Insulin: Anorexic?

James,

Sometimes it is necessary to simplify complex systems when trying to explain them to the public. Often times, very complex systems need to be simplified so much that the descriptions are no longer accurate.
I am very well aware of the multivariate problem that is insulin resistance. When I wrote to Robb that “the brain becomes insulin resistant upon chronic exposure to insulin”, I assumed he knew I was simplifying things to the point of inaccuracy.
Know, however, that there is literature to support the notion that constant high levels of insulin causes insulin resistance. The studies are based on experiments that involved glucose overfeeding to human subjects.

See: (1) “Effect of Sustained Physiologic Hyperinsulinaemia and Hyperglycaemia on Insulin Secretion and Insulin Sensitivity in Man”, Del Prato, S.; Leonetti, F.; Simonson, D.C.; Sheelhan, P.; Matsuda, M.; DeFonzo, R.A.; Diabetologia, 1994, 37, 1025–1035. (2) “Production of Insulin Resistance by Hyperinsulinaemia in Man”, Rizza, R. A.; Mandarino, L. J.; Genest, J.; Baker, B. A.; Gerich, G. E.; Diabetologia, 1985, 28, 70–75. (3) “Regulation of the Insulin Receptor Kinase by Hyperinsulinism”, Treadway, J. L.; Whittaker, J.; Pessin, J. E.; The Journal of Biological Chemistry, 1989, 264, 15136–15143.

However, as I’m sure you know, the notion that glucose or high levels of insulin cause insulin resistance has been challenged. In 1980, a glucose and fructose overfeeding study indicated that “high-glucose feeding caused no significant changes in insulin binding or insulin sensitivity whereas high-fructose feeding was accompanied by a significant reduction both of insulin binding and insulin sensitivity” See:”Impaired Cellular Insulin Binding and Insulin Sensitivity Induced by High-Fructose Feeding in Normal Subjects”; Beck-Nielsen, H.; Pedersen, O.; Lindskov, H. O.; The American Journal of Clinical Nutrition, 1980, 33, 273–278.
More recently, it has been shown that fructose impairs leptin sensitivity and exacerbates weight gain. See: “Fructose-Induced Leptin Resistance Exacerbates Weight Gain in Response to Subsequent High-Fat Feeding”, Shapiro, A; Mu, W.; Roncal, C.; Cheng, K.-Y.; Johnson, R.J.; Scarpace, P. J.; Am. J. Physiol. Regul. integr. Comp. Physiol. 2008, 295, R1370–R1375.

Interestingly, the muscular fat deposits that you refer to as a cause for insulin resistance are thought to be the result of fructose metabolism. See: “Sugar: The bitter Truth” by Robetr Lustig, MD on Youtube

Fructose is a carbohydrate and telling people to avoid carbohydrates in general typically minimizes exposure to fructose. Sure, other factors such as lectins, gut health, lack of exercise, lack of fiber in the diet, etc…are involved. Nevertheless, the avoidance of carbohydrate, specifically fructose, does seem to help people. We now have anecdotal evidence that even excess fruit, even though it contains fiber that slows down fructose absorption, can mess up cholesterol profiles and biomarkers of health.

http://heartscanblog.blogspot.com/2010/02/diabetes-from-fruit.html

This is one reason why we tell people to eat low-carb. Interestingly enough, the Kitavans have little to no fructose or lectins in their diet given that the preponderance of carbohydrate originates from starchy tubers.

So did I write something that was false in order to quickly communicate a piece of information? Yes I did. Guilty as charged. But then again, you also made an error by neglecting to differentiate acute and chronic responses to insulin.

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Going completely off memory on that, care to share that paper?
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Here’s the reference for the original paper:

Sims et al. Experimental Obesity in Man. Trans Assoc Am Physicians. 1968; 81:153-170

A series of papers were published after that one. You can do a PubMed search for EA Sims.

