Identifying Patients with Diabetic Kidney Disease in Need of More Aggressive Treatment

Posted on 11.06.2021

Even though researchers have identified nearly 100 genetic variants associated with diabetes, they make up less than 10% disease variance. In terms of genetic variants and diabetic late complications, the results are even more disappointing. But now Danish and Australian researchers are teaming up with the goal of better understanding the correlation. 

“Our goal is to understand the burden, natural history and propensity of the Danish population, with or at risk of diabetes, to develop complications,” they say. “To outline the clinical, metabolic and epigenetic correlates of diseases in order ultimately to predict, treat and prevent diabetic kidney disease.” An important sub-goal is to find those patients with diabetic kidney disease who need more aggressive treatment.

The Danish researchers work at University College Copenhagen, Faculty of Health, Department of Technology, Biomedical Laboratory Science and Steno Diabetes Center Copenhagen. The project is headed by Professor Peter Rossing. The Australian contribution comes from Professor Sam El-Osta, Central Clinical School at Monash University, Melbourne, Australia. Sam El-Osta is Head of the Epigenetics in Human Health and Disease Program in the Department of Diabetes. He has just been awarded a grant of DKK 250,000 by the Danish Diabetes Academy to come to Denmark as a Visiting Professor and contribute his knowledge.

The researchers are delighted about this opportunity, because the task is a major one. Diabetes is the fastest growing chronic condition in Denmark and in Australia, increasing more swiftly than other chronic diseases such as heart disease and cancer.

“Prevention and successful management of diabetic complications are important, and the greatest cost of diabetes is due to the development of late complications such as blindness, amputations, coronary heart disease, stroke, kidney failure and premature mortality,” says Professor Sam El-Osta. He emphasizes that, despite the major progress vis-à-vis detection and management, optimal diabetes control is insufficient to prevent the development and progression of diabetic complications. “The numerous complications in the wake of the diabetes epidemic is affecting 400 million adults throughout the world. If we are to tackle them, we need to develop new strategies,” he says.

Genetic differences part of the explanation
It is clear that genetic differences may explain why some people develop certain conditions or complications, while others remain unaffected, despite similar environmental exposure.

“Although genetic determinism remains a main focus in translational research, it is now clear that, even with extensive sequencing, only part of the variation in complex phenotypical traits can be explained by genetic variations. Apart from rare monogenetic diseases, the pathogenic disease appears to be caused by complex interactions between environmental factors and predisposition to disease,” says Sam El-Osta.

Evaluating DNA methylation using PROFIL Diabetes Registry
In recent years, there has been increased interest in the field of epigenetics, which is the study of DNA modifications without changes in the genetic sequence. Because it is understood that genetic heredity cannot fully explain susceptibility to diabetic kidney disease, the Danish and Australian researchers will evaluate DNA methylation, using the PROFIL Diabetes Registry of Steno Diabetes Center Copenhagen.

“We assume that epigenetic pathways, specifically DNA methylation, determine why some people with diabetes are programmed to develop complications, while others do not, despite a similar duration of diabetes, treatment intensity and average exposure to glucose,” says the Australian researcher. Given the importance of epigenetic programming in the development and progression of diabetic renal disease, he and his Danish colleagues will define the risk score of Danish methylation.

In their application to the Danish Diabetes Academy for funding, they emphasized that, by using modern genomic technologies that have never before been studied in PROFIL, in parallel with a detailed study of the clinical patterns and methylation determinants among Danish populations, they expect the new project to reveal the main pathways associated with diabetic kidney disease.

Functional, network-based analysis of differentially methylated genes may ultimately lead to the development of new therapies, biomarkers and prevention strategies to reduce the suffering and harmful consequences of diabetes on the kidneys and possibly other vascular sites.

Sam El-Osta will work in Denmark from September this year to March next year. At the same time, a number of early-career scientists from Denmark and Australia will work in Denmark and Australia, and fostering greater technology exchange and collaboration, in the laboratories of Sam El-Osta and Peter Rossing, to help achieve the goal – a better opportunity to predict, treat and prevent diabetic kidney disease.

Professor Sam El-Osta, PhD, Monash University, Epigenetics in Human Health and Disease, Melbourne, Australia
Awarded a grant of DKK 250,000 from the Danish Diabetes Academy
Title of project: Loss of Methylation Predicts Risk of Nephropathy in the Steno PROFIL Diabetes Registry
Research institution in Denmark: University College Copenhagen, Faculty of Health, Department of Technology, Biomedical Laboratory Science Copenhagen, and Steno Diabetes Center Copenhagen
Host in Denmark: Professor, Chief Physician and Head of Complications Research Peter Rossing, Steno Diabetes Center Copenhagen

Sam El-Osta
Tel: +61 425 706 008 

Peter Rossing
Tel: +45 30 91 33 83

Danish Diabetes Academy
Managing Director Tore Christiansen
Tel: +45 29 64 67 64

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