REDUCED BETA-ADRENERGIC SENSITIVITY IN HEALTHY-VOLUNTEERS INDUCED BY HYPOGLYCEMIA

A single causative mechanism for development of hypoglycemia unawarene ss in insulin-dependent diabetes mellitus IDDM) is not yet apparent. R educed adrenergic sensitivity may be part of the explanation. This stu dy was carried out to investigate the effect of hypoglycemia on beta-a drenergic sensitivity. Ten healthy male subjects (age 19-23 years) gav e informed consent to take part in the study. They were hospitalized o vernight at the University Hospital of Tromso Department of Clinical R esearch, on two occasions. Isoprenaline and metoprolol sensitivity tes ts were performed the morning after hospitalization: once after an int ravenous (iv) injection of placebo (0.9% NaCl), and once after an iv i njection of insulin (0.15 IU insulin/kg body weight) to induce hypogly cemia. The dose of isoprenaline needed to increase heart rate (HR) by 25 beats per minute (bpm) (I-25), and the dose of metoprolol (M(-12.5) ) needed to inhibit I-25 with 50% or 12.5 bpm, when injected simultane ously, were used as determinants of isoprenaline and metoprolol sensit ivity. In this study, there was a significant (p < 0.05) increase both in I-25 and M(-12.5) after hypoglycemia. The dose-response curve of i soprenaline/HR was significantly shifted to the right after hypoglycem ia. This study shows that acute hypoglycemia induces a reduction in be ta-adrenegic sensitivity, and it supports the hypothesis of reduced be ta-adrenergic sensitivity as an important pathophysiological mechanism in hypoglycemia unawareness in IDDM.