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Additive effect of metabolic dysfunction-associated fatty liver disease on left ventricular function and global strain in type 2 diabetes mellitus patients: a 3.0 T cardiac magnetic resonance feature tracking study

Cardiovascular Diabetology volume 23, Article number: 317 (2024) Cite this article

Abstract

Background

Type 2 diabetes mellitus (T2DM) and metabolic-associated fatty liver disease (MAFLD) are both metabolic disorders that negatively impact the cardiovascular system. This study comprehensively analyzed the additive effect of MAFLD on left ventricular function and global strain in T2DM patients by cardiac magnetic resonance (CMR).

Methods

Data of 261 T2DM patients, including 109 with and 152 without MAFLD, as well as 73 matched normal controls from our medical center between June 2015 and March 2022 were retrospectively analyzed. CMR-derived parameters, including LV function and global strain parameters, were compared among different groups. Univariate and multivariate linear regression analyses were conducted to investigate the impact of various factors on LV function and global strain.

Results

Our investigation revealed a progressive deterioration in LV functional parameters across three groups: control subjects, T2DM patients without MAFLD, and T2DM patients with MAFLD. Statistically significant increases in left ventricular end-diastolic volume index (LVEDVI), left ventricular end-systolic volume index (LVESVI), left ventricular mass index (LVMI) were observed, along with decreases in left ventricular ejection fraction (LVEF) and left ventricular global function index (LVGFI). Among these three groups, significant reductions were also noted in the absolute values of LV global radial, circumferential, and longitudinal peak strains (GRPS, GCPS, and GLPS), as well as in peak systolic (PSSR) and peak diastolic strain rates (PDSR). MAFLD was identified as an independent predictor of LVEF, LVMI, LVGFI, GRPS, GCPS, and GLPS in multivariate linear analysis. Besides, the incidence of late gadolinium enhancement was higher in MAFLD patients than in non-MAFLD patients (50/109 [45.9%] vs. 42/152 [27.6%], p = 0.003). Furthermore, escalating MAFLD severity was associated with a numerical deterioration in both LV function parameters and global strain values.

Conclusions

This study thoroughly compared CMR parameters in T2DM patients with and without MAFLD, uncovering MAFLD’s adverse impact on LV function and deformation in T2DM patients. These findings highlight the critical need for early detection and comprehensive management of cardiac function in T2DM patients with MAFLD.

Background

Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disorder characterized by hyperglycemia due to insulin resistance or inadequate insulin secretion [1]. Concurrently, metabolic-associated fatty liver disease (MAFLD), previously known as non-alcoholic fatty liver disease (NAFLD), has emerged as the most common liver disorder globally, often co-existing with T2DM [2]. Noticeably, both T2DM and MAFLD are recognized for their profound impact on cardiovascular health, with an increasing body of evidence linking them to a higher risk of developing cardiovascular diseases [3, 4].

In addition to individual impacts of T2DM and MAFLD on cardiovascular health, the synergistic relationship between T2DM and MAFLD exacerbates cardiovascular risk, potentially leading to a deterioration in cardiac function and structure due to their combined metabolic and inflammatory pathways [5]. Previous studies have shown that the coexisting of NAFLD or MAFLD in patients with T2DM was associated with an aggravated risk of a series of cardiac disease, including heart valve calcification [6], heart block [7], ventricular arrhythmias [8], sympathetic/parasympathetic imbalance [9], impaired myocardial glucose uptake [10]. In addition, a review integrating ten echocardiographic studies revealed that NAFLD is a sign of left ventricular (LV) diastolic dysfunction in T2DM patients [11].

Cardiac Magnetic Resonance (CMR), with its advanced imaging capabilities and myocardial feature tracking technology, offers a unique opportunity to assess cardiac function and detect subtle myocardial damage not visible with traditional imaging modalities [12]. Prior studies leveraging CMR have provided insights into the cardiovascular implications of T2DM and other metabolic disorders individually [13,14,15,16,17], but there remains a gap in our understanding of how MAFLD, combined with T2DM, affects LV function and global peak strain.

