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      The impact of diabetes on the pathogenesis of sepsis

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          Abstract

          Diabetes is associated with an increased susceptibility to infection and sepsis. Conflicting data exist on whether the mortality of patients with sepsis is influenced by the presence of diabetes, fuelling the ongoing debate on the benefit of tight glucose regulation in patients with sepsis. The main reason for which diabetes predisposes to infection appears to be abnormalities of the host response, particularly in neutrophil chemotaxis, adhesion and intracellular killing, defects that have been attributed to the effect of hyperglycaemia. There is also evidence for defects in humoral immunity, and this may play a larger role than previously recognised. We review the literature on the immune response in diabetes and its potential contribution to the pathogenesis of sepsis. In addition, the effect of diabetes treatment on the immune response is discussed, with specific reference to insulin, metformin, sulphonylureas and thiazolidinediones.

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          THE CHEMOTACTIC EFFECT OF MIXTURES OF ANTIBODY AND ANTIGEN ON POLYMORPHONUCLEAR LEUCOCYTES

          Stephen V. Boyden (1962)
          An in vitro technique is described for assessing the chemotactic activity of soluble substances on motile cells. Antibody-antigen mixtures when incubated (37°C) in medium containing fresh (i.e. non-inactivated) normal rabbit serum exert a strong chemotactic effect on rabbit polymorphonuclear leucocytes. Results are described which indicate that, when antibody-antigen complexes are incubated (37°C) in fresh serum, a heat-stable (56°C) substance (or substances) is produced which acts directly as a chemotactic stimulus on the polymorphs. This heat-stable chemotactic substance is not produced when antibody-antigen complexes are incubated in serum which has been heated at 56°C for 30 minutes.
          Article 0 comments Cited 276 times – based on 0 reviews     Review now
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            Impaired leucocyte functions in diabetic patients.

            M Delamaire, D Maugendre, M. Moreno … (1997)
            This study evaluates polymorphonuclear neutrophil (PMN) cell performance in 61 diabetic patients free of infection (40 Type 1, 21 Type 2), using tests that explore all the functional steps of PMN: (1) adherence: expression of adhesion molecules, CD 11a, CD 11b, CD 11c; nylon fiber adherence test; (2) chemotaxis under agarose towards the bacterial oligopeptide FMLP and complement fractions, used as attracting agents; (3) phagocytosis of opsonized latex microbeads; (4) bactericidal activity: chemiluminescence assessment of the oxidative killing potential before and after stimulation by opsonized zymosan and PMA; nitroblue tetrazolium reduction test. Results were analysed according to potentially influential factors: metabolic control (HbA1C, glycaemia), age of patient, type of diabetes, disease duration, and existence of vascular complications. PMN chemotaxis was significantly lower in patients than in healthy controls (p < 0.001) and associated with spontaneous adherence and increased expression of adhesion molecules (CD 11b, CD 11c). The increased response to chemiluminescence reflects spontaneous activation of PMN cells and increased free radical production; after stimulation, response was lower than in controls. The type of diabetes, the age of patients, HbA1C level and disease duration did not affect the responses. Chemotaxis and chemiluminescence were further reduced in patients with vascular complications and hyperglycaemia. We conclude that all steps of PMN functioning are altered in diabetic patients, which may increase the risk of vascular complications and infectious episodes.
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              Prognosis and outcomes of patients with community-acquired pneumonia. A meta-analysis.

              M J Fine, M A Smith, C A Carson … (1996)
              To systematically review the medical literature on the prognosis and outcomes of patients with community-acquired pneumonia (CAP). A MEDLINE literature search of English-language articles involving human subjects and manual reviews of article bibliographies were used to identify studies of prognosis in CAP. Review of 4573 citations revealed 122 articles (127 unique study cohorts) that reported medical outcomes in adults with CAP. Qualitative assessments of studies' patient populations, designs, and patient outcomes were performed. Summary univariate odds ratios (ORs) and rate differences (RDs) and their associated 95% confidence intervals (CIs) were computed to estimate a summary effect size for the association of prognostic factors and mortality. The overall mortality for the 33,148 patients in all 127 study cohorts was 13.7%, ranging from 5.1% for the 2097 hospitalized and ambulatory patients (in six study cohorts) to 36.5% for the 788 intensive care unit patients (in 13 cohorts). Mortality varied by pneumonia etiology, ranging from less than 2% to greater than 30%. Eleven prognostic factors were significantly associated with mortality using both summary ORs and RDs: male sex (OR = 1.3; 95% CI, 1.2 to 1.4), pleuritic chest pain (OR = 0.5; 95% CI, 0.3 to 0.8), hypothermia (OR = 5.0; 95% CI, 2.4 to 10.4), systolic hypotension (OR = 4.8; 95% CI, 2.8 to 8.3), tachypnea (OR = 2.9; 95% CI, 1.7 to 4.9), diabetes mellitus (OR = 1.3; 95% CI, 1.1 to 1.5), neoplastic disease (OR = 2.8; 95% CI, 2.4 to 3.1), neurologic disease (OR = 4.6; 95% CI, 2.3 to 8.9), bacteremia (OR = 2.8; 95% CI, 2.3 to 3.6), leukopenia (OR = 2.5, 95% CI, 1.6 to 3.7), and multilobar radiographic pulmonary infiltrate (OR = 3.1; 95% CI, 1.9 to 5.1). Assessments of other clinically relevant medical outcomes such as morbid complications (41 cohorts), symptoms resolution (seven cohorts), return to work or usual activities (five cohorts), or functional status (one cohort) were infrequently performed. Mortality for patients hospitalized with CAP was high and was associated with characteristics of the study cohort, pneumonia etiology, and a variety of prognostic factors. Generalization of these findings to all patients with CAP should be made with caution because of insufficient published information on medical outcomes other than mortality in ambulatory patients.
              Article 0 comments Cited 198 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                : +44-1223-336844 , +44-1223-336846 , gavin.koh@gmail.com
                Journal
                Journal ID (nlm-ta): Eur J Clin Microbiol Infect Dis
                Title: European Journal of Clinical Microbiology & Infectious Diseases
                Publisher: Springer-Verlag (Berlin/Heidelberg )
                ISSN (Print): 0934-9723
                ISSN (Electronic): 1435-4373
                Publication date (Electronic): 30 July 2011
                Publication date PMC-release: 30 July 2011
                Publication date (Print): April 2012
                Volume: 31
                Issue: 4
                Pages: 379-388
                Affiliations
                [1 ]The Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK
                [2 ]Center for Experimental and Molecular Medicine (CEMM), Department of Infectious Diseases, Tropical Medicine & AIDS, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
                [3 ]Department of Infection and Tropical Medicine, Heartlands Hospital, Bordesley Green, Birmingham, UK
                [4 ]Department of Medicine, University of Cambridge, Box 157, Level 5, Addenbrooke’s Hospital, Cambridge, CB2 2QQ UK
                Article
                Publisher ID: 1337
                DOI: 10.1007/s10096-011-1337-4
                PMC ID: 3303037
                PubMed ID: 21805196
                SO-VID: e49a6965-8bf1-47f6-9fc3-717acb601f84
                Copyright © © The Author(s) 2011
                History
                Date received : 4 April 2011
                Date accepted : 21 June 2011
                Categories
                Subject: Review
                Custom metadata
                issue-copyright-statement © Springer-Verlag 2012

                ScienceOpen disciplines: Infectious disease & Microbiology
                Data availability:
                ScienceOpen disciplines: Infectious disease & Microbiology

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