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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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Suicide can’t be predicted by asking about suicidal thoughts : Study

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Most people who died of suicide deny they experience suicidal thoughts when asked by doctors in the weeks and months leading up to their death, a major Australian study has found.

The findings, co-authored by clinical psychiatrist and Professor Matthew Large from UNSW’s School of Psychiatry, Sydney that published in the journal BJPsych Open The meta-analysis challenge the widely-held assumption that psychiatrists can predict who will suicide by asking if they are preoccupied with thoughts of killing themselves.

The study showed that 80% of patients who were not undergoing psychiatric treatment and who died of suicide reported not to have suicidal thoughts when asked by their psychiatrist or GP.

“If you meet someone who has suicidal ideation there is a 98 per cent chance that they are not going to suicide,” said Professor Large, an international expert on suicide risk assessment who also works in the emergency department of a major Sydney hospital.

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“But what we didn’t know was how frequently people who go on to suicide have denied having suicidal thoughts when asked directly,” he added.

“This study proves we can no longer ration psychiatric care based on the presence of suicidal thoughts alone. We need to provide high-quality, patient-centred care for everyone experiencing mental illness, whether or not they reveal they are experiencing suicidal thoughts,” Professor Large said.

About one in 10 people will have suicidal ideation in their lifetime. But the study showed suicidal ideation alone was not rational grounds for deciding who gets treatment and who does not, Professor Large said.

“We know that suicide feeling is pretty common and that suicide is actually a rare event, even among people with severe mental illness,” Professor Large added.

Suicidal ideation tells us an awful lot about how a person is feeling, their psychological distress, sometimes their diagnosis and their need for treatment but it’s not a meaningful test of future behaviour.

Suicidal feelings can fluctuate rapidly and people may suicide very impulsively after only a short period of suicidal thoughts.

But, people had good reasons not to disclose thoughts of suicide, fearing stigma, triggering over-reactions or upsetting family and friends, and being involuntarily admitted for psychiatric treatment, Professor Large said.

Professor Large emphasized that clinicians should not assume that patients experiencing mental distress without reporting suicidal ideas were not at elevated risk of suicide.

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