Therefore, the current study aims to bridge this knowledge gap by employing CMR to evaluate the additive effect of MAFLD on LV function and global strain in T2DM patients.

Methods

Study population

This study retrospectively enrolled patients diagnosed with T2DM following the American Diabetes Association guidelines [18], who underwent CMR examinations and non-enhanced abdominal computed tomography at our hospital between June 2015 and March 2022. We excluded individuals diagnosed with Type 1 Diabetes Mellitus, those who had previously received coronary artery bypass grafting or stenting, had primary cardiomyopathy, severe aortic or mitral valve diseases, congenital heart disease, severe renal dysfunction with an estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73m2, any contraindications to CMR examination, poor CMR image quality, or incomplete clinical records. MAFLD is defined as hepatic steatosis accompanied by one or more of the following conditions: overweight or obesity, type 2 diabetes mellitus (T2DM), or metabolic disorders such as insulin resistance, dyslipidemia, or hypertension [19, 20]. Hepatic steatosis was identified by liver attenuation values less than 40 HU or at least 10 HU lower than those of the spleen, as diagnosed by non-enhanced abdominal computed tomography (CT). The severity of MAFLD in our study was classified based on these hepatic steatosis criteria. Moderate to severe hepatic steatosis was characterized by spleen-to-liver attenuation ratios greater than 1.1 [21,22,23]. Ultimately, 261 patients with T2DM (median age: 59 years, IQR: 51–66 years) were included in the current study and was divided into two groups: T2DM without MAFLD (N = 152, 58.2%) or with MAFLD (N = 109, 41.8%). To assess the influence of MAFLD severity on LV global peak strain, individuals diagnosed with T2DM and MAFLD were divided into two groups: those with mild MAFLD (N = 76) and those with moderate to severe MAFLD (N = 33).

We retrospectively included 73 subjects aged 40 and above to serve as the control group, as over 90% of the T2DM patients in this study were over 40 years old. The inclusion criteria for these controls included the absence of T2DM or impaired glucose tolerance, no history of diseases that could compromise cardiac function (e.g., cardiomyopathy, coronary heart disease, valvular heart disease, hypertension, or systemic diseases), and no abnormalities on CMR imaging such as decreased left ventricular ejection fraction (LVEF), abnormal ventricular motion, or perfusion defects. Additionally, individuals with MAFLD were also excluded. The Biomedical Research Ethics Committee of our hospital approved the study protocol. Due to the study’s retrospective design, the requirement for written informed consent was waived.

Clinical characteristics and laboratory data collection

The clinical characteristics of T2DM patients with and without MAFLD, including gender, age, body mass index (BMI), body surface area (BSA), resting heart rate, blood pressure, smoking history, diabetes duration, and the use of antidiabetic and lipid-lowering medications, were extracted from the hospital’s medical records. Additionally, laboratory data such as glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST), hemoglobin (HGB), total protein, albumin, eGFR, and serum creatinine levels were also obtained. All laboratory data were obtained from the hospital’s digital medical records conducted by big data center, ensuring consistency in data sources. Each medical record was independently reviewed by two radiologists to ensure accuracy and consistency.