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The irony here is that people were hungry AT ALL in a hyper caloric state. According to YOUR hypothesis this should not be happening.
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“My” hypothesis? What hypothesis? I never presented a hypothesis.

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Also, there appeared to be a remarkable variety amongst those individuals as to HOW they responded to both the over feeding and subsequent fat loss, centered on hormonal response.
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No, Robb, you are ASSUMING it is all centered on hormonal response.

You need to look at the growing body of studies on non-exercise activity thermogenesis (NEAT), which is basically spontaneous physical activity. There is strong evidence that NEAT has a strong genetic component. There is also strong evidence that NEAT explains a large portion of the variations in weight gain in response to overfeeding. In other words, some people, when they overfeed, spontaneously increase their physical activity (I don’t mean exercise….I mean overall activity which ranges from fidgeting to walking around), while others do not. The people who spontaneously increase their activity gain less weight than the people who don’t, and also lose the weight faster when the overfeeding is done. The fact is, some people’s bodies “sense” an energy surplus better than others, and their bodies respond accordingly….without even the person consciously thinking about it.

The factors regulating NEAT are still not well understood, but some factors that have been found to play a role include sympathetic nervous system activity as well as orexins.

Matthew,

Here are my comments. First, in regards to the papers you cited:

“Effect of Sustained Physiologic Hyperinsulinaemia and Hyperglycaemia on Insulin Secretion and Insulin Sensitivity in Man”

In this paper, the model they used is simply not relevant to what happens in the human body. They used chronic insulin infusion, which does not mimic the natural swings in insulin that happens in someone eating food. They also used chronic glucose infusion, which again does not mimic the natural swings in blood glucose that happens when someone eats food.

The same holds true with the other papers you cited….chronic insulin infusion. Now, these models may be relevant to someone who already has insulin resistance (and hyperinsulinemia as a result)…..it can start a vicious cycle where the hyperinsulinemia exacerbates the insulin resistance futher, which exacerbates the hyperinsulinemia, and so on. But the papers you cite don’t support the concept that a high carbohydrate diet will cause hyperinsulinemia (unless the carbs are being consumed all day long, which in that case you’re simply overeating on calories).

And in regards to Robert Lustig, the problem with his lecture is that he doesn’t take into consideration dose or context. Alan Aragon does an excellent critique of Lustig’s lecture here:

http://www.alanaragonblog.com/2010/01/29/the-bitter-truth-about-fructose-alarmism/

I expanded on this in my most recent blog post:

http://www.thebsdetective.com/2010/02/partial-bullsht-of-day-fructose-makes.html

Robb,

I’ve actually know Jim Levine, the primary research guy on NEAT. He works out of the Mayo Clinic. He’s got some great review papers on it.

He’s also done some interesting studies where people had to wear a special underwear that could sense their movement and body position so that their NEAT could be tracked under free-living conditions.

James,

I cited those studies to offer a plausible explanation for the origin of the “excess insulin causes insulin resistance” hypothesis. I did not cite them because I thought they were correct. I am very well aware that research has since established that high fasting insulin levels are the result, not the cause, of metabolic syndrome.
This blog post started because you also failed to take into account dose or context when you discussed the anorexigenic effects of insulin. This whole discussion is just a problem of working from different contexts and doses. You are working from a context of caloric deficit (or neutral) as well as acute and short-term exposure with moderate to low doses. Robb and I are working from the context of caloric surplus, as well as chronic and long-term exposure with high doses. We do so because it reflects the reality that we see in our gyms and practices. Clients that come into our gyms have metabolic syndrome, are eating too much, some of them have a really low tolerance to carbohydrate irrespective of the presence or absence of metabolic syndrome, inflammation is out of control. We teach them the importance of omega-6:omega-3 ratios, avoidance of grains and other prolamine proteins, avoidance of lectins and phytates and we get them to reduce their carbohydrate intake to become fat adapted. And it works really well. Telling them that insulin is anorexigenic, although scientifically accurate within specific contexts, doesn’t help.