Grant: Canada Postdoctoral Research Award (CPRA) program

In type 1 diabetes (T1D), the immune system attacks and kills cells in the pancreas that produce insulin, a hormone that enables cells to use nutrients for energy. Without insulin, blood sugar levels rise, and this can cause damage to blood vessels. Therefore, heart disease is a major complication of T1D, a life-long disease usually diagnosed in childhood that has no cure. Studies have shown that damage to blood vessels is already present in children with T1D. This suggests that heart disease is occurring much earlier in the disease. However, the timing and factors that cause the blood vessel damage in children with T1D are unknown. A preliminary study on gene expression in the body's largest blood vessel from the mouse model of pediatric diabetes identified the presence of immune cells at diabetes onset. Since immune cells are responsible for inflammation and blood vessel clogging, I will identify when and how immune cells damage blood vessels in children with T1D. For this study, I will collect samples from both male and female mouse models of pediatric diabetes at diabetes onset and 4 weeks post-onset. A similar number of age- and sex-matched control mice will be collected to compare the result. I will characterize the immune cells and identify their functions and interactions with other cells by analyzing the gene expression data. Blood samples from children (age 8-17 years) will also be collected at the first diagnosis of T1D and every six months for two years. The presence of different types of immune cells will be identified, and immune cell-derived cytokines will be quantified as circulating indicators of inflammation. Overall, this study will help understand how and when immune cells damage blood vessels in T1D and identify targets to reduce heart disease in children with T1D. Together, it will help reshape clinical practice guidelines for the treatment of these children.