Hepatic Steatosis Index Research Articles

Impairments of insulin and glucagon sensitivity in Chinese women with gestational diabetes mellitus.

To evaluate insulin and glucagon sensitivity in Han Chinese women with and without gestational diabetes mellitus (GDM). In total, 81 women with GDM and 81 age-matched healthy controls were evaluated with a 75 g oral glucose tolerance test (OGTT) at gestational weeks 24-28. Plasma glucose concentrations were measured at fasting and 1 h and 2 h post-OGTT. Fasting plasma insulin, glucagon and amino acids were also measured. Insulin and glucagon sensitivity were assessed by the homeostatic model assessment of insulin resistance (HOMA-IR) and glucagon-alanine index, respectively. As expected, plasma glucose concentrations were higher at fasting and 1 h and 2 h post-OGTT in GDM participants (p < .001 each). Both the HOMA-IR and the glucagon-alanine index were higher in GDM participants. There was a weak positive correlation between HOMA-IR and glucagon-alanine index (r = 0.24, p = .0024). Combining the HOMA-IR and the glucagon-alanine index yielded better capacity (area under the curve = 0.878) than either alone (area under the curve = 0.828 for HOMA-IR and 0.751 for glucagon-alanine index, respectively) in differentiating GDM from healthy participants. While the majority of GDM participants (64%) exhibited both reduced insulin and glucagon sensitivity, a third of them presented either reduced insulin (20%) or glucagon (14%) sensitivity alone. HOMA-IR and glucagon-alanine index correlated differentially with fasting glucose, triglycerides, low-density lipoprotein cholesterol, sum of amino acids and hepatic steatosis index. Impairments of both insulin and glucagon sensitivity occur frequently in Chinese women with GDM, which may, individually or together, drive metabolic derangements in GDM. These observations provide new insights into the pathophysiology of GDM and support the need to target insulin or glucagon resistance, or both, in the management of GDM.

Impact of Korean Military Service on the Prevalence of Steatotic Liver Disease: A Longitudinal Study of Pre-enlistment and In-Service Health Check-Ups.

Young Korean men are obligated to serve in the military for 18 to 21 months. We investigated the effects of military service on steatotic liver disease (SLD) and other metabolic parameters. Pre-enlistment health check-up performed from 2019 to 2022 and in-service health check-up performed from 2020 to 2022 were merged as paired data. SLD was defined as a hepatic steatosis index of 36 or higher. Hypertension (HTN) and hypertriglyceridemia were also included in the analysis. A total of 503,136 paired cases were included in the analysis. Comparing pre-enlistment and in-service health check-ups, the prevalence of SLD (22.2% vs 17.6%, p<0.001), HTN (7.6% vs 4.3%, p<0.001), and hypertriglyceridemia (8.1% vs 2.9%, p<0.001) decreased during military service. In terms of body mass index, the proportion of underweight (8.2% vs 1.4%, p<0.001) and severely obese (6.1% vs 4.9%, p<0.001) individuals decreased over time. Regarding factors associated with SLD development and resolution, age was positively associated with SLD development (odds ratio, 1.146; p<0.001) and a health check-up interval of <450 days was a protective factor for SLD development (odds ratio, 0.746; p<0.001). Those serving in the marines were less likely to develop SLD, whereