Counterregulatory hormones oscillate during steady-state hypoglycemia

During hypoglycemia, the magnitude of the counterregulatory response depends on the extent of plasma glucose reduction. However, our clinical observations during steady-state hypoglycemia indicate that symptom severity can change independently of plasma glucose concentrations, i.e., symptoms appeared to fluctuate despite stable glucose levels. This study was therefore designed to test the hypothesis that hormonal and symptomatic responses to hypoglycemia are pulsatile. Seven healthy subjects had serial blood sampling at 3-min intervals during 90 min of insulin-induced hypoglycemia. Mean ± SE plasma glucose levels plateaued at 62 ± 3 mg/dl. Counterregulatory hormones were significantly elevated (P < 0.05–0.01, except norepinephrine) and strikingly pulsatile. Cluster analysis revealed pulses of large magnitude in plasma glucagon, epinephrine, and norepinephrine concentrations. Amplitudes were, respectively, 72 ± 4, 64 ± 8, and 48 ± 3% of the mean. Interpeak intervals were 27 ± 7, 19 ± 4, and 25 ± 5 min, res...