Novel Use of Glucagon in a Closed-Loop System for Prevention of Hypoglycemia in Type 1 Diabetes

Abstract

OBJECTIVE: To minimize hypoglycemia in subjects with type 1 diabetes by automated glucagon delivery in a closed-loop insulin delivery system. RESEARCH DESIGN AND METHODS: Adult subjects with type 1 diabetes underwent one closed-loop study with insulin plus placebo and one study with insulin plus glucagon, given at times of impending hypoglycemia. Seven subjects received glucagon using high-gain parameters, and six subjects received glucagon in a more prolonged manner using low-gain parameters. Blood glucose levels were measured every 10 min and insulin and glucagon infusions were adjusted every 5 min. All subjects received a portion of their usual premeal insulin after meal announcement. RESULTS: Automated glucagon plus insulin delivery, compared with placebo plus insulin, significantly reduced time spent in the hypoglycemic range (15 +/- 6 vs. 40 +/- 10 min/day, P = 0.04). Compared with placebo, high-gain glucagon delivery reduced the frequency of hypoglycemic events (1.0 +/- 0.6 vs. 2.1 +/- 0.6 events/day, P = 0.01) and the need for carbohydrate treatment (1.4 +/- 0.8 vs. 4.0 +/- 1.4 treatments/day, P = 0.01). Glucagon given with low-gain parameters did not significantly reduce hypoglycemic event frequency (P = NS) but did reduce frequency of carbohydrate treatment (P = 0.05). CONCLUSIONS: During closed-loop treatment in subjects with type 1 diabetes, high-gain pulses of glucagon decreased the frequency of hypoglycemia. Larger and longer-term studies will be required to assess the effect of ongoing glucagon treatment on overall glycemic control.