Heterogeneity in Epinephrine Response to Experimental Hypoglycemia in Type 1 Diabetes and Controls

Context: The epinephrine response (Epi) to a first episode of hypoglycemia (HG) has been proposed to be predictive of Epi in subsequent HG and to provide insight into the risk for developing HG-associated autonomic failure (HAAF) in healthy controls (HCs). Objective: To determine if Epi and symptom response (SR) to the first episode of HG predicts who will develop HAAF after exposure to recurrent HG in volunteers with type 1 diabetes (T1D) and in HCs. Design: Review of data collected between 2013 and 2019. Setting: Academic clinical research unit. Patients or Participants: Volunteers with T1D and HCs. Interventions: Subjects participated in a preinduction protocol where they were exposed to three 2-hour episodes of clamped HG over 2 days. Data collected during clamp 1 were compared with data collected during clamp 3. Main outcome measure: Difference in Epi and SR. Results: Using the standard definition of HAAF in which HG-induced Epi during clamp 3 is at least 20% lower than during clamp 1, 21/28 HCs and 13/19 volunteers with T1D developed HAAF. Epi during clamp 1 was significantly higher in those subjects who developed HAAF than in those who did not in both groups (P=0.02). If HAAF is defined as achieving a 20% reduction in HG-induced SR measured during clamp 3 compared with clamp 1, 10/27 HCs and 10/19 volunteers with T1D developed SR-based HAAF. Conclusion: There was heterogeneity in the response to the preinduction protocol. Epi during clamp 1 was higher than in clamp 3 in HCs and in those with T1D who developed HAAF.