Wednesday, March 28, 2018

Glucose Outside and Inside Cells

When we speak of glucose levels, we're usually referring to the levels of glucose in the blood, or blood glucose (BG). And this level is important, because the glucose in the blood travels throughout the body to provide nourishment for our cells. It can also react chemically with tissues that are exposed to blood, for instance the endothelial cells that line the blood vessels, and damage them, especially when BG levels are high.

However, BG isn't the whole story. The level of glucose inside cells is also important. Outside of research studies, we don't measure this. But because too much glucose within the cells could cause damage, many types of cells won't take up glucose unless they have insulin to facilitate its transport across the cell membrane.

This is where insulin resistance comes in. Insulin resistance can be protective, keeping too much glucose from getting in some cells when it's not needed. In 2015, I blogged about the benefits of insulin resistance in the heart.

Insulin resistance can also function as a way to get glucose to tissues that need it. For example, when you have an infection or trauma, or when you're starving, or when you're in late pregnancy, your muscles become insulin resistant. This means the muscles won't grab all the glucose, thus making more glucose available for the cells that really need it, such as the site of infection or trauma, or the brain when you're starving. In late pregnancy, it ensures that the mother doesn't grab all the glucose and leave the developing baby with too little.

In other words, insulin resistance is a mechanism to select which tissues get glucose. If you're starving, you want to make sure the brain has enough glucose, because even though the brain can function on mostly ketones, derived from the breakdown of fat, it still needs a little bit of glucose. No point in wasting it on muscles.

However, if you're starving you still want to be able to hunt and gather, so the body overrides the insulin resistance in working muscle so  you can run after that impala and get a decent meal.

When it comes to obesity, the basic dogma goes like this: For some reason, maybe genetic, you have more insulin resistance than normal. The insulin resistance means you have to produce more insulin than normal. And the high insulin levels make you gain weight. The increased weight makes you even more insulin resistant. So you have a vicious cycle going.

This means that in terms of obesity, insulin resistance is bad and you should do whatever you can to reduce it.

But there's some evidence that maybe we have it backward. Maybe it's insulin sensitivity that makes you gain weight and the ensuing insulin resistance is the body's effort to control this weight gain.

Grizzly bears are very insulin sensitive in the late summer and fall when they're packing on the pounds. Then when they're snoozing in their dens, they become insulin resistant and lose weight by burning their stored fat.

There's some indication that a similar effect, minus the winterlong snoozing, can occur in humans. One study in 1991 showed that among the Pima Indians, known for their high diabetes rates in modern times, the ones with the most insulin resistance put on the least weight (other studies showed exceptions to this concept in some ethnic groups).

This all makes sense. If you're insulin sensitive, your cells will take up more glucose, and with more glucose in the cells, the body can make and store more fat. You might have less insulin in the blood, but that insulin will be effective in keeping the stored fat in place.

So what do we really need for health?

What we really need is for our cells to not only take up glucose from the blood, reducing BG, but to burn that glucose in the cells, so the internal glucose levels don't get too high. We can burn all the glucose that gets taken up by not eating more than necessary, and by working our muscles to burn a little extra. Exercise is good but less effective than diet when it comes to controlling weight.

This sounds a lot like "diet and exercise," and for eons that has been the standard treatment for type 2 diabetes. Of course, we'd all like a pill that would allow us to overeat as most Americans do while simultaneously making us slim and muscular. But so far, no such pills have emerged.

So all this blather about insulin resistance has no practical application. But it should give you a new perspective on the issue of insulin resistance.


  1. Wanted to thank you for writing the book The First Year : Type 2 Diabetes. Reading it has been the best thing that has happened to me after being diagnosed diabetic last January. It is a pity that medical science has yet to fully understand insulin resistance. We should by now be able to go for a test of insulin resistance instead of the A1c. Or for a test to see, like others claim, if our cells are full of fat and there is no room for glucose. Maybe someday. Best regards.

  2. Thanks, Luis. There *is* a test to give a rough estimate of IR on the basis of fasting glucose and fasting insulin. It's called HOMA. It's not perfect, and the "gold standard" is the hyperinsulinemic-euglycemic insulin clamp study. I had it done at Joslin as part of a study, and two doctors were working to measure my BG levels and adjust insulin drip for several hours, so it's obviously not practical except in research.

    The HOMA test is used when testing large populations in clinical studies but may not be accurate for individuals. However, it gives you a rough estimate.

  3. Luis, here's something: