Where Does Type 2 Come From?

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Last Friday, I went to a seminar on a new kind of surgery for weight loss. The talk was held at the Center for Obesity Assessment, Study, and Treatment (COAST) at the University of California, San Francisco. At the end of the seminar, Robert Lustig, MD, said, “This surgery [vagotomy, or cutting the vagus nerve] won’t work for the kind of overweight that contributes to Type 2 diabetes. This is for the other kind of obesity.”

Kinds of obesity? Causing Type 2? So I started wondering, what does cause Type 2? We know that insulin resistance plays a role in Type 2 diabetes. But what causes insulin resistance (IR)? Is it a germ, an autoimmune response, the body’s response to fat, or what? For three days, I got lost in the wilds of biochemistry, only to realize with a shock that I knew the answer already. Here’s what I found.

Types of Insulin Resistance
There are several types of IR. All of them involve cells refusing to open up for the glucose that insulin is transporting. Many different proteins are involved in helping insulin transport glucose into cells. Problems with any of them can cause resistance.

Several of these proteins and hormones are mentioned in this study from Japan. Other scientists report that the resistance that happens in muscles is different from what happens in an insulin-resistant liver. At the cellular level, IR sounds very complicated.

But how do cells become insulin-resistant? Some IR is inherited. Scientists at Yale found changes in the mitochondria of insulin-resistant children. Mitochondria are our cells’ “power plants.” They are where the glucose gets used for energy. The insulin resistance in these children is a kind of genetic insulin resistance.

Diet can also contribute to IR, sometimes in surprising ways. Salt intake may increase IR, as indicated by this Tokyo study. The same study cited evidence that high blood pressure (hypertension) promotes IR. The insulin resistance connection may be why hypertension often predicts future Type 2.

But the belief in medical circles now says that fat in the cells causes the most IR. A widely-cited article entitled “Etiology [Cause] of insulin resistance” by two Yale scientists claims strong evidence that “insulin resistance is a result of accumulation of intracellular lipid metabolites [fatty acids]… in skeletal muscle and [liver cells].” This explanation seems to be gaining wider acceptance as the general panic over obesity spreads, and it seems to be true in some cases. Confused? Well that’s not all. Inflammation and “oxidative stress” have also been blamed for IR in many studies. And inflammation and oxidation each have several different molecular pathways.

What’s the Real Cause, Then?
But actually, when you look at all the dizzying research on IR at the cellular level, none of it is that impressive. Scientists are certainly gaining more biochemical knowledge, but what does it have to do with what is really making people sick? I was getting more and more confused.

After two days looking at molecular chemistry, I found this study from Boston University. Called “Physical Inactivity Rapidly Induces Insulin Resistance and Microvascular Dysfunction in Healthy Volunteers,” it reports on 20 healthy young people who were restricted to bed rest for 5 days. The article states that, “Bed rest led to a 67% increase in the insulin response” — that’s right, 67% in five days — “to glucose loading, suggesting increased insulin resistance, and produced increases in total cholesterol and triglycerides.” The authors also found that arteries became tighter and systolic blood pressure (the top number, representing the pressure when the heart contracts) increased with bed rest.

In my book, Diabetes: Sugar-Coated Crisis, I wrote that insulin resistance is sometimes just a fancy word for physical inactivity. Glucose is fuel. If your muscles aren’t using the fuel, of course they won’t want any more. It’s like trying to pump gas into your car when the tank is already full. The gas spills all over the place. Before you can pump more gas, you have to drive the car.

But physical inactivity isn’t the only cause with striking supporting evidence. There is also stress. A 2006 study from The Cleveland Clinic found that “Hostility and stress [predict] insulin resistance.” “Hostility” was measured on a psychological scale including cynicism, hostile attitudes, and aggressive behaviors. “Stress” was measured by the amount of stress hormones found in the urine.

Lead author Jiangping Zhang, MD, said that “people with higher hostility don’t always have worse insulin resistance, but they do when they are under stress, especially high levels of chronic stress.” But even without “hostility,” stress has been linked to IR in dozens of studies.

Somehow I got so lost in the biochemistry that I forgot what was really important for most people with Type 2 or prediabetesstress reduction and physical activity. But that is the same path to nowhere that our entire medical system has been on for decades. They hunt down the molecular targets so they can develop new drugs. But there are so many proteins and hormones involved in insulin function that we could never cover them all. The important things are to relax and to move our bodies when we can.

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