Grant: Project Grant - PA: Healthy pregnancy/early child dev. in Indigenous contexts

Rationale: T2D in childhood continues to increase worldwide and affects Indigenous children and families more than non-Indigenous populations. Childhood onset T2D is associated with high rates of early onset rapidly progressive kidney disease. Exposure to T2D in the womb is accepted to be a strong risk factor for the development of childhood T2D. A negative impact of exposure to maternal diabetes on the developing beta cells (which secrete insulin) and kidneys may explain the high risk of T2D and kidney complications in these children. The Next Generation Birth Cohort (NextGen) is a unique prospective birth cohort designed to examine metabolic and anthropometric outcomes of offspring in the first year of life, born to mothers diagnosed in childhood. The overall aim of this project is to determine how exposure to maternal T2D and adiposity impact the natural history of the development of T2D and early renal dysfunction in First Nations children by looking at the beta cell function and renal function in the offspring during childhood (ages 5-7 years) before they are diagnosed with pre-diabetes or T2D. To accomplish this we will build upon the current study frame work to extend follow up of the children to age 5-7 years to meet the following goals: 1. To look for early differences beta cell function and whole body insulin resistance in offspring exposed to maternal T2D compared to offspring unexposed. 2.To look for early differences in renal function in offspring exposed to maternal T2D compared to offspring unexposed. 3. To look at how the HNF1a carrier status impacts both beta cell function and renal function in offspring exposed and unexposed to maternal T2D. The information from this study will help us determine when and how to screen these high risk kids for early evidence of metabolic dysfunction and renal dysfunction before they get sick, and suggest novel personalized medication/intervention strategies to prevent overt T2D from developing.