Ilyas F. Mustafajev1, Marijn S. Hendriksz1, Julia I.P. van Heck1, Clementine E.M. Verhulst1, Bastiaan E. de Galan1-3, Rinke Stienstra1,4, Cees J., Tack1, 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 School for Cardiovascular Diseases, Maastricht University, Maastricht, The Netherlands; 4, Division of Human Nutrition and Health, Wageningen University, Wageningen, The Netherlands.
Ilyas.Mustafajev@radboudumc.nl
Background: Hypoglycaemia increases cardiovascular risk through inflammatory and prothrombotic responses. We hypothesize that the prothrombotic effect stems from it’s effect on erythropoiesis driven by the counterregulatory adrenaline surge. This study examined the effect of hypoglycaemia and adrenaline infusion on erythropoiesis in people with type 1 diabetes (T1DM) or without diabetes (CON).
Methods: Data is derived from two studies, in the first, 25 T1DM and 16 CON underwent a 60-min hyperinsulinaemic-hypoglycaemic(2.75±0.01mmoL/L) clamp. In the second, 15 T1DM and 15 CON received adrenaline intravenously at 0.04 µg/kg/min for 60 minutes. Blood samples were collected before hypoglycaemia or adrenaline infusion (T0), after 60 minutes (T60) and seven day thereafter (T7). Both studies measured, red blood cells (RBCs) reticulocytes counts using flowcytometry (Sysmex XN-450). Serial data were analyzed with mixed model analysis. The data are shown mean±SE. No group differences (T1DM vs CON) were observed results are reported collectively, unless specified otherwise.
Results: In study 1(hypoglycaemia), adrenaline levels at T60 averaged 1.35±0.15nmol/L and 1.92±0.38nmol/L in T1DM and CON, respectively (P=0.12), whereas in study 2 (adrenaline infusion), these were 2.12±0.31nmol/L and 2.24±0.28nmol/L, respectively (P=1.0). Neither RBCs nor reticulocytes changed at T60 after hypoglycaemia. Reticulocytes, increased from 0.056±0.003*1012/L to 0.074±0.003*1012/L at T7 (P<0.001). Same trend in reticulocytes displayed as fraction of RBCs, from 1.15±0.06% to 1.55±0.07%, P<0.001. In study 2, RBCs rose at T60 from 4,32±0.12*1012/L to 4.70±0.12*1012/L (P<0.001), and remained elevated at T7 4.75±0.09*1012/L (P<0.001). Reticulocytes rose from 0.045±0.002*1012/L to 0.053±0.003*1012/L (P<0.001) at T60, remaining elevated at T7 0.057±0.003*1012/L (P<0.001). Same trend in reticulocytes as a fraction of RBCs, from 1.05±0.05% to 1.11±0.06% (P<0.001) and at T7, 1.20±0.06% (P=0.002).
Discussion/Conclusion: Hypoglycaemia has a sustained stimulating effect on erythropoiesis in people with or without type 1 diabetes, which seems largely mediated by adrenaline.