Elucidating the heterogeneity of impaired awareness of hypoglycemia in Type 1 Diabetes (T1D) Clinical Centers (U01 Clinical Trial Required)

The purpose of this FOA is to establish a clinical consortium to determine the factors that contribute to the heterogeneity in the restoration of impaired awareness of hypoglycemia (IAH) and improved counter-regulatory responses in adult individuals with Type 1 Diabetes (T1D). Individuals with IAH are often excluded from clinical trials and this omission contributes greatly to a lack of knowledge regarding the clinical characteristics which determine or predict an individuals ability to restore hypoglycemic awareness. New technologies such as continuous glucose monitors (CGM) and closed loop systems (i.e. artificial pancreas) have been shown to reduce hypoglycemic events. However, despite a reduction in hypoglycemic events, restoration of hypoglycemia awareness does not occur in all individuals and the effects on improving the counter-regulatory responses are not known. The goals of the clinical consortium will be to 1) determine if state-of-the-art diabetes technology to optimize HbA1c while minimizing hypoglycemia can restore awareness of hypoglycemia and improve counter-regulatory responses in individuals with T1D; 2) identify the magnitude and duration of time in range (TIR), time spent in hypoglycemia or other CGM metrics that are associated with restoration of awareness of hypoglycemia; and 3) validate current self-report assessments of impaired awareness of hypoglycemia with physiological measurements. It is expected that state of the art techniques such as hypoglycemic, hyperinsulinemic clamps (with or without stable isotopes) for the measurement of counter-regulatory responses and endogenous glucose production will be utilized to determine restoration of awareness and validate self-report assessments.