Effects of Preceding Ethanol Intake on Glucose Response to Low-Dose Glucagon in Individuals With Type 1 Diabetes: A Randomized, Placebo-Controlled, Crossover Study

OBJECTIVE This study investigated whether preceding ethanol intake impairs glucose response to low-dose glucagon in individuals with type 1 diabetes. RESEARCH DESIGN AND METHODS This was a randomized, crossover, placebo-controlled study in 12 insulin pump–treated individuals (median [interquartile range] age, 37 [31–51] years; HbA 1c , 57 [51–59] mmol/mol or 7.3% [6.8–7.5]; and BMI, 23.9 [22–25] kg/m 2 ). During two overnight study visits, a 6 p.m. dinner (1 g carbohydrates/kg) was served with diet drink (placebo) or diet drink and ethanol (0.8 g/kg). After 8–9 h, ethanol was estimated to be metabolized, and a subcutaneous (s.c.) insulin bolus was given to induce mild hypoglycemia. When plasma glucose (PG) was ≤3.9 mmol/L, 100 µg glucagon was given s.c., followed by another s.c. 100 µg glucagon 2 h later. Primary end point was incremental peak PG induced by the first glucagon bolus. RESULTS Ethanol was undetectable before insulin administration at both visits. The insulin doses (mean ± SEM: 2.5 ± 0.4 vs. 2.7 ± 0.4 IU) to induce hypoglycemia (3.7 ± 0.1 vs. 3.9 ± 0.1 mmol/L) did not differ and caused similar insulin levels (28.3 ± 4.6 vs. 26.1 ± 4.0 mU/L) before glucagon administration on ethanol and placebo visits (all, P > 0.05). The first glucagon bolus tended to cause lower incremental peak PG (2.0 ± 0.5 vs. 2.9 ± 0.3 mmol/L, P = 0.06), lower incremental area under the curve (87 ± 40 vs. 191 ± 37 mmol/L × min, P = 0.08), and lower 2-h PG level (3.6 ± 1.0 vs. 4.8 ± 0.4 mmol/L, P = 0.05) after ethanol compared with placebo. The second glucagon bolus had similar responses between visits, but PG remained 1.8 ± 0.7 mmol/L lower after ethanol compared with placebo. CONCLUSIONS The ability of low-dose glucagon to treat mild hypoglycemia persisted with preceding ethanol intake, although it tended to be attenuated.