The Lundquist Institute (TLI) announced that its Institute for Translational Genomics and Populations Sciences contributed to a new study published today in Nature Genetics of the DNA of more than 55,000 people worldwide. The study sheds light on how humans maintain healthy blood sugar levels after we have eaten, with implications for our understanding of how the process goes wrong in type 2 diabetes. The findings could help inform future treatments of type 2 diabetes, which affects over 460 million people worldwide and nearly 38 million people in the U.S.
Several factors contribute to an increased risk of type 2 diabetes, such as older age, being overweight or having obesity, physical inactivity, and genetic predisposition. If untreated, type 2 diabetes can lead to complications, including eye and foot problems, nerve damage, and increased risk of heart attack and stroke.
A key player in the development of the condition is insulin, a hormone that regulates blood sugar – glucose – levels. People who have type 2 diabetes are unable to correctly regulate their glucose levels, either because they don't secrete enough insulin when glucose levels increase, for example after eating a meal, or because their cells are less sensitive to insulin, a phenomenon known as 'insulin resistance.'
Our specific contribution to this groundbreaking paper was to studies of insulin response to an oral glucose challenge, both the clinical studies, genotyping, and participating in the statistical analysis, and as part of the consortium steering committee that oversaw the work."
Jerome Rotter, MD, Director of the TLI Institute for Translational Genomics and Population Sciences
Dr Alice Williamson, who carried out the work while a PhD student at the Wellcome-MRC Institute of Metabolic Science, said: "What's exciting about this is that it shows how we can go from large scale genetic studies to understanding fundamental mechanisms of how our bodies work – and in particular how, when these mechanisms go wrong, they can lead to common diseases such as type 2 diabetes."
Given that problems regulating blood glucose after a meal can be an early sign of increased type 2 diabetes risk, the researchers are hopeful that the discovery of the mechanisms involved could lead to new treatments in future.
Professor Claudia Langenberg, Director of the Precision Healthcare University Research Institute (PHURI) at Queen Mary University of London and Professor of Computational Medicine at the Berlin Institute of Health, Germany, said: "Our findings open a potential new avenue for the development of treatments to stop the development of type 2 diabetes. It also shows how genetic studies of dynamic challenge tests can provide important insights that would otherwise remain hidden."
Williamson, A., et al. (2023). Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake. Nature Genetics. doi.org/10.1038/s41588-023-01408-9.