CMR protocol

All participants in this study were scanned using a 3.0 T MAGNETOM Trio Tim or MAGNETOM Skyra whole-body scanner (Siemens Medical Solutions, Erlangen, Germany) equipped with a 32-channel body phased-array coil, positioned supine. According to an article published in JACC Cardiovasc Imaging, the difference in MR vendor had no effect on the cardiac magnetic resonance feature tracking (CMR-FT) strain measurements [24]. All participants underwent CMR imaging using the same standardized protocol, ensuring uniformity in data collection. All participants had their T2DM and MAFLD diagnoses at similar stages relative to their CMR examinations, with the time between T2DM diagnosis and CMR imaging being within three months for all individuals. CMR data collection was facilitated by a standard ECG-triggering device during a breath-hold. Cine images capturing LV short-axis and long-axis views, including two-, three-, and four-chamber views, were acquired employing a steady-state free precession (SSFP) sequence. The scanning parameters were as follows: temporal resolution: 40.35 or 32.45 ms; echo time (TE):1.20 or 1.28 ms; field of view (FOV): 286 × 340 or 250 × 300 mm2; flip angle: 50° or 41°; slice thickness: 8.0 mm; and matrix size: 192 × 162 or 208 × 139 pixels. A gadolinium-based contrast agent was administered intravenously at a dosage of 0.2 mmol/kg of body weight, with an injection rate ranging from 2.5 to 3.0 mL/s. This was immediately followed by a 20 mL saline flush administered at a rate of 3.0 mL/s. LGE images were subsequently obtained after approximately 10 to 15 min of contrast administration by utilizing a phase-sensitive inversion recovery sequence (TR:750ms or 598 ms, TE: 1.16 or 1.24 ms, FOV: 240 mm×300 mm2 or 270 × 360mm2, flip angle 40°, slice thickness 8.0 mm, and matrix size 256 × 162 or 256 × 125) [25].

CMR analysis

CMR image analysis was conducted offline utilizing cvi42 software (version 5.11.2; Circle Cardiovascular Imaging Inc., Calgary, Alberta, Canada) by two experienced radiologists blinded to the patients’ clinical backgrounds. We utilized global 3D strain to evaluate LV function and global strain parameters for each subject, including LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), LV stroke volume (LVSV), LV myocardial mass (LVM), and LV ejection fraction (LVEF). Subsequently, to enable comparisons adjusted for BSA, these parameters were normalized using the Mosteller formula [26], yielding indexed values: LVEDVI, LVESVI, LVSVI, and LVMI. These processes necessitated meticulous manual delineation of the epicardial and endocardial boundaries of the LV myocardium in short-axis cine images captured at end-systole and end-diastole phases. Moreover, the LV global function index (LVGFI) was calculated using the formula [27]: LVGFI = {LVSV / [(LVEDV + LVESV) / 2 + (LVM / 1.05)]} × 100.

For a comprehensive assessment of LV global strain parameters, including global radial peak strain (GRPS), global circumferential peak strain (GCPS), and global longitudinal peak strain (GLPS), manual tracing was extended to all layers of the short-axis and a single layer of the 4-chamber, 3-chamber, and 2-chamber long-axis cine slices. The study utilized global myocardial strains to reflect the heart’s contractile behavior, noting that while GLPS and GCPS are negative, GRPS is positive. Figure 1 presents representative pseudocolor CMR images taken at end-diastole, along with CMR-derived peak strain curves. Additionally, the study automatically derived peak systolic strain rate (PSSR) and peak diastolic strain rate (PDSR) in the radial, circumferential, and longitudinal directions using the above software.

Fig. 1
figure 1

Representative pseudocolor CMR images captured at end-diastole (upper part), accompanied by CMR-derived peak strain curves (lower part). A A 63-year-old male patient from the control group; B A 59-year-old female patient with T2DM but without MAFLD; C A 58-year-old male patient with both T2DM and MAFLD. CMR: cardiac magnetic resonance, T2DM: Type 2 diabetes mellitus, MAFLD: metabolic-associated fatty liver disease

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Reproducibility of LV strain

The intra-observer variability regarding the global strain parameters of the LV was assessed by comparing initial measurements from 70 randomly selected cases, including 50 patients with T2DM and 20 control subjects, to those from a re-analysis carried out by the same observer one month later. The inter-observer variability was evaluated by comparing the measurements from the same population by another independent double-blinded experienced observer.

