Impact of Congenital Hyperinsulinism on Trajectories of Neurocognitive Function Across School Age

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PROJECT SUMMARY/ABSTRACT The overall objective of this K23 application is to provide support for the additional training and experience that the principal investigator, a pediatric endocrinologist and epidemiologist, needs to develop an independent, patient-oriented research program in hyperinsulinism. Congenital hyperinsulinism (HI) is the most common cause of persistent hypoglycemia in infants and children. Onset of hypoglycemia in HI overlaps with a critical period of neurocognitive development that occurs in the first years of life. While children with HI are more likely to have neurocognitive deficits, little is known about the factors influencing trajectories of neurocognitive development in affected children. This project will: (1) identify neurocognitive trajectories in children with HI employing an accelerated longitudinal design, and (2) examine the relationship between timing of hypoglycemia exposure and neurocognitive outcomes through comparison of two clinical phenotypes of HI with natural variation in clinical course. To accomplish these aims a comprehensive neurocognitive battery will be administered at baseline and repeated at 1- and 2-years after baseline, to school-aged children with cured, focal HI (hypoglycemia exposure limited to early life), diffuse HI (early life and ongoing hypoglycemia exposure), and age, sex, and socioeconomic status matched healthy controls. The results of this project will fill critical gaps in knowledge about the impact of hyperinsulinemic hypoglycemia during periods of marked brain development and carry significant implications for clinical practice. This study may also have broad implications for other disorders associated with hyperinsulinemic hypoglycemia, including diabetes mellitus. The principal investigator will take full advantage of the rich scientific environment and outstanding resources afforded by the Children’s Hospital of Philadelphia and University of Pennsylvania to achieve her research and training goals. The proposal includes advanced training in longitudinal data analysis and longitudinal neurocognitive outcome assessment, which will be achieved through a combination of didactic coursework, practical research experience, and support form an expert, multidisciplinary mentorship and advisory team. The support of this K23 will enable the principal investigator to launch a successful career as an independent investigator dedicated to optimizing neurocognitive outcomes for children with hyperinsulinism.