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Diabetes drugs act as powerful curb for immune cells in controlling inflammation

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WASHINGTON — A common class of drugs used to treat diabetes has been found to exert a powerful check on macrophages by controlling the metabolic fuel they use to generate energy, according to a news study.

When tissues are damaged, one of the body’s first inflammatory immune-system responders are macrophages, cells which are commonly thought of as ‘construction workers’ that clear away damaged tissue debris and initiate repair.

The findings are detailed in a study published online this month in Genes and Development led by Mitchell Lazar, MD, PhD, director of the Institute for Diabetes, Obesity, and Metabolism in the Perelman School of Medicine at the University of Pennsylvania.

Keeping macrophages from going overboard on the job may inhibit the onset of obesity and diabetes following tissue inflammation.

“When this happens, macrophages infiltrate the affected tissues, sequester free fatty acids, and help repair damaged tissue, essentially acting as a protector of the body during times of metabolic stress,” said Lazar.

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However, extended stress on these tissues activates inflammatory characteristics in macrophages that contribute to several systemic effects of obesity including diabetes, atherosclerosis, and cardiovascular disease.

Diabetes drugs called thiazolidinediones (TZDs) control gene expression by targeting a factor called PPAR gamma.
Lazar’s team found that the TZDs, working through PPAR gamma, promote the metabolism of an amino acid called glutamine, a protein building block necessary for macrophage activation.

The team found that macrophages lacking PPAR gamma are unable to use glutamine as an energy source and therefore are more susceptible to inflammatory stimulation.

“These findings are highly relevant to treatment strategies that use TZDs for diabetes and enhance the justification for using TZDs to treat systemic inflammation that accompanies many types of disease, including obesity and diabetes,” said Lazar.

With Agency Inputs

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Diabetes drug might ease heart failure risk

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A new research has showed that the diabetes drug Farxiga might do double-duty for patients, helping to ward off another killer, heart failure.

According to the findings were published in the New England Journal of Medicine to coincide with their presentation at the annual meeting of the American Heart Association in Chicago, Type 2 diabetics who took Farxiga saw their odds of hospitalization for heart failure drop by 27 percent compared to those who took a placebo.

Farxiga is a type of drug called a SGLT2 inhibitor. The compound is called dapagliflozin.

The study included more than 17,000 type 2 diabetes patients aged 40 and older. Nearly 7,000 had heart disease and more than 10,000 had numerous risk factors for heart disease, Wiviott’s group said.

Patients were randomly assigned to take a dummy placebo pill or 10 milligrams of Farxiga each day.

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“When it comes to helping our patients control and manage blood glucose, the ‘how’ appears to be as important [as] the ‘how much,” said study author Dr Stephen Wiviott, a cardiovascular medicine specialist at Brigham and Women’s Hospital in Boston.

“When choosing a therapy, trial results like these can help us make an informed decision about what treatments are not only safe and effective for lowering blood glucose but can also reduce risk of heart and kidney complications,” Wiviott said in a hospital news release.

Taking the drug did not reduce the risk of heart attack, stroke and cardiovascular-related death, the research team noted. However, patients who took the drug did see healthy declines in their blood sugar levels, plus an added bonus: a 27 percent decrease in their risk of hospitalization for heart failure.

Their risk of kidney failure and death from kidney failure also fell, researchers noted.

Two other recent studies of this class of drugs show that they “robustly and consistently improve heart and kidney outcomes in a broad population of patients with diabetes,” Wiviott noted.

With Inputs from HealthDay

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