Global registry analysis identifies diabetes as an independent predictor of exacerbations, hospitalisation, and mortality in bronchiectasis.
Diabetes is emerging as one of the most important comorbidities in bronchiectasis, with new data from more than 30,000 patients, including over 600 Australians, showing that its presence is associated with more severe disease, greater healthcare utilisation, altered airway microbiology, and significantly increased mortality.
Researchers say the findings support incorporating diabetes into routine risk stratification models and management pathways for bronchiectasis.
Results of their study have been published in The Lancet Respiratory Medicine.
“These data highlight that patients with diabetes and bronchiectasis are a high-risk group,” the researchers wrote.
“These findings should be used to inform guidelines and monitoring of patients with a holistic multidisciplinary approach to patient care.
“Strict diabetes control is part of the management of cystic fibrosis, in part because of the recognition of diabetes as a common comorbidity in cystic fibrosis and the poor outcomes associated with cystic fibrosis-related diabetes.
“Findings from this study suggest that a similar relationship exists between diabetes and bronchiectasis, which could have implications for patient screening, management, and risk stratification.”
In what they said was the largest analysis of its kind, the researchers pooled data from four major bronchiectasis registries spanning 33 countries across Europe, Asia, and Australasia.
The study included 30,263 adults with CT-confirmed bronchiectasis, of whom 2487 (8.2%) had diabetes. Diabetes prevalence varied considerably between regions, ranging from 3.9% in China and 6.8% in Australia to 10.2% in Europe and 13.6% in India and neighbouring South Asian countries.
Patients with diabetes represented a clinically distinct phenotype. They were older, more likely to be male, more likely to have a history of smoking, and more likely to be overweight or obese than those without diabetes.
Almost one-third had a BMI of at least 30 kg/m², nearly double the proportion observed among patients without diabetes.
The presence of diabetes was associated with a markedly greater burden of multimorbidity.
Cardiovascular disease affected 53.5% of patients with diabetes compared with 21.8% of those without diabetes. COPD was present in 34.3% versus 19.0%, while asthma affected 27.5% versus 21.0%. Chronic renal failure was almost four times more common among patients with diabetes, and rates of stroke, osteoporosis, and malignancy were also significantly elevated.
Differences extended to the underlying causes of bronchiectasis. Patients with diabetes were more likely to have bronchiectasis associated with COPD, asthma, rheumatoid arthritis, and previous tuberculosis, while post-infective bronchiectasis and primary ciliary dyskinesia were less common.
The researchers suggested these associations may reflect shared inflammatory pathways, corticosteroid exposure, or broader interactions between chronic respiratory disease and metabolic dysfunction.
Across virtually every marker of disease severity, outcomes were worse in patients with diabetes, they found.
Median Bronchiectasis Severity Index scores were higher, indicating more advanced disease. Patients reported greater breathlessness, with almost 30% recording Medical Research Council dyspnoea scores of 3 or 4 compared with 16% of those without diabetes. Lung function was also significantly reduced, with lower median FEV1 and FVC values.
Recent disease activity was similarly increased. More than 42% of patients with diabetes had required at least one hospital admission during the previous year, compared with 37% of patients without diabetes.
Meanwhile, 27.6% experienced three or more exacerbations annually, reinforcing the link between diabetes and a more unstable disease course.
These differences translated into worse long-term outcomes. Follow-up data from more than 11,000 patients demonstrated that diabetes independently predicted future exacerbations, increasing annual exacerbation rates by 18%.
Hospitalisations were 57% more frequent among patients with diabetes, even after adjustment for age, sex, obesity, lung function, smoking history, cardiovascular disease, COPD, asthma, and chronic Pseudomonas infection.
The most striking finding was the impact on survival. During follow-up, 1077 deaths were recorded. Patients with diabetes had an 80% higher risk of all-cause mortality over five years compared with those without diabetes, a relationship that persisted after extensive adjustment for confounding factors.
The biological analyses provide potential clues to the mechanisms underlying these poorer outcomes. Routine sputum cultures showed significantly higher rates of Enterobacteriaceae, Moraxella catarrhalis, and Haemophilus influenzae among patients with diabetes.
Enterobacteriaceae have been increasingly recognised as clinically important pathogens in bronchiectasis and have been linked to more frequent exacerbations in several populations, the researchers said.
A detailed microbiome analysis of sputum samples from a representative subgroup revealed significant differences in overall microbial community structure according to diabetes status.
Although microbial diversity itself was not significantly reduced, patients with diabetes showed depletion of commensal organisms including Fusobacterium and Granulicatella and enrichment of Firmicutes-related taxa and Micrococcaceae species.
The findings suggested diabetes may influence the airway ecosystem in ways that favour chronic infection or inflammation.
Systemic inflammatory profiling identified elevated levels of galectin-4 and growth differentiation factor-15 in patients with diabetes.
Both biomarkers are well-established indicators of cardiovascular risk and adverse outcomes in diabetes, raising the possibility that cardiovascular and respiratory disease progression may be driven by overlapping inflammatory pathways.
Traditional neutrophilic inflammatory markers associated with severe bronchiectasis were not elevated, suggesting diabetes may contribute a distinct biological signature rather than simply amplifying established bronchiectasis inflammation.
The investigators also explored whether metformin therapy modified outcomes, prompted by emerging preclinical evidence suggesting potential disease-modifying effects in bronchiectasis.
However, no significant differences were observed in exacerbation rates, hospitalisation or mortality among patients receiving metformin. Likewise, outcomes were broadly similar between those with type 1 and type 2 diabetes, although the overwhelming majority had type 2 disease.
Related
Bronchiectasis management is increasingly shifting towards personalised risk-based treatment. Current European Respiratory Society guidance identifies several factors associated with poor outcomes and increased exacerbation risk, but diabetes is not presently included among them.
The researchers said that the consistency and magnitude of the observed associations now justified recognising diabetes as a major prognostic marker in bronchiectasis.
Future research should examine whether improved glycaemic control, newer antidiabetic agents such as GLP-1 receptor agonists, or targeted interventions addressing shared inflammatory pathways can alter the trajectory of disease in this vulnerable group.
The researchers noted the study had important limitations. Due to the observational nature of this work, there were missing data, particularly in sputum culture results, as these were dependent on the physician practices in different regions.
“Notably, data on patient treatments, diabetes type, and outcomes were not recorded in all regions, so these data are not necessarily generalisable to regions not included in these analyses,” they wrote.
“Aetiology was based on investigator opinion, which might result in inaccuracies. Although the datasets were designed to be interoperable from the outset, which is a major strength of this analysis, the conduct of individual registries was different as reflected by the scarcity of follow-up data in some registries.
“This could have resulted in some differences in data completeness or quality between registries. Within this analysis, and the registries, the geographical balance of patients was not even due to high recruitment in certain regions.”
Despite this, the consistency of results between registries suggested that this imbalance did have an undue impact on the conclusions reached, they wrote.
“Overall, in this analysis of four large international registries, we show that diabetes is consistently a high-risk comorbidity for patients with bronchiectasis,” they concluded.
“These findings support inclusion of diabetes as a risk factor in individualised risk assessment as promoted by the 2025 European Respiratory Society bronchiectasis guidelines. Further work is needed to optimise treatments for this high-risk group.”
