Intensive Care Medicine

, Volume 36, Issue 9, pp 1548–1555

Type 2 diabetes mellitus is associated with impaired cytokine response and adhesion molecule expression in human endotoxemia

Authors

    • Centre of Inflammation and Metabolism, Department of Infectious DiseasesUniversity Hospital Rigshospitalet
    • Intensive Care Unit 4131University Hospital Rigshospitalet
  • Theis Pedersen-Skovsgaard
    • Centre of Inflammation and Metabolism, Department of Infectious DiseasesUniversity Hospital Rigshospitalet
  • Ronan M. G. Berg
    • Centre of Inflammation and Metabolism, Department of Infectious DiseasesUniversity Hospital Rigshospitalet
  • Kira Dynnes Svendsen
    • Department of BiostatisticsUniversity of Copenhagen
  • Bo Feldt-Rasmussen
    • Department of NephrologyUniversity Hospital Rigshospitalet
  • Bente K. Pedersen
    • Centre of Inflammation and Metabolism, Department of Infectious DiseasesUniversity Hospital Rigshospitalet
  • Kirsten Møller
    • Centre of Inflammation and Metabolism, Department of Infectious DiseasesUniversity Hospital Rigshospitalet
    • Intensive Care Unit 4131University Hospital Rigshospitalet
Original

DOI: 10.1007/s00134-010-1845-1

Cite this article as:
Andreasen, A.S., Pedersen-Skovsgaard, T., Berg, R.M.G. et al. Intensive Care Med (2010) 36: 1548. doi:10.1007/s00134-010-1845-1

Abstract

Purpose

Type 2 diabetes is associated with an increased risk of acquiring infectious diseases and developing sepsis. This may partly be due to immune dysfunction. We investigated the in vivo innate immune response of type 2 diabetic persons to an intravenous injection of E. coli lipopolysaccharide (LPS).

Methods

After ethics approval, informed consent and a thorough physical examination, 19 type 2 diabetic patients and 23 healthy controls were included. LPS was given as an intravenous bolus injection of 0.3 ng/kg. Physiological variables, white blood cell count, and plasma concentrations of tumour necrosis factor (TNF), interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1ra), and the adhesion molecules E-selectin, vascular adhesion molecule (VCAM)-1, and intracellular adhesion molecule (ICAM)-1 were measured hourly for 8 h.

Results

LPS injection induced a systemic inflammatory response with increases in neutrophils, temperature, heart rate and plasma concentrations of cytokines and adhesion molecules in healthy and type 2 diabetic volunteers. Type 2 diabetes was associated with less pronounced LPS-induced increases in TNF, IL-1ra, VCAM-1 and ICAM-1. There was a trend towards an attenuated upregulation of E-selectin in diabetics, even though the plasma concentration tended to be generally higher compared to healthy controls.

Conclusions

Patients with type 2 diabetes exhibit an attenuated increase in plasma levels of TNF and IL-1ra, as well as an attenuated upregulation of VCAM-1 and ICAM-1 to LPS in vivo. This finding may provide a mechanistic explanation for the adverse outcome seen during infectious diseases in diabetic patients.

Keywords

Type 2 diabetesSepsisInflammationLPSCytokinesAdhesion molecules

Copyright information

© Copyright jointly held by Springer and ESICM 2010