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13-02-2011 | Diabetes | Article

Leptin resistance may protect against ARDS in Type 2 diabetes patients

Abstract

Free abstract

MedWire News: Leptin resistance may contribute to the lower incidence and less severe cases of acute respiratory distress syndrome (ARDS) seen in diabetic versus nondiabetic patients, report US researchers.

"Previously it was hypothesized that hyperglycemia, the hallmark of diabetes, might be responsible for the lower level of ARDS seen in these patients," said study author Gökhan Mutlu from Northwestern University Feinberg School of Medicine in Chicago, Illinois.

"However, subsequent studies have indicated that hyperglycemia exacerbates inflammation and worsens lung injury. Our findings provide support for the hypothesis that leptin resistance plays a key role in offering protection against ARDS in diabetic subjects."

As reported in the American Journal of Respiratory and Critical Care Medicine, Mutlu and team assessed the degree of lung injury and fibroproliferation in normal and diabetic (leptin resistant) mice treated with the chemotherapy agent bleomycin.

Diabetic mice did not develop lung fibrosis. This may be, at least partly, because they had higher levels of peroxisome proliferator-activated receptor-γ, which inhibits the cytokine transforming growth factor (TGF)-β1, which promotes the fibroproliferation seen in ARDS. They also had low levels of leptin.

Further experiments on normal human lung fibroblasts showed that leptin enhances the fibroproliferative activity of TGF-β1.

An association between leptin concentration and ARDS was confirmed when bronchoalveolar lavage (BAL) fluid taken from ARDS patients was found to have a six-fold increase in leptin levels compared with fluid taken from controls. In addition, leptin levels in samples taken from these patients were positively correlated with concentrations of TGF-β1.

People with Type 2 diabetes commonly develop resistance to leptin. Coupled with the results of this study, this may explain the previously observed significant reduction (around 50%) in ARDS incidence seen in diabetic patients who are also less likely to die from ARDS than nondiabetic patients.

"Leptin is an attractive potential therapeutic target as most of its normal effects are mediated in the brain and it is relatively easy to develop drugs that are not delivered to the brain," commented Mutlu.

He concluded: "The results of our study and those of other groups studying the effects of leptin signaling on the development of injury and fibrosis in other organs highlight the need for further prospective studies examining the influence of leptin in the outcome of patients suffering from ARDS."

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2011

By Helen Albert