To investigate the relationship between serum uric acid (SUA) levels and metabolic dysfunction-associated steatotic liver disease (MASLD) in newly diagnosed type 2 diabetic patients.

We performed this retrospective research among 1087 inpatients with new-onset type 2 diabetes millitus (T2DM). Data were analyzed according to gender. Then, the populations were stratified according to their body mass index (BMI) levels in men and women, respectively. The physical and biochemical indicators were measured and recorded. The relationship between SUA and MASLD was estimated using logistic regression analysis, and the unadjusted and adjusted odds ratios (ORs) were calculated.

After adjusting for age, BMI, and other components of the metabolic syndrome, SUA was independently associated with MASLD only in men, but not in women. In addition, for men, the SUA levels were independently associated with MASLD in both non-overweight/obesity and overweight/obesity group. However, for women, the SUA levels were independently related to MASLD in non-overweight/obesity group. There was no association between SUA and MASLD in women with overweight/obesity.

In newly diagnosed type 2 diabetic patients, elevated SUA is an independent predictor for the risk of MASLD in males. In females, the relationship between SUA and MASLD may depend on BMI, with significance only in non-overweight/obese individuals.

Previous studies have suggested an association between beta-cell and autonomic function and metabolic-associated fatty liver disease (MAFLD). We explored the association between controlled attenuated parameter (CAP) and insulin secretion and action, as well as sympathetic and parasympathetic activity in normal (NGT) and impaired (IGT) glucose tolerance.

Twenty-five NGT (age 44.8±9.6 years; body mass index (BMI) 32.3±6.9 kg/m2) and 27 IGT (47.6±11.8 years; 31.0±6.5 kg/m2) subjects underwent a 75 g oral glucose tolerance test (OGTT) and a mixed meal tolerance test (MMTT) for assessment of glucose and insulin secretion. Parameters of beta-cell function and insulin sensitivity were calculated. Body composition was assessed by bioimpedance analysis (Inbody720). Autonomic function was assessed by ANX V.3.0 monitoring system. CAP was determined by Fibroscan (Echosense) and presence of MAFLD was defined as CAP >233 dB/m.

A CAP >233 dB/m was found in 72% of subjects with NGT and 67% of subjects with IGT. Subjects with MAFLD, irrespective of glucose tolerance, had higher BMI and waist circumference, lower insulin secretion and action, and lower parasympathetic activity. On a matrix analysis, after adjustment for age and BMI, CAP was positively related to systolic blood pressure (SBP); insulin action was negatively related to parasympathetic activity. Regression analysis showed that AUC-insulin MMTT remained independently related to MAFLD: OR 24.4 (95% CI 2.17 to 274.77; p=0.010). A "cut-off" value of 15,620 uIU/mL-1*180 min-1 provided a 75% sensitivity and 75% specificity for CAP >233 dB/m.

Our results do not support a role for parasympathetic activity in MAFLD. Rather, they show that stimulated hyperinsulinemia may be associated with greater risk of MAFLD irrespective of glucose tolerance in a high-risk population without diabetes.

Background: Probiotics, prebiotics, and synbiotics have been suggested as a possible therapy for non-alcoholic fatty liver disease (NAFLD). However, their efficacy in improving blood glucose levels in NAFLD patients remains uncertain. Objective: The aim of this study was to assess the effects of supplementation with probiotics, prebiotics, or synbiotics on fasting blood glucose (FBG) levels in NAFLD patients. Methods: We searched PubMed, Web of Science, and Google Scholar for relevant trials published up to March 2024. Out of 3369 identified studies, 24 randomized controlled trials (RCTs) were included. Results: Probiotic, prebiotic, or synbiotic supplementation substantially reduced FBG (n = 23; standard mean difference (SMD) = -0.17; 95% confidence interval (CI): -0.30, -0.03; P = 0.02), fasting insulin levels (n = 12; SMD = -0.28; 95% CI: -0.49, -0.07; P = 0.01), and homeostatic model assessment for insulin resistance (HOMA-IR; n = 14; SMD = -0.28; 95% CI: -0.47, -0.09; P = 0.004). However, glycosylated hemoglobin (HbA1c; n = 3; SMD = -0.17; 95% CI: -0.48, 0.13; P = 0.27) was not significantly affected. The FBG-decreasing effect diminished as the body mass index (BMI) of volunteers increased in the baseline. Additionally, the number of probiotic strains and geographic region were shown to significantly affect FBG levels. Conclusion: This meta-analysis indicates that supplementation with probiotics, prebiotics, or synbiotics may aid in controlling glucose homeostasis in patients with NAFLD.

Liver fibrosis is a pathological condition characterized by the abnormal proliferation of liver tissue, subsequently able to progress to cirrhosis or possibly hepatocellular carcinoma. The development of artificial intelligence and deep learning have begun to play a significant role in fibrosis detection. This study aimed to develop SMART AI-PATHO, a fully automated assessment method combining quantification of histopathological architectural features, to analyze steatosis and fibrosis in nonalcoholic fatty liver disease (NAFLD) core biopsies and employ Metavir fibrosis staging as standard references and fat assessment grading measurement for comparison with the pathologist interpretations. There were 146 participants enrolled in our study. The correlation of Metavir scoring system interpretation between pathologists and SMART AI-PATHO was significantly correlated (Agreement = 68%, Kappa = 0.59, p-value <0.001), which subgroup analysis of significant fibrosis (Metavir score F2-F4) and nonsignificant fibrosis (Metavir score F0-F1) demonstrated substantial correlated results (agreement = 80%, kappa = 0.61, p-value <0.001), corresponding with the correlation of advanced fibrosis (Metavir score F3-F4) and nonadvanced fibrosis groups (Metavir score F0-F2), (agreement = 89%, kappa = 0.74, p-value <0.001). SMART AI-PATHO, the first pivotal artificially intelligent diagnostic tool for the color-based NAFLD hepatic tissue staging in Thailand, demonstrated satisfactory performance as a pathologist to provide liver fibrosis scoring and steatosis grading. In the future, developing AI algorithms and reliable testing on a larger scale may increase accuracy and contribute to telemedicine consultations for general pathologists in clinical practice.

Glucokinase (GK) plays a key role in glucose metabolism. In the liver, GK is regulated by GK regulatory protein (GKRP) with nuclear sequestration at low plasma glucose level. Some GK activators (GKAs) disrupt GK-GKRP interaction which increases hepatic cytoplasmic GK level. Excess hepatic GK activity may exceed the capacity of glycogen synthesis with excess triglyceride formation. It remains uncertain whether hypertriglyceridemia associated with some GKAs in previous clinical trials was due to direct GK activation or impaired GK-GKRP interaction.

Using publicly available genome-wide association study summary statistics, we selected independent genetic variants of GCKR and GCK associated with fasting plasma glucose (FPG) as instrumental variables, to mimic the effects of impaired GK-GKRP interaction and direct GK activation, respectively. We applied two-sample Mendelian Randomization (MR) framework to assess their causal associations with lipid-related traits, risks of metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiovascular diseases. We verified these findings in one-sample MR analysis using individual-level statistics from the Hong Kong Diabetes Register (HKDR).

