Research Description
Rising rates of childhood obesity are especially concerning because childhood-onset obesity and type 2 diabetes have worse clinical outcomes, including mortality, than when onset begins in adulthood. The reasons for these outcomes have not been fully clear, nor have the mechanisms for why some individuals with obesity develop type 2 diabetes more readily than others. New technologies have enabled the mapping of cellular subpopulations in adult fat tissue (adipose), and evidence has been found that certain cell subtypes in adipose correlate with type 2 diabetes. While evidence from mice suggests that the cellular landscape may look and behave differently in early development, very little is known about the developmental progression of adipose tissue during human childhood, or how this process may influence the worsened outcomes in childhood obesity and type 2 diabetes. This proposal aims to test the hypothesis that human adipose tissue undergoes cellular changes during childhood development, and that these developmental changes influence metabolic outcomes in childhood onset-obesity. Advanced methods in single-cell RNA sequencing will be used to define cellular populations and to build an cellular atlas of adipose tissue across childhood development, and relevant cell populations will be isolated for experimental study. The proposed experiments will build a framework for understanding how adipose tissue develops during childhood and how disturbance of this normal process contributes to the development of type 2 diabetes in children. Study of adipose tissue in a diverse pediatric population will also build a knowledge base for future personalized medicine approaches.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 research is intended to study the mechanisms by which type 2 diabetes develops in children with obesity. Approximately 1 in 4 children in the US have a BMI which qualifies for obesity, which places them at particular risk for development of type 2 diabetes and its complications, more so than when obesity begins in adulthood. Studies in adults suggest that dysfunction of fat tissue (adipose) is a stronger predictor of insulin resistance and diabetes than a patient's size alone, but we know little about either normal adipose development during childhood or the initial steps of adipose dysfunction in childhood obesity. I am collecting a diverse biorepository of adipose tissue in children of all ages and sizes, to learn more about how adipose development occurs in the life of a healthy child and how it goes wrong in a child with obesity or type 2 diabetes. We hope that the information learned through this research will help identify therapeutic targets or provide opportunities for precision medicine for children who are at risk for development of type 2 diabetes.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?Right now, we don't know enough about why kids with excess weight develop type 2 diabetes, or especially why this happens for some children more readily than others. My project will help to identify differences in the health and cellular makeup of fat tissue (adipose) in kids of varying ages, sizes, and demographic backgrounds. We hope that this will lead to better identification of at-risk children and better drug targets for precision medicine to prevent or treat youth-onset type 2 diabetes.
Why important for you, personally, to become involved in diabetes research? What role will this award play?I am a clinician who specializes in pediatric obesity medicine and the treatment of children and adolescents with severe obesity and/or type 2 diabetes. I see firsthand every week the suffering and fear that families live with when a child is diagnosed with type 2 diabetes, especially in families who have already seen severe diabetes complications in their older family members. Not enough attention has yet been paid to this young population, so there is much we do not know about how to treat youth-onset type 2 diabetes and which children are most at risk. This award will be invaluable in funding my efforts to identify potential diabetes risk factors within fat tissue (adipose) in children of diverse ages, sizes, and demographic backgrounds.
In what direction do you see the future of diabetes research going?I believe that precision medicine approaches will be increasingly needed in the fields of obesity and type 2 diabetes, particularly in the youth population which has special social, emotional, and biological needs. The field of childhood obesity has particularly called for increased research into precision medicine approaches, and I hope with my research to help fill this void.