Statistical analysis

In this study, we used the Kolmogorov-Smirnov test to assess normality and found that all LV function and global strain parameters did not follow a normal distribution. Continuous variables were represented as medians with interquartile ranges (IQR), while categorical variables were depicted by frequencies and percentages. The comparison of continuous variables across different groups utilized the Kruskal-Wallis test for non-normally distributed data and ANOVA for normally distributed data, while categorical variables were analyzed using the Chi-square test. The relationship between LV function parameters and global strain parameters was examined using Spearman’s correlation coefficient. To explore the associations between LV function or global strain parameters and various clinical factors, univariable linear regression analysis were conducted. Initially, univariable analysis identified clinical variables significantly associated with LV function and global strain parameters. Additionally, we conducted a variance inflation factor (VIF) analysis to check for multicollinearity, excluding variables with VIF values exceeding 10. These variables were then included in the multivariable models to assess the independent predictors of cardiac function. We used the intra-class correlation coefficient (ICC) to evaluate both intra-observer and inter-observer reliability of the measurements [28]. The specific ICC model applied was the two-way random-effects model. The ICC values were interpreted as follow: ICC < 0.5: poor reliability; 0.5 ≤ ICC < 0.75: moderate reliability; 0.75 ≤ ICC < 0.9: good reliability; ICC ≥ 0.9: excellent reliability. All analyses were conducted using R software (R studio Version 2024.04.1 + 748). A two-tailed p value below 0.05 was considered statistically significant.

Results

Patients’ characteristics

Table 1 delineates the baseline characteristics of the entire cohort diagnosed with T2DM, comparing those with (N = 109) and without (N = 152) MAFLD. Individuals with MAFLD demonstrated a higher proportion of males (81/109 [74.3%] vs. 84/152 [55.3%], P = 0.002) compared to those without this comorbidity, and they tended to be younger (median: 54.5 vs. 61.0 years, P < 0.001) with elevated BMI (median: 25.72 vs. 24.22, P = 0.010) and BSA (median: 1.74 vs. 1.65 m2, P < 0.001). Additionally, T2DM cases with MAFLD displayed more pronounced hepatic biochemical abnormalities, including elevated levels of ALT, GGT, AST, total cholesterol, and reduced HDL cholesterol. Other baseline factors were comparable between T2DM patients with and without MAFLD.

Table 1 Baseline characteristics of the total cohort
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Comparison of LV function and global strain among T2DM patients with and without MAFLD, and control subjects

Comparisons of CMR-derived parameters were conducted among normal controls, T2DM patients with and without MAFLD, focusing on LV function and global peak strain (Table 2). The LV function parameters, including LVEDVI, LVESVI, LVEF, LVMI, and LVGFI, displayed a progressive augmentation from controls through T2DM patients without MAFLD, to those with MAFLD. Conversely, the variations in LVSVI among the groups were comparatively minor (Fig. 2A-F). Regarding LGE, among patients with T2DM, those with MAFLD were significantly more likely to exhibit LGE, with a prevalence of 45.9% (50/109) (8 focal pattern, 42 diffuse pattern) compared to 27.6% (42/152) (17 focal pattern, 25 diffuse pattern) in those without MAFLD (P = 0.003, Fig. 2G).

Table 2 Comparison of CMR-derived parameters among normal controls, T2DM patients with and without MAFLD
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Fig. 2
figure 2

Comparison of LV function parameters and the incidence of LGE among patients of normal control, T2DM patients without MAFLD, and T2DM patients with MAFLD. A-F: Comparison of LVEDVI, LVESVI, LVSVI, LVEF, LVMI, and LVGFI among the three groups; G: Comparison of LGE among the three groups

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In a similar vein, when examining LV global strain parameters derived from CMR, a significant and progressive deterioration is observed across the groups. The absolute value of GRPS, GCPS, and GLPS, along with PSSR and PDSR in radial, circumferential and longitudinal orientations, manifest a pronounced decline moving from control subjects to T2DM patients without MAFLD, and further deteriorating in those with MAFLD (Fig. 3).

