Reduced beta-adrenergic sensitivity in healthy volunteers induced by hypoglycemia

A single causative mechanism for development of hypoglycemia unawareness in insulin-dependent diabetes mellitus (IDDM) is not yet apparent. Reduced adrenergic sensitivity may be part of the explanation. This study was carried out to investigate the effect of hypoglycemia on beta-adrenergic sensitivity. Ten healthy male subjects (age 19-23 years) gave informed consent to take part in the study. They were hospitalized overnight at the University Hospital of Tromsø, Department of Clinical Research, on two occasions. Isoprenaline and metoprolol sensitivity tests were performed the morning after hospitalization: once after an intravenous (iv) injection of placebo (0.9% NaCl), and once after an iv injection of insulin (0.15 IU insulin/kg body weight) to induce hypoglycemia. The dose of isoprenaline needed to increase heart rate (HR) by 25 beats per minute (bpm) (I25), and the dose of metoprolol (M-12.5) needed to inhibit I25 with 50% or 12.5 bpm, when injected simultaneously, were used as determinants of isoprenaline and metoprolol sensitivity. In this study, there was a significant (p < 0.05) increase both in I25 and M-12.5 after hypoglycemia. The dose-response curve of isoprenaline/HR was significantly shifted to the right after hypoglycemia. This study shows that acute hypoglycemia induces a reduction in beta-adrenergic sensitivity, and it supports the hypothesis of reduced beta-adrenergic sensitivity as an important pathophysiological mechanism in hypoglycemia unawareness in IDDM.