Genetically-proxied impaired GK-GKRP interaction increased plasma triglycerides, low-density lipoprotein cholesterol and apolipoprotein B levels with increased odds ratio (OR) of 14.6 (95% CI 4.57-46.4) per 1 mmol/L lower FPG for MASLD and OR of 2.92 (95% CI 1.78-4.81) for coronary artery disease (CAD). Genetically-proxied GK activation was associated with decreased risk of CAD (OR 0.69, 95% CI 0.54-0.88) and not with dyslipidemia. One-sample MR validation in HKDR showed consistent results.

Impaired GK-GKRP interaction, rather than direct GK activation, may worsen lipid profiles and increase risks of MASLD and CAD. Development of future GKAs should avoid interfering with GK-GKRP interaction.

In this prospective cohort study, 1197 patients with type 2 diabetes (T2D) were divided into two groups (360 patients with NAFLD and 847 without NAFLD) and were followed for a median of 5 years for the incidence of CVD. Cox regression analysis was used to assess the association between NAFLD, liver enzyme level, aspartate aminotransferase to platelet ratio index (APRI), and the incidence risk of CVD and its subgroups (i.e., myocardial infarction, chronic heart disease, coronary artery bypass grafting, and percutaneous coronary intervention). There was a significant positive association between CVD incidence and NAFLD (HR = 1.488, 95% CI = 1.041-2.124, p value = 0.029). Although patients with NAFLD had higher levels of ALT and AST levels (p value = <0.001), there was no significant association between liver enzymes and the incidence risk of CVD when adjusted for different variables. Furthermore, NAFLD was associated with NAFLD APRI Q (2), APRI Q (3), and APRIQ (4) (1.365 (1.046-1.781), 1.623 (1.234-2.135), and 3.373 (2.509-4.536)), respectively.

NAFLD increased the incidence risk of CVD in T2D. However, there was no association between liver enzymes (ALT, AST, ALK-P, and GGT) and a higher incidence risk of CVD in T2D when adjusted for confounding variables.

Virtually the entire spectrum of liver disease is observed in association with type 2 diabetes mellitus (T2DM); indeed, T2DM is now the most common cause of liver disease in the U.S. We conducted a pilot study to investigate the relevance of increased microbial translocation and systemic inflammation in the development of liver injury in patients with T2DM.

Patients with T2DM (n = 17) and non-diabetic controls (NDC; n = 11) aged 25-80 yrs. participated in this study. Serum levels of endotoxin, calprotectin, soluble CD14 and CD163, and several inflammatory cytokines were measured. In addition to standard liver injury markers, ALT and AST, novel serum markers of liver injury, keratin 18 (K-18) M30 (apoptosis-associated caspase-cleaved keratin 18), and M65 (soluble keratin 18) were evaluated. Statistical analyses were performed using the Mann-Whitney test to assess differences between study groups. Pearson's correlation analysis was performed to determine the strength of association between two variables using GraphPad Prism 9.5.0 software.

Patients with T2DM had significantly higher levels of sCD14 in comparison to NDC, suggesting an increase in gut permeability, microbial translocation, and monocyte/macrophage activation. Importantly, relevant to the ensuing inflammatory responses, the increase in sCD14 in patients with T2DM was accompanied by a significant increase in sCD163, a marker of hepatic Kupffer cell activation and inflammation. Further, a positive correlation was observed between sCD163 and endotoxin and sCD14 in T2DM patients but not in NDC. In association with these changes, keratin 18 (K-18)-based serum markers (M65 and M30) that reflect hepatocyte death were significantly higher in the T2DM group indicating ongoing liver injury. Notably, both M65 and M30 levels correlated with sCD14 and sCD163, suggesting that immune cell activation and hepatic inflammation may be linked to the development of liver injury in T2DM.

These findings suggest that the pathogenic changes in the gut-liver axis, marked by increased microbial translocation, may be a major component in the etiology of hepatocyte inflammation and injury in patients with T2DM. However, larger longitudinal studies, including histological evidence, are needed to confirm these observations.

Epidemiological and clinical studies have indicated a higher risk of nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM), implying a potentially shared genetic etiology, which is still less explored. Genetic links between T2DM and NAFLD were assessed using linkage disequilibrium score regression and pleiotropic analysis under composite null hypothesis. European GWAS data have identified shared genes, whereas SNP-level pleiotropic analysis under composite null hypothesis has explored pleiotropic loci. generalized gene-set analysis of GWAS data determines pleiotropic pathways and tissue enrichment using eQTL mapping to identify associated genes. Mendelian randomization analysis was used to investigate the causal relationship between NAFLD and T2DM. Linkage disequilibrium score regression analysis revealed a strong genetic correlation between T2DM and NAFLD, and identified 24 pleiotropic loci. These single-nucleotide polymorphisms are primarily involved in biosynthetic regulation, RNA biosynthesis, and pancreatic development. generalized gene-set analysis of GWAS data analysis revealed significant enrichment in multiple brain tissues. Gene mapping using these 3 methods led to the identification of numerous pleiotropic genes, with differences observed in liver and kidney tissues. These genes were mainly enriched in pancreas, brain, and liver tissues. The Mendelian randomization method indicated a significantly positive unidirectional causal relationship between T2DM and NAFLD. Our study identified a shared genetic structure between NAFLD and T2DM, providing new insights into the genetic pathogenesis and mechanisms of NAFLD and T2DM comorbidities.

The global prevalence of non-alcoholic fatty liver disease (NAFLD) is nearly 25% and is increasing rapidly. The spectrum of liver damage in NAFLD ranges from simple steatosis to non-alcoholic steatohepatitis, characterised by the presence of lobular inflammation and hepatocyte ballooning degeneration, with or without fibrosis, which can further develop into cirrhosis and hepatocellular carcinoma. Not only is NAFLD a progressive liver disease, but numerous pieces of evidence also point to extrahepatic consequences. Accumulating evidence suggests that patients with NAFLD are also at increased risk of cardiovascular disease (CVD); in fact, CVDs are the most common cause of mortality in patients with NAFLD. Obesity, type 2 diabetes and higher levels of LDL are common risk factors in both NAFLD and CVD; however, how NAFLD affects the development and progression of CVD remains elusive. In this review, we comprehensively summarise current data on the key extrahepatic manifestations of NAFLD, emphasising the possible link between NAFLD and CVD, including the role of proprotein convertase substilisin/kenin type 9, extracellular vesicles, microbiota, and genetic factors.

The progression of metabolic dysfunction-associated steatotic liver disease (MASLD) has been found to manifest in a series of hepatic and extrahepatic complications. A comprehensive meta-analysis of the longitudinal outcomes associated with MASLD has yet to be conducted.

To investigate the longitudinal outcomes associated with MASLD, Medline and Embase databases were searched to identify original studies that evaluated the longitudinal risks of incident clinical outcomes among MASLD patients compared with non-MASLD individuals. DerSimonian Laird random-effects meta-analysis was performed. Pooled effect estimates were calculated, and heterogeneity among studies was evaluated.

