113-OR: ADA Presidents' Select Abstract: Dishabituation with High Intensity Exercise Improves Epinephrine Response and Symptomatic Awareness to Hypoglycemia in People with Type 1 Diabetes and Impaired Awareness of Hypoglycemia

Impaired awareness of hypoglycemia (IAH) affects approx. 20-25% of all people with type 1 diabetes (T1D) and is a major risk factor for severe hypoglycemia. We recently proposed that IAH may develop as a form of adaptive memory to repeated hypoglycemia; referred to as Habituation. Consistent with this hypothesis, we demonstrated restoration of defective counterregulatory (CRR) responses to hypoglycemia in a rodent model of IAH following introduction of a novel stress stimulus [high intensity exercise (HIT)]; referred to as Dishabituation. In this study we sought to further test our hypothesis by examining whether a single episode of HIT would amplify counterregulatory response to subsequent hypoglycemia in people with T1D who had IAH (assessed by Gold score ≥4, Modified Clark score≥4 or DAFNE hypoglycaemia awareness rating 2 or 3). We recruited 12 participants to a single-centre, randomized, cross-over study. Individuals were randomized to one episode of HIT (4 x 30 s cycle sprints [2 min recovery] at 150% of max Watts achieved during VO_2peak assessment) or rest. The following day they underwent a 90-minute hyperinsulinaemic hypoglycemic clamp study at 2.5 mmol/l with measurement of hormonal CRR and symptom scores. Each clamp study was separated by at least 2-weeks. We found that a single episode of HIT led to a 30% increase in the epinephrine response [mean (SEM) 418.8 +/- 62.84 vs. 541.1 +/- 70.5 pg/ml; p<0.05] accompanied by a significant increase in total symptom scores (Edinburgh Hypoglycemia scale: 24.25 +/- 2.96 vs. 27.5 +/- 3.9, p<0.05) during equivalent hypoglycemia induced the following day. These findings are consistent with the hypothesis that IAH develops in people with T1D as a habituated response and that introduction of a novel stressor can restore, at least partially, the CRR response to hypoglycemia. HIT may represent a novel therapeutic intervention for people with IAH.