Intranasal (IN) Naloxone as a Novel Therapy to Preserve Hypoglycemia Counterregulatory (CR) Response after Exercise in Type 1 Diabetes (T1D)

Hypoglycemia (HG) is common after exercise in people with T1D. Antecedent exercise leads to attenuation of CR response during subsequent HG. In healthy humans, IV administration of naloxone during exercise preserved CR response to HG the following day. We tested the hypothesis that IN administration of naloxone during exercise will preserve CR response to HG in people with T1D with intact awareness of HG. We performed a single-blind randomized cross over trial to compare the impact of IN naloxone vs. IN saline administered during exercise on day 1 (D1) on the symptoms and epinephrine (Epi) response to HG on day 2 (D2). On D1, participants underwent two 90-min hyperinsulinemic-euglycemic clamps during exercise at 60% VO2max with IN naloxone (4 mg at start and +45 min each exercise period) or IN saline exposure; on D2 a HG clamp (target 50 mg/dl) was performed. 27 subjects (10F, age 29 ± 8 yrs) participated in the protocol. Outcomes included D2 average symptom scores (SS) and peak Epi level over HG clamp’s last 30 min. A general linear mixed model for each of SS and Epi with effects for naloxone vs. saline, treatment order (naloxone 1st vs. 2nd), and time (Part 1 vs. Part 2) was performed. SS and Epi response on D2 were not different following IN naloxone compared to placebo. In people with T1D, administration of IN naloxone during exercise did not alter symptom or EPI response to subsequent HG. Disclosure A.Moheet: None. E.R.Seaquist: Consultant; Zucara Therapeutics. L.E.Eberly: None. S.Inkollu: None. A.Kumar: None. A.C.Alvear: None. Y.Zhang: None. L.Coles: None. N.Evanoff: None. D.R.Dengel: None. Funding JDRF