Diabetes Complications

Inflammation – Not Obesity – Leads to Diabetes

Did anyone ever tell you that you have a “lifestyle disease” because you have type 2 diabetes? Even if no one ever said that to your face, you can be sure that some people have thought that and even said so behind your back.

Lots of people see type 2 diabetes as preventable if only we would eat less. They think that diabetes results from a choice, just as other lifestyle choices like cigarette smoking and heavy alcohol consumption lead to other diseases. It’s blame-the-victim time.

Even the government’s Centers for Disease Control and Prevention (CDC) buys into this argument. “We know obesity causes about two-thirds of diabetes,” this U.S. government organization told state health agencies in 2005, according to Fat Politics: The Real Story Behind America’s Obesity Epidemic by J. Eric Oliver (New York: Oxford University Press, 2006), pp. 49-50.

In fact, no one has ever demonstrated that obesity causes diabetes or even insulin resistance. But why is there such a large overlap between being heavy and type 2 diabetes?

The numbers never did add up to show a casual link between weight and diabetes. More than one-third of all American adults are overweight. Plus, nearly one-third of the people in this country are obese.

By comparison, 7 percent of adult Americans have diabetes. So being heavy can’t be the cause of diabetes. Even when we consider the one-fourth of Americans with prediabetes, there’s got to be more to causing diabetes than being well upholstered.

Now, however, researchers at the University of California, San Diego, School of Medicine have discovered the connection between body fat and diabetes. Just this month they published their findings in Cell Metabolism as “JNK1 in Hematopoietically Derived Cells Contributes to Diet-Induced Inflammation and Insulin Resistance without Affecting Obesity.”

While the article shows 11 co-authors, the corresponding authors are Jerrold M. Olefsky and Michael Karein. Dr. Olefsky’s office kindly sent me a pre-print of the article in Microsoft Word format. The abstract is online.

Inflammation is the key. Their research proves that obesity without inflammation does not result in insulin resistance, much less diabetes. Dr. Olefsky explains that when an animal or a person becomes obese, they develop steatosis, which is increased fat in the liver. The steatosis leads to liver inflammation and hepatic insulin resistance.

Macrophages, found in white blood cells in the bone marrow, are the key players in the immune response. These macrophages are a type of white blood that takes in foreign invaders like infectious microorganisms.

When these immune cells get into tissues, such as fat or liver tissue, they release cytokines, which are chemical messenger molecules used by immune and nerve cells to communicate. These cytokines cause the neighboring liver, muscle, or fat cells to become insulin resistant. That in turn can lead to type 2 diabetes.

The UCSD research team showed in a mouse model that the macrophage is the cause of this cascade of events. They did this by knocking out a key enzyme in the inflammatory pathway in the macrophage. This is the same enzyme that Dr. Robert Lustig, a pediatric endocrinologist at the University of California, San Francisco, referred to in my most recent article here. In the liver, fructose initiates this enzyme, which they call “c-jun N-terminal kinase-1” or just JNK-1 or Junk-1.

While the mice in the research study did develop fatty livers, they did not develop inflammation. “Their livers remained normal in terms of insulin sensitivity,” says Dr. Olefsky. This shows that insulin resistance can also be disassociated from fatty liver, he says.

“We aren’t suggesting that obesity is healthy, but indications are promising that, by blocking the macrophage pathway, scientists may find a way to prevent the type 2 diabetes now linked to obesity and fatty livers,” Dr. Olefsky says. He expects that their discovery may lead to new drugs to prevent type 2 diabetes.

I wrote here two years ago about the dangers of fatty liver, which I had at that time. I am particularly sensitive to the dangers of fatty liver, because if we don’t control it, it can lead to liver failure. Early this year my wife, Catherine, who also had type 2 diabetes, died of liver failure.

None of this is to deny that we can control our diabetes better when we lose weight. I know from my experience of losing a lot of weight in the past two years how much better my numbers are and how much better I feel. Now, we have drugs to help people with diabetes regulate their weight. Maybe in a few years, as people appreciate that inflammation causes both obesity and diabetes and as more and more of us lose weight, people will stop blaming us for being overweight. They may even stop labeling type 2 diabetes a lifestyle disease.

This article is based on an earlier version of my article published by HealthCentral.

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