One hundred twenty-nine studies were included in the meta-analysis. Meta-analysis revealed a significant increase in the risk of cardiovascular outcomes (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.27-1.60; P < .01), various metabolic outcomes such as incident hypertension (HR, 1.75; 95% CI, 1.46-2.08; P < .01), diabetes (HR, 2.56; 95% CI, 2.10-3.13; P < .01), pre-diabetes (HR, 1.69; 95% CI, 1.22-2.35; P < .01), metabolic syndrome (HR, 2.57; 95% CI, 1.13-5.85; P = .02), chronic kidney disease (HR, 1.38; 95% CI, 1.27-1.50; P < .01), as well as all cancers (HR, 1.54; 95% CI, 1.35-1.76; P < .01) among MASLD patients compared with non-MASLD individuals. By subgroup analysis, MASLD patients with advanced liver disease (HR, 3.60; 95% CI, 2.10-6.18; P < .01) were also found to be associated with a significantly greater risk (P = .02) of incident diabetes than those with less severe MASLD (HR, 1.63; 95% CI, 1.0-2.45; P = .02) when compared with non-MASLD.

The present study emphasizes the association between MASLD and its clinical outcomes including cardiovascular, metabolic, oncologic, and other outcomes. The multisystemic nature of MASLD found in this analysis requires treatment targets to reduce systemic events and end organ complications.

To investigate the risk of non-alcoholic fatty liver disease (NAFLD) for cardiovascular disease and all cause death in patients with type 2 diabetes mellitus (T2DM).

Nationwide population based study.

Longitudinal cohort study in Korea.

7 796 763 participants in the National Health Screening Programme in 2009 were divided into three groups based on NAFLD status: no NAFLD (fatty liver index<30); grade 1 NAFLD (30≤fatty liver index<60); and grade 2 NAFLD (fatty liver index≥60). Median follow-up was 8.13 years.

The primary outcome was incident cardiovascular disease (myocardial infarction, ischaemic stroke) or all cause death.

Of 7 796 763 participants, 6.49% (n=505 763) had T2DM. More patients with T2DM had grade 1 NAFLD (34.06%) and grade 2 NAFLD (26.73%) than those without T2DM (grade 1 NAFLD: 21.20%; grade 2 NAFLD: 10.02%). The incidence rate (per 1000 person years) of cardiovascular disease and all cause death increased in the order of no NAFLD, grade 1 NAFLD, and grade 2 NAFLD, and the incidence rates in patients with T2DM were higher than those in patients without T2DM. The five year absolute risk for cardiovascular disease and all cause death increased in the order of no NAFLD, grade 1 NAFLD, and grade 2 NAFLD in patients without and with T2DM (no NAFLD, without T2DM: 1.03, 95% confidence interval 1.02 to 1.04, and 1.25, 1.24 to 1.26, respectively; grade 1 NAFLD, without T2DM: 1.23, 1.22 to 1.25, and 1.50, 1.48 to 1.51, respectively; grade 2 NAFLD, without T2DM: 1.42, 1.40 to 1.45, and 2.09, 2.06 to 2.12, respectively; no NAFLD, with T2DM: 3.34, 3.27 to 3.41, and 3.68, 3.61 to 3.74, respectively; grade 1 NAFLD, with T2DM: 3.94, 3.87 to 4.02, and 4.25, 4.18 to 4.33, respectively; grade 2 NAFLD, with T2DM: 4.66, 4.54 to 4.78, and 5.91, 5.78 to 6.05, respectively). Patients with T2DM and without NAFLD had a higher five year absolute risk for cardiovascular disease and all cause death than those without T2DM and with grade 2 NAFLD. Risk differences for cardiovascular disease and all cause death between no NAFLD and grade 1 or grade 2 NAFLD were higher in patients with T2DM than in those without T2DM.

NAFLD in patients with T2DM seems to be associated with a higher risk of cardiovascular disease and all cause death, even in patients with mild NAFLD. Risk differences for cardiovascular disease and all cause death between the no NAFLD group and the grade 1 or grade 2 NAFLD groups were higher in patients with T2DM than in those without T2DM.

Nonalcoholic fatty liver disease (NAFLD) is a leading cause of cirrhosis but is underrecognized in primary care. Cirrhosis management requires complex monitoring, and the quality of care (QoC) for NAFLD cirrhosis patients in primary care may be inadequate.

In this retrospective-prospective cohort study of primary care patients with diabetes mellitus, we identified patients with NAFLD cirrhosis by 1) evidence of cirrhosis from abdominal imaging identified by natural language processing, or 2) existence of International Classification of Diseases code for cirrhosis. A finding of either was followed by manual chart review for confirmation of both cirrhosis and NAFLD. We then determined if cirrhosis care measures were up-to-date, including hepatitis A and B vaccination, Model for End-Stage Liver Disease score components, esophagogastroduodenoscopy, and hepatocellular carcinoma screening. We created a composite score quantifying overall QoC (scale 0-8), with high QoC defined as ≥6 points.

Among 3,028 primary care patients with diabetes mellitus, we identified 51 (1.7%) with NAFLD cirrhosis. Although 78% had ≥3 average primary care visits/year, only 24% completed hepatocellular carcinoma screening at least annually in at least 75% of years since diagnosis. The average QoC composite score was 4.9 (SD 2.4), and less than one-third had high QoC.

NAFLD cirrhosis is prevalent but underdiagnosed in primary care, and receipt of comprehensive QoC was suboptimal. Given the rising incidence of NAFLD cirrhosis, primary care providers need improved awareness and mechanisms to ensure high QoC for this population.

Nonalcoholic Fatty Liver Disease (NAFLD) is proving to be a globally prevalent condition. Moreover, NAFLD may be an independent risk factor associated with higher cardiovascular (CVD) morbidity and mortality. Further studies are needed to assess whether NAFLD needs to be included in the atherosclerotic risk score algorithms or whether patients with NAFLD need to be screened early on to assess their CVD risk especially since imaging such as positron emission tomography can be used to assess both NAFLD and CV disease at the same time. Therefore employing cardiovascular imaging modalities to investigate the incidence, extent, and nature of atherosclerotic lesions in NAFLD may be beneficial. Additionally, whether treating NAFLD halts the progression of CVD on imaging remains to be seen. Further research to delineate NAFLD and CVD associations, deciphering screening imaging modalities, and investigating targeted interventions could improve CVD morbidity and mortality in NAFLD.

We conducted a systematic review and meta-analysis to study the association between non-alcoholic fatty liver disease (NAFLD) and incident cardiovascular disease (CVD).

We searched Medline, Embase, Cochrane database and TRIP database. Random-effects model meta-analyses were used to obtain pooled effect sizes and 95% confidence intervals. The certainty in evidence was rated using the GRADE tool.

