Thursday, February 24, 2011

Guest rant: Insulin resistance

Today you get a guest rant. This post was inspired by Matt Lalonde's response to a question on insulin resistance when he was a guest on Robb Wolf's podcast, the Paleo Solution. The guest rant is from Mike, the Other Sexy Paleo Chemist. Yes, there are two. To help you distinguish, I have made this handy list of attributes:

Similarities
  • chemist
  • precise speech
  • loves long-winded explanations
  • sexy
  • Paleo
Differences
  • Mike - physical chemist, Matt Lalonde - organic chemist
  • Mike - American, Matt Lalonde - Canadian
Enough introduction, on to the good stuff.

Insulin Resistance
by Mike

Ok, so I've heard/read descriptions of insulin resistance from: a science journalist, a biochemist, and an organic chemist, now it's time for the physical chemist's take on it. See, physical chemists spend their entire lives worrying about the tiny details, yet we know that no one really cares about the details, they just want the "simple physical picture". So after we get the details we (try to) make up a simple story to capture the main points. That's what I think is missing in most of the nutrition discussions out there: People get caught up in the details, but forget to tie it back to real life. So here's my take on insulin resistance.

In the paleoblogosphere we "know" that insulin resistance is bad and that we should avoid that. Why do we think it's bad? Well for the majority of the unhealthy grain-eating population it is bad because it's tied to hyperglycemia. And since we really only see it with sick people we've correlated insulin resistance to being sick. So everyone out there says we have to decrease our insulin resistance (increase our insulin sensitivity) because that makes us healthier. But is that REALLY the case? It turns out that there are two kinds of insulin resistance which I'll label the "good" kind and the "bad" kind (actually there's a third kind that I'll touch on at the end that's kind of interesting too).

First, let's talk about the "good" kind of insulin resistance. So let's say you're eating a good healthy low-carb paleo-inspired diet. Most of your diet is protein and good saturated fat. Now, your brain wants to run on glucose, we all know that; and we all know that through gluconeogenesis we can turn proteins (well the subset of glucogenic amino acids that make up proteins) into glucose, so there's truly NO essential carbohydrates that we need to eat. However, gluconeogenesis is slow and costly, so given the choice your body would rather just feed your brain the glucose it gets from carbs before it has to resort to gluconeogenesis. So your brain looks at the level of fat in your blood and say's "hey, there's lots of fat here, and I want the glucose, so I'm going to turn up the insulin resistance a bit".

Remember, insulin's main job is to pull glucose out of the blood and put it into either the muscles for fuel or the fat for storage. It's really bad to have sugar hanging out in your blood, so your pancreas has a sugar meter in there and when it sees sugar in the blood, it turns on the insulin to get it out. However, that's half the story. The insulin works as a "signal" to the muscle and fat cells to start pumping the sugar out of the blood (and into themselves), but if the cells are "insulin resistant" they don't listen to that signal. So in this healthy low-carb state, your pancreas sees a little sugar and turns on the insulin signal. But your brain sees the high-fat and tells your muscles and fat cells to ignore that signal because it wants all the glucose for itself. This is perfectly fine because your brain burns the glucose and your blood sugar goes down and everyone is happy.

So what's the "bad" kind of insulin resistance? Well, remember that sugar meter that your pancreas has? Well, it's not a sugar meter so much as a glucose meter. The other kind of sugar, fructose, is invisible to your pancreas. [Note: ALL carbohydrates you eat are polymers of glucose and/or fructose, and when they're digested they are broken down into the requisite monomers to make it through the gut lining. So it doesn't matter at all what the carbohydrates you eat start out as, your body only sees them as glucose and fructose.] So if you're eating a high-carb diet, and in particular a high-fructose diet (I don't care if your high-fructose is coming from HFCS or from fresh fruits from your local farmers market, it's all the same: evil), your pancreas is responding to the glucose and turning on the insulin and getting that glucose out of the blood and stored away where it's safe. That's not too terrible, you'll get a little fatter, but you can burn it later when your inuslin is low. But that fructose which is invisible to everybody ends up in the liver which does most (75%) of the processing of fructose. It's really the only guy who sees fructose. So now your liver takes that fructose and starts packaging it up into glycogen. This is good, as it can now be used for fuel for your muscles. However, it's really easy to top off those hepatic (liver) glycogen stores, and the liver needs to do something else with all that fructose you're consuming.

When your liver is full of glycogen and you're still eating a high-carb diet, it needs to do something else with all of that fructose coming in. So it starts packaging it up as fat (technically triglycerides). Now you have fat roaming around your bloodstream, normally no big deal. But remember back to the "good" kind of insulin resistance, where did it come from? Your brain saw the fat and said "hey, you're eating a high-fat diet, I need you to conserve glucose for me". So now your brain sees the fat packaged from your liver that comes from your high-carb diet and sends out the command to become insulin resistant. But now there's way too much glucose for your brain to burn, so your blood sugar stays high and the sugar meter in your pancreas says more insulin is needed which triggers more fat to be stored which tells your brain to send more insulin resistance signals which yet again slows the sugar getting out of your blood. And your pancreas sees this and turns on more insulin. You can see the downward spiral we get here.

In the best case, this downward spiral just leads to excessive fat accumulation (obesity), but after enough time of this competing "ignore the insulin"/"make more insulin" feed back loop, your pancreas just gives up. It can't make enough insulin. So now it's "ignore the insulin"/"not enough insulin" and your blood sugar is chronically high. This is Type-2 Diabetes. This is when all of the advanced glycation end products (AGEs) get produced and cause bad things. Chronically high (but not high enough to get rid of the sugar) insulin also causes a host of problems, not the least of which is the fact that you cannot use fat for fuel in the presence of insulin. So you're eating all of these carbs which are being stored as fat and but you can't get it back out as fuel. So you move less (not because you're lazy, but because you don't have available fuel) and you get hungry and eat more. Another evil spiral.

So why do we care about this? Actually, we don't! I think insulin resistance is another measure like cholesterol where 1) it's easy to measure and 2) it's correlated with unhealthy people. However, I argue that 1) being insulin resistant doesn't necessarily mean you're unhealthy and that 2) lowering your insulin resistance doesn't necessarily make you healthier. If you're a healthy weight, active, and eating a low-carb diet, you can be insulin resistant with no issues. But if you're hyperglycemic, overweight, inactive, and eating a high-carb diet, you will be insulin resistant, but you already knew you were unhealthy anyway. So in either case, don't worry about your level of insulin resistance.

As promised, here's the "third" kind of insulin resistance, and this results in a intergenerational downward spiral of obesity and sickness, i.e., you're making your kids fat (and sick) and they're making their kids fat (and sick). So first, remember back to the "good" kind of insulin resistance: your brain says "ignore that insulin so I can get the sugar". Well when a healthy woman is pregnant, she becomes natually a little more insulin resistant for the same reason: to give the fuel to the developing fetus. So what happens when an hyperglycemic insulin resistant woman is pregnant? Well those same horomones tell her to become even MORE insulin resistant. So now the developing fetus sees a HUGE sugar load. Since it's developing in what it thinks is a naturally hyperglycemic state it develops a super strong pancreas (i.e., more beta cells), so that it can produce even more insulin. So now you'll have a newborn baby whose pancreas is really strong and makes tons of insulin at the slightest hint of glucose. Which means the baby's body will store anything consumed as fat which is not available for fuel, so the "bad" kind of insulin resistance will hit earlier in life each generation.

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