Research Description
In recent years, there has been a fast increase in the number of people with diabetes. This is because of changes in our diet, including in higher sugar content. One of the most effective classes of drugs is called glucagon-like peptide-1 (GLP-1) receptor agonists (GLP1RAs). Not all patients respond similarly to treatment. For some patients, these drugs are not very beneficial and can even cause side effects. One key mechanism in our body’s response to a meal is the release of signals by our gut, including GLP1. It stimulates the pancreas to produce insulin that lowers our blood glucose. However, these responses, including the production of GLP-1, are not the same in all people. One reason for this might be a genetic predisposition. Moreover, studies have shown that metformin, a drug very often used in diabetes treatment, might increase the release of GLP-1 in response to food consumption. Because of this, we propose this study, to understand how genetics influences blood sugar and GLP-1 responses to a meal. We will study this by analyzing their levels in blood samples of 1000 patients after they consumed a meal, and explore if and how genetics and metabolites influence these responses. We will also study how metformin affects these influences, by analyzing data from the MMTT repeated after 5 days of receiving metformin. We hope that our study will help to understand how genetics influence human response to meals.Research Profile
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?My project relates to the fields of incretin signaling, nutrigenomics, metabolite profiling and pharmacogenomics within the greater field of diabetes precision medicine. My goal is to characterize the mechanisms and influence of genetic background and circulating metabolites on human glucagon-like peptide-1 (GLP-1) response to a meal and how this response is modified by acute metformin treatment. Our findings on genetic and metabolic predispositions to endogenous GLP-1 secretion may contribute to a better understanding of susceptibility to the response to exogenous GLP-1 receptor agonists (GLP-1RAs) in diabetes treatment and prevention.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?GLP-1 receptor agonists are the new class of drugs for the treatment of type 2 diabetes and obesity. My aim is to understand how genetics and circulating metabolites influence GLP-1 secretion in response to a meal and how this response is modified by metformin. Based on this, we may be able to identify people who will respond better to these therapies and reduce drug-related complications.
Why important for you, personally, to become involved in diabetes research? What role will this award play?My dedication to diabetes research is mainly motivated by the extraordinarily heavy burden of metabolic disease carried by the people I grew up with in Eastern Poland, including my family members, where access to cutting-edge diabetes medicine remains limited and rudimentary. My long-term career aspirations are to become an independent investigator and physician-scientist, leading an innovative academic translational research program dedicated to delivering precision medicine in diabetes that will be accessible to all people. This project will facilitate me in acquiring a solid foundation of knowledge in diabetes genetics research, together with nutrigenomics and pharmacogenomics, and significantly improve my data analysis and computational skills.
In what direction do you see the future of diabetes research going?In my opinion, the future of diabetes research will be focused on advancing precision medicine in diabetes care. Ideally, the diagnostic algorithms will incorporate lifestyle, genetic and environmental factors to precisely classify patients based on the underlying pathogenesis of diabetes development, so that their risk of complications and burden of managing the disease can be reduced. To achieve this, we need to better understand the mechanisms leading to hyperglycemia, which will enable the precise stratification of patients with diabetes and facilitate the discovery of new therapeutic agents targeting these diverse pathways.