COUNTERREGULATORY HORMONES OSCILLATE DURING STEADY-STATE HYPOGLYCEMIA

During hypoglycemia, the magnitude of the counterregulatory response d epends on the extent of plasma glucose reduction. However, our clinica l 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 su bjects had serial blood sampling at S-min intervals during 90 min of i nsulin-induced hypoglycemia. Mean +/- SE plasma glucose levels plateau ed at 62 +/- 3 mg/dl. Counterregulatory hormones were significantly el evated (P < 0.05-0.01, except norepinephrine) and strikingly pulsatile . Cluster analysis revealed pulses of large magnitude in plasma glucag on, epinephrine, and norepinephrine concentrations. Amplitudes were, r espectively, 72 +/- 4, 64 +/- 8, and 48 +/- 3% of the mean. Interpeak intervals were 27 +/- 7, 19 +/- 4, and 25 +/- 5 min, respectively. Sym ptom score and cardiovascular responses were also pulsatile; their pea ks were found to coincide with epinephrine peaks. We conclude that hor monal and symptomatic counterregulation in hypoglycemia, while critica lly driven by plasma glucose levels, is also influenced by an endogeno us pulsatility that exists despite steady-state glucose concentrations .