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.
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-α and interleukin-1β, 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-α and interleukin-1β, 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
AN - SCOPUS:85165572603
SN - 1462-8902
VL - 25
SP - 3114
EP - 3124
JO - Diabetes, Obesity and Metabolism
JF - Diabetes, Obesity and Metabolism
IS - 11
ER -