Between 2002 and 2009, 7400 patients with community acquired pneumonia were included in the German community acquired pneumonia competence network (CAPNETZ) registry. Of these, 509 were excluded because of missing information on death, leaving 6891 patients from 12 clinical centres throughout Germany for analysis (see supplementary figure 1). At the time of enrolment, 1114 (16.2%) patients had a diagnosis of diabetes. The mean age of participants was 59.8 (SD 18.5) years and 3805 (55.2%) were men. Table 1 provides an overview of the participants’ baseline characteristics and the hazard ratios of death within 90 days of admission for community acquired pneumonia. In total, 4671 (67.8%) participants were treated as inpatients.
Table 1 Baseline characteristics in 6891 patients with community acquired pneumonia and hazard ratio for death within 90 days after admission to hospital
Admission hyperglycaemia and mortality
Overall, 324 (4.7%) participants died within 28 days, 514 (7.5%) within 90 days, and 648 (9.4%) within 180 days. Overall mortality on days 28, 90, and 180 was significantly higher in participants with diabetes than without diabetes (day 90: 14.5% v 6.1%; crude hazard ratio 2.47, 95% confidence interval 2.05 to 2.98; P<0.001). Mortality increased according to CRB-65 score (P<0.001). Being male and having comorbidities were also associated with increased mortality within 90 days (P<0.001). Table 1 shows crude associations between mortality within 90 days and patient baseline characteristics.
Higher serum glucose levels were associated with increased mortality in all patients (P for trend <0.001). Compared with patients with normal serum glucose concentrations (4-5.99 mmol/L), mortality within 90 days increased in a stepwise manner in those with glucose concentrations of 6-10.99 mmol/L (crude hazard ratio 2.89, 95% confidence interval 2.27 to 3.69), 11-13.99 mmol/L (4.01, 2.78 to 5.81), and ≥14 mmol/L (6.04, 4.18 to 8.74); fig 1).
Fig 1Cumulative incidence of death (%) within 90 days in participants with community acquired pneumonia stratified by serum glucose levels on admission overall (n=6016) (top) and without diabetes (n=5141) (bottom). The 875 participants with missing (more ...)
Participants without diabetes on admission showed a clear trend towards an increasing mortality after 90 days with higher than normal serum glucose levels on admission. This observation was highly significant (P for trend <0.001; fig 1).
Participants without diabetes and normal serum glucose levels had the lowest mortality (3%) after 90 days (fig 2), whereas the mortality rate in those without diabetes but with high serum glucose levels was 10% (adjusted hazard ratio 1.72, 95% confidence interval 1.33 to 2.23) and those with diabetes was 14% (1.88, 1.42 to 2.47). Although the risk of mortality from community acquired pneumonia was significantly higher in patients with than without diabetes, the relation between glucose levels on admission and mortality was not significant in this cohort (P=0.18). Generally, low serum glucose levels (<4 mmol/L) were not associated with mortality in participants without diabetes (hazard ratio 0.68, 95% confidence interval 0.33 to 1.42).
Fig 2Cumulative incidence of death (%) within 90 days in participants with community acquired pneumonia with and without pre-existing diabetes (top) and without diabetes but stratified according to high or low serum glucose levels on admission (more ...)
The association between hyperglycaemia on admission and mortality was also evident up to day 28. Participants with increased serum glucose levels on admission were more likely to die within the first 28 days after admission than those with normal serum glucose levels (adjusted P for trend <0.001). Supplementary table 1A shows that participants with diabetes had a higher 28 day mortality than those without diabetes (P=0.042). Compared with participants with normal serum glucose levels and without pre-existing diabetes, the adjusted hazard ratio for death within 28 days after admission in those with diabetes was 1.92 (95% confidence interval 1.34 to 2.75) and in those with hyperglycaemia without diabetes was 1.71 (1.22 to 2.40; P for trend 0.001). The same applied to 90 day mortality for the previously used cut-offs for increased fasting and the cut-offs for increased post-prandial serum glucose levels (see supplementary table 2). Table 2 summarises the multivariable hazard ratios of overall mortality in participants with and without diabetes. Analyses of mortality up to 28 days and up to 180 days showed the same associations with serum glucose levels as the main analyses of 90 day mortality (see supplementary tables 1A-C).
