Variations in four inflammatory genes may predispose Mexican Americans to insulin resistance

t use insulin properly. As a result, the pancreas tries to keep up with the demand for insulin by producing more, causing excess sugar to build up in the blood. Over time, insulin resistance leads to heart disease, diabetes, high blood pressure, obesity and polycystic ovarian syndrome. In fact, about 25 percent 68 million adult Americans have insulin resistance, with Mexican Americans having the highest prevalence.

"Because insulin resistance and heart disease are so common in the Mexican American population and we know that chronic low-grade inflammation is associated with these diseases, our group wanted to investigate whether specific inflammatory genes might be involved," Rotter said.

To determine whether specific variations in the genes that control inflammatory responses were directly linked to insulin resistance, researchers at Cedars-Sinai and the University of California, Los Angeles, studied a large, high-risk population of Mexican Americans. Using the most precise diagnostic and genetic tests, the investigators examined the link between variations in 31 of the most common inflammatory genes and insulin resistance.

The researchers examined the DNA of 656 Mexican American family members participating in the study and identified 41 variations in the 31 inflammatory genes. Among these family members, 394 adult offspring and their spouses were then tested for insulin sensitivity with the glucose clamp, the most precise diagnostic test for insulin resistance, by receiving an infusion of insulin in one arm over a two-hour period. At the same time, blood samples were drawn from the other arm to measure how much glucose was present in the blood. Depending on blood glucose levels, sugar was added to see how well the cells used it. Patients were found to be less insulin resistant when the samples showed low blood sugar levels even when glucose was added, indicating that the cells were taking up glucose. However, when little or

Contact: Kelli Hanley
Cedars-Sinai Medical Center

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