Low Carbohydrate Diet Impairs the Effect of Glucagon in the Treatment of Insulin-Induced Mild Hypoglycemia: A Randomized Cross-Over Study

OBJECTIVE: This study compared the ability of glucagon to restore plasma glucose (PG) after mild hypoglycemia in patients with type 1 diabetes on isocaloric high carbohydrate diet (HCD) versus a low carbohydrate diet (LCD).

RESEARCH DESIGN AND METHODS: Ten patients with insulin pump-treated type 1 diabetes randomly completed 1 week of the HCD (>250 g/day) and 1 week of the LCD (<50 g/day). After each week, mild hypoglycemia was induced by a subcutaneous insulin bolus in the fasting state. When PG reached 3.9 mmol/L, 100 µg glucagon was given subcutaneously, followed by 500 µg glucagon 2 h later.

RESULTS: Compared with the HCD, the LCD resulted in lower incremental rises in PG after the first (mean ± SEM: 1.3 ± 0.3 vs. 2.7 ± 0.4 mmol/L, P = 0.002) and second glucagon bolus (4.1 ± 0.2 vs. 5.6 ± 0.5 mmol/L, P = 0.002). No differences were observed between the diets regarding concentrations of insulin, glucagon, and triglycerides.

CONCLUSION: The LCD reduces the treatment effect of glucagon on mild hypoglycemia. Carbohydrate intake should be considered when low-dose glucagon is used to correct hypoglycemia.