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

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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.

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Acknowledgements

Ruth Rousing, Hanne Villumsen, Annette Vinding and Andreas Haltorp are acknowledged for their technical assistance. The Centre of Inflammation and Metabolism is supported by a grant from the Danish National Research Foundation (# 02-512-55). This study was further supported by the Beckett Foundation, the Larsen Foundation, the Foundation of Brdr. Hartmann, the Foundation of Direktør Emil Hertz og Hustru Inger Hertz, the A.P. Møller Foundation, the Foundation of the Danish Diabetes Association, the Lærdal Foundation, and the Foundation of Kong Christian den Tiende.

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Authors and Affiliations

  1. Centre of Inflammation and Metabolism, Department of Infectious Diseases, University Hospital Rigshospitalet, Rigshospitalet-M 7641, Blegdamsvej 9, 2100, Copenhagen, Denmark

    Anne Sofie Andreasen, Theis Pedersen-Skovsgaard, Ronan M. G. Berg, Bente K. Pedersen & Kirsten Møller

  2. Intensive Care Unit 4131, University Hospital Rigshospitalet, Copenhagen, Denmark

    Anne Sofie Andreasen & Kirsten Møller

  3. Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark

    Kira Dynnes Svendsen

  4. Department of Nephrology, University Hospital Rigshospitalet, Copenhagen, Denmark

    Bo Feldt-Rasmussen

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  1. Anne Sofie Andreasen
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  2. Theis Pedersen-Skovsgaard
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  3. Ronan M. G. Berg
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Correspondence to Anne Sofie Andreasen.

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Andreasen, A.S., Pedersen-Skovsgaard, T., Berg, R.M.G. et al. Type 2 diabetes mellitus is associated with impaired cytokine response and adhesion molecule expression in human endotoxemia. Intensive Care Med 36, 1548–1555 (2010). https://doi.org/10.1007/s00134-010-1845-1

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  • DOI: https://doi.org/10.1007/s00134-010-1845-1

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