Altogether 36 studies including a total of 7,068,007 participants were included in the systematic review and meta-analysis. Pooled data from 19 cohort studies demonstrated a significant increase in the risk of non-fatal CVD events in patients with NAFLD (HR 1.57, 95% CI 1.33-1.85, I2 = 95%). Pooled data from eight studies showed a significant increase in fatal CVD (HR 1.40, 95% CI 1.24-1.57, I2 =27%), and eight cohort studies suggested a significant increase in combined non-fatal and fatal CVD (HR 1.41, 95% CI 1.13-1.76, I2 =80%). Meta-analysis of studies reporting adjusted estimates in NAFLD patients with fibrosis revealed a significant increase in CVD events with acceptable level of heterogeneity (HR 1.64, 95% CI 1.25-2.16, I2 = 31%). The anticipated absolute increase in the risk of combined fatal and non-fatal CVD was estimated to be 29 more per thousand with NAFLD; that of fatal CVD events 16 more per thousand and that of non-fatal CVD events 19 more per thousand with NAFLD. The GRADE rating ranged from very low to low for overall and subgroup analyses.

The present systematic review suggests that NAFLD increases the risk of incident CVD. Cohort studies with the ability to analyze subgroup effects based on severity, along with randomized controlled trials that provide experimental evidence demonstrating a decrease in cardiovascular disease events through the treatment of non-alcoholic fatty liver disease, are necessary to validate and reinforce these findings.

Investigating the effect of finerenone on liver function, cardiovascular and kidney composite outcomes in patients with chronic kidney disease and type 2 diabetes, stratified by their risk of liver steatosis, inflammation and fibrosis.

Post hoc analysis stratified patients (N = 13 026) by liver fibrosis and enzymes: high risk of steatosis (hepatic steatosis index >36); elevated transaminases [alanine transaminase (ALT) >33 (males) and >25 IU/L (females)]; and fibrosis-4 (FIB-4) index scores >3.25, >2.67 and >1.30. Liver enzymes were assessed by changes in ALT, aspartate aminotransferase and gamma-glutamyl transferase. Composite kidney outcome was defined as onset of kidney failure, sustained estimated glomerular filtration rate decline ≥57% from baseline over ≥4 weeks or kidney death. Composite cardiovascular outcome was defined as cardiovascular death, non-fatal myocardial infarction, non-fatal stroke or hospitalization for heart failure.

ALT, aspartate aminotransferase and gamma-glutamyl transferase levels were consistent between treatment groups and remained stable throughout. Finerenone consistently reduced the risk of composite kidney outcome, irrespective of altered liver tests. Higher FIB-4 score was associated with higher incidence rates of composite cardiovascular outcome. Finerenone reduced the risk of composite cardiovascular outcome versus placebo in FIB-4 subgroups by 52% (>3.25), 39% (>2.67) and 24% (>1.30) (p values for interaction = .01, .13 and .03, respectively).

Finerenone has neutral effects on liver parameters in patients with chronic kidney disease and type 2 diabetes. Finerenone showed robust and consistent kidney benefits in patients with altered liver tests, and profound cardiovascular benefits even in patients with higher FIB-4 scores who were at high risk of developing cardiovascular complications.

The progressive potential of liver damage in type 2 diabetes mellitus (T2DM) towards advanced fibrosis, end-stage liver disease, and hepatocarcinoma has led to increased concern for quantifying liver injury and individual risk assessment. The combination of blood-based markers and imaging techniques is recommended for the initial evaluation in NAFLD and for regular monitoring to evaluate disease progression. Continued development of ultrasonographic and magnetic resonance imaging methods for accurate quantification of liver steatosis and fibrosis, as well as promising tools for the detection of high-risk NASH, have been noted. In this review, we aim to summarize available evidence regarding the usefulness of non-invasive methods for the assessment of NAFLD in T2DM. We focus on the power and limitations of various methods for diagnosis, risk stratification, and patient monitoring that support their implementation in clinical setting or in research field.

The study aimed to investigate an association of increased liver fibrosis with acute myocardial infarction (AMI), and to investigate the mediating effect of serum follistatin-like protein 3 (FSTL3) on the association in patients with type 2 diabetes mellitus (T2DM).

A total of 1424 participants were included in this study, and were firstly divided into two groups: 429 T2DM patients and 995 T2DM patients with NAFLD to assess the association of NAFLD and AMI. Then 995 T2DM co-existent NAFLD patients were categorized by NAFLD fibrosis risk to explore the association between NAFLD fibrosis risk and AMI. Immunohistochemistry staining and semi-quantitative analysis of liver FSTL3 were performed in 60 patients with NAFLD. There were 323 individuals (191 without AMI and 132 with AMI) in T2DM co-existent NAFLD patients who had serum samples, and serum FSTL3 was tested and mediation effect of FSTL3 in association of NAFLD fibrosis and AMI was performed.

First, increased NAFLD fibrosis risk was an independent risk factor for AMI in patients with T2DM and co-existent NAFLD. In addition, analysis of Gene Expression Omnibus (GEO) database and immunohistochemical staining confirmed the increased expression of FSTL3 in the liver of NAFLD patients with fibrosis. Serum FSTL3 significantly increased in patients with high NAFLD fibrosis risk and AMI, and closely associated with NAFLD fibrosis and AMI severity in T2DM patients with co-existent NAFLD. Most importantly, analysis of the level of mediation revealed that increased serum FSTL3 partially mediated the association of increased NAFLD fibrosis risk with AMI in T2DM patients with co-existent NAFLD.

NAFLD fibrosis was closely associated with AMI in T2DM patients. FSTL3 expression was enriched in the liver of NAFLD patients with significant and advanced fibrosis, and serum FSTL3 partially mediated the association of increased liver fibrosis risk with AMI in T2DM patients.

Acute coronary syndrome (ACS) and non-alcoholic fatty liver disease (NAFLD) are two clinically common disease entities that share numerous risk factors. This review aimed to discuss the impacts of NAFLD on ACS.

In an era of improved control of traditional risk factors, the substantial burden of cardiometabolic abnormalities has caused widespread concern. NAFLD is considered the hepatic component of metabolic syndrome, which can exert an impact on human health beyond the liver. Accumulating studies have demonstrated that NAFLD is closely related to cardiovascular disease, especially coronary artery disease. Interestingly, although recent data have suggested an association between NAFLD and the incidence and outcomes of ACS, the results are not consistent. In this review, we comprehensively summarized evidence and controversies regarding whether NAFLD is a contributor to either the development of ACS or worse outcomes in patients with ACS. The potential pathophysiological and molecular mechanisms involved in the impacts of NAFLD on ACS were also elucidated.

Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are independent risk factors for cardiovascular disease (CVD).

To examine the clinical utility of liver fat quantification for determining CVD risk among a well-phenotyped cohort of patients with T2DM.

This was a cross-sectional analysis of a prospective cohort of adults aged ≥50 with T2DM. Liver fat was quantified with magnetic resonance imaging proton-density-fat-fraction (MRI-PDFF), an advanced imaging-based biomarker. Patients were stratified into a higher liver fat group (MRI-PDFF ≥ 14.6%), and a lower liver fat group (MRI-PDFF < 14.6%). The co-primary outcomes were CVD risk determined by Framingham and Atherosclerotic Cardiovascular Disease (ASCVD) risk scores. High CVD risk was defined by risk scores ≥20%.

Of the 391 adults (66% female) in this study, the mean (±SD) age was 64 (±8) years and BMI 30.8 (±5.2) kg/m2 , respectively. In multivariable analysis, adjusted for age, gender, race, and BMI, patients in the higher liver fat group had higher CVD risk [OR = 4.04 (95% CI: 2.07-7.88, p < 0.0001)] and ASCVD risk score [OR = 2.85 (95% CI: 1.19-6.83, p = 0.018)], respectively.

