Physiologic Response to Glucagon in Type 1 Diabetes After Alcohol Consumption

Individuals with type 1 diabetes who experience mild hypoglycemia after the consumption of alcohol may benefit from treatment with glucagon 100 µg, as it has the potential to increase plasma glucose by 2.0 mmol/L, according to a study published in Diabetes Care.

Researchers conducted a randomized, crossover, placebo-controlled study in Demark to determine whether the ability of low-dose glucagon to increase plasma glucose would be impaired in individuals with type 1 diabetes (T1D) who had consumed ethanol.

In this study, the researchers recruited 12 individuals with T1D to complete 2 visits during which they were randomly assigned to receive a meal plus a drink with placebo or a meal plus a drink with ethanol for their first visit, and vice versa during their second visit.

Participants were admitted to the research facility and stayed the night during this study. After consuming their meal with their blinded drink, hypoglycemia was induced in all participants, followed by the administration of glucagon and measurement of blood glucose levels. The primary outcome of the study was the incremental peak of plasma glucose as a result of the first dose of glucagon administered.

The researchers found that the time to reach a hypoglycemic state was 60 minutes shorter in individuals who consumed ethanol compared with the placebo group (127±17 vs 186±15 min; P =.002). When the researchers administered the glucagon bolus, individuals in the ethanol group had a tendency to produce a lower incremental plasma glucose peak (primary end point: 2.0±0,5 vs 2.9±0.3 mmol/L; P =.06), as well as lower incremental area under the curve and lower 2-hour plasma glucose level (87±40 vs 191±37 mmol/L×min [P =.08]; and 3.6±1.0 vs 4.9±0.4 mmol/L [P =.05], respectively) vs the placebo group. Interestingly, the number of insulin doses required to induce a hypoglycemic state in individuals in both groups was similar (2.5±0.4 vs 2.7±0.4 IU; P =.7)

Postprandial growth hormone (GH) responses were found to be lower in the ethanol group vs placebo, whereas the postprandial cortisol peak was found to be higher in the ethanol group vs placebo (area under the curve, 16±26 vs 325±185 ng/mL [P = .05]; and 216±17 vs 167±32 nmol/L [P = .04], respectively). When compared with placebo, GH levels were significantly lower 3 hours after the meal (0.67±0.5 vs 6.2±2.1 ng/mL; P =.007) and remained lower during sleep in the ethanol group (area under the curve, 445±142 vs 2393±502 nmol/L×min; P =.0003). In addition, cortisol levels were significantly higher at the time of insulin bolus administration in the ethanol group vs the placebo group (277±23 vs 142±17 nmol/L; P =.0001).

The researchers concluded that the individuals with type 1 diabetes who ingested ethanol were found to have a “lower incremental glucose peak and a lower overall glucose response compared with placebo.” Further, the glucose response to the second dose of glucagon did not differ in either treatment group or from the glucose response to the first bolus of glucagon.

The researchers found the time it took to reach hypoglycemia was shorter in the ethanol group despite both groups receiving a similar number of insulin doses. Finally, the researchers concluded that the glucose response to glucagon after ethanol intake was reduced 8 to 9 hours after ingestion when compared with placebo; however, glucagon was still able to increase plasma glucose by 2.0 mmol/L in patients who ingested ethanol.

Therefore, clinicians should consider the use of low-dose glucagon as an effective therapeutic option in individuals with type 1 diabetes experiencing mild hypoglycemia after ethanol ingestion.

Reference

Ranjan A, Nørgaard K, Tetzschner R, et al. Effects of preceding ethanol intake on glucose response to low-dose glucagon in individuals with type 1 diabetes: a randomized, placebo-controlled, crossover study [published online January 22, 2018]. Diabetes Care. doi: 10.2337/dc17-1458