Short-term fasting (<24 h) is common in individuals with type 1 diabetes (T1D), but it is associated with increased risk of hypoglycemia. Current strategies to mitigate this risk include changing the timing and/or dose of insulin; however, it is unclear whether counterregulatory hormone secretion is diminished, which would also contribute to this elevated risk. The current experiments were conducted to determine whether short-term fasting affects the hormonal and hepatic responses to insulin-induced hypoglycemia in those with T1D. Nine C-peptide–negative individuals with T1D gave their informed consent to participate in a randomly assigned crossover-design metabolic trial. In one study, participants ate an isocaloric breakfast and lunch before undergoing a hyperinsulinemic/hypoglycemic metabolic challenge in the evening (FED); in the other, they fasted before the hypoglycemic challenge (FAST). Immediately before insulin-induced hypoglycemia, glucagon concentrations were 43% lower in FAST compared with FED (31 ± 5 and 54 ± 6 pg/mL, respectively; P < 0.001), and endogenous glucose production (EGP) was 28% lower (3.4 ± 0.2 and 4.6 ± 0.3 mg/kg/min, respectively; P < 0.01). During insulin-induced hypoglycemia, the area under the curve for glucagon remained lower by 42% in FAST compared with FED (1,598 ± 229 and 2,768 ± 422 pg/mL ∗ 60 min, respectively; P < 0.01), as did EGP (41 ± 4 and 78 ± 12 mg/kg ∗ 60 min, respectively; P = 0.01). These data demonstrate that fasting lowers glucagon concentrations and EGP under euglycemic/normoinsulinemic metabolic conditions and during insulin-induced hypoglycemia. This reduction in metabolic flexibility, in addition to hyperinsulinemia, enhances susceptibility to fasting-induced low blood glucose in individuals with T1D and should be considered when developing strategies to avoid hypoglycemia.
- Fasting is associated with increased risk of hypoglycemia in patients with type 1 diabetes (T1D); however, little is known about how the counterregulatory responses to low blood sugar are affected under these metabolic conditions.
- During insulin-induced hypoglycemia, fasting (compared with eating normal meals for breakfast and lunch) glucagon concentrations were lower by 42% and endogenous glucose production by 47% in individuals with T1D.
- The secretion of other counterregulatory hormones during hypoglycemia was not affected by fasting (e.g., epinephrine, norepinephrine, cortisol).
- Fasting diminishes glucagon levels under hypoglycemic conditions in those with T1D, which may increase their susceptibility to hypoglycemia.
Leave a Reply