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New findings can lead to a new principle for treating diabetic kidney damage

One in three people with diabetes will face some form of renal impairment in the course of their lives. Studies conducted by researchers at the Lund University Diabetes Centre may lead to the development of an entirely new principle for treating type 2 diabetes and preventing kidney damage in the future.

Previous analyses have not been able to identify genetic causes as to why some people have a higher risk of developing kidney damage.

“This may be due to the fact that previous analyses did not consider the impact of epigenetic mechanisms on the body’s ‘metabolic memory’”, says Dr. Yang de Marinis, who conducted the study.

“Metabolic memory” means that the body “remembers” unhealthy blood sugar levels, and triggers processes in our cells long before the outbreak of the disease.

“When someone is diagnosed with type 2 diabetes, their elevated blood sugar levels could already have resulted in permanent damage to the kidneys”, says Professor Leif Groop who is the researcher mainly responsible for the articles published in Kidney International and Biochemical and Biophysical Research Communications.

Our genome, the genetic code of our DNA, cannot be changed; however, so-called epigenetic changes affected by the environment (diet, medicines, pollution, etc.) can affect the activity of our genes and how they are used. Therefore, knowledge on how to influence epigenetic changes is of interest when developing new drugs to treat diabetes and its complications.

The same principle has already been used in cancer treatments, to prevent cells from multiplying. However, this is the first time that researchers are on their way to come up with how it can be used to treat complications related to diabetes.

“We want to achieve the opposite – we want to protect kidney cells from dying”, says Yang de Marinis.

Through animal testing, and by using cells from mice and humans, the researchers have studied whether the so-called epigenetic mechanisms could be a contributing factor in the development of diabetic kidney damage – and concluded that this is the case.

The studies show that elevated blood sugar levels lead to epigenetic changes in two genes, TXNIP and osteopontin, which have been previously known for playing a significant role in the development of kidney damage, as they contribute to inflammation of the blood vessels and glucotoxicity. Glucotoxicity means that cells exposed to glucose die, and the study shows that this also affects kidney cells.

By chemically neutralising the epigenetic changes in the gene, the researchers found that the activity of the TXNIP gene decreased.

“This method could enable us to restore and normalise the gene’s function”, says Yang the Marinis. However, a lot of research is still needed before the findings could lead to the development of new drugs.

“Further research is required to eventually be able to apply the method to humans”, she concludes

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Lund University Diabetes Centre, CRC, SUS Malmö, Entrance 72, House 91:12. SE-205 02 Malmö. Telephone: +46 40 39 10 00