Association of hepatic steatosis with subclinical cardiac dysfunction in asymptomatic people with type 2 diabetes

Abstract Introduction Non-alcoholic fatty liver disease is highly prevalent among people with type 2 diabetes (T2D) and is an emerging risk factor for heart failure with preserved ejection fraction (HFpEF). Whether excess liver adiposity is simply a marker of the coexisting adverse cardiometabolic risk profile or independently contributes to the development of HFpEF is unclear. Purpose To assess the association between liver fat fraction and subclinical cardiac dysfunction in adults with T2D. Methods Prospective cross-sectional study. Two-hundred and thirty-eight adults with T2D (mean age 63±7 years, 62% males, HbA1c 7.2±1.5%, diabetes duration 10±8 years) with no signs, symptoms, or evidence of cardiovascular disease and 40 age-, sex-, and ethnicity-matched non-diabetic controls (mean age 61±8 years, 63% males, HbA1c 5.2±1.2%) underwent comprehensive phenotyping with echocardiography and multiparametric cardiac MRI including adenosine stress and rest perfusion. Volumetric liver fat fraction (VLFF) was measured using a histologically validated, proprietary MRI technique blinded to all participant details. Inter-study reproducibility was assessed in participants (n=28) who underwent a repeat MRI within two weeks. Linear regression analysis was performed to assess any independent associations between VLFF and identified markers of subclinical cardiac dysfunction in subjects with T2D. Results People with T2D had evidence of concentric left ventricular (LV) remodelling (higher LV mass/volume), extracellular matrix expansion (higher ECV fraction), both systolic and diastolic dysfunction (lower global longitudinal systolic strain and E/A ratio, respectively), and coronary microvascular dysfunction (lower myocardial perfusion reserve) (Table 1). VLFF demonstrated excellent inter-study reproducibility with an intra-class correlation coefficient (ICC) of 0.988 (0.974–0.994). T2Ds had higher VLFF compared to controls [7.5 (3.8–13.7)% vs 2.9 (1.7–4.7)%, p<0.001]. In multivariable regression analysis adjusting for age, sex, ethnicity, body mass index, ambulatory systolic blood pressure, HbA1c, and low-density lipoprotein, VLFF (β=−0.161, p=0.027) was independently associated with E/A, but not other imaging measures of subclinical cardiac dysfunction. Conclusion Liver fat fraction is elevated in people with T2D and is independently associated with early LV diastolic dysfunction. These results add to the growing evidence that ectopic fat plays an important role in the pathogenesis of HFpEF and may be a potential target for intervention. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): National Institute for Health Research (NIHR) United Kingdom through a Research Professorship award (RP-2017-08-ST2-007).British Heart Foundation through a Clinical Research Training Fellowship (FS/16/47/32190).