title: Effect of hyperglycaemia on inflammatory and stress responses and clinical outcome of pneumonia in non-critical-care inpatients: results from an observational cohort study.
abstract: OBJECTIVE
  Despite the condition's high prevalence, the influence of hyperglycaemia on clinical outcomes in non-critical-care inpatients with infections remains ill defined. In this study, we analysed associations of glucose levels at admission and during initial inpatient treatment with the inflammatory response and clinical outcome in community-acquired pneumonia (CAP) patients.
  
  
  METHODS
  This secondary observational analysis included 880 confirmed CAP patients. We used severity-adjusted multivariate regression models to investigate associations of initial and 96 h mean glucose levels with serially measured biomarker levels over 7 days (C-reactive protein [CRP], procalcitonin, white blood cell count [WBC], pro-adrenomedullin [ProADM]) and adverse clinical course (death and intensive-care unit admission).
  
  
  RESULTS
  In the 724 non-diabetic patients (82.3% of the study population), moderate or severe hyperglycaemia (glucose 6-11 mmol/l and >11 mmol/l, respectively) was associated with increased risk for adverse clinical course (adjusted OR [95% CI] 1.4 [0.8, 2.4] and 3.0 [1.1, 8.0], respectively) and with higher CRP, WBC and ProADM levels over 7 days (p < 0.05, ANOVA, all days). In diabetic patients (n = 156), no similar associations were found for initial hyperglycaemia, although mean 96 h glucose levels  ≥ 9 mmol/l were associated with adverse clinical course (adjusted OR 5.4 [1.1, 25.8]; p = 0.03). No effect modification by insulin treatment was detected (interaction terms p > 0.2 for all analyses).
  
  
  CONCLUSIONS
  Initial hyperglycaemia in non-diabetic CAP patients, and prolonged hyperglycaemia in diabetic or non-diabetic CAP patients, are associated with a more pronounced inflammatory response and CAP-related adverse clinical outcome. Optimal glucose targets for insulin treatment of hyperglycaemia in non-critical-care settings should be defined.
authors.affiliation: University Department of Internal Medicine, Kantonsspital Aarau, Tellstrasse, 5001, Aarau, Switzerland, schuetzph@gmail.com.
authors.forename: Philipp
authors.initials: P
authors.lastname: Schuetz
authors.forename: Natalie
authors.initials: N
authors.lastname: Friedli
authors.forename: Eva
authors.initials: E
authors.lastname: Grolimund
authors.forename: Alexander
authors.initials: A
authors.lastname: Kutz
authors.forename: Sebastian
authors.initials: S
authors.lastname: Haubitz
authors.forename: Mirjam
authors.initials: M
authors.lastname: Christ-Crain
authors.forename: Robert
authors.initials: R
authors.lastname: Thomann
authors.forename: Werner
authors.initials: W
authors.lastname: Zimmerli
authors.forename: Claus
authors.initials: C
authors.lastname: Hoess
authors.forename: Christoph
authors.initials: C
authors.lastname: Henzen
authors.forename: Beat
authors.initials: B
authors.lastname: Mueller
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism*; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000378:metabolism; D002116:Calcitonin / Q000097:blood; D015740:Calcitonin Gene-Related Peptide; D017714:Community-Acquired Infections / Q000097:blood; D003920:Diabetes Mellitus / Q000097:blood / Q000276:immunology*; D005260:Female; D006760:Hospitalization; D006801:Humans; D006943:Hyperglycemia / Q000097:blood* / Q000276:immunology; D007249:Inflammation / Q000097:blood* / Q000276:immunology; D007958:Leukocyte Count; D008297:Male; D011014:Pneumonia / Q000097:blood* / Q000188:drug therapy / Q000276:immunology; D011379:Prognosis; D011446:Prospective Studies; D011498:Protein Precursors / Q000097:blood; D016032:Randomized Controlled Trials as Topic; D013312:Stress, Physiological / Q000276:immunology*
chemical_list: D000900:Anti-Bacterial Agents; D015415:Biomarkers; D001786:Blood Glucose; C000606589:CALCA protein, human; D011498:Protein Precursors; D002116:Calcitonin; D002097:C-Reactive Protein; D015740:Calcitonin Gene-Related Peptide