Insulin Resistance

I received a great question a few days ago and wanted to look at some nuances of insulin resistance. Here is the question:

Robb:
Idea for future post. Can you explain the mechanism of insulin resistance with regard to obesity? I have learned that obesity causes insulin resistance, which leads to NIDDM. It seems counterintuitive that resistance to insulin (i.e. inefficient storage) can cause fat. Instead it should cause a release of TG from the adipose. So improving insulin sensitivity can make us fatter in the setting of a hypercaloric intake. Or, am I missing something? Why is it not optimal to have some mild insulin resistance.
Thanks
Sleepdoc

So…there is a lot going on in this question. Here are a few things to keep track of:

1-Insulin resistance is a relative phenomena, from person to person AND more importantly from TISSUE to TISSUE.

2-Insulin resistance may or may not lead to overt obesity. Obesity may or may not be characterized by insulin resistance.

In the case of insulin resistance from person to person an individual may have a “normal” glucose tolerance test and insulin response as compared to statistical averages. That person however may have characteristics of hyperinsulinemia such as high blood pressure, altered blood lipids etc. Nothing too shocking here as it’s just another way of saying that people are different. Perhaps more interesting and germane to sleepdoc’s question is the issue of insulin sensitivity from tissue to tissue. In general adipose tissue is more insulin sensitive than muscular tissue and thus stores blood glucose relatively better than does muscle. This is played out amidst complex mechanisms designed to maintain blood glucose levels within certain operating parameters. If glucose gets too high we have serious problems with advanced glycation end products (AGE’s) and a loss of valuable nutrients as the glucose spills over into the urine at the kidney level. On the other hand, if glucose gets too low we can face a life threatening situation. Even during ketosis some tissues, particularly in the brain, still require glucose.

So on one end of a spectrum we could be highly insulin sensitive (on the whole body level) and all of our blood glucose would get shuttled into the muscle and fat leaving nothing for the brain and other tissues that need a constant titration. At the other end we have extreme insulin resistance that does not allow any glucose into cells, which oddly enough results in the same phenomena as low blood glucose…no fuel is available to maintain life despite large concentrations of circulating glucose and likely a large yet inaccessible fat mass.

The above description covers the two extremes of full body (all tissues) insulin sensitivity AND full body (all tissues) insulin resistance. What happens if we are relatively more or less insulin sensitive at our more metabolically active tissue, the muscle? If we are relatively sensitive at the muscular level we will tend to deposit/uptake nutrients into the muscle. Folks who have this “problem” tend to build muscle relatively easily and tend to not gain fat even in a hypercaloric state. An extreme version of this condition is the post workout state in which insulin sensitivity is high and in fact there are mechanisms for non-insulin mediated nutrient transport. In this scenario glucose, fats and amino acids get a free ride into the muscles without the action of insulin. If we reverse this process however and decrease the sensitivity of the muscles we will tend to store nutrients in the fat mass. I THINK this is what happens in the typical hard-gainer scenario…too many carbs, too often which reduces insulin sensitivity at the muscular level and a tendency to just get doughy and soft. It’s a great look, I wore it well for many years!

With the above in mind it’s easier to explain an obese individual who has a “normal” glucose tolerance test. This individual is relatively insulin sensitive at the fat level and resistant at the muscular level…on average, more nutrients get shuttled into the fat mass. What happens if this individual becomes progressively more insulin resistant at the fat level? This individual becomes VERY hungry and will eat enough food (typically refined carbs) to elicit enough of an insulin response to get nutrients into the muscle, brain and fat. Sine the fat is the most insulin sensitive tissue for these folks, the lions share of those nutrients get sequestered into the fat mass and then the cycle starts again in 2-3 hours.

Good Calories, Bad Calories is exhaustive in it’s detail of this topic if you care to dig deeper.

Robb Wolf

Robb Wolf, author of The Paleo Solution and Wired to Eat, is a former research biochemist and one of the world’s leading experts in Paleolithic nutrition. Wolf has transformed the lives of tens of thousands of people around the world via his top ranked iTunes podcast and wildly popular seminar series.