Fig. 3
figure 3

Comparison of LV global strain parameters among patients of normal control, T2DM patients without MAFLD, and T2DM patients with MAFLD. A-I Comparison of GRPS, GCPS, GLPS, PSSR_R, PSSR_C, PSSR_L, PDSR_R, PDSR_C, and PDSR_L among the three groups GRPS: global radial peak strain, GCPS: global circumferential peak strain, GLPS: global longitudinal peak strain, PSSR_R: radial peak systolic strain rate, PSSR_C: circumferential peak systolic strain rate, PSSR_L: longitudinal peak systolic strain rate, PDSR_R: radial peak diastolic strain rate, PDSR_C: circumferential peak diastolic strain rate, PDSR_L: longitudinal peak diastolic strain rate

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Similarly, when examining LV global strain parameters derived from CMR, a significant and progressive deterioration is observed across the groups. The absolute values of GRPS, GCPS, and GLPS, along with PSSR and PDSR in radial, circumferential, and longitudinal orientations, show a clear and statistically significant decline moving from control subjects to T2DM patients without MAFLD, and further deteriorating in those with MAFLD (Fig. 3).

Comparison of LV function and global strain among T2DM patients with different MAFLD severities

In the MAFLD(−), mild MAFLD, and moderate to severe MAFLD patient groups, LVESVi exhibited a gradually increasing trend, while LVEF and LVGFi showed a progressively decreasing trend (Fig. 4A-F). Besides, there was a noticeable decrease in the absolute value of global strain across radial, circumferential, and longitudinal dimensions, as well as in PSSR and PDSR, across the three dimensions, progressing from those without MAFLD, through mild MAFLD, to moderate to severe MAFLD (Fig. 4G-O). In the comparison of LV function and global strain parameters, statistically significant differences were observed between T2DM patients without MAFLD and those with any level of MAFLD. However, with the exception of GRPS, this significance was not observed in the comparison between the mild and moderate to severe MAFLD groups, possibly due to the small sample sizes when segmented by MAFLD severity. In terms of LGE occurrence, a higher, though not statistically significant, prevalence of LGE was noted in patients with moderate to severe MAFLD compared to those with mild MAFLD (19/33 [57.6%] vs. 31/76 [40.8%], P = 0.143, Fig. 2K).

Fig. 4
figure 4

Comparison of LV function parameters and LV global strain parameters among T2DM patients without MAFLD, with mild MAFLD, or moderate-to-severe MAFLD. The three points on the line segment represent the median and the 95% confidence interval LV: left ventricular; LVEDVI: NS: not significant

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Correlation analysis of LV function and global strain among T2DM patients

We further explored the correlation between CMR-derived LV function and global strain parameters. As illustrated in Fig. 5A, the LVGFI shows a strong positive correlation with LVEF (r = 0.91), highlighting its essential role in assessing overall cardiac performance. We also identified robust correlations between LV function parameters, specifically LVEF and LVGFI, and strain metrics, namely GRPS, GCPS, and GLPS. Conversely, the correlations of PSSR and PDSR with LV function parameters were found to be relatively weaker. These findings hold true for T2DM patients with and without MAFLD (Fig. 5B-C).

Fig. 5
figure 5

Correlation analysis among LV function and global strain parameters. (A) All patients with T2DM; (B) T2DM patients with MAFLD; (C) T2DM patients without MAFLD. The Spearman correlation coefficient for every pair of parameters is shown in the respective cell GCPS: global circumferential peak strain, GLPS: global longitudinal peak strain, GRPS: global radial peak strain, LV: left ventricular, LVEDVI: LV end-diastolic volume index, LVEF: LV ejection fraction, LVESVI: LV end-systolic volume index, LVGFI: LV global function index, LVMI: LV myocardial mass index, LVSVI: LV stroke volume index, MAFLD: metabolic-associated fatty liver disease, PDSR_C: circumferential peak diastolic strain rate, PDSR_L: longitudinal peak diastolic strain rate, PDSR_R: radial peak diastolic strain rate, PSSR_C: circumferential peak systolic strain rate, PSSR_L: longitudinal peak systolic strain rate, PSSR_R: radial peak systolic strain rate, T2DM: Type 2 diabetes mellitus

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Association of clinical variables with LV function and global strain parameters in T2DM patients

This study assessed the impact of clinical parameters on LVEF, LVMI, and LVGFI using univariate and multivariate linear regression analyses (Table 3). Univariate analysis identified gender, HDL-cholesterol, and MAFLD as common predictors for all LV function metrics. LVEF was also linked to heart rate, SBP, albumin, ALT, GGT, AST, and total protein; LVMI to age, BMI, fasting plasma glucose, and creatinine; and LVGFI to age, BSA, heart rate, SBP, albumin, ALT, AST, creatinine, and total protein. Multivariate analysis confirmed MAFLD as an independent predictor of LVEF, LVMI, and LVGFI. Heart rate, SBP and ALT independently influenced LVEF; gender, age, BMI, and creatinine predicted LVMI; while gender, heart rate, and ALT significantly influenced LVGFI.

