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  • The influence of pre-existing diabetes mellitus on the host immune response and outcome of pneumonia: analysis of two multicentre cohort studies

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Respiratory infection
The influence of pre-existing diabetes mellitus on the host immune response and outcome of pneumonia: analysis of two multicentre cohort studies
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  1. Sachin Yende1,2,
  2. Tom van der Poll3,
  3. MinJae Lee1,4,
  4. David T Huang1,2,5,
  5. Anne B Newman6,
  6. Lan Kong4,
  7. John A Kellum1,2,
  8. Tamara B Harris7,
  9. Doug Bauer8,
  10. Suzanne Satterfield9,
  11. Derek C Angus1,2,
  12. for the GenIMS and Health ABC study
  1. 1The Clinical Research, Investigation, and Systems Modeling of Acute Illness (CRISMA) Laboratory, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
  2. 2Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
  3. 3Center of Infection and Immunity Amsterdam (CINIMA) and Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
  4. 4Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
  5. 5Department of Emergency Medicine, University of Pittsburgh, Pennsylvania, USA
  6. 6Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
  7. 7Laboratory of Epidemiology, Demography and Biometry, National Institute on Ageing, Bethesda, Maryland, USA
  8. 8Department of Epidemiology and Biostatistics and Medicine, University of California, San Francisco, California, USA
  9. 9Department of Preventive Medicine, University of Tennessee, Memphis, Tennessee, USA
  1. Correspondence to Sachin Yende, CRISMA laboratory, Department of Critical Care Medicine, University of Pittsburgh, 642A Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15261, USA; yendes{at}upmc.edu

Abstract

Background Although diabetes mellitus is implicated in susceptibility to infection, the association of diabetes with the subsequent course and outcome is unclear.

Methods A retrospective analysis of two multicentre cohorts was carried out. The effect of pre-existing diabetes on the host immune response, acute organ function and mortality in patients hospitalised with community-acquired pneumonia (CAP) in the GenIMS study (n=1895) and on mortality following either CAP or non-infectious hospitalisations in the population-based cohort study, Health ABC (n=1639) was determined. Measurements included the mortality rate within the first year, risk of organ dysfunction, and immune responses, including circulating inflammatory (tumour necrosis factor, interleukin 6, interleukin 10), coagulation (Factor IX, thrombin–antithrombin complexes, antithrombin), fibrinolysis (plasminogen-activator inhibitor-1 and D-dimer) and cell surface markers (CD120a, CD120b, human leucocyte antigen (HLA)-DR, Toll-like receptor-2 and Toll-like receptor-4).

Results In GenIMS, diabetes increased the mortality rate within the first year after CAP (unadjusted HR 1.41, 95% CI 1.12 to 1.76, p=0.002), even after adjusting for pre-existing cardiovascular and renal disease (adjusted HR 1.3, 95% CI 1.03 to 1.65, p=0.02). In Health ABC, diabetes increased the mortality rate within the first year following CAP hospitalisation, but not after hospitalisation for non-infectious illnesses (significant interaction for diabetes and reason for hospitalisation (p=0.04); HR for diabetes on mortality over the first year after CAP 1.87, 95% CI 0.76 to 4.6, p=0.16, and after non-infectious hospitalisation 1.16, 95% CI 0.8 to 1.6, p=0.37). In GenIMS, immediate immune response was similar, as evidenced by similar circulating immune marker levels, in the emergency department and during the first week. Those with diabetes had a higher risk of acute kidney injury during hospitalisation (39.3% vs 31.7%, p=0.005) and they were more likely to die due to cardiovascular and kidney disease (34.4% vs 26.8% and 10.4% vs 4.5%, p=0.03).

Conclusions Pre-existing diabetes was associated with a higher risk of death following CAP. The mechanism is not due to an altered immune response, at least as measured by a broad panel of circulating and cell surface markers, but may be due to worsening of pre-existing cardiovascular and kidney disease.

  • Pneumonia

https://doi.org/10.1136/thx.2010.136317

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    Supplementary materials

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    Footnotes

    • Funding GenIMS was funded by NIGMS R01 GM61992 with additional support from GlaxoSmithKline for enrolment and clinical data collection, and Diagnostic Products Corporation for the cytokine assays. Health ABC was funded by NIA (N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106), NHLBI (R01HL74104) and NIAID (27913 and 39482). Health ABC was supported in part by the Intramural Research Program of the NIH, National Institute on Ageing. SY is supported by K23GM083215.

    • Competing interests None.

    • Ethics approval This study was conducted with the approval of the ethics committee at each participating site.

    • Provenance and peer review Not commissioned; externally peer reviewed.