Table 2 Mortality after 90 days, comorbidities, and baseline characteristics of participants with and without diabetes mellitus (n=6870)
Mortality in participants with diabetes
Estimates for the cumulative incidence of death within 90 days were significantly higher in participants with than without diabetes (P<0.001). After adjustment for baseline covariates, overall mortality was significantly higher in participants with diabetes (adjusted hazard ratio 1.26, 95% confidence interval 1.04 to 1.54; P=0.022). The adjusted hazard ratio for mortality up to 28 days was 1.29 (95% confidence interval 1.01 to 1.65; P<0.001) and up to 180 days was 1.29 (1.08 to 1.54, see supplementary tables 1A-C). Figure 3 shows a higher mortality in participants with diabetes, regardless of serum glucose level on admission, and without diabetes with high serum glucose levels (≥6 mmol/L) on admission. Increases in mortality appeared higher in participants with diabetes in crude analyses but of a similar magnitude in adjusted analyses.
Fig 3Crude and adjusted analyses of cohorts with the highest mortality. Results from all 6891 participants after multiple imputation
CRB-65 and serum glucose levels on admission
In an analysis stratified according to CRB-65 score as a measure of pneumonia severity, serum glucose levels were associated with mortality in participants with a low CRB-65 score (0 points, see supplementary figure 3A) and moderate scores (1 or 2 points, see supplementary figure 3B), but not in those with high scores (3 or 4 points, see supplementary figure 3C). Tests for interaction between trends across serum glucose levels and severity of pneumonia and association with serum glucose levels were borderline positive (see supplementary table 3 for the corresponding hazard ratios across serum glucose levels).
Supplementary table 4 and figure 4 present the results from landmark analyses with a cut-off at 28 days. The association of mortality with serum glucose levels was driven by short term mortality up to 28 days, with statistical trends observed for corresponding P values for interaction with time (0 to 28 days v 29 to 90 days).
Examination of data missingness
Overall, 509 of 7400 participants (6.8%) were excluded from the analysis owing to missing information on vital status. Such participants tended to have a higher CRB-65 score (36% scored 0 or 1 v 72% in complete cases), and a higher proportion had diabetes (26% v 16%), congestive heart failure (31% v 18%), and cerebrovascular disease (35% v 10%) compared with those with complete information on mortality (see supplementary table 5). Among the remaining 6891 patients, 875 (12.7%) had no information on serum glucose levels on admission and 21 (0.3%) had no information on baseline diabetes status. Information on CRB-65 scores was missing for 749 participants (10.9%). Thirty one participants had data missing on chronic respiratory tract disease, 39 on malignant tumour, 33 on chronic liver disease, 30 on congestive heart failure, 29 on cerebrovascular disease, 34 on chronic renal disease, and 163 on smoking status. Differences in missingness according to vital status were found for current smoking (64 (12%) in participants who survived up to 90 days v 99 (1.6%) in participants who died) and for serum glucose levels (48 (9%) v 827 (13%), respectively). Participants with missing data on current smoking had higher CRB-65 scores (P<0.001) and a shorter survival time (P<0.001), whereas the opposite was found for serum glucose levels (P<0.001 and P=0.046, respectively). Complete datasets to assess the severity of community acquired pneumonia by calculating severity scores (CRB-65) were available for 6142 of the participants (89%), and severity of community acquired pneumonia was distributed: 40% with 0 points, 41% with 1 point, 15.5% with 2 points, 3.2% with 3 points, and 0.3% with 4 points. Overall mortality on day 90 was 7.5%.
In total, 5231 (71%) participants had complete data on covariates. Supplementary table 6 compares these participants with those with incomplete data on covariates. Supplementary table 7 reports results of a complete case analysis in these 5231 participants.