Diabetes is associated with reduced survival in controls but not in patients with idiopathic pulmonary arterial hypertension

Background

Idiopathic pulmonary arterial hypertension (IPAH) is a rare and progressive disease characterized by pulmonary vascular remodelling. As the age at diagnosis increases, comorbidities become more common, including diabetes mellitus (DM). Previous studies suggest that DM may be associated with more advanced pulmonary vascular disease and poorer outcomes in IPAH.

Purpose

Investigate the presence of DM in a nationwide cohort of patients with IPAH five years before and after diagnosis and assess the effect of DM on survival compared to a control population without PAH.

Methods

Retrospective observational case-control study including adult patients diagnosed with IPAH from the Swedish PAH registry 2008-2021. The control group consisted of five individuals per patient matched on sex, age and geographical area at the time of PAH patients’ diagnosis. The study was based on individual level data compiled from several interlinked Swedish national health data registries, data was available from five years before and after index (patient diagnose date). DM type 1 was defined as filled prescription of insulin (A10A) but no non-insulin DM-drugs (A10B) during the pre-index period; DM type 2 was defined as at least two prescription fills of non-insulin DM-drugs (A10B) during the pre-index period. The impact of IPAH and diabetes and their interaction on survival was tested with a Cox regression analysis (Hazard Ratio, HR (95% Confidence Interval, CI)) using age as time-scale with left truncation.

Results

The study comprised 394 patients with IPAH and 1970 controls. At index, prevalence of DM was three times higher in the IPAH group compared to controls (IPAH 29% vs. control 10%, p <0.001) (Figure 1). Patients with DM were younger than controls with DM (mean age 69±2 years vs. 71±1 years, p=0.037). DM was more common in men than women in both groups (IPAH: men 35% vs. women 23% and controls: men 12% vs. women 8%). Oral DM therapy was more frequent among controls (57% vs 48%) while combined oral and insulin therapy was more common in IPAH (22% vs 14%). DM type 1 was rare in both groups but nearly twice as common in IPAH compared to controls (1.3% vs. 0,8%).

Diagnosis of IPAH and diabetes were independently associated with reduced survival (HR 7.51 (CI 5.77–9.78) and HR 1.42 (CI 1.05–1.93), respectively) whereas their interaction was not. After stratification for disease status, diabetes remained associated with reduced survival in controls (HR 1.59 (CI 1.23–2.07)) but not in IPAH (HR 1.09 (CI 0.83–1.43)).

Conclusion

DM was three times more prevalent in patients with IPAH than in matched controls at diagnosis and this relative difference was seen already five years before diagnosis. The distribution of DM between sexes was comparable between groups. Despite a higher DM burden in IPAH, this did not adversely affect survival in IPAH, whereas in the control group, DM was associated with increased mortality.For image description, please refer to the figure legend and surrounding text.