Discussion
Diabetes mellitus has been frequently associated with respiratory infections. We performed a large cohort retrospective study that allowed detailed nationwide estimates of DM prevalence in CAP hospital admissions as well as comparisons to national DM prevalence in Portugal. We found a high burden of DM in patients hospitalized with CAP (25.9%), in agreement with the high rates obtained in previous studies of 21.4% and 16% performed elsewhere.12 ,18 The burden of DM increased over the period under analysis (2009–2012), similar to what was observed in a recent study estimating the burden of CAP, between 1997 and 2011, in the UK.19 In line with studies that suggest that patients with DM are at higher risk for CAP (reviewed in8), we observed that the DM prevalence in CAP admissions between 2009 and 2012 was consistently higher, and more than double, when compared to the estimations of the DM prevalence in Portugal (figure 2).
Figure 2Diabetes prevalence in CAP admissions and the general Portuguese population from 2009 to 2012. Diabetes prevalence in CAP admissions consistently progressed from 2009 to 2012, as compared to the general Portuguese population, in the age range 20–79 years. CAP, community-acquired pneumonia.
Our study covered admissions from all Portuguese public hospitals over a period of 4 years to analyze the impact of DM in CAP hospitalizations. We corrected our analyses for gender and age and excluded immunocompromised individuals. Nevertheless, these analyses have several inherent limitations. The data are derived from a database that did not contain direct clinical measures and we did not have access to clinical records. Therefore, we could not include in the analyses possible confounding factors, namely related to diabetes and CAP severity, therapies and vaccination, smoking history or lifestyles. We have also to take into account that diabetes is a frequent cause for hospitalization, and that this potential bias could overestimate the incidence of diabetes in respiratory infections and lead one to suspect that diabetes is a risk factor for susceptibility.20 In our study, case identification was based in medical record information following the international coding system that was applied by specifically trained medical staff in according a methodology that was previously validated.10 Thus, we reason that misclassification in the hospital discharge database is likely to be relatively small, although underestimation of diabetes in hospital settings has been reported elsewhere.21 Although we did not follow a study design specific to compare the target population with the general population,22 we consider that contrasting our results with the general population in Portugal will help to contextualize the burden of DM in hospitalized patients with CAP.
In agreement with two prospective studies in Spain12 ,18 we found that age distribution in CAP-DM patients was skewed to older ages as compared to CAP patients without DM, which reflects the age of DM onset. The median age of CAP admissions showed a trend to increase from 2009 to 2012, in accordance with Froes et al,10 which also reported a 5% increase in the average age of patients admitted with CAP between 2000 and 2009 in Portugal. As reported in other studies, CAP infections affected more men than women.10 ,12 ,18 Interestingly, the prevalence of diabetes among CAP admissions was higher in women than in men (25.1% vs 22.8%), as opposed to what is observed in the general population (10.2% vs 14.6%) (figure 3), suggesting a higher risk of women with DM to develop CAP infections.
Figure 3Gender differences in diabetes prevalence in 2009 in the general Portuguese population patients and in patients with CAP. Diabetes prevalence is higher in women as compare to men in CAP admissions but not in the general Portuguese population.
We found a longer length of stay in patients with CAP with DM, in line with other studies indicating significantly higher rates of hospitalization in patients with CAP-DM.11 ,12 This may be attributable to effects of diabetes mellitus in exacerbating underlying comorbidities, which is supported by the observation that in the young age range (20–39 years) patients with CAP-DM showed a higher length of stay (table 2). Indeed, Di Yacovo et al18 performed an observational analysis of a prospective cohort of immunocompetent hospitalized adults with CAP and found that patients with DM had distinctive clinical features. Patients with DM had more in-hospital acute metabolic complications18 and more severe pneumonia.12 ,23 Additionally, it has been shown that patients with CAP with diabetes have a higher frequency of other concomitant conditions,12 including chronic pulmonary diseases (eg, 32.6% in CAP with DM18 and 22% in pneumonia with DM23).
The impact of DM in hospital mortality (table 1) was mainly contributed by the 20–39 age group which showed higher mortality (table 2). This is in agreement with several other studies where patients with DM had a higher risk of death from CAP12 ,24 or from pneumonia.25 Kornum et al11 also reported that people with diabetes <40 years (15–39 years) were three times more likely to be hospitalized with pneumonia than individuals without diabetes of similar age, with the relative risk decreasing with ageing in individuals with DM. As expected, type 1 diabetes was over-represented in the youngest age group (20–39 years; 26.8%) as compared to the 40–59 and 60–79 age groups (3.3% and 1.4%, respectively). Nevertheless, individuals with type 1 diabetes in the youngest age group showed lower length of hospital stay (10.2±7.1 vs 11.2±11.6) and lower in-hospital mortality (4.2% vs 5.6%) than the total group with DM (type 1+type 2 diabetes), indicating that inclusion of patients with type 1 diabetes did not influence our analysis. On the other hand, we could not ascertain whether the severity of metabolic imbalances, namely ketoacidosis, would contribute to the observed increased mortality in young patients with diabetes.
Taken together, our nationwide results are in line with other reports, suggesting that patients with DM are at increased risk of CAP.8 ,9 ,11–14 This longitudinal study provides indications that patients with DM acquiring CAP are older, have a longer hospitalization time and have higher mortality rates as compared to patients with CAP without DM. Our study also highlights that the relative impact of diabetes was greatest in younger adults (20–39 years) and in women. Thus, this nationwide study identified people with DM as a priority group for adoption of general measures to prevent CAP (eg, smoking cessation and control of chronic illnesses), and more specifically for flu and prophylactic pneumococcal vaccination. These results have informative value for strategies of patient guidance and future healthcare policies, particularly in people with diabetes under 40 years and in women with DM.