Association between Non-Alcoholic Steatohepatitis and Left Ventricular Diastolic Dysfunction in Type 2 Diabetes Mellitus

Abstract

Background: Impaired diastolic heart function has been observed in persons with non-alcoholic fatty liver disease (NAFLD) and/or with type 2 diabetes mellitus (T2DM). However, it is unclear whether NAFLD fibrotic progression, i.e., non-alcoholic steatohepatitis, poses an independent risk for diastolic dysfunction in T2DM. We investigated the association between liver fibrosis and left ventricular (LV) diastolic dysfunction in T2DM.

Methods: We analyzed 606 patients with T2DM, aged ≥50 years, who had undergone liver ultrasonography and pulsed-wave Doppler echocardiography. Insulin sensitivity was measured by short insulin tolerance test. Presence of NAFLD and/or advanced liver fibrosis was determined by abdominal ultrasonography and NAFLD fibrosis score (NFS). LV diastolic dysfunction was defined according to transmitral peak early to late ventricular filling (E/A) ratio and deceleration time, using echocardiography.

Results: LV diastolic dysfunction was significantly more prevalent in the NAFLD versus non-NAFLD group (59.7% vs. 49.0%, P=0.011). When NAFLD was stratified by NFS, subjects with advanced liver fibrosis exhibited a higher prevalence of diastolic dysfunction (49.0%, 50.7%, 61.8%; none, simple steatosis, advanced fibrosis, respectively; P for trend=0.003). In multivariable logistic regression, liver fibrosis was independently associated with diastolic dysfunction (odds ratio [OR], 1.58; 95% confidence interval [CI], 1.07 to 2.34; P=0.022) after adjusting for insulin resistance and cardiometabolic risk factors. This association remained significant in patients without insulin resistance (OR, 4.32; 95% CI, 1.73 to 11.51; P=0.002).

Conclusions: Liver fibrosis was associated with LV diastolic dysfunction in patients with T2DM and may be an independent risk factor for diastolic dysfunction, especially in patients without systemic insulin resistance.

Keywords: Diabetes mellitus, type 2; Diabetic cardiomyopathies; Heart failure; Insulin resistance; Non-alcoholic fatty liver disease.

Fig. 1. Prevalence of left ventricular diastolic dysfunction. (A) Prevalence according to sonographic grade of steatosis. (B) Prevalence according to presence of liver fibrosis predicted by non-alcoholic fatty liver disease fibrosis score. P for trend by chi-square test for linear-by-linear association. Pairwise comparisons corrected by Holm-Bonferroni method.

Fig. 2. Adjusted odds ratio for left ventricular diastolic dysfunction by presence of non-alcoholic fatty liver disease (NAFLD). (A) Multivariable logistic regression in all subjects. Model 1, unadjusted; model 2, adjusted for age, sex, and body mass index (BMI); model 3, further adjusted for hypertension, smoking status, diabetes mellitus duration, fasting glucose, triglyceride, high density lipoprotein cholesterol, and alanine transaminase; model 4, further adjusted for insulin resistance. (B) Subgroup analyses and their interactions with NAFLD. Multivariable logistic regression with full model (model 4). OR, odds ratio; CI, confidence interval; HbA1c, glycosylated hemoglobin.

Fig. 3. Adjusted odds ratio for left ventricular diastolic dysfunction by presence of liver fibrosis predicted by non-alcoholic fatty liver disease (NAFLD) fibrosis score. (A) Multivariable logistic regression in all subjects. Model 1, unadjusted; model 2, adjusted for age, sex, and body mass index (BMI); model 3, further adjusted for hypertension, smoking status, diabetes mellitus duration, fasting glucose, triglyceride, high-density lipoprotein-cholesterol, and alanine transaminase; model 4, further adjusted for insulin resistance. (B) Subgroup analyses and their interactions with liver fibrosis. Multivariable logistic regression with full model (model 4). OR, odds ratio; CI, confidence interval; HbA1c, glycosylated hemoglobin.