Table 3 Associations between clinical parameters and LV dysfunction
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The study also explored predictors for GRPS, GCPS, and GLPS (Table 4). Univariate analysis revealed mutual associations with gender, age, BSA, ALT, HDL-cholesterol, and MAFLD. Additionally, total protein influenced GRPS, while heart rate, SBP, GGT, and AST were significant for GCPS. For GLPS, heart rate, total cholesterol, and creatinine were relevant. Multivariate analysis identified gender, total protein, and MAFLD as independent determinants of GRPS. GCPS was independently influenced by gender, heart rate, SBP, ALT, total protein, and MAFLD, while GLPS was influenced by heart rate, HDL-cholesterol, creatinine, and MAFLD.

Table 4 Associations between clinical parameters and LV global strains
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Inter- and intra-observer variability

The inter- and intra-observer correlation coefficients demonstrated that the ICC values for LV global peak strain across all three axes exceeded 0.8, indicating high reliability (Table 5).

Table 5 Inter- and intra-observer variability
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Discussion

This study examined the additive impact of MAFLD on LV function and global strain in T2DM patients using CMR-derived features. The main findings of our study were as follows: [1] MAFLD significantly impairs LV function parameters and global peak strain in all three directions (radial, circumferential, and longitudinal) in T2DM patients, with an increase in MAFLD severity associated with a more pronounced decline in strain parameters. [2] GGT and HDL-cholesterol were independent predictors of GCPS and GLPS, respectively. After adjusting for other adverse clinical factors affecting cardiac function and deformation, MAFLD remains an independent adverse predictor. [3] LGE was higher in T2DM patients with MAFLD than in T2DM patients without MAFLD. Our study underscores the significant clinical impact of MAFLD on LV function and global strain in patients with T2DM. The observed progressive deterioration in LV function and strain parameters highlights the critical need for early detection and comprehensive management. These findings suggest that incorporating CMR into routine evaluations could enhance monitoring and treatment strategies, ultimately improving cardiovascular outcomes for these patients.

Several studies have investigated the relationship between NAFLD and cardiac function in patients with T2DM. It is crucial to recognize that, while MAFLD and NAFLD are related, they represent distinct conditions [29]. The term MAFLD emphasizes metabolic dysfunction as a core criterion, whereas NAFLD primarily focuses on excluding significant alcohol consumption as the cause of liver fat accumulation. Consequently, these terms are not entirely synonymous, and their pathophysiological implications may differ. This study significantly highlights the detrimental effect of MAFLD on LV function and global strain in T2DM patients using CMR, which was consistent with several previous echocardiographic researches investigating the impact of NAFLD on cardiac function and strain in T2DM patients [11, 30,31,32]. Furthermore, our study revealed that as the severity of MAFLD increased, the LV global strain parameters of T2DM patients deteriorated correspondingly. This observation aligns with existing echocardiographic literature that underscores the progressive nature of NAFLD and its compounding effects on cardiovascular health in T2DM patients [31, 32]. Targher et al. demonstrated that patients with more severe forms of NAFLD exhibited significantly worse cardiac function and increased cardiovascular mortality rates [33]. The association between advanced hepatic steatosis and adverse cardiac outcomes is likely mediated by exacerbated insulin resistance, heightened inflammatory responses, ectopic fat deposition in the liver and other tissues, and more pronounced dyslipidemia, all of which are well-documented contributors to cardiovascular pathology [34, 35]. Furthermore, the progression of MAFLD often leads to increased fibrosis and hepatocellular injury, which may amplify systemic inflammation and endothelial dysfunction, thereby worsening myocardial strain [34, 35].

