Hypoglycemia in Children & Adolescents with T1DM: Mechanisms and Prevention

Nelly Mauras, Principal Investigator

Larry Fox,Co-Investigator

Funding: National Institutes of Health

This grant is part of the second phase of the Diabetes Research in Children Network (DirecNet-II). In this project we proposed to study subjects with type 1 diabetes (T1DM) with recurrent episodes of hypoglycemia and hypoglycemia unawareness and age-, BMI- and HbA1C-matched diabetic controls without frequent hypoglycemia. The primary aims are: 1) To characterize the metabolic and hormonal profile of these children, including measures of endogenous glucose production, gluconeogenesis, total energy expenditure and hormonal counterregulation, during controlled glucose concentrations. 2) To assess if improvement in control (decreased A1C and/or mathematical measures of glucose variability) and scrupulous avoidance of hypoglycemia, achieved by maximal utilization of insulin delivery systems and CGS (including an artificial pancreas system if available), positively impact the above parameters over time. 3) To investigate if the nighttime administration of the oral amino acid glutamine affects rates of gluconeogenesis and reduces the incidence of hypoglycemia, as well as whether glutamine decreases the frequency of hypoglycemia during exercise, without worsening diabetes control. As secondary aims we will assess if there are neurocognitive differences in brain function of the above-described children and analyze these changes during intervention. Overall, the studies will provide new data on whether children with recurrent hypoglycemia have both altered glucose production and utilization. If the experiments using amino acids demonstrate the stated hypothesis to be true, this could have major therapeutic applications as a simple, inexpensive adjunct in the prevention of this dreaded complication of diabetes therapy.