue. As you probably gather from the blog, I have a lot of respect for scientific research. But it’s important to remember that science isn’t limited to RCTs. Anthropological study, evolutionary biology, observation and plain old common sense are also important. When there’s a conflict in the data, I think it’s wise to look back on the hundreds of thousands of years of human history and see what our healthy ancestors (who were free of modern, chronic disease) ate. Modern research can give us some answers, but there’s too much we still don’t understand. That’s especially true when it comes to the immune system, which is so vastly complex we’re only beginning to have the faintest idea of how it works.
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