Aspirin (search) and related drugs may have something to teach us about how insulin (search) resistance develops.

Insulin resistance can lead to obesity and type 2 diabetes (search). How this occurs is unclear, although researchers believe that low levels of inflammation may be associated with the development of insulin resistance, which later increases the risks of other conditions.

In a recent experiment on mice with signs of type 2 diabetes, an aspirin-like drug helped tame low-grade inflammation linked to insulin resistance. The drug also reversed the signs of type 2 diabetes.

However, it’s too soon to try aspirin for diabetes prevention. Losing extra weight, getting regular exercise, and eating healthfully are the best ways to reduce your risk of developing type 2 diabetes, say the researchers.

The study was conducted at Boston’s Joslin Diabetes Center, which is affiliated with Harvard Medical School. The report by Steven Shoelson, MD, PhD, and colleagues appears in Nature Medicine’s advance online edition.

The study focused on mice, but for people it may have lessons about a link between obesity, inflammation, and insulin resistance — markers for type 2 diabetes and heart disease.

More and more Americans have problems with insulin, a hormone that controls blood sugar.

Insulin resistance occurs when the body doesn’t fully respond to insulin (search). As a result, the pancreas has to make more insulin to control blood sugar. If it can’t produce enough insulin to be effective, blood sugar increases and diabetes may develop.

About 18 million Americans have diabetes, says the American Diabetic Association. Metabolic syndrome, a cluster of risk factors linked to diabetes and heart disease, is also increasing. Insulin resistance is one of the components of metabolic syndrome.

Obesity, Inflammation, and Insulin

In the study, the scientists conducted a series of tests. First, they put mice on a high-fat diet. These fat mice developed insulin resistance. The researchers show that the livers of the mice increased the production of NF-kB, a marker of inflammation.

The same might be true for humans. When people put on weight, it’s not just their waistline that suffers. Fat burdens the entire body. When too much fat gathers in the liver, inflammation might result, as it did in the mice.

Next, the researchers studied healthy mice of normal weight. They manipulated the genes of the mice to boost NF-kB production. These mice had normal weight and appearance. However, their genetics prompted “a cascade of inflammatory responses” in the mice, says Shoelson in a news release.

The low level of inflammation had a big effect. It prompted insulin resistance like that seen in the obese mice. That suggests that low-grade inflammation leads to insulin problems, say the researchers.

Since obesity can also prompt inflammation, the problems can start with extra pounds.

Stopping Inflammation

Lastly, the researchers tried to stop the inflammation. They treated the genetically altered mice with a salicylate, a class of anti-inflammatory drugs that includes aspirin. They had used salicylates in past experiments on rodents and humans, improving insulin sensitivity.

This time, the drug helped calm the mice’s inflammation and insulin problems. Inflammatory markers including NF-kB were blocked, and insulin resistance was reversed.

“Insulin resistance seems to be treatable,” write the researchers. More studies are needed before any recommendations can be made to patients, says Shoelson in the news release.

By Miranda Hitti, reviewed by Brunilda Nazario, MD

SOURCES: Cai, D. Nature Medicine, advance online publication, Jan. 30, 2005. American Diabetes Association. WebMD Medical Reference from Healthwise: “Metabolic Syndrome — Topic Overview.” WebMD Medical Reference from Healthwise: “Metabolic Syndrome — Insulin Resistance.” News release, Joslin Diabetes Center.