Steroid-induced diabetes, a temporary form of diabetes, affects up to half of hospital patients treated with high-dose steroids. This class of drugs, called corticosteroids, is commonly used to reduce inflammation in patients with conditions including arthritis or asthma. Although central to the body's defense mechanisms, inflammation can cause harm and autoimmune disease when unchecked, making it a key target for therapy.

Steroids help prevent inflammation by targeting the RELA gene, which regulates the expression of proteins involved in inflammation. However, within weeks of starting or increasing corticosteroid medications, patients can develop steroid-induced diabetes. Previously, the link between inflammation and diabetes was not well understood.

The researchers sought to learn about the mechanisms behind inflammation and how to better target it. Using mice to study the genes that control inflammation, they found that removing the RELA gene led to abnormally high blood sugar levels. Mice lacking the RELA gene became prediabetic due to impaired insulin secretion in the pancreas.

The researchers next investigated the cells lacking RELA using next-generation DNA analysis. They found that the protein that RELA produces switches on a genetic program required for beta cells in the pancreas to produce insulin. This indicated that, although inflammation and diabetes are linked, RELA regulates blood sugar and inflammation independently. The findings suggest that RELA plays an essential role in keeping blood sugar levels normal, even when there is no inflammation.

The discovery sheds new light on the complex network of factors governing glucose metabolism, and how it goes awry in diabetes. The knowledge that RELA coordinates the expression of other genes essential for glucose control may have implications for understanding and preventing steroid-induced diabetes.

The researchers said that, while their research has uncovered a fundamental facet of how the body maintains normal blood glucose levels, their results could also help improve the clinical management of patients who require long-term or high-dosage corticosteroid treatment. They hope their work furthers the development of more tailored therapies for these patients, which could potentially be achieved using treatment strategies that prevent inflammation without targeting RELA.

"By understanding how insulin-producing cells and systems in the pancreas are regulated by RELA, it may be possible to balance the inhibition of inflammation without disrupting the function of insulin-producing cells," senior author Shane Grey, head of Garvan's Transplant Immunology Lab, noted in a statement. "This could lead to the development of medications that reduce inflammation without bringing on steroid-induced diabetes as a side effect."

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