Although numerous studies have shown that low-grade inflammation is linked to heart disease and diabetes, more recent studies have shown that inflammation plays a role in insulin resistance, a syndrome that leads to diabetes and heart disease and affects about one in four adults in the United States. But exactly how inflammation triggers insulin resistance is not fully understood.
Now, researchers at Cedars-Sinai Medical Center and the University of California, Los Angeles, have found that variations in four genes that control inflammation are linked to insulin resistance, the precursor of diabetes, in Mexican Americans. Their findings, reported at the American Diabetes Association's 65th Annual Scientific Sessions, may enable physicians to identify patients at the highest risk for developing diabetes and to design therapies that target these genes to prevent insulin resistance.
"This study is the first to show that four inflammatory pathway genes – IL4, IL4R, IL6 and C5 – contribute to the development of insulin resistance," said Jerome I. Rotter, M.D., director of research, Medical Genetics Institute at Cedars-Sinai Medical Center.
Low-grade inflammation originates in numerous places throughout the body, including excess fat, and is often triggered by some type of injury or infection. In heart disease, the idea is that the coronary arteries become inflamed, causing the plaque or fatty build-up in the arteries to rupture. But because the inflammation is internal and not "seen," doctors use a simple blood test to measure for high levels of C-reactive protein (CRP) – a marker for inflammation. High levels of CRP are linked to an increased risk of heart attack, stroke, diabetes and more recently, insulin resistance.
Insulin, which is secreted by the pancreas, helps cells to take in glucose and convert it to energy. Insulin resistance occurs when muscle, fat, and liver cells do not 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.