Higher liver fat content increases CVD risk independently of age, gender, ethnicity and BMI. These findings raise the question whether liver fat quantification should be incorporated into risk calculators to further stratify those with higher CVD risk.

The association between liver fibrosis and oral or gut microbiota has been studied before. However, epidemiological studies in the general population are limited owing to the difficulty of noninvasive liver-fibrosis assessment. FibroScan-asparate aminotransferase (FAST) scores can be used to accurately and non-invasively evaluate liver fibrosis. This study aimed to determine the association between liver fibrosis and oral or gut microbiota using the FAST score in the general population. After propensity score matching of 1059 participants based on sex, age, body mass index, homeostasis model assessment of insulin resistance, and triglyceride levels, 125 (non-liver-fibrosis group, 100; liver fibrosis group, 25) were included. The diversity of gut microbiota differed significantly between the two groups; however, no significant differences were noted in their oral microbiota. The liver fibrosis group showed an increase in the relative abundance of Fusobacteria strains and a decrease in the relative abundance of Faecalibacterium, with the presence of Fusicatenibacter in the gut microbiota. Feacalibacterium was not identified as an independent factor of liver fibrosis in adjusting the fatty liver index. In the general population, gut microbiota may be more involved in liver fibrosis than oral microbiota.

To investigate the relationship between uric acid to high-density lipoprotein cholesterol ratio (UHR) levels and nonalcoholic fatty liver disease (NAFLD) in nonoverweight/obese patients with type 2 diabetes.

A retrospective study was designed including a total of 343 inpatients with type 2 diabetes whose BMI<24 kg/m2. The population was divided into three groups as the UHR tertiles. Logistic regression analysis was performed to estimate odds ratios (ORs) of UHR for NAFLD. ROC curve analysis was used to estimate the diagnostic value of UHR for NAFLD.

The prevalence rat of NAFLD enhanced progressively from the tertile 1 to tertile 3 of UHR (30.70% vs. 56.52% vs. 73.68%). Logistic regression analysis showed that participants in the higher UHR groups, compared with those in the first tertile group, had higher occurrence risks for NAFLD. The positive association between UHR and NAFLD was independent of age, BMI, blood pressure, hepatic enzymes, and other components of metabolic disorders. ROC curve analysis showed that the area under curve (AUC), sensitivity, and specificity for UHR were 0.697, 0.761, and 0.553, respectively.

In type 2 diabetic patients without overweight or obesity, UHR is significantly associated with NAFLD and can be used as a novel and useful predictor for NAFLD onset.

While alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) enzymes are commonly used indicators of liver dysfunction recent studies have suggested that these may also serve as predictive biomarkers in the assessment of extrahepatic morbidity. In order to shed further light on the interactions between serum liver enzyme abnormalities, factors of lifestyle and health status we examined ALT and GGT activities in a population-based sample of 8743 adult individuals (4048 men, 4695 women from the National FINRISK 2002 Study, mean age 48.1 ± 13.1 years) with different levels of alcohol drinking, smoking, physical activity, body weight and the presence or absence of various pre-existing medical conditions. The assessments also included laboratory tests for inflammation, lipid status and fatty liver index (FLI), a proxy for fatty liver. The prevalence of ALT and GGT abnormalities were significantly influenced by alcohol use (ALT: p < 0.0005 for men; GGT: p <0.0005 for both genders), smoking (GGT: p <0.0005 for men, p =0.002 for women), adiposity (p < 0.0005 for all comparisons), physical inactivity (GGT: p <0.0005; ALT: p <0.0005 for men, p <0.05 for women) and coffee consumption (p <0.0005 for GGT in both genders; p <0.001 for ALT in men). The total sum of lifestyle risk factor scores (LRFS) influenced the occurrence of liver enzyme abnormalities in a rather linear manner. Significantly higher LRFS were observed in the subgroups of individuals with pre-existing medical conditions when compared with those having no morbidities (p <0.0005). In logistic regression analyses adjusted for the lifestyle factors, both ALT and GGT associated significantly with fatty liver, diabetes and hypertension. GGT levels also associated with coronary heart disease, angina pectoris, cardiac insufficiency, cerebrovascular disease, asthma and depression. Combinations of abnormal ALT and GGT activities significantly increased the odds for hypertension coinciding with abnormalities in biomarkers of inflammation, lipid status and FLI. The data indicates that ALT and GGT activities readily respond to unfavorable factors of lifestyle associating also with a wide array of pre-existing medical conditions. The data supports close links between both hepatic and extrahepatic morbidities and lifestyle risk factors and may open new insights on a more comprehensive use of liver enzymes in predictive algorithms for assessing mechanistically anchored disease conditions.

The medical disorders of alcoholism rank among the leading public health problems worldwide and the need for predictive and prognostic risk markers for assessing alcohol use disorders (AUD) has been widely acknowledged. Early-phase detection of problem drinking and associated tissue toxicity are important prerequisites for timely initiations of appropriate treatments and improving patient's committing to the objective of reducing drinking. Recent advances in clinical chemistry have provided novel approaches for a specific detection of heavy drinking through assays of unique ethanol metabolites, phosphatidylethanol (PEth) or ethyl glucuronide (EtG). Carbohydrate-deficient transferrin (CDT) measurements can be used to indicate severe alcohol problems. Hazardous drinking frequently manifests as heavy episodic drinking or in combinations with other unfavorable lifestyle factors, such as smoking, physical inactivity, poor diet or adiposity, which aggravate the metabolic consequences of alcohol intake in a supra-additive manner. Such interactions are also reflected in multiple disease outcomes and distinct abnormalities in biomarkers of liver function, inflammation and oxidative stress. Use of predictive biomarkers either alone or as part of specifically designed biological algorithms helps to predict both hepatic and extrahepatic morbidity in individuals with such risk factors. Novel approaches for assessing progression of fibrosis, a major determinant of prognosis in AUD, have also been made available. Predictive algorithms based on the combined use of biomarkers and clinical observations may prove to have a major impact on clinical decisions to detect AUD in early pre-symptomatic stages, stratify patients according to their substantially different disease risks and predict individual responses to treatment.

To investigate the association between non-alcoholic fatty liver disease (NAFLD) and liver enzymes with the incidence of microvascular complications (neuropathy, retinopathy, and nephropathy) in a cohort of Iranian patients with type 2 diabetes.

For a total population of 3123 patients with type 2 diabetes, a prospective study was designed for 1215 patients with NAFLD and 1908 gender and age-matched control patients without NAFLD. The two groups were followed for a median duration of 5 years for the incidence of microvascular complications. The association between having NAFLD, the level of liver enzymes, aspartate aminotransferase to platelet ratio index (APRI), Fibrosis-4 (FIB-4) value, and the incidence risk of diabetic retinopathy, neuropathy, and nephropathy were assessed through logistic regression analysis.

