Hypoglycaemia induces recruitment of non-classical monocytes and cytotoxic lymphocyte subsets in type 1 diabetes
To the Editor: We recently reported enhanced ex vivo cytokine production of immune cells during hypoglycaemia in humans . Chronic inflammation contributes to cardiovascular disease and atherosclerosis and may link hypoglycaemia to increased cardiovascular risk and mortality observed in individuals with diabetes .
Hypoglycaemia induces leucocytosis, possibly mediated by marked increases in plasma adrenaline (epinephrine) and cortisol levels. Adrenaline recruits immune cells from the marginal pool (vascular endothelium), likely by interfering with CD11a- and CX3CR1-dependent adhesion of leucocytes to the vessel wall . Indeed, gene expression levels of CD11a and CX3CR1 were increased in peripheral blood mononuclear cells (PBMCs) isolated during hypoglycaemia .
It remains unknown which specific immune cell subsets are recruited in response to hypoglycaemia. To identify these subsets, we analysed blood samples collected during clamped euglycaemia or hypoglycaemia from seven...
KeywordsHypoglycaemia Inflammation Type 1 diabetes
Peripheral blood mononuclear cell
The authors thank all volunteers for participating in this work. We are indebted to K. Saini and A. Hofboer-Kapteijns (Clinical Research Center Nijmegen, Radboud University Medical Center, the Netherlands) for assistance during the glucose clamps.
JR, HR, BdG, CT and RS designed the study. JR performed and analysed flow cytometry experiments. HR recruited patients and performed clamps. CJ assisted in performance and analysis of flow cytometry measurements. JR and RS wrote the paper. HR, CJ, BdG and CT critically revised the paper for important intellectual content. All authors approved the final manuscript to be published. RS is the guarantor of this work.
Research support from the Dutch Diabetes Research Foundation (DFN 2012.00.1542), Sanofi (unrestricted research grant) and the European Foundation for the Study of Diabetes is gratefully acknowledged. RS is supported by a VIDI-grant from The Netherlands Organisation for Scientific Research (NWO) and a senior fellowship from the Dutch Diabetes Foundation.
Duality of interest
The authors declare no potential conflicts of interests relevant to this study.
- 4.Wiegers EC, Rooijackers HM, Tack CJ et al (2018) Effect of lactate administration on brain lactate levels during hypoglycemia in patients with type 1 diabetes. J Cereb Blood Flow Metab. https://doi.org/10.1177/0271678X18775884
- 8.Weber C, Shantsila E, Hristov M et al (2016) Role and analysis of monocyte subsets in cardiovascular disease. Joint consensus document of the European Society of Cardiology (ESC) Working Groups “Atherosclerosis & Vascular Biology” and “Thrombosis”. Thromb Haemost 116:626–637CrossRefPubMedGoogle Scholar