Grant: Team Grant: CIHR-JDRF Type 1 Diabetes and Precision Medicine

Type 1 diabetes (T1D) affects >300,000 Canadians. An underappreciated factor that raises the risk of T1D is whether an individual is a man or woman. Men have an 80% higher risk of developing T1D (age 15-34). While lifestyle factors contribute to this increased T1D risk in men, studies in animal models show biological sex also plays a key role. Unfortunately, we do not fully understand why males are at a higher risk of T1D because most research does not include both sexes. In T1D, the immune system destroys beta cells, which make insulin. To develop better T1D treatments, we need more information on why the immune system attacks beta cells. Recent studies point to beta cell problems and changes to the insulin gene as contributing factors to T1D. Because beta cells make huge amounts of insulin, which causes stress, even small changes in the cell's ability to make insulin tip beta cells into an unhealthy state and lead to immune system attack. Our team has evidence that male and female beta cells differ in their ability to make insulin, and to stay healthy despite the stress of insulin production. Our goal is to test whether sex differences in beta cells affect the sex-biased T1D risk. We will interfere with specific steps of insulin production and quality control in human beta cells and mice to see whether beta cell health is affected in either males or females. This information will help scientists to match males and females with appropriate T1D therapies.