Limited impact of impaired awareness of hypoglycaemia and severe hypoglycaemia on the inflammatory profile of people with type 1 diabetes

Namam Ali*, Anna W.M. Janssen, Martin Jaeger, Lisa Van de Wijer, Wouter van der Heijden, Rob ter Horst, Priya Vart, Alain van Gool, Leo A.B. Joosten, Mihai G. Netea, Rinke Stienstra, Bastiaan E. De Galan, Cees J. Tack

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

4 Citations (Scopus)


Aim: To investigate whether a history of severe hypoglycaemia (SH) or the associated presence of impaired awareness of hypoglycaemia (IAH) is characterized by a pro-inflammatory profile in people with type 1 diabetes. Research design and methods: We measured circulating inflammatory markers and pro- and anti-inflammatory cytokine production after ex vivo stimulation of peripheral blood mononuclear cells (PBMCs) in a well-characterized cohort of individuals with type 1 diabetes (n = 239) and in people without diabetes (n = 56). Data were corrected for confounders by using multivariate linear regression models. Results: People with type 1 diabetes had higher circulating concentrations of high-sensitivity C-reactive protein (hs-CRP; 0.91 [0.36–2.25] vs. 0.52 [0.20–0.98] pg/mL, P < 0.001 and interleukin-18-binding protein (IL-18BP; 1746 [1304–2112] vs. 1381 [1191–1807] pg/mL; P = 0.001) than those without diabetes. In multivariate analysis, only higher hs-CRP concentrations persisted. Neither circulating immune cells nor ex vivo cytokine levels produced by PBMCs in response to an extensive panel of stimuli differed in groups defined by awareness state or a history of SH, apart from elevated IL-18BP in people with, versus those without, history of SH (1524 [1227–1903] vs. 1913 [1459–2408] pg/mL; P < 0.001). Conclusions: IAH or history of SH in people with type 1 diabetes was not associated with altered inflammatory profiles, arguing against chronically elevated inflammatory activity mediating the increased cardiovascular risk associated with hypoglycaemia. The finding of higher circulating concentrations of IL-18BP in individuals with a history of SH requires further investigation.

Original languageEnglish
Pages (from-to)2427-2436
JournalDiabetes, Obesity and Metabolism
Issue number12
Early online date16 Aug 2020
Publication statusPublished - Dec 2020


  • cardiovascular disease
  • cohort study
  • diabetes complications
  • hypoglycaemia
  • type 1 diabetes


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