Exploring the Heterogeneity in the Restoration of Awareness of Hypoglycemia in T1DM

September 2021 Council

Lead Division/Office

DEM

Point(s) of Contact

Karen L. Teff, Ph.D.

Executive Summary

Repeated episodes of hypoglycemia result in impaired awareness of hypoglycemia (IAH) and blunting of counter-regulatory responses (CRR) required to restore normal glycemia. T1DM individuals with IAH experience severe hypoglycemic episodes with increased risk of morbidity and mortality. New technologies including continuous glucose monitors (CGM) and artificial pancreas devices alert patients to declining levels of glucose, reduce hypoglycemic events and restore hypoglycemia awareness in some but not all individuals. T1DM patients with IAH are often excluded from clinical trials resulting in minimal progress in our understanding of the clinical characteristics or physiological mechanisms that predict an individual’s ability to restore hypoglycemic awareness or improve CRR. A clinical consortium is proposed to identify clinical and physiological factors that restore awareness of hypoglycemia and improve CRR in adults with T1DM and IAH. The consortium will 1) determine if a hybrid closed loop system and hypoglycemia avoidance education can restore awareness of hypoglycemia and improve CRR 2) identify glycemic metrics associated with restoration of hypoglycemia awareness and improvements in CRR and 3) validate current self-report assessments with physiological measurements. The study will follow participants for 2 years. The primary outcome variables will be a measure of hypoglycemia awareness and a physiological measure derived during a hypoglycemic, hyperinsulinemic clamp.