Prognostic impact of lean diabetes mellitus on aortic stenosis

Abstract Background Obesity and type 2 diabetes mellitus (DM) has traditionally been thought to coexist. Lean DM is a distinct condition defined by body mass index (BMI) < 25, associated with elevated insulin resistance, rapid beta-cell failure, absence of ketosis and malnutrition. Lean DM has been linked to poor cardiovascular outcomes, but remains an understudied entity in valvular heart disease. Purpose This study aims to demonstrate the prognostic implications of lean DM on aortic stenosis (AS). Methods Between 2011 to 2021, 700 consecutive patients with index echocardiographic diagnoses of aortic stenosis were stratified into 4 groups, namely lean (BMI < 25) DM, lean non-DM, obese (BMI > 25) DM, and obese non-DM. Demographics, co-morbidities, echocardiographic findings and clinical outcomes were collected. Clinical outcomes were compared using Kaplan-Meier curves and a multivariate Cox regression model was constructed. Results 396 (56.6%) patients were female, and 435 (62.1%) patients were of Chinese ethnicity. 279 (39.9%) patients had DM, of whom 155 (55.6%) patients had lean DM. The mean BMI in the lean group was 21.4 ± 2.4 kg/m² compared to 29.5 ± 4.9 kg/m² in the obese group. Irregardless of BMI, higher proportions of DM patients were on baseline antiplatelets and statins compared to non-DM patients. Echocardiographically, obese DM had smaller indexed left ventricular volumes and mass - left ventricular end diastolic volume index (LVEDVi) (65.7 ± 21.7 ml/m² vs. 70.8 ± 23.6 ml/m², p = 0.002) and left ventricular mass index (LVMi) (115.7 ± 31.9 g/m² vs. 116.3 ± 36.5 g/m², p = 0.401) compared to lean DM respectively. Obese DM was associated with more cardiovascular risk factors compared to lean DM in terms of hypertension (91.9%, n = 114 vs. 89.0%, n = 138, p < 0.001), hyperlipidaemia (82.3%, n = 102 vs. 73.5%, n = 114, p < 0.001) and chronic kidney disease (50.8%, n = 62 vs. 45.5%, n = 70, p < 0.001). On the contrary, lean DM was associated with more cardiovascular sequelae of acute myocardial infarction (36.8%, n = 57 vs. 24.2%, n = 30, p < 0.001) compared to obese DM. AS patients with lean DM experienced the highest significant all-cause mortality (71%, n = 110 in lean DM vs. 58.9%, n = 73 in obese DM vs. 49.1%, n = 86 in obese non-DM vs. 65%, n = 160 in lean non-DM, p < 0.001) compared to all other groups. On the contrary, AS patients with lean DM had the lowest heart failure incidence (17.4%, n = 27 in lean DM vs. 23.4%, n = 29 in obese DM vs. 33.1%, n = 58 in obese non-DM vs. 23.2%, n = 57 in lean non-DM, p = 0.009). On multivariate analyses adjusted for age, comorbidities, and echocardiographic parameters, lean DM was an independent predictor of worse all-cause mortality in AS patients (HR 1.60, CI: 1.19 - 2.16, p = 0.010). Conclusion Lean DM in AS patients was associated with worse all-cause mortality. Lean DM was a prognostic marker of all-cause mortality in patients with AS.Figure 1