6-023 Is skeletal myosteatosis independently associated with exercise capacity in asymptomatic people with type 2 diabetes?

Introduction People living with Type 2 Diabetes (T2D) are 2.5 times at greater risk of developing heart failure (HF), particularly HF with preserved ejection fraction (HFpEF). Skeletal muscle composition, particularly fat infiltration (myosteatosis) is associated with reduced exercise capacity in HFpEF. We hypothesised that myosteatosis would be independently associated with maximal exercise capacity in asymptomatic people living with T2D. Methods Post-hoc pooled analysis of baseline data from two phase II prospective, randomised, open-label blinded endpoint trials: DIASTOLIC (NCT02590822) and LYDIA (NCT02043054) and comparison with healthy non-diabetic volunteers. Key inclusion criteria: adults aged 18–65 years with established T2D (>3 months), and BMI >30 kg/m2 (>27 kg/m2 for South Asian/ Black ethnicity). Key exclusion criteria: T2D duration >12 years, cardiovascular disease (history, signs, or symptoms), weight loss >5 kg in the preceding 6 months, and inability to exercise. A 1-minute incremental bicycle exercise test with expired gas analysis was used to quantify peak oxygen consumption (VO2). Cardiac magnetic resonance at 1.5T (Siemens, Germany) was performed to quantify left ventricular (LV) volumes, ejection fraction, and myocardial strain analysis. 2-point Dixon sequence at the lumbar region was performed and used to quantify paravertebral muscle mass and fat percentage across five 5mm slices. Cases and controls were compared using independent t-test, Mann-Whitney, and Chi-square tests. Associations between skeletal muscle parameters and peak VO2 were analysed using generalised linear regression, adjusted for age, sex, ethnicity, and BMI. Results One hundred and fifty participants with T2D were included and well-matched to the 36 healthy controls (table 1). T2D had higher BMI, evidence of concentric remodelling and poorer exercise capacity. Significantly higher skeletal myosteatosis was observed in T2D which remained significant after adjusting for covariates (p = 0.031). In T2D, paravertebral muscle volume was positively associated with peak VO2 on univariable analysis (β = 0.022, p = 0.001) and remained statistically significant after adjustment covariates (β =0.008, p< 0.043). Skeletal muscle fat percentage was inversely associated with peak VO2 on univariable analysis in T2D (β =-2.05, p<0.001) and remained independent after adjusting for covariates (β =-1.13, p <0.001). Conversely in healthy controls, whilst skeletal muscle fat percentage was inversely associated with peak VO2 in univariable analysis (β = -9.842, p < 0.001), this association did not remain significant after adjustment (β = -1.736, p= 0.568). Conclusion Skeletal myosteatosis is independently and inversely associated with maximal exercise capacity in people with T2D at risk of developing HF. Future research should explore strategies to reduce fat infiltration and assess the impact on exercise, cardiac function and clinical outcomes in T2D populations.