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

• Published in: Diabetes care Vol. 33; no. 6; pp. 1282 - 1287
• Main Authors: Castle, Jessica R, Engle, Julia M, Youssef, Joseph El, Massoud, Ryan G, Yuen, Kevin C.J, Kagan, Ryland, Ward, W. Kenneth
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.06.2010
• Subjects: Accuracy; Adult; adults; adverse effects; analysis; Biological and medical sciences; blood glucose; Blood Glucose - analysis; Blood sugar; Diabetes; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 1 - drug therapy; Diabetes therapy; Diabetes. Impaired glucose tolerance; Diabetics; drug therapy; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; FDA approval; Female; Glucagon; Glucagon - adverse effects; Glucagon - therapeutic use; glycemic control; Hormones; Hormones - adverse effects; Hormones - therapeutic use; Humans; hypoglycemia; Hypoglycemia - prevention & control; Insulin; insulin-dependent diabetes mellitus; Male; Medical sciences; Metabolic diseases; Miscellaneous; Original Research; Prevention; prevention & control; Public health. Hygiene; Public health. Hygiene-occupational medicine; Sensors; Studies; therapeutic use; Treatment Outcome; Type 1 diabetes; Endocrinopathy; Human; Immunopathology; Pancreatic hormone; Glucagon; Nutrition; Hyperglycemic substances; Use; Peptide hormone; Autoimmune disease; Metabolic diseases; Hypoglycemia; Prevention; Closed systems; Type 1 diabetes; Endocrinology
• DOI: 10.2337/dc09-2254
• ISSN: 0149-5992; 1935-5548

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.