Key Factor Identified That Links Metabolic Syndrome

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Metabolic Syndrome

A new study led by researchers at Joslin Diabetes Center has identified insulin resistance in the liver as a key factor in the cause of metabolic syndrome and its associated atherosclerosis, disorders that put tens of millions of Americans at high risk of cardiovascular disease.

The findings, published in the February issue of Cell Metabolism, provide not only an understanding of how metabolic syndrome occurs, but also pinpoint a target for treatment of the condition. This represents the work of Sudha Biddinger, M.D., Ph.D., and a team led by C. Ronald Kahn, M.D., Head of the Joslin Research Section on Obesity and Hormone Action and the Mary K. Iacocca Professor of Medicine at Harvard Medical School.

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"This is one of the first true insights into the role of the liver in the metabolic syndrome and provides guidance for future therapies,'' said senior investigator Dr. Kahn, an internationally recognized researcher in diabetes and metabolism. "Showing this connection between atherosclerosis and insulin resistance is one of the most dramatic findings I've seen in 35 years.''

Metabolic syndrome is a collection of medical problems related to insulin resistance, including obesity, glucose intolerance, hypertension, lowered HDL ("good") cholesterol and elevated triglycerides. Together these are associated with an increased risk of atherosclerosis, the buildup of plaque in the coronary arteries that leads to heart attack and stroke.

The findings indicate that many of the most important features of the metabolic syndrome do have a common cause, thus challenging a joint position statement issued by the American Diabetes Association and the European Association for the Study of Diabetes that questioned the very existence of the metabolic syndrome (Diabetes Care. 2005;8:2289-2304).

"This study clearly indicates that metabolic syndrome is not merely a collection of abnormalities that should be considered and treated independently, as some experts have advocated,'' said Kahn and Biddinger. "Rather, it appears that metabolic syndrome is truly a group of closely linked disturbances in glucose and cholesterol metabolism that stem from a defect in insulin signaling in the liver."

Dr. Biddinger said the study sought to understand whether insulin resistance - a condition where the pancreas makes insulin but the body doesn't respond to it - could increase the risk of atherosclerosis.

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