Rick I. Meijer¹, Ilyas F. Mustafajev^1, Marijn S. Hendriksz^1, Rinke Stienstra¹, Cees J., Tack¹, Bastiaan E. de Galan^1,2,3,

1. Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
2. Department of Internal Medicine, Maastricht University Medical Centre, MUMC+, Maastricht, The Netherlands
3. CARIM Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands

rick.meijer@radboudumc.nl

Objective: People with type 1 diabetes have a significantly increased risk for cardiovascular morbidity and mortality. The use of beta blockers is discouraged in people with type 1 diabetes, because of presumed suppression of autonomic symptoms that would increase hypoglycemia risk. We investigated the effect of adrenergic blockade on symptoms during experimental hypoglycemia.

Research Design and methods: Twelve people with type 1 diabetes and 11 people without diabetes underwent a hyperinsulinemic euglycemic-hypoglycemic (60 minutes at 2.8 mmol/l) glucose clamp, once during combined alpha- and beta-adrenergic blockade and once during placebo (saline infusion). Symptoms of hypoglycaemia were assessed at baseline, normoglycaemia, and twice during hypoglycaemia using the modified Edinburgh Hypoglycaemia Score. Symptoms were divided into autonomic, neuroglycopenic, and general.

Results: In T1DM, autonomic symptoms in response to hypoglycaemia increased from 1.9±0.8 to 9.3±1.4 (p<0.001) and from 1.6±0.7 to 5.3±1.2 (p<0.01) in the presence of adrenergic blockade and with placebo, respectively (p=NS between groups). Similarly, in CON, these symptoms increased from 2.3±0.5 to 6.3±0.8 (p<0.01) and from 2.3± to 6.1±1.2  (p<0.01) (p=NS between groups). Adrenergic blockade did not diminish neuroglycopenic symptom responses to hypoglycaemia, neither in T1DM, nor in CON. In fact, none of individual autonomic symptoms thought to be mediated by adrenaline were suppressed by adrenergic blockade. On the contrary, sweating, hunger and warmness were all significantly higher during adrenergic blockade compared to placebo (p<0.05). Glucose infusion rates (GIR) during hypoglycaemia, as a proxy for the inverse of endogenous glucose production, did not differ between adrenergic blockade and placebo conditions in neither group.

Conclusions: Our results demonstrate that hypoglycaemia-induced neuroglycopenic and autonomic symptom responses are not diminished by combined adrenergic  blockade. This suggests that cautioning against adrenergic blockade in people with T1DM is unwarranted.