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Adrenaline partly mediates the pro-thrombotic effect of hypoglycaemia

Adrenaline partly mediates the pro-thrombotic effect of hypoglycaemia

Ilyas F. Mustafajev1*, A.K. Stroobants, S. Rijpma, Marijn S. Hendriksz1*, Rinke Stienstra1,4, Cees J., Tack1, Bastiaan E. de Galan1,2,3, Rick I. Meijer1

  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
  4. Division of Human Nutrition and Health, Wageningen University, Wageningen, The Netherlands

† Shared last authorship

ilyas.mustafajev@radboudumc.nl

Background: Hypoglycaemia is increases the risk for cardiovascular disease, possibly through inducing a prothrombotic state. We investigated whether the counterregulatory hormone adrenaline mediates this response by measuring prothrombotic effects of hypoglycaemia in the presence or absence of alpha- and beta-adrenergic blockade in people with type 1 diabetes (T1DM) or without diabetes (CON).

Research Design and methods: 12 T1DM and 11 CON underwent a hyperinsulinaemic euglycaemic-hypoglycaemic (glucose 2.8 mmol/l) clamp, once with α- and β-adrenergic receptor blockade, and once with saline in a single-blinded cross-over design. Blood samples were collected before hypoglycaemia (T0), after 60 minutes (T60) one day (D1) and seven days (D7). We measured erythrocytes, haematocrit,  FVIII activity (FVIIIa), fibrinogen and D-dimer. Data were analysed with mixed model analysis.

Results: Hypoglycaemia caused acute (T60) and sustained (D7) increases of all prothrombotic parameters, except for D-dimer which only increased at D7 in T1DM, but not in CON. In both groups, adrenergic blockade suppressed the increases of erythrocytes, haematocrit and FVIIIa in response to hypoglycaemia at T60 (p<0.05), but not those at D7. Adrenergic blockade had no effect on the increase in thrombocytes from D1 up to D7 in both groups. Adrenergic blockade also suppressed the acute increase of fibrinogen at T60 in both groups and in part that at D7 in T1DM, but not in CON, and partly the increase in D-dimer in T1DM at D7.

Conclusions: Hypoglycaemia induces an acute and 7-days sustained pro-thrombotic state. The acute effect of hypoglycaemia, but not the sustained effect, is mediated by adrenaline.