NAFLD was found to be associated with incidence of diabetic neuropathy and nephropathy (Odds ratio: 1.338 (95% confidence interval: 1.091-1.640) and 1.333 (1.007-1.764), respectively). Alkaline-phosphatase enzyme was found to be associated with higher risks of diabetic neuropathy and nephropathy ((Risk estimate: 1.002 (95% CI: 1.001-1.003) and 1.002 (1.001-1.004), respectively)). Moreover, gamma-glutamyl transferase was associated with a higher risk of diabetic nephropathy (1.006 (1.002-1.009). Aspartate aminotransferase and alanine aminotransferase were inversely associated with the risk of diabetic retinopathy (0.989 (0.979-0.998) and 0.990 (0.983-0.996), respectively). Furthermore, ARPI_T (1), ARPI_T (2), and ARPI_T (3) were shown to be associated with NAFLD (1.440 (1.061-1.954), 1.589 (1.163-2.171), and 2.673 (1.925, 3.710), respectively). However, FIB-4 score was not significantly associated with risk of microvascular complications.

Despite the benign nature of NAFLD, patients with type 2 diabetes should be always assessed for NAFLD to ensure early diagnosis and entry into proper medical care. Regular screenings of microvascular complications of diabetes is also suggested for these patients.

Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome (MetS) and has been correlated with coronary atherosclerosis (CAS). Since NAFLD was renamed metabolic-associated fatty liver disease(MAFLD) in 2020, no studies have evaluated the correlation between MAFLD and CAS. The aim of this study was to evaluate the relationship between MAFLD and CAS. A total of 1330 patients underwent continuous coronary computed tomography angiography (CCTA) and abdominal ultrasound as part of a routine physical examination. Ultrasonography was used to assess fatty liver, and CCTA was used to assess coronary artery plaques, degree of stenosis, and diseased blood vessels. Univariate and multivariate logistic regression analyses were performed with plaque type and degree of stenosis as dependent variables and MAFLD and traditional cardiovascular risk factors as independent variables to analyze the correlation between MAFLD and CAS. Among the 1164 patients, 680 (58.4%) were diagnosed with MAFLD through a combination of ultrasound and auxiliary examinations. Compared with the non-MAFLD group, the MAFLD group had more cardiovascular risk factors,and the MAFLD group had more likely to have coronary atherosclerosis, coronary stenosis and multiple coronary artery stenosis.In the univariate logistic regression, MAFLD was significantly correlated with overall plaque, calcified plaques, noncalcified plaques, mixed plaques,and significant stenosis in the coronary arteries.(p < 0.05). After adjusting for cardiovascular risk factors , MAFLD was correlated with noncalcified plaques (1.67; 95% confidence interval (CI) 1.15-2.43; p = 0.007) and mixed plaques (1.54; 95% CI 1.10-2.16; p = 0.011). In this study, MAFLD group had more cardiovascular risk factors, MAFLD was correlated with coronary atherosclerosis,and significant stenosis.Further study found independent associations between MAFLD and noncalcified plaques and mixed plaques, which suggest a clinically relevant link between MAFLD and coronary atherosclerosis.

The effect of change in non-alcoholic fatty liver disease (NAFLD) status on incident diabetes has not been well studied. We aimed to investigate the association of NAFLD development and remission with the risk of incident diabetes during a median of 3.5-year follow-up.

A total of 2690 participants without diabetes were recruited in 2011-2012 and assessed for incident diabetes in 2014. Abdominal ultrasonography was used to determine the change of NAFLD. 75 g oral glucose tolerance test (OGTT) was performed to determine diabetes. NAFLD severity was assessed using Gholam's model. The odds ratios (ORs) for incident diabetes were estimated by logistic regression models.

NAFLD was developed in 580 (33.2%) participants and NAFLD remission occurred in 150 (15.9%) participants during a median of 3.5-year follow-up. A total of 484 participants developed diabetes during follow-up, including 170 (14.6%) in consistent non-NAFLD group, 111 (19.1%) in NAFLD developed group, 19 (12.7%) in NAFLD remission group, and 184 (23.2%) in sustained NAFLD group. The development of NAFLD increased the risk of incident diabetes by 43% (OR, 1.43; 95%CI, 1.10-1.86) after adjustment for multiple confounders. Compared with sustained NAFLD group, remission of NAFLD reduced the risk of incident diabetes by 52% (OR, 0.48; 95%CI, 0.29-0.80). The effect of NAFLD alteration on incident diabetes was not changed after adjustment for body mass index or waist circumference, change of body mass index or waist circumference. In NAFLD remission group, participants with non-alcoholic steatohepatitis (NASH) at baseline were more likely to develop diabetes (OR, 3.03; 95%CI, 1.01-9.12).

NAFLD development increases the risk of incident diabetes, whereas NAFLD remission reduces the risk of incident diabetes. Moreover, presence of NASH at baseline could attenuate the protective effect of NAFLD remission on incident diabetes. Our study suggests that early intervention of NAFLD and maintenance of non-NAFLD are important for prevention of diabetes.

The atherogenic index of plasma (AIP) is the base-10 logarithmic conversion of the triglyceride to high-density lipoprotein cholesterol ratio [AIP = log10 (triglyceride/HDL cholesterol)]. Some studies have found a link between low serum vitamin D levels, AIP, and fatty liver. This study was conducted to evaluate the relationship between AIP levels, fatty liver, and vitamin D levels in obese adolescents aged 10-17 years.

This study included 136 adolescents, including 83 obese and 53 healthy controls, in the age range of 10-17 years. Thirty-nine of the obese adolescents had fatty livers. Those with ultrasonography grades 2 or 3 of fat were in the fatty liver group. The AIP value was calculated as the logarithmic conversion of the ratio (triglyceride/HDL cholesterol) at the base of 10. Vitamin D and other laboratory tests were analyzed biochemically. Statistical evaluations were made with the SPSS program.

The AIP, body mass index (BMI), homeostatic model assessment for insulin resistance (HOMA-IR), and insulin averages of obese adolescents with fatty liver were significantly higher than those of obese adolescents without fatty liver and the healthy control group (p < 0.05). Again, the mean AIP of obese patients without fatty liver was pointedly higher than that of the healthy control group (p < 0.05). There was a positive, moderate relationship between AIP and BMI, AIP and HOMA-IR, and AIP and insulin levels (p < 0.05), whereas there was a negative, moderate (37.3%) relationship between AIP and vitamin D (p = 0.019).

AIP levels were higher in obese adolescents, and this increase was higher in obese adolescents with fatty liver in this study. Moreover, we detected a negative correlation between AIP and vitamin D levels and a positive correlation with BMI, insulin resistance, and insulin levels. Based on our data, we concluded that AIP can be a useful predictor of fatty liver in obese adolescents.

