Refining insights on type 2 diabetes and aortic valve replacement

Davis and colleagues' longitudinal Fremantle Diabetes Study Phase II study makes a pivotal contribution by demonstrating that type 2 diabetes doubles the risk of incident aortic valve replacement (AVR) with distal symmetrical polyneuropathy (DSPN) and intensive glucose-lowering therapy as key associates.1 Its strengths include rigorous age, sex and postcode matching, long-term follow-up from 2008 to 2021, and integration of competing risk models that address critical limitations of prior research and reinforce the clinical relevance of its findings. Several underdeveloped dimensions could further enhance the study's translational value and we aim to elaborate on targeted recommendations to address these aspects. Our core suggestions focus on three interconnected areas to deepen understanding and clinical applicability. First, subgroup stratification is essential as the study aggregates type 2 diabetes participants. Stratifying by diabetes duration, such as less than 5 years, 5–10 years and more than 10 years, would clarify whether AVR risk accumulates linearly or if thresholds exist. Distinguishing between glucose-lowering medication classes, such as sodium-glucose cotransporter 2 inhibitors versus insulin, could reveal if specific therapies modify valvular risk.2 Second, a mechanistic exploration of the DSPN-AVR association is needed beyond the common soil hypothesis.3 Investigating sarcopenia as a mediator, given its links to both DSPN and aortic stenosis progression,4 could identify modifiable targets like resistance training. Third, outcome granularity matters in distinguishing urgent versus elective AVR as the former carries a higher perioperative risk.5 Assessing post-AVR non-mortality outcomes, such as infections and renal dysfunction, would provide a more comprehensive view of the diabetes-related burden and guide perioperative management. These recommendations build on the study's robust foundation without undermining its core findings. By addressing subgroup-specific risk, mechanistic mediators and outcome detail, future research can refine risk stratification, identify targeted interventions and optimize personalized care for adults with type 2 diabetes at risk of severe valvular heart disease. Davis and colleagues' work rightly highlights the need for heightened clinical suspicion of aortic stenosis in older adults with type 2 diabetes, and these extensions will further strengthen its translational impact. Peng Liu and Xiaoyu He: conceptualization, writing—original draft. Zejun Song: conceptualization, writing—review and editing. None. The authors received no specific funding for this work. The authors declare that there are no conflicts of interest.