TY - JOUR
T1 - Hypoglycaemia induces a sustained pro-inflammatory response in people with type 1 diabetes and healthy controls
AU - Verhulst, Clementine E.M.
AU - van Heck, Julia I.P.
AU - Fabricius, Therese W.
AU - Stienstra, Rinke
AU - Teerenstra, Steven
AU - McCrimmon, Rory J.
AU - Tack, Cees J.
AU - Pedersen-Bjergaard, Ulrik
AU - de Galan, Bastiaan E.
AU - Hypo-RESOLVE Consortium
N1 - Funding Information:
This study has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 777460. The JU receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA and T1D Exchange, JDRF, International Diabetes Federation (IDF), and The Leona M. and Harry B. Helmsley Charitable Trust.
Publisher Copyright:
© 2023 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.
PY - 2023/11
Y1 - 2023/11
N2 - Aim: To determine the duration and the extension of the pro-inflammatory response to hypoglycaemia both in people with type 1 diabetes and healthy controls. Materials and Methods: Adults with type 1 diabetes (n = 47) and matched controls (n = 16) underwent a hyperinsulinaemic-euglycaemic hypoglycaemic (2.8 ± 0.1 mmoL/L [49.9 ± 2.3 mg/dL]) glucose clamp. During euglycaemia, hypoglycaemia, and 1, 3 and 7 days later, blood was drawn to determine immune cell phenotype, monocyte function and circulating inflammatory markers. Results: Hypoglycaemia increased lymphocyte and monocyte counts, which remained elevated for 1 week. The proportion of CD16+ monocytes increased and the proportion of CD14+ monocytes decreased. During hypoglycaemia, monocytes released more tumour necrosis factor-a and interleukin-1ß, and less interleukin-10, after ex vivo stimulation. Hypoglycaemia increased the levels of 19 circulating inflammatory proteins, including high sensitive C-reactive protein, most of which remained elevated for 1 week. The epinephrine peak in response to hypoglycaemia was positively correlated with immune cell number and phenotype, but not with the proteomic response. Conclusions: Overall, despite differences in prior exposure to hypoglycaemia, the pattern of the inflammatory responses to hypoglycaemia did not differ between people with type 1 diabetes and healthy controls. In conclusion, hypoglycaemia induces a range of pro-inflammatory responses that are sustained for at least 1 week in people with type 1 diabetes and healthy controls.
AB - Aim: To determine the duration and the extension of the pro-inflammatory response to hypoglycaemia both in people with type 1 diabetes and healthy controls. Materials and Methods: Adults with type 1 diabetes (n = 47) and matched controls (n = 16) underwent a hyperinsulinaemic-euglycaemic hypoglycaemic (2.8 ± 0.1 mmoL/L [49.9 ± 2.3 mg/dL]) glucose clamp. During euglycaemia, hypoglycaemia, and 1, 3 and 7 days later, blood was drawn to determine immune cell phenotype, monocyte function and circulating inflammatory markers. Results: Hypoglycaemia increased lymphocyte and monocyte counts, which remained elevated for 1 week. The proportion of CD16+ monocytes increased and the proportion of CD14+ monocytes decreased. During hypoglycaemia, monocytes released more tumour necrosis factor-a and interleukin-1ß, and less interleukin-10, after ex vivo stimulation. Hypoglycaemia increased the levels of 19 circulating inflammatory proteins, including high sensitive C-reactive protein, most of which remained elevated for 1 week. The epinephrine peak in response to hypoglycaemia was positively correlated with immune cell number and phenotype, but not with the proteomic response. Conclusions: Overall, despite differences in prior exposure to hypoglycaemia, the pattern of the inflammatory responses to hypoglycaemia did not differ between people with type 1 diabetes and healthy controls. In conclusion, hypoglycaemia induces a range of pro-inflammatory responses that are sustained for at least 1 week in people with type 1 diabetes and healthy controls.
KW - C-reactive protein
KW - clamp
KW - counterregulatory hormones
KW - diabetes
KW - hypoglycaemia
KW - inflammation
KW - white blood cells
U2 - 10.1111/dom.15205
DO - 10.1111/dom.15205
M3 - Article
C2 - 37485887
SN - 1462-8902
VL - 25
SP - 3114
EP - 3124
JO - Diabetes Obesity & Metabolism
JF - Diabetes Obesity & Metabolism
IS - 11
M1 - 15205
ER -