Discussion
This population-based study showed that the incidence of all types of pneumonia analyzed was significantly higher in patients with T2DM than in patients with non-T2DM.
The incidence of CAP observed in our study is consistent with our earlier findings and with the findings of other authors.26 27 In the USA, among 46 237 subjects aged >65 years, it was found that patients with diabetes had a 1.52 (95% CI 1.29 to 1.78) higher risk of CAP than those without this disease.28 In Canada, the IRR for pneumonia was 1.46 times higher (95% CI 1.42 to 1.49) for patients with diabetes.12 In Denmark, a study found that T2DM increased the risk of pneumonia-related hospitalization 1.2-fold.11 They concluded that a longer duration of diabetes and poor glycemic control increase the risk of CAP-related hospitalization.11
The higher incidence of VAP and NV-HAP in patients with T2DM is consistent with previous Spanish reports.29 30 Karatas et al reported a 1.2-fold increased risk of VAP among diabetes sufferers.31 A longer duration of the disease and poor glycemic control have been associated with a greater risk of VAP, as described for CAP.32
Surgery is a well-established risk factor for pneumonia.33 34 A population-based study in Spain reported that patients with T2DM had a 1.21-fold higher risk (IRR, 1.21 95% CI 1.03 to 1.42) of suffering from postoperative pneumonia than those without diabetes and concluded that increased risk in patients with T2DM might be related to longer length of stay and higher rates of readmission.29
The use of non-invasive mechanical ventilation was higher in patients with diabetes admitted with CAP than in non-diabetic controls. In a study about mechanical ventilation use in 56 158 patients with CAP who received ventilator support, the authors found an increase in the prevalence of comorbidities over time that could partially explain the higher need for ventilatory support.35
We agree with other authors who found that mechanical ventilation was a strong risk factor for IHM in patients with diabetes with CAP and NV-HAP.26 29
Our study supports that patients with T2DM and CAP had significantly higher rates of dialysis use than control patients, and dialysis was a risk factor associated with IHM for the three types of pneumonia analyzed. Similar results have been reported previously, suggesting that altered immune function and greater healthcare contact make dialysis patients an especially susceptible risk group for any type of pneumonia.36 37
Regarding the pathogens isolated, S. pneumoniae was the most frequent infectious agent among patients with T2DM with CAP. It has been suggested that the increase in coverage of pneumococcal vaccination may in part reduce the role of this pathogen over time.38 In Spain, this vaccine is recommended and provided free of charge for T2DM sufferers and all subjects aged 65 years or older.39
Among patients with diabetes suffering VAP and NV-HAP, the most frequently isolated pathogens were Gram-negative bacteria, among which Pseudomonas was found in 3.97% of patients with VAP and 2.86% of patients with NV-HAP. Similar findings were reported by other authors.40 41
The mortality associated with pneumonia seems to be decreasing over time in Spain.42 Our study highlights key differences in IHM. The mortality rate in patients with T2DM with CAP was lower than that in matched controls, and no significant differences were found regarding VAP and NV-HAP in patients with T2DM. These results add important evidence to previous information which indicated that the presence of T2DM was not a risk factor for death during admission for CAP.43 Several studies have suggested that hyperglycemia or comorbid conditions and not diabetes itself are responsible for higher IHM after CAP and HAP.44 Another suggested explanation for the lower mortality among patients with diabetes after CAP is the obesity paradox.26 45 Furthermore, in our opinion, it is possible that patients with CAP and T2DM are admitted to the hospital and are not sent home with oral treatment more frequently than patients without diabetes with equal clinical severity. This would result in a selection bias that could partly explain the lower IHM among patients with T2DM.
As we expected, older age and comorbidity were factors associated with IHM for the three types of pneumonia analyzed. Different studies highlighted that elderly individuals frequently suffer comorbid conditions, which is a factor associated with poor prognosis.28 46 Another predictor of higher postoperative mortality was pressure ulcers in patients with CAP and NV-HAP. In the USA, a study using the National Inpatient Sample database from 2008 to 2012 found that among 670 767 patients with pressure ulcers, the pneumonia mortality rate was five times higher (OR 5.08, CI: 5.03 to 5.1; p<0.001) than that in patients without pressure ulcers.47
Female sex was a risk factor for mortality in patients with T2DM with VAP. Sharpe et al described that the incidence of CAP is lower among women than men, but when women have this disease, they have significantly higher IHM (24% vs 15%; p=0.009). Differences in the type of CAP could justify this finding.48 Similar results have been described by Ali et al, confirming the worse prognosis of female patients with VAP.49
Previous surgery was a factor associated with lower mortality in patients with VAP and NV-HAP. We think that patients with T2DM with older age and worse health status are possibly less likely to undergo surgery, which may have resulted in this association.
The strengths of this study included the use of comprehensive, nationwide, population-based register data. We used a case definition for pneumonia hospitalization with increased specificity by using POA as an indicator assigned according to the ICD-10-CM Guidelines.
Several limitations to our investigation must be considered. First, in our investigation we excluded patients under the age of 40 years. The reasons to do this is that according to data from the BDCAP, the SNHS2017 and a report by the Spanish Society of Epidemiology, the prevalence of T2DM becomes significant in adults aged 40 years or older.16 17 50 Prevalence figures for those below 40 years are under 1%.16–18 50 Furthermore, the prevalence of T1DM is higher than T2DM in subjects under 40 years; therefore, the risk of misclassification of a patient as T2DM when he really suffers T1DM is higher for those under 40 years. Finally, this age cut-off point has also been used by previous studies conducted to analyze pneumonia among patients with T2DM.26 29 30
Second, our data source (RAE-CMBD) is limited by the lack of laboratory or radiology results, treatments, such as information on oxygen or corticoids therapy and clinical characteristics of the pneumonias. Furthermore, we do not have information on duration of ventilatory support, days in the intensive care unit, vaccinations or severity of the respiratory disease.
Third, regarding the characteristics of diabetes, we lack information on disease duration, complications, glycemic control and specific treatment.
Fourth, in most cases of a pneumonia acquired during the hospital admission pathogens are not cultured. This has also been reported in a recent investigation from the USA where of 110 HAP in only 46 (42%) a pathogen was reported.6
In conclusion, the incidence rates of the three types of pneumonia were higher in patients with T2DM than in patients with non-T2DM. IHM was significantly lower among patients with T2DM with VAP than matched patients without diabetes, and no differences in IHM were found for CAP or NV-HAP.
Higher mortality rates in patients with diabetes with any pneumonia type were associated with increasing age, presence of comorbidity and dialysis. In patients with VAP, the risk of IHM was higher among females.