New trigger discovered for metabolic syndrome, a risk factor for diabetes

People at risk for metabolic syndrome have elevated levels of a receptor triggering destructive inflammation that eventually lead to diabetes and heart disease, according to new research from University of California at Davis.

The researchers at UC Davis Medical Center focused their study on two Toll-like receptors (TLRs), called TLR2 and TLR4. These sensors on cells initiate a fast immune response to infections but also trigger harmful inflammation.

Past research has implicated TLR2 and TLR4 in the development of diabetes and heart disease.

Study focused on pre diabetes

The UC Davis study evaluated 90 people aged 21 to 70 years. Of the group, 49 of them had at least three features of metabolic syndrome (also known as "pre diabetes") – hypertension, low HDL-cholesterol, high triglycerides and obesity. Members of the control group had no more than two of these features.

Results of blood comparisons showed that the metabolic syndrome group had significantly higher levels of cell-surface receptor proteins TLR2 and TLR4 and messenger RNA than the control group.

The metabolic syndrome group also had higher levels of the master switch of inflammation in the nucleus, and a much higher concentration of immune “soldiers” in the blood, like cytokines, that create inflammation.

Researchers found that levels of free fatty acids were twice as high in the blood of people in the metabolic syndrome group. The levels of the product of gram-negative bacteria and endotoxin were three times as high as the control group. Both explain the raised levels of TLR4, in part.

Weight loss and diet can supress TLR activity

According to UC Davis, patients can suppress TLR activity with weight loss and with diet, exercise and medicines that target TLR2 and TLR4. This might prove effective in treating heart disease, diabetes and other conditions linked to metabolic syndrome.

Metabolic syndrome is a cluster of cardio-metabolic risk factors. It is a high-risk state of obesity that increases the risk of developing diabetes at least five-fold and heart disease by two- to four-fold, according to UC Davis.

One third of American adults have metabolic syndrome, according to UC Davis.

The research was published in the February 22 issue of Diabetes Care.

Source: UC Davis Health System

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