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

Abstract

Context The epinephrine response (Epi) to a first episode of hypoglycemia (HG) has been proposed to be predictive of Epi to subsequent HG and to provide insight into the risk for developing hypoglycemia associated autonomic failure (HAAF) in healthy controls (HC). Objective To determine if the 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 HC. Design Review of data collected 2013-2019 Setting Academic clinical research unit Patients or Participants Volunteers with T1D and HC 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 was compared to data collected during clamp 3. Main outcome measure Difference in Epi and SR Results Using the standard definition of HAAF where HG-induced Epi during clamp 3 is at least 20% lower than during clamp 1, 21/28 HC and 13/19 T1D developed HAAF. Epi during clamp 1 was significantly higher in those subjects who developed HAAF than they were 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 to clamp 1, 10/27 HC and 10/19 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 HC and T1D who developed HAAF.