Fatty liver has been suggested to be associated with the development of hypertension. However, whether this association is related to glycemia has not been elucidated. Therefore, we investigated whether the fatty liver index (FLI) predicts the development of hypertension among individuals with and without dysglycemia in a general Japanese population. A total of 3114 participants (1036 males and 2078 females) without hypertension who underwent a Specific Health Checkup in the fiscal year 2013 were followed up until 2018. The participants were divided into six groups based on FLI tertiles (low, moderate, or high) and whether they had dysglycemia. We estimated the hazard ratios (HRs) of each group by sex using the Cox proportional hazard model. Models were adjusted for age, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, smoking, and alcohol consumption and further adjusted for systolic blood pressure (SBP). During the mean follow-up period of 2.8 years, 160 of the 3114 participants developed hypertension. Using the low FLI group with normoglycemia as a reference, the HR for incident hypertension was increased in the high FLI group with and without dysglycemia in both sexes after adjusting for confounders, except SBP (HR [95% confidence interval]: male: 1.52 (1.06-2.17) in normoglycemia and 2.05 (1.43-2.92) in dysglycemia, and female: 1.86 (1.43-2.42) in normoglycemia and 2.98 (2.19-4.07) in dysglycemia). Furthermore, in females, this association was observed after adjusting for SBP. We concluded that FLI was independently associated with an increased risk of incident hypertension in individuals with and without dysglycemia.

To investigate the association between adipose distribution and hepatic steatosis in American adults and to assess whether this association varies among different blood glucose states.

Data from the American National Health and Nutrition Examination Survey (NHANES) 2017-2018 were analyzed. The subjects were divided into three groups: diabetes, prediabetes and normal glucose tolerance (NGT). Hepatic steatosis was quantified by median controlled attenuation parameter (CAP), which was measured by ultrasound transient elastography. Total abdominal fat volume, visceral adipose tissue (VAT) volume, total percent fat, trunk percent fat, android percent fat and android to gynoid ratio (AGR) was measured by dual-energy X-ray absorptiometry (DXA).

Data pertaining to 2986 participants (1581 with hepatic steatosis) were included in the analysis. In the NGT group, the proportion of S0 (<5% of the hepatocytes with fatty infiltration) was 58.9%, and 25.2% for S3 (≥66% of the hepatocytes with fatty infiltration). In contrast, the proportion of S0 was 11.1%, while S3 accounts for as high as 68.7% in the diabetes group. In the NGT group, all parameters of fat distribution revealed a positive relation with the occurrence of hepatic steatosis (p<0.05) except total percent fat (p=0.872) after adjusting for confounding factors. In the prediabetes group, VAT volume, trunk percent fat, android percent fat and AGR had significant influence on hepatic steatosis (p<0.05). As for diabetes, only AGR remained significantly correlated with hepatic steatosis (p=0.004).

For NGT individuals, high level of total abdominal fat volume, VAT volume, trunk percent fat, android percent fat and AGR all can be used to predict hepatic steatosis. For diabetes, only AGR can predict hepatic steatosis among the surveyed parameters of adipose distribution.

Background: There are still open questions with respect to the optimal dietary treatment in patients with type 2 diabetes (T2D) and coexisting non-alcoholic steatohepatitis (NASH). The aim of this study is to investigate, in patients with T2D, the association between NASH, dietary component intake, food groups and adherence to the Mediterranean diet. Methods: Cross-sectional analysis of 2026 people with T2D (1136 men and 890 women). The dietary habits were assessed with the European Prospective Investigation into Cancer and Nutrition (EPIC) questionnaire. NASH was identified by the Index Of NASH (ION). Based on the cluster analysis two dietary patterns were identified: the NASH and the NO-NASH pattern. Results: The macronutrient composition of the diet was similar in the two patterns. However, the NASH pattern compared with the NO-NASH pattern was characterized by a significantly lower content of fibre (p < 0.001), β-carotene (p < 0.001), vitamin C (p < 0.001), vitamin E (p < 0.001), polyphenols (p = 0.026) and antioxidant capacity (p < 0.001). With regard to food consumption, the NASH pattern compared with NO-NASH pattern was characterized by higher intake of rice (p = 0.021), potatoes (p = 0.013), red (p = 0.004) and processed meat (p = 0.003), and a lower intake of wholegrain bread (p = 0.019), legumes and nuts (p = 0.049), vegetables (p = 0.047), fruits (p = 0.002), white meat (p = 0.001), fatty fish (p = 0.005), milk and yogurt (p < 0.001). Conclusions: NO-NASH dietary pattern was characterized by a food consumption close to the Mediterranean dietary model, resulting in a higher content of polyphenols, vitamins, and fibre. These finding highlight the potential for dietary components in the prevention/treatment of NASH in people with T2D.

Non-alcoholic fatty liver disease (NAFLD) is an overlooked complication of type 2 diabetes (T2D). Current recommendations for the management of NAFLD are mainly focused on weight reduction, overlooking the role of macronutrient composition. Although dietary carbohydrates play a major role in intrahepatic fat synthesis, their association with the progression of liver steatosis has not been fully investigated in patients with T2D.

To investigate the association between higher carbohydrate intake and the presence of liver steatosis in patients with T2D.

This cross-sectional study included men and women aged 18-60 years diagnosed with T2D. Anthropometric measurements, hepatic steatosis assessment using the controlled attenuation parameter (CAP), blood samples, and dietary data were analyzed. Participants were divided into two groups: NAFLD and NAFLD-free. A two-sample t-test was used to evaluate the differences between the two groups. Stepwise multiple linear regression models adjusted for potential confounders were used to determine the association between CAP values and higher carbohydrate intake.

In total, 358 participants were included. NAFLD was present in 79.3% of the participants. Body mass index, waist circumference, ALT, HbA1c, and triglycerides showed direct, while HDL-Cholesterol revealed inverse associations with CAP values. No significant relationship was found between carbohydrate intake and steatosis in the total study sample; however, multiple linear regression analysis revealed a significant relationship between carbohydrate intake and CAP values in patients aged ≤50 years.

In patients with T2D, higher carbohydrate intake was associated with liver steatosis in those aged 50 years and below. Further studies are required to confirm the causality between carbohydrate intake and liver steatosis.

Type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) commonly coexist. However, NAFLD's effect on mortality in Asian patients with type 2 diabetes awaits full elucidation. Therefore, we examined NAFLD-related all-cause and cause-specific mortality in a nationwide Asian population with type 2 diabetes.

We included patients who had undergone general health checkups between 2009 and 2012 using the National Health Insurance Service database linked to death-certificate data. Hepatic steatosis was defined as a fatty liver index (FLI) ≥ 60, and advanced hepatic fibrosis was determined using the BARD score.

During the follow-up period of 8.1 years, 222,242 deaths occurred, with a mortality rate of 14.3/1000 person-years. An FLI ≥ 60 was significantly associated with increased risks of all-cause and cause-specific mortality including cardiovascular disease (CVD)-, cancer-, and liver disease (FLI ≥ 60: hazard ratio [HR] = 1.02, 95% confidence interval [CI] 1.01-1.03 for all-cause; 1.07, 1.04-1.10 for CVD; 1.12, 1.09-1.14 for cancer; and 2.63, 2.50-2.77 for liver disease). Those with an FLI ≥ 60 and fibrosis (BARD ≥ 2) exhibited increased risks of all-cause (HR, 95% CI 1.11, 1.10-1.12), CVD- (HR, 95% CI 1.11, 1.09-1.14), cancer- (HR, 95% CI 1.17, 1.15-1.19), and liver disease-related (HR, 95% CI 2.38, 2.29-2.49) mortality.