Notably, CMR imaging is a pivotal tool in the non-invasive assessment of cardiac function and anatomy [36]. It offers several advantages over echocardiography, including non-operator dependence, high reproducibility, superior image quality, and the ability to differentiate tissue types while detecting myocardial fibrosis and edema. Prior to our study, a small cohort CMR study reported the separate adverse effects of MAFLD and T2DM on patients’ cardiac structure and function [37]. However, it remained unclear whether MAFLD further deteriorates cardiac function and strains in T2DM patients and if this potential deterioration could be detected by CMR. Therefore, our findings on the incremental effect of MAFLD on LV function and global strain in T2DM patients using CMR are highly significant.

In the current study, we observed that liver function parameters, notably ALT, AST, and GGT, are established as reliable indicators of liver health, which has been reported in previous studies. Our findings revealed a significant elevation in GGT levels among T2DM patients with MAFLD, compared to those without MAFLD (47.00 vs. 29.00, p < 0.001). Conversely, HDL-cholesterol levels were notably lower in T2DM patients with MAFLD than in those without (1.06 vs. 1.17, p = 0.031). These results align with a previous cross-sectional study encompassing 1434 T2DM patients, wherein the MAFLD group exhibited a higher GGT/HDL ratio than the non-MAFLD group [38]. Past investigations have established a link between liver enzymes with an increased risk of cardiovascular disease or cardiovascular mortality [39, 40]. Similarly, global longitudinal strain and global circumferential strain have been found to be inversely correlated with LDL-C [41]. Our study extends this understanding by demonstrating a correlation between liver function markers and cardiac strain, with GGT being an independent predictor of GCPS and HDL-cholesterol being an independent predictor of GLPS. Of note, we also found that the existence of MAFLD, even after being corrected by these liver function-related plasma biochemistry parameters and other clinical parameters related to LV function and strain, is still an important independent factor in predicting LV function and deformation. Therefore, in the clinical management of T2DM patients, dynamic monitoring plasma level of liver function parameters such as GGT and HDL-C can assist cardiologists and hepatologists in the early detection of cardiac impairment caused by MAFLD, and optimizing the diagnosis and treatment process of MAFLD-related heart disease.

LGE serves as a crucial parameter in CMR imaging, significantly enhancing the visualization and quantification of myocardial fibrosis or scar areas [42]. Our investigation observed a significantly higher prevalence of LGE among patients with T2DM who concurrently suffer from MAFLD. Similarly, previous study demonstrated that NAFLD was independently associated with the LV fibrosis size evaluated by LGE in heart failure patients [43]. Notably, individuals with moderate to severe MAFLD exhibited a greater frequency of LGE compared to those with mild MAFLD. Furthermore, our study found that LVMI (62.26 vs. 51.80, p < 0.001) were higher among T2DM patients with MAFLD compared to those without. This could be influenced by several factors, including potential increases in collagen fibers, myocardial triglyceride accumulation, and other metabolic or inflammatory processes. It is important to note that differences in heart size and function can also impact strain measurements, and further research is needed to elucidate these mechanisms. Previous studies have established a strong correlation between LGE and adverse cardiovascular outcomes including ventricular arrhythmia, heart failure hospitalization, sudden cardiac death [44,45,46]. Therefore, the early identification of LGE can assist clinicians in cardiac risk stratification, reduce the incidence of adverse cardiovascular events, and improve the prognosis of T2DM patients with MAFLD.

This study is subject to several limitations. Firstly, as a single-center, retrospective study, it is inherently constrained by design limitations and prone to selection and exclusion bias, which may affect the generalizability of the findings. Secondly, machine calibration, imaging protocols, and resolution differences from two CMR machines can impact LV function and strain measurements, potentially confounding the results. However, according to a recent article, difference in MR vendor had no effect on the cardiac magnetic resonance feature tracking (CMR-FT) strain measurements [24]. Besides, our analysis indicated that individuals with moderate to severe MAFLD exhibited worse global strain and a higher incidence of LGE compared to those with mild MAFLD. However, the small sample size may have constrained the statistical significance of these findings. Furthermore, the optimal temporal resolution of CMR cine images for the strain rate analyses needs to be further studied in the future. Lastly, as a retrospective analysis, parametric mapping was not routinely performed in our center. Future studies will include these to enhance myocardial tissue characterization.

