Hypoglycemia-dependent beta2-adrenoceptor downregulation: a contributing factor to hypoglycemia unawareness in...

To evaluate the influence of the incidence and unawareness of hypoglycemia on lymphocyte beta2-adrenoceptor densities, we measured beta2-adrenoceptor density using [125I]-iodocyanopindolol and CGP 12177 before and after 1 week of treatment optimization in 33 adults with type-1 diabetes mellitus. Diabetes treatment of all patients was modified to improve their glycemic control. During this week, all patients had to complete a protocol with 7 daily glucose measurements, one of which was at night. The subjective symptoms were evaluated in case of hypoglycemia. A significant correlation between a hypoglycemia incidence below (but not above) the threshold of 2.75 mmol/l (50 mg/dl) and beta2-adrenoceptor densities on lymphocytes was found after the study week (r = -0.72, p < 0.00001). Nine patients suffering from hypoglycemia unawareness had a significantly higher incidence of hypoglycemia (p < 0.002) and lower beta2-adrenoceptor densities on lymphocytes compared to 24 patients who recognized all of their hypoglycemic episodes (p < 0.004). We conclude that downregulation of beta2-adrenoceptor densities on lymphocytes occurs as a result of recurrent hypoglycemia defined as glucose levels of < 2.75 mmol/l. Beta2-adrenoceptor densities are decreased in patients with subjective hypoglycemia unawareness and might contribute to the reduced beta-adrenergic sensitivity in this subgroup of patients.