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

OBJECTIVEThis study investigated whether preceding ethanol intake impairs glucose response to low-dose glucagon in individuals with type 1 diabetes.RESEARCH DESIGN AND METHODSThis 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 mu g glucagon was given s.c., followed by another s.c. 100 mu g glucagon 2 h later. Primary end point was incremental peak PG induced by the first glucagon bolus.RESULTSEthanol 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 x 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.CONCLUSIONSThe ability of low-dose glucagon to treat mild hypoglycemia persisted with preceding ethanol intake, although it tended to be attenuated.