TY - JOUR
T1 - Association between recent exposure to continuous glucose monitoring-recorded hypoglycaemia and counterregulatory and symptom responses to subsequent controlled hypoglycaemia in people with type 1 diabetes
AU - Svensson, Cecilie H.
AU - Fabricius, Therese W.
AU - Verhulst, Clementine E.M.
AU - Kristensen, Peter L.
AU - Tack, Cees J.
AU - Heller, Simon R.
AU - Amiel, Stephanie A.
AU - McCrimmon, Rory J.
AU - Evans, Mark
AU - Holst, Jens J.
AU - de Galan, Bastiaan E.
AU - Pedersen-Bjergaard, Ulrik
N1 - Funding Information:
This project 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\u2019s Horizon 2020 research and innovation programme and EFPIA and T1D Exchange, JDRF, IDF, HCT. Any dissemination of results must indicate that it reflects only the author's view and that the JU is not responsible for any use that may be made of the information it contains. The University of Cambridge has received salary support for ME through the National Health Service in the East of England through the Clinical Academic Reserve.
Funding Information:
CHS, CV and PLK have no conflicts of interest to declare. TWF has been employed by Novo Nordisk after the completion of the study. CT has received research support from AstraZeneca, received lecture fees from AstraZeneca and Novo Nordisk, and served on advisory boards for Bayer, MSD, Boehringer\u2010Ingelheim and Novo Nordisk. BG has received research support from Novo Nordisk. UPB has served on advisory boards for Sanofi, Novo Nordisk and Vertex, and has received lecture fees from Novo Nordisk and Sanofi. MLE has been a member of advisory panels and/or received speakers fees and/or research support from Novo Nordisk, Eli Lilly, Abbott Diabetes Care, Medtronic, Dexcom, Astra Zeneca, Ypsomed, Pila Pharma and Zucara. JJH is supported by the Novo Nordisk Foundation. SAA has served on advisory boards for Medtronic and Novo Nordisk and spoken at educational events sponsored by Sanofi and Novo Nordisk.
Publisher Copyright:
© 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.
PY - 2024/8
Y1 - 2024/8
N2 - Aim: Experimental hypoglycaemia blunts the counterregulatory hormone and symptom responses to a subsequent episode of hypoglycaemia. In this study, we aimed to assess the associations between antecedent exposure and continuous glucose monitoring (CGM)-recorded hypoglycaemia during a 1-week period and the counterregulatory responses to subsequent experimental hypoglycaemia in people with type 1 diabetes. Materials and Methods: Forty-two people with type 1 diabetes (20 females, mean ± SD glycated haemoglobin 7.8% ± 1.0%, diabetes duration median (interquartile range) 22.0 (10.5-34.9) years, 29 CGM users, and 19 with impaired awareness of hypoglycaemia) wore an open intermittently scanned CGM for 1 week to detect hypoglycaemic exposure before a standardized hyperinsulinaemic-hypoglycaemic [2.8 ± 0.1 mmol/L (50.2 ± 2.3 mg/dl)] glucose clamp. Symptom responses and counterregulatory hormones were measured during the clamp. The study is part of the HypoRESOLVE project. Results: CGM-recorded hypoglycaemia in the week before the clamp was negatively associated with adrenaline response [β −0.09, 95% CI (−0.16, −0.02) nmol/L, p =.014], after adjusting for CGM use, awareness of hypoglycaemia, glycated haemoglobin and total daily insulin dose. This was driven by level 2 hypoglycaemia [<3.0 mmol/L (54 mg/dl)] [β −0.21, 95% CI (−0.41, −0.01) nmol/L, p =.034]. CGM-recorded hypoglycaemia was negatively associated with total, autonomic, and neuroglycopenic symptom responses, but these associations were lost after adjusting for potential confounders. Conclusions: Recent exposure to CGM-detected hypoglycaemia was independently associated with an attenuated adrenaline response to experimental hypoglycaemia in people with type 1 diabetes.
AB - Aim: Experimental hypoglycaemia blunts the counterregulatory hormone and symptom responses to a subsequent episode of hypoglycaemia. In this study, we aimed to assess the associations between antecedent exposure and continuous glucose monitoring (CGM)-recorded hypoglycaemia during a 1-week period and the counterregulatory responses to subsequent experimental hypoglycaemia in people with type 1 diabetes. Materials and Methods: Forty-two people with type 1 diabetes (20 females, mean ± SD glycated haemoglobin 7.8% ± 1.0%, diabetes duration median (interquartile range) 22.0 (10.5-34.9) years, 29 CGM users, and 19 with impaired awareness of hypoglycaemia) wore an open intermittently scanned CGM for 1 week to detect hypoglycaemic exposure before a standardized hyperinsulinaemic-hypoglycaemic [2.8 ± 0.1 mmol/L (50.2 ± 2.3 mg/dl)] glucose clamp. Symptom responses and counterregulatory hormones were measured during the clamp. The study is part of the HypoRESOLVE project. Results: CGM-recorded hypoglycaemia in the week before the clamp was negatively associated with adrenaline response [β −0.09, 95% CI (−0.16, −0.02) nmol/L, p =.014], after adjusting for CGM use, awareness of hypoglycaemia, glycated haemoglobin and total daily insulin dose. This was driven by level 2 hypoglycaemia [<3.0 mmol/L (54 mg/dl)] [β −0.21, 95% CI (−0.41, −0.01) nmol/L, p =.034]. CGM-recorded hypoglycaemia was negatively associated with total, autonomic, and neuroglycopenic symptom responses, but these associations were lost after adjusting for potential confounders. Conclusions: Recent exposure to CGM-detected hypoglycaemia was independently associated with an attenuated adrenaline response to experimental hypoglycaemia in people with type 1 diabetes.
KW - continuous glucose monitoring
KW - counterregulation
KW - counterregulatory hormone and symptom responses
KW - diabetes
KW - hyperinsulinaemic-hypoglycaemic clamp
KW - hypoglycaemia
KW - hypoglycaemia awareness
KW - type 1 diabetes
U2 - 10.1111/dom.15649
DO - 10.1111/dom.15649
M3 - Article
SN - 1462-8902
VL - 26
SP - 3213
EP - 3222
JO - Diabetes Obesity & Metabolism
JF - Diabetes Obesity & Metabolism
IS - 8
ER -