{
  "abstract": "Introduction Type 2 diabetes (T2D) is a significant risk factor for the development of heart failure with preserved ejection fraction (HFpEF). Liver fat accumulation has been hypothesised to promote systemic inflammation that can lead to adverse cardiac remodelling. We aimed to explore the putative role of hepatic fat on cardiac remodelling in adults with obesity and T2D.Methods This is a secondary analysis of the DIASTOLIC trial ( NCT02590822). Adults with obesity and T2D free of symptomatic cardiovascular disease were randomised to receive either routine care, exercise regime or a low-calorie meal replacement plan over 12-weeks. Participants across treatment arms were pooled for this analysis. Prior to randomisation those with T2D were compared to healthy controls for case-control analysis. Hepatic fat was quantified using 2-point Dixon fat-water magnetic resonance imaging (MRI). Cardiac MRI was conducted on a 1.5T platform for assessment of cardiovascular structure and function. Changes in (Δ) liver fat and cardiovascular parameters were calculated as difference between week 12 and baseline. Generalised linear modelling was performed to determine associations between Δ liver fat and Δ cardiovascular parameters. Model 1 adjusted for the baseline dependent variable and model 2 further adjusted for Δ BMI.Results Sixty-eight participants with T2D (58% male, 61% White European) completed the 12-week intervention period with quantification of liver fat. Prior to randomisation, participants with T2D were obese, dysglycaemic and had a high burden of metabolic dysfunction-associated steatotic liver disease. Compared to controls those with T2D had evidence of stage B heart failure with smaller chamber sizes, higher LV mass/volume, diastolic dysfunction and increased cardiac output (CO), stroke volume (SV) and aortic stiffness. After 12-weeks of intervention, participants had a mean liver fat reduction of 4.8%, weight loss of 5.6kg, reduced SV, CO, aortic stiffness and increased LV end diastolic and systolic volume indices ( table 1). In model 1, liver fat reduction was associated with an increased end systolic volume index and reduced CO and SV indices. After adjustment for Δ BMI, the relationship between liver fat reduction and reduction in CO and SV indices persisted (table 2); additionally, hepatic fat reduction was significantly associated with a reduction in aortic velocity (table 2).Conclusions This cohort of participants with obesity and T2D demonstrated signs of stage B HF prior to randomisation and had evidence of high resting CO state, a phenomenon observed in obesity and advanced liver disease HFpEF phenotypes. Liver fat reduction was associated with normalisation of CO and SV independent of changes in BMI. This suggests accumulation of liver fat contributes to adverse haemodynamic changes which in turn may promote increased myocardial workload, diastolic pressures and LV hypertrophy and amelioration of liver fat may reverse these changes.Abstract 5-027 Table 1Key parameter levels demonstrated pre- and post-intervention Parameters Baseline Post-intervention Mean change (95% CI) Weight (kg) 103 ± 15.9 97.3 ± 15.4 5.62 (4.11, 7.13) Systolic blood pressure (mmHg) 140 ± 15.5 133 ± 15.5 6.88 (3.38, 10.37) HbA1c (%) 7.3 ± 1.03 6.9 ± 1.09 0.37 (0.18, 0.56) Liver fat (%) 16.2 ± 9.75 11.4 ± 8.87 4.83 (2.75, 6.91) Cardiac output index (L/min/m²) 3.37 ± 0.59 3.14 ± 0.62 0.24 (0.082, 0.39) Stroke volume index (mL/m2) 45.79 ± 7.07 45.72 ± 8.13 0.077 (-1.13, 1.29) LV mass/volume 0.84 ± 0.12 0.82 ± 0.12 0.009 (-0.009, 0.027) LV EDVi (mL/m2) 67.4 ± 10.1 69.8 ± 12.9 -2.15 (-3.66, -0.64) LV ESVi (mL/m2) 21.7 ± 6.44 24.1 ± 7.0 -2.26 (-3.45, -1.07) All data is presented as a mean ± standard deviation; LV = left ventricular; EDVi = end diastolic volume index; ESVi = end systolic volume indexAbstract 5-027 Table 2Multiple linear regression model demonstrating associations between Δ liver fat and Δ cardiac parameters adjusting for the baseline levels of the dependent variable being tested and Δ BMI Δ Liver fat (independent variable) Dependent variable β coefficient 95% CI p value Δ LV end systolic volume index -0.060 -0.224, 0.103 0.471 Δ LV stroke volume index 0.178 0.009, 0.348 0.039* Δ LV ejection fraction 0.078 -0.093, 0.249 0.371 Δ LV cardiac output index 0.021 0.002, 0.039 0.026* Δ Peak filling rate index 1.47 -0.044, 2.99 0.057 Δ Aortic pulse wave velocity 0.050 0.018, 0.082 0.002* LV = left ventricularAbstract 5-027 Figure 1Scatter plots semonstrationg the relationship between change in (Δ) liver fat and (a) Δ cardiac output index and (b) Δ strike volume. Further along the x and y axes demonstractes a greater reduction in Δ liver fat, Δ cardiac output index and Δ stoke volume respectively",
  "authors": [
    {
      "affiliations": [
        "Department of Cardiovascular Sciences, University of Leicester and the National Institute of Health Research (NIHR) Leicester Biomedical Research Centre, Leicester, UK"
      ],
      "name": "P Ramesh"
    },
    {
      "affiliations": [
        "Department of Cardiovascular Sciences, University of Leicester and the National Institute of Health Research (NIHR) Leicester Biomedical Research Centre, Leicester, UK"
      ],
      "name": "L Althagafi"
    },
    {
      "affiliations": [
        "Department of Cardiovascular Sciences, University of Leicester and the National Institute of Health Research (NIHR) Leicester Biomedical Research Centre, Leicester, UK"
      ],
      "name": "Kelly Parke"
    },
    {
      "affiliations": [
        "Diabetes Research Centre, NIHR Leicester Biomedical Research Centre, Leicester, UK"
      ],
      "name": "MJ Davies"
    },
    {
      "affiliations": [
        "Department of Cardiovascular Sciences, University of Leicester and the National Institute of Health Research (NIHR) Leicester Biomedical Research Centre, Leicester, UK"
      ],
      "name": "GS Gulsin"
    },
    {
      "affiliations": [
        "Department of Cardiovascular Sciences, University of Leicester and the National Institute of Health Research (NIHR) Leicester Biomedical Research Centre, Leicester, UK"
      ],
      "name": "GP McCann"
    },
    {
      "affiliations": [
        "Department of Cardiovascular Sciences, University of Leicester and the National Institute of Health Research (NIHR) Leicester Biomedical Research Centre, Leicester, UK"
      ],
      "name": "EM Brady"
    }
  ],
  "title": "5-027 Liver fat reduction is associated with favourable haemodynamic changes in adults with obesity and type 2 diabetes: a secondary analysis of the DIASTOLIC randomised controlled trial",
  "uid": "0139f02e-6b43-5e07-9b0b-0528c1e37176"
}