{ "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.\n\nMaterials 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).\n\nResults: 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).\n\nConclusions: 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.\n\nTrial Registration: NCT04304963", "abstract_shown": true, "affiliations": [ "Department of Internal Medicine Radboud University Medical Center Nijmegen the Netherlands", "Diabetes Department St Vincents University Hospital Dublin Ireland", "Department of Diabetes, School of Cardiovascular and Metabolic Medicine and Sciences, Faculty of Life Sciences and Medicine King's College London London UK", "Diabetes Research Centre University of Leicester Leicester UK", "Department of Endocrinology and Nephrology Copenhagen University Hospital—North Zealand Hillerød Denmark", "Department of Diabetes Treatment Steno Diabetes Center Copenhagen Herlev Denmark", "Institute of Clinical Medicine University of Copenhagen Copenhagen Denmark", "Systems Medicine, School of Medicine University of Dundee Dundee UK", "Institute of Metabolic Science and Department of Medicine University of Cambridge Cambridge UK", "Division of Endocrinology and Diabetology, Department of Internal Medicine Medical University of Graz Graz Austria", "Department of Internal Medicine Maastricht University Medical Centre, MUMC+ Maastricht the Netherlands", "CARIM Cardiovascular Research Institute Maastricht Maastricht University Maastricht the Netherlands", "Division of Human Nutrition and Health Wageningen University Wageningen the Netherlands" ], "article_type": "research article", "arxiv": null, "author_total": 16, "authors": [ { "affs": [ 0 ], "name": "Mandala Ajie", "orcid": "0000-0003-0310-7842" }, { "affs": [ 0 ], "name": "Namam Ali", "orcid": "0000-0003-4302-7820" }, { "affs": [ 0 ], "name": "Marijn S. Hendriksz", "orcid": "0009-0002-3027-6369" }, { "affs": [ 1 ], "name": "Patrick Divilly" }, { "affs": [ 0 ], "name": "Marloes J. Rietveld" }, { "affs": [ 0 ], "name": "Evertine J. Abbink" }, { "affs": [ 2, 3 ], "name": "Pratik Choudhary" }, { "affs": [ 4, 5 ], "name": "Julie Maria Bøggild Brøsen" }, { "affs": [ 4, 6 ], "name": "Ulrik Pedersen‐Bjergaard", "orcid": "0000-0003-0588-4880" }, { "affs": [ 7 ], "name": "Rory J. McCrimmon", "orcid": "0000-0002-3957-1981" }, { "affs": [ 8 ], "name": "Mark Evans", "orcid": "0000-0001-8122-8987" }, { "affs": [ 9 ], "name": "Julia K. Mader", "orcid": "0000-0001-7854-4233" }, { "affs": [ 0, 10, 11 ], "name": "Bastiaan E. de Galan" }, { "affs": [ 0, 12 ], "name": "Rinke Stienstra" }, { "affs": [ 0 ], "name": "Cees J. Tack", "orcid": "0000-0003-0322-1653" }, { "name": "the Hypo‐RESOLVE Consortium" } ], "bibtex": "https://research.draconitic.com/paper/esnpk5hfq5msg.bib", "cited_by": 0, "doi": "10.1111/dom.71321", "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13730974/", "id": "esnpk5hfq5msg", "issns": [ "1462-8902", "1463-1326" ], "landing_url": "https://doi.org/10.1111/dom.71321", "language": "en", "licence": "CC-BY-NC-ND-4.0", "licence_label": "CC BY-NC-ND 4.0", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/", "metadata_licence": null, "native_subjects": [ [ "heading", "Original Article" ], [ "openalex", "2712|Diabetes Management and Research" ] ], "openalex": "W7213552887", "pdf_url": "https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/dom.71321", "pmcid": "PMC13730974", "pmid": "42755124", "published": "2026-09-17", "publisher": null, "ris": "https://research.draconitic.com/paper/esnpk5hfq5msg.ris", "sources": [ { "first_seen": "2026-11-08T12:21:16Z", "native_id": "PMC13730974", "source": "pmc", "url": "https://doi.org/10.1111/dom.71321" } ], "subjects": [ { "field": "medicine", "origin": "openalex:2712|Diabetes Management and Research", "subfield": "endocrinology-metabolism" } ], "title": "Sensor‐Detected Hypoglycaemia Is Associated With Inflammatory Protein and Immune Cell Alterations in People With Diabetes: Findings From the Hypo‐METRICS Study", "title_text": "Sensor‐Detected Hypoglycaemia Is Associated With Inflammatory Protein and Immune Cell Alterations in People With Diabetes: Findings From the Hypo‐METRICS Study", "type": "peer-reviewed", "updated_at": "2026-11-08T12:21:16Z", "url": "https://research.draconitic.com/paper/esnpk5hfq5msg", "venue": "Diabetes, Obesity & Metabolism", "versions": [] }