Researchers have identified a reason for why long-term use of steroids increases the risk of diabetes.
Between one and three per cent of people in the Western world are estimated to take glucocorticoid steroid drugs. These anti-inflammatory drugs are taken for a wide range of reasons from treating symptoms of autoimmune diseases, such as asthma, to being needed for transplantation surgery.
While steroids are a very useful treatment, they can have significant side effects that affect metabolism, especially when higher doses of steroids are taken over an extended period of time. Two of the known side-effects are steroid-induced diabetes and development of fatty liver.
The research team included researchers from the Helmholtz Zentrum München and the Ludwig Maximilians University of Munich (LMU) and was led by Professor Henriette Uhlenhaut of the Helmholtz Zentrum München.
It is known that glucocorticoids bind to a receptor inside cells which prompts a series of metabolic genes to be switched on and off. The goal of the researchers was to investigate and understand the sequence of events that take place.
Charlotte Hemmer, a doctoral candidate at the Institute for Diabetes and Obesity (IDO) at the Helmholtz Zentrum Münche, said: “What struck us most was the E47 transcription factor, which – along with the glucocorticoid receptor – is responsible for the changes in gene expressio, particularly in liver cells.”
The scientists then undertook further tests to check the findings using a model that lacked the E47 gene. “We were able to identify the underlying pathway by conducting genome-wide analyses and genetic studies. The loss of E47 actually protected against the negative impact of glucocorticoids, while an intact E47 gene led to metabolic changes such as high blood sugar, elevated blood fat levels or a fatty liver as a response to steroid treatment,” Charlotte Hemmer added.
The research has so far been carried out on cells in the lab. Prof. Uhlenhaut and her team are keen to investigate whether their findings can be translated into human studies. Prof. Uhlenhaut said, “If this is the case, it could open up new opportunities for therapeutic intervention and the use of safer immuno-suppressants in order to combat the side effects of steroid therapy.”
The study has been published in the Nature Communications journal.

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