There are many different types of diabetes, and type 1 and type 2 are just the two primary classifications. Types of diabetes induced by a single genetic change are referred to as monogenic diabetes. The most prevalent clinical subtype of monogenic diabetes, maturity-onset diabetes of the young (MODY), generally manifests in young adults.
Now, an international team of researchers have discovered a new variant of the HNF1A gene, which can cause MODY that accounts for almost seven percent of all cases of diabetes in Greenland and is found nowhere else in the world.
“We were excited to make this discovery of a new genetic variant that is responsible for close to seven percent all cases of diabetes in Greenland. Discoveries like these, which was made possible thanks to a generous collaboration with the Greenlandic people, help us better understand the complexity of diabetes,” says Professor Torben Hansen from the Novo Nordisk Foundation Center for Basic Metabolic Research at the University of Copenhagen. He led the research together with Professors Anders Albrechtsen and Ida Moltke from the Department of Biology at the University of Copenhagen.
Potential for precision medicine
People with HNF1A-MODY are often misdiagnosed with either type 1 or type 2 diabetes and given medication that is not effective. Instead, sulphonylurea tablet therapy, which is rarely used nowadays in the treatment of type 2 diabetes, is the most efficient way to treat HNF1A-MODY.
Therefore, scientists are optimistic that this finding will open the door to precision medicine in Greenland. Genetic studies can determine whether other family members also have the inherited form of diabetes known as monogenic diabetes.
We were excited to make this discovery of a new genetic variant that is responsible for close to seven percent all cases of diabetes in Greenland. Discoveries like these, which was made possible thanks to a generous collaboration with the Greenlandic people, help us better understand the complexity of diabetes.
Professor Torben Hansen
“This discovery is good news for the treatment of diabetes in Greenland, because most people with MODY can be treated with a simple and cheap tablet treatment and avoid insulin and other more complex forms of diabetes treatment. Therefore, we now offer genetic testing for MODY to all our patients with diabetes, and when we find people with HNF1A-MODY, we systematically offer that family members are also tested,” says senior physician and professor Marit Eika Jørgensen at the Steno Diabetes Center Greenland.
Marit Eika Jørgensen coordinated the research in Greenland, which involved more than 4,000 Greenlanders.
Monogenic diabetes more common in Greenland than in Western populations
Together with a previously described high-impact variant TBC1D4 variant, close to 1 in 5 Greenlanders with diabetes are carriers of common high-impact variants. As a result, monogenic diabetes is far more common in Greenland than it is in Western countries, where it is thought to account for only about 1 in 50 instances of diabetes.
“This discovery clearly demonstrates how common diseases are much more complex than we previously thought. Thanks to the breakthroughs in genetic research and data science capabilities, many people around the world may benefit from new personalized medicine approaches that take ancestral, genetic, and environmental backgrounds into account,” says PhD Student Anne Cathrine Baun Thuesen from CBMR, who was co-first author together with Frederik Filip Stæger from the Department of Biology at the University of Copenhagen.
This research is a collaboration between researchers at the University of Copenhagen, University of Greenland, Steno Diabetes Center Greenland, Steno Diabetes Center Copenhagen, the University of Bergen, Haukeland University Hospital Bergen, Max Planck Institute for Metabolism Research, Helmholtz Zentrum München, University of Southern Denmark, TUM School of Medicine Münich, and the Western Norway University of Applied Sciences.
