Sensor‐Detected Hypoglycaemia Is Associated With Inflammatory Protein and Immune Cell Alterations in People With Diabetes: Findings From the Hypo‐METRICS Study
13 affiliations
- 1Department of Internal Medicine Radboud University Medical Center Nijmegen the Netherlands
- 2Diabetes Department St Vincents University Hospital Dublin Ireland
- 3Department of Diabetes, School of Cardiovascular and Metabolic Medicine and Sciences, Faculty of Life Sciences and Medicine King's College London London UK
- 4Diabetes Research Centre University of Leicester Leicester UK
- 5Department of Endocrinology and Nephrology Copenhagen University Hospital—North Zealand Hillerød Denmark
- 6Department of Diabetes Treatment Steno Diabetes Center Copenhagen Herlev Denmark
- 7Institute of Clinical Medicine University of Copenhagen Copenhagen Denmark
- 8Systems Medicine, School of Medicine University of Dundee Dundee UK
- 9Institute of Metabolic Science and Department of Medicine University of Cambridge Cambridge UK
- 10Division of Endocrinology and Diabetology, Department of Internal Medicine Medical University of Graz Graz Austria
- 11Department of Internal Medicine Maastricht University Medical Centre, MUMC+ Maastricht the Netherlands
- 12CARIM Cardiovascular Research Institute Maastricht Maastricht University Maastricht the Netherlands
- 13Division of Human Nutrition and Health Wageningen University Wageningen the Netherlands
Abstract
Aims: Experimental hypoglycaemia induces a persistent inflammatory response. We investigated whether real‐life sensor‐detected hypoglycaemia (SDH) is associated with immune parameters in people with Type 1 and Type 2 diabetes and explored potential differences between the groups.
Materials and Methods: In a multi‐center observational study, 177 people with Type 1 diabetes and 185 with insulin‐treated Type 2 diabetes were recruited to wear blinded glucose sensors for 10 weeks. SDH metrics derived from these sensors included SDH frequency, SDH duration, and time below range (TBR). At the end of the observation period, fasting blood was drawn to measure levels of circulating inflammatory proteins (Type 1 n = 177, Type 2 n = 185), ex vivo monocyte function (Type 1 n = 59; Type 2 n = 90), and circulating immune cell counts (Type 1 n = 29; Type 2 n = 87).
Results: Four circulating inflammatory proteins (CCL28, CX3CL1, IL‐17A, IL‐17C) were positively associated with SDH frequency, SDH duration and TBR in both groups (all p < 0.05). In Type 1 diabetes, pro‐inflammatory responses of monocytes to pathogenic stimuli were inversely associated with SDH frequency, SDH duration and TBR, particularly Pam3Cys‐induced IL‐6 production (all p < 0.05); similar but less pronounced associations were observed in Type 2 diabetes. SDH frequency and TBR were inversely associated with total circulating immune cell, neutrophil and monocyte counts in Type 1 diabetes (all p < 0.05).
Conclusions: Exposure to real‐life hypoglycaemia is associated with immune alterations in people with Type 1 and Type 2 diabetes, including increased levels of circulating inflammatory proteins in both diabetes types and reduced monocyte function and immune cell counts, particularly in Type 1 diabetes.
Trial Registration: NCT04304963
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BibTeX
@article{ajie2026sensordetected,
title = {{Sensor‐Detected Hypoglycaemia Is Associated With Inflammatory Protein and Immune Cell Alterations in People With Diabetes: Findings From the Hypo‐METRICS Study}},
author = {Mandala Ajie and Namam Ali and Marijn S. Hendriksz and Patrick Divilly and Marloes J. Rietveld and Evertine J. Abbink and Pratik Choudhary and Julie Maria Bøggild Brøsen and Ulrik Pedersen‐Bjergaard and Rory J. McCrimmon and Mark Evans and Julia K. Mader and Bastiaan E. de Galan and Rinke Stienstra and Cees J. Tack and the Hypo‐RESOLVE Consortium},
journal = {Diabetes, Obesity \& Metabolism},
year = {2026},
month = sep,
doi = {10.1111/dom.71321},
url = {https://doi.org/10.1111/dom.71321},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Sensor‐Detected Hypoglycaemia Is Associated With Inflammatory Protein and Immune Cell Alterations in People With Diabetes: Findings From the Hypo‐METRICS Study
AU - Mandala Ajie
AU - Namam Ali
AU - Marijn S. Hendriksz
AU - Patrick Divilly
AU - Marloes J. Rietveld
AU - Evertine J. Abbink
AU - Pratik Choudhary
AU - Julie Maria Bøggild Brøsen
AU - Ulrik Pedersen‐Bjergaard
AU - Rory J. McCrimmon
AU - Mark Evans
AU - Julia K. Mader
AU - Bastiaan E. de Galan
AU - Rinke Stienstra
AU - Cees J. Tack
AU - the Hypo‐RESOLVE Consortium
PY - 2026
DA - 2026/09/17
JO - Diabetes, Obesity & Metabolism
DO - 10.1111/dom.71321
UR - https://doi.org/10.1111/dom.71321
AB - Aims: Experimental hypoglycaemia induces a persistent inflammatory response. We investigated whether real‐life sensor‐detected hypoglycaemia (SDH) is associated with immune parameters in people with Type 1 and Type 2 diabetes and explored potential differences between the groups. Materials and Methods: In a multi‐center observational study, 177 people with Type 1 diabetes and 185 with insulin‐treated Type 2 diabetes were recruited to wear blinded glucose sensors for 10 weeks. SDH metrics derived from these sensors included SDH frequency, SDH duration, and time below range (TBR). At the end of the observation period, fasting blood was drawn to measure levels of circulating inflammatory proteins (Type 1 n = 177, Type 2 n = 185), ex vivo monocyte function (Type 1 n = 59; Type 2 n = 90), and circulating immune cell counts (Type 1 n = 29; Type 2 n = 87). Results: Four circulating inflammatory proteins (CCL28, CX3CL1, IL‐17A, IL‐17C) were positively associated with SDH frequency, SDH duration and TBR in both groups (all p < 0.05). In Type 1 diabetes, pro‐inflammatory responses of monocytes to pathogenic stimuli were inversely associated with SDH frequency, SDH duration and TBR, particularly Pam3Cys‐induced IL‐6 production (all p < 0.05); similar but less pronounced associations were observed in Type 2 diabetes. SDH frequency and TBR were inversely associated with total circulating immune cell, neutrophil and monocyte counts in Type 1 diabetes (all p < 0.05). Conclusions: Exposure to real‐life hypoglycaemia is associated with immune alterations in people with Type 1 and Type 2 diabetes, including increased levels of circulating inflammatory proteins in both diabetes types and reduced monocyte function and immune cell counts, particularly in Type 1 diabetes. Trial Registration: NCT04304963
SN - 1462-8902
SN - 1463-1326
ER -