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Influence of Renin-Angiotensin System Inhibitors on Lower Respiratory Tract Infections in Type 2 Diabetes: The Fremantle Diabetes Study Phase II

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posted on 02.07.2020 by Timothy M E Davis, Wendy A Davis
Objective: To determine whether angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) protect against lower respiratory tract infections complicating type 2 diabetes.

Research design and methods: Of 1,732 participants with diabetes recruited to the longitudinal observational Fremantle Diabetes Study Phase II (FDS2) between 2008 and 2011, 1,482 had confirmed type 2 diabetes (mean age of 65.8 years, 51.6% were males, median diabetes duration 9.0 years). All were followed for hospitalizations for/with, or deaths from, pneumonia/influenza ascertained from validated administrative data linkage from study entry to end-2016. Cox and competing risk regression were used to identify independent predictors of this outcome.

Results: Two-thirds of participants (n=982) were taking an ACEi and/or ARB at study entry (498 (33.6%) ACEi, 408 (27.5%) ARB, 76 (5.1%) both). During 9,511 person-years of follow-up (mean 6.4±2.0 years), 174 participants had incident pneumonia/influenza (156 hospitalizations, 18 deaths without hospitalization). In Cox regression analysis, baseline ACEi/ARB use was independently associated with a reduced risk of incident pneumonia/influenza (cause-specific hazard ratio (HR) (95% confidence interval) 0.64 (0.45, 0.89), P=0.008). Allowing for the competing risk of death did not change this finding (subdistribution HR 0.67 (0.48, 0.95), P=0.024), and similar reductions were seen for ACEi, ARB alone, and ACEi/ARB combination therapy. There was no significant change in use of ACEi/ARB during follow-up (interaction with ln(time), P=0.70). Other significant predictors of incident pneumonia/influenza were previously reported, clinically plausible variables.

Conclusions: ACEi/ARB reduce the risk of pneumonia/influenza in community-based people with type 2 diabetes.


The present study was funded by the National Health and Medical Research Council of Australia (project grants 513781 and 1042231). TMED is supported by a Medical Research Future Fund Practitioner Fellowship. The funding bodies had no involvement in the study design, data collection, analysis and interpretation of results or writing this manuscript.