Hepatic steatosis and advanced fibrosis were significantly associated with risks of overall and cause-specific mortality in patients with type 2 diabetes. Our results provide evidence that determining the presence of hepatic steatosis and/or fibrosis potentially plays a role in risk stratification of mortality outcomes in patients with type 2 diabetes mellitus.

Although non-alcoholic fatty liver disease (NAFLD) is associated with metabolic disorders, its influence on albuminuria has not been determined. The aim of this study was to identify the relationship between NAFLD and albuminuria in the general Korean population.

Data from the Korea National Health and Nutrition Examination Surveys (KNHANES) of 2008-2011 were analyzed (n = 1795). Albuminuria was defined as an albumin-to-creatinine ratio of ≥30 mg/g in random spot urine samples. NAFLD was defined as a fatty liver index (FLI) ≥60 or NAFLD liver fat score (LFS) > -0.64.

A total of 289 (16.1 %) subjects were classified as having albuminuria. Subjects with NAFLD exhibited a higher rate of albuminuria than subjects without NAFLD (crude odds ratios [ORs] = 2.60-2.95, all P < 0.001). Regardless of hypertension, insulin resistance, or obesity, the risk for albuminuria was higher in the NAFLD group than in the group without NAFLD (measured by either FLI or LFS; all P < 0.001). When subjects with NAFLD had sarcopenia, the risk of albuminuria further increased (OR = 4.33-4.64, all P < 0.001). Multiple logistic regression analyses also demonstrated that NAFLD was independently associated with albuminuria (OR = 2.58, 95 % confidence interval [CI] = 1.66-4.02, P < 0.001 for FLI, OR = 1.87, 95 % CI = 1.28-2.75, P = 0.001 for LFS).

NAFLD was associated with an increased risk of albuminuria in the general Korean population. This association was independent of hypertension, insulin resistance, chronic kidney disease, diabetes and obesity, and stronger in subjects with sarcopenia.

Cardiovascular disease (CVD) is the first cause of death in patients with non-alcoholic fatty liver disease (NAFLD) and risk stratification is recommended by current guidelines. The aim of this study is to assess the prevalence of peripheral arterial disease (PAD) in patients with NAFLD and its association with all-cause and cardiovascular disease (CVD) mortality.

9145 participants 40 years or older attended a mobile examination center visit in the 1999-2004 cycles of the National Health and Nutrition Examination Survey. PAD was defined as an ankle-brachial index (ABI) < 0.90 in either of the legs and mortality data through December 2015 were obtained from the National Death Index. NAFLD was defined by a fatty liver index ≥ 60 in the absence of other liver conditions, leading to a final sample of 3094 subjects.

The overall prevalence of PAD was 5.9% (95% CI 5.0-6.9). Over a median follow-up of 13 years, 876 participants died, 208 of cardiovascular causes. Incidence rates of all-cause mortality (for 1000 person-years) were 20.2 (95% CI 18.7-21.7) and 70.0 (95% CI 60.1-81.6) for participants without and with PAD, respectively. Multivariable-adjusted Cox proportional hazard models showed that PAD was associated with a higher risk of all-cause (1.8, 95% CI 1.4-2.4) and cardiovascular mortality (HR 2.5, 95% CI 1.5-4.3) after adjustment for potential confounders including prevalent CVD.

Current guidelines strongly encourage the screening of CVD in patients with NAFLD and the use of the simple and inexpensive measurement of ABI in routine clinical practice may find indication.

The increasing burden of non-alcoholic fatty liver disease (NAFLD) worldwide imposes an emerging public health issue. We perform the current study to estimate the global prevalence, incidence, disease progression, and clinical outcomes of NAFLD.

A systematic search was conducted in Medline, Embase, Web of Science, Google Scholar, and Cochrane CENTRAL that screened articles in English language published from January 2000 to December 2021. NAFLD prevalence, incidence, rate of disease progression, and outcomes were calculated with the DerSimonian-Laird random effects model with arcsine transformation.

Our search identified 59,156 records, of which 578 studies fulfilled our inclusion criteria. The overall prevalence of NAFLD was 29.38% (95% confidence interval [CI] 28.09-30.69) regardless of the diagnostic techniques. Looking at the group in which the diagnosis was made by ultrasound exclusively, the pooled prevalence was 30.49% (95% CI 29.55-31.43). NAFLD has become more prevalent during the year 2011-2021 (31.63%, 95% CI 30.23-33.04) compared with year 2000-2010 (27.94%, 95% CI 26.23-29.69). The pooled estimation of non-alcoholic steatohepatitis prevalence was 8.26% (95% CI 1.13-21.01), 46.49% (95% CI 35.93-57.20), and 46.72% (95% CI 37.57-55.98) in general population, NAFLD patients, and severe/morbidly obese patients, respectively. Based on a total of 110,142 newly developed NAFLD patients, the pooled incident rate was estimated as 46.24 cases per 1000 person-years (95% CI 43.21-49.30). In patients with NAFLD, the incident rate of hepatocellular carcinoma was 1.46 (95% CI 0.90-2.03) cases per 1000 person-years. The overall pooled estimate of NAFLD related mortality was 23.91 (95% CI 13.55-37.18) death per 1000 person-years.

The prevalence of NAFLD is increasing globally. It is contributing to poor clinical outcomes including hepatocellular carcinoma and death. Rising awareness and urgent actions are warranted to control the NAFLD pandemic across the globe.

PROSPERO, No. CRD42020171104.

Obesity is a global epidemic that drives morbidity and mortality through cardiovascular disease, diabetes, and non-alcoholic fatty liver disease (NAFLD). No definitive therapy has been approved to improve glycemic control and treat NAFLD in obese patients. Here, we investigated a semi-synthetic, long chain, structurally-engineered fatty acid-1024 (SEFA-1024), as a treatment for obesity-induced hyperglycemia, insulin-resistance, and fatty liver disease in rodent models. A single dose of SEFA-1024 was administered to evaluate glucose tolerance and active glucagon-like peptide 1 (GLP-1) in lean rats in the presence and absence of a DPP-4 inhibitor. The effects of SEFA-1024 on weight loss and glycemic control were assessed in genetic (ob/ob) and environmental (high-fat diet) murine models of obesity. Liver histology, serum liver enzymes, liver lipidomics, and hepatic gene expression were also assessed in the high-fat diet murine model. SEFA-1024 reversed obesity-associated insulin resistance and improved glycemic control. SEFA-1024 increased active GLP-1. In a long-term model of diet-induced obesity, SEFA-1024 reversed excessive weight gain, hepatic steatosis, elevated liver enzymes, hepatic lipotoxicity, and promoted fatty acid metabolism. SEFA-1024 is an enterohepatic-targeted, eicosapentaenoic acid derivative that reverses obesity-induced dysregulated glucose metabolism and hepatic lipotoxicity in genetic and dietary rodent models of obesity. The mechanism by which SEFA-1024 works may include increasing aGLP-1, promoting fatty acid oxidation, and inhibiting hepatic triglyceride formation. SEFA-1024 may serve as a potential treatment for obesity-related diabetes and NAFLD.