Insulin Resistance: Mechanism

 We all know that insulin resistance (IR) is one of the main causes of type 2 diabetes. Many people with type 2 can produce some insulin, but it's just not enough to overcome the IR.

What causes this sluggishness? No one knows for sure.

A recent paper suggests that the key is ATP, the energy-containing molecule that is produced when you eat and can then be used to drive other reactions in the cell.

I always thought ATP was good to have, and the more ATP the more energy. But this author (Jianping Ye) suggests that too much ATP can cause what he calls overheating. In the winter, it's nice to get heat from your furnace; the heat is nice, but you don't want it to get up to 100 degrees. He suggests the same is true of ATP.

Ye says that when you have too much ATP, the cells become insulin resistant to prevent overburdening the cells with too much energy. Hence, cells are insulin sensitive under conditions of energy deficiency and insulin resistant when there's an energy surplus.

So insulin sensitivity/resistance is an index of energy demand.

Interestingly the drug metformin inhibits ATP production.

He notes that as we age, energy demand decreases. If you're 95, you're not apt to go out and play three sets of tennis, so you need less food.

We all know that, but many of us eat portions determined by habit rather than by need. Restaurants don't serve meals adjusted for need. Everyone gets the same thing, although of course someone who just spent the day mountain climbing can order more than someone who spent the day reading. But how many of us act on that? In our "clean plates club" society, we often eat more than we really need. This is especially true in people who eat all their meals out.

In support of Ye's hypothesis, it has been known for about 60 years that elevated ATP is a risk factor for insulin resistance. But he says its importance hasn't been appreciated because of technical difficulties in measuring ATP in various tissues.

Interestingly the drug metformin inhibits ATP production

So is one solution to the diabetes epidemic simply to eat less? Sadly, that's often difficult to do. If  you eat out a lot, one solution is to get a tightly sealed container, carry it in a nice handbag, and use it to take at least half of the meal home without carrying around those awful plastic things restaurants usually put leftovers into.

We need food. We need energy. We need ATP. But as with many things in our lives, we just don't need too much.

ACCORD Revisited

 In 2008, the results of the ACCORD "landmark" trial were published and were interpreted by some to mean that people with diabetes shouldn't get their blood glucose (BG) levels down to normal or below. This is because those whose diabetes was treated aggressively in this trial had greater mortality than those with less aggressive treatment.

Sadly, some physicians used these results to urge their patients to have higher hemoglobin A1c levels. Patients were reporting on diabetes lists that their doctors told them that their normal A1c levels were too low and they should get them up.

Careful analysis showed that in fact, the patients with increased mortality were those who used very aggressive treatment but despite this did not lower their A1c. So they had harm from the treatment without compensating benefit from lower BG levels. Those who got aggressive treatment and did lower their A1c got benefit.

"It has been recognized that patients treated intensively in ACCORD who attained a lower HbA1c had reduced risk of death compared to those treated intensively with little HbA1c reduction."

Unfortunately, these analyses did not get the wide publicity that the initial results did, so many busy physicians may not have read about them.

Now a new analysis of ACCORD  says that there is a subtype of type 2 that shows real benefit from intensive glycemic treatment.

Now, most patients will not be given genetic tests to determine if they are in this subgroup. And there might be other subgroups that these researchers did not study. However the analysis suggests that you should not accept without question the results of big studies of diabetes patients as applying to you. They probably will, but they might not.

If you're a physician, you need to work on the assumption that big trial results will apply to most of your patients, so you start by following their recommendations. But most of us aren't treating others, so what we really care about his how some approach will affect us.

This means we should test as much as we can, not just BG levels but other factors that affect our health, to see what works for us. We're fortunate these days because if we can afford it, we have access to a  lot of tests.

Stay informed. Read about the latest big studies. But read them critically and try to figure out if they make sense for you. Try what they suggest is beneficial, but don't apply the suggestions blindly.

In the long run, we have to be in charge of our health.

Self-control

Some time ago, in an online suport group I started, one woman said her biggest problem was that she couldn't stop eating potato chips after she'd had one.

I knew she lived alone, so I asked why she bought potato chips, and she said, "Because I like them."

I think this is a common problem. 

The most important thing you can do when you're diagnosed with type 2 diabetes is to accept that your life is going to have to change if you want to control it. Of course, that's not easy. If you live with others who aren't diabetic, you're probably going to keep buying food you shouldn't eat. That's difficult.

It should be easier if you live alone. If something makes your blood glucose spike, keep it out of the house. I suppose there are people with iron self-control who can eat just one bite of a cookie and no more. I'm not one of them.

Once before I got diabetes, I was on a diet to lose weight. I was avoiding sweets and they no longer had any appeal for me. Out of curiosity, I went into a bakery, and nothing looked good, but I bought a bag of cookies anyway to see if they'd taste good. I planned to eat just one, but as soon as I did I craved more and ate the whole bag.

So much for that approach. After that I just kept the cookies and pies out of the house. If I learn that a comet is headed for the earth and will destroy all life, I'm not going to call my nearest and dearest to say good-bye. I'm going to the bakery to buy a blueberry pie, and then I'm going to eat the whole thing.

Just my luck the comet will change course and we'll all be saved and my blood glucose will go over 500. Oh well. It would be fun while the pie lasted.

But until then I won't make pies, and I won't buy them. It's easier than trying to have self-control.

Obesity Benefit

 Most of the news about people who are overweight or obese is bad. We see a constant stream of articles saying obese people are at higher risk of this and they're at higher risk of that.

But here is an article saying that obesity protects you from dying from severe bacterial infections. In this study, 26 percent in the normal weight group were dead within a year. The corresponding figures in the groups with higher BMI were 9-17 percent. Full text is here. The authors note that although obesity is associated with higher survival in bacterial infections, it's associated with lower survival in viral infections. The authors have no explanation for this.

Other studies have shown similar effects, and this is called the obesity survival paradox.

 So does this mean we should all stuff ourselves with pies and cakes, hoping we'd become obese and thus have a better chance of surviving a bacterial infection? No. For one thing, we don't know we're going to get a severe bacterial infections, and for another, too many negative side effects are associated with overweight.

So as so many authors conclude, "more studies are needed."