Conclusions

In conclusion, our study demonstrated that MAFLD significantly impaired LV function and global strain parameters in patients with T2DM, with greater severity of MAFLD correlating with more pronounced deterioration in cardiac function and deformation. The adverse effect of MAFLD was independent of other adverse clinical factors. Our findings highlight the critical need for early detection and comprehensive management of cardiac function in T2DM patients with MAFLD.

Data availability

All patients’ data are available upon reasonable request from the corresponding author.

Abbreviations

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

BMI:

Body mass index

BSA:

Bbody surface area

CMR:

Cardiac Magnetic Resonance

eGFR:

Estimated glomerular filtration rate

FOV:

Field of view

FPG:

Fasting plasma glucose

GCPS:

Global circumferential peak strain

GGT:

Gamma-glutamyl transferase

GLPS:

Global longitudinal peak strain

GRPS:

Global radial peak strain

HbA1c:

Glycated hemoglobin

HDL:

High-density lipoprotein

HGB:

Hemoglobin

ICC:

Intra-class correlation coefficient

IQR:

Interquartile ranges

LDL:

Low-density lipoprotein

LGE:

Late gadolinium enhancement

LV:

Left ventricular

LVEDV:

Left ventricular end-diastolic volume

LVEF:

Left ventricular ejection fraction

LVEF:

Left ventricular ejection fraction

LVESV:

Left ventricular end-systolic volume

LVGFI:

Left ventricular global function index

LVM:

Left ventricular myocardial mass

LVSV:

Left ventricular stroke volume

MAFLD:

Metabolic-associated fatty liver disease

NAFLD:

Non-alcoholic fatty liver disease

PDSR:

Peak diastolic strain rate

PSSR:

Peak systolic strain rate

SSFP:

Steady-state free precession

T2DM:

Type 2 diabetes mellitus

TC:

Total cholesterol

TE:

Echo time

TG:

Triglycerides

TR:

Repetition time

VIF:

Variance inflation factor

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Acknowledgements

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Funding

This research was funded by the Natural Science Foundation of Sichuan Province [grant number 2023NSFSC1725, 2023NSFSC1720] and the 1·3·5 project for disciplines of excellence of West China Hospital, Sichuan University (ZYGD23019).

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Authors and Affiliations

  1. Department of Radiology, West China Hospital, Sichuan University, 37# Guo Xue Xiang, Chengdu, 610041, Sichuan, China

    Xin Tang, Rui Shi, Li Jiang, Wei-Feng Yan, Pei-Lun Han, Wen-Lei Qian, Zhi-Gang Yang & Yuan Li

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  1. Xin Tang
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  2. Rui Shi
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Contributions

XT, YL and ZGY participated in the study design. XT, RS, LJ and WFY collected the data. XT, LJ, PLH and WLQ analyzed the data. XT drafted the manuscript. YL and ZGY revised the manuscript. All authors read and approved the final manuscript.

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Correspondence to Yuan Li.

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The study was conducted in accordance with the Decla-ration of Helsinki, and approved by the Biomedical Research Ethics Committee of West China Hospital. Patients’ written informed consent was waived due to the retro-spective nature of this study.

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The authors declare no competing interests.

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Tang, X., Shi, R., Jiang, L. et al. Additive effect of metabolic dysfunction-associated fatty liver disease on left ventricular function and global strain in type 2 diabetes mellitus patients: a 3.0 T cardiac magnetic resonance feature tracking study. Cardiovasc Diabetol 23, 317 (2024). https://doi.org/10.1186/s12933-024-02410-z

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Keywords

Cardiovascular Diabetology

ISSN: 1475-2840