Restoration of Impaired Awareness of Hypoglycemia U01 Consortium: University of Kentucky

Abstract This grant application is in response to RFA-DK-21-020 U01 Research Project (Cooperative Agreement) that seeks to establish a 10-site clinical consortium to determine the factors that contribute to the heterogeneity in the restoration of impaired awareness of hypoglycemia (IAH) and improved counterregulatory responses in adult individuals with Type 1 Diabetes (T1D). For people with T1D and impaired awareness of hypoglycemia, it is proposed to test whether a combination of, 1) advanced diabetes care technology comprised of a hybrid closed loop insulin pump with continuous glucose monitor (CGM), coupled with, 2) intensive hypoglycemia avoidance education, will lead to a decrease in the frequency/severity of hypoglycemia (as determined by CGM analysis) and that a near complete avoidance of hypoglycemia will, 1) improve the awareness of hypoglycemia (as determined by hypoglycemia questionnaire responses and symptom responses during a hypoglycemic clamp), and 2) improve the counterregulatory response (as determined by the hormonal response during a hypoglycemic clamp). The specific aims of this proposal, as outlined in the RFA, are; 1) determine if the most up-to-date management strategies using diabetes technology to optimize HbA1c while minimizing hypoglycemia (i.e. a hybrid closed loop system and hypoglycemia avoidance education) can restore awareness of hypoglycemia and improve counterregulatory responses in individuals with T1D and IAH; 2) determine the physiological factors that are associated with restoration of hypoglycemia awareness and counterregulatory response, including but not limited to age, duration of diabetes and metrics of glycemia (eg, time in range, time spent in hypoglycemia or other CGM metrics), and 3) determine the association of current or newly developed self-reported measures of IAH with counterregulatory responses to elucidate the heterogeneity in restoration of hypoglycemia awareness.