Recent studies indicate that endogenous
epinephrine provides protection against
hypoglycemia in fasted elderly patients with
type 2 diabetes treated with sulfonylureas. To establish a dose-response relationship and further characterize this hormonal action, 10 subjects with
type 2 diabetes aged 67 +/- 1.3 years and receiving
glyburide 20 mg daily were studied on 3 separate occasions. Saline placebo, half dose
epinephrine ([Epi] 0.375 microg/min), and full dose Epi (0.75 microg/min) were infused during the final 10 hours of a 28-hour fast in a paired, randomized single-blind study to simulate physiologic
epinephrine levels. Substrate and hormonal parameters and
glucose production (Rd), disposal (Rd), and metabolic clearance rates were determined every 30 minutes. In the placebo study, the mean decline in plasma
glucose during the final 10 hours of fasting was -2.7 +/- 0.6 mmol/L, compared with -0.3 +/- 0.3 mmol/L in the half dose Epi study and an actual increase in
glucose of 1.0 +/- 0.8 mmol/L in the full dose Epi study (P < .001). There was a similar decline in the
glucose Ra in all 3 studies, and the
glucose Rd was not significantly different among the 3 study conditions. The baseline-adjusted metabolic clearance rate of
glucose was significantly decreased during the
epinephrine studies compared with the placebo study (P = .01). The concentration of other counterregulatory
hormones did not differ between the studies. We conclude that low physiologic concentrations of
epinephrine prevent the progressive decline in plasma
glucose observed during fasting in elderly sulfonylurea-treated patients with
type 2 diabetes. This finding may be attributable to a relative
insulin resistance induced by
epinephrine, resulting in a decreased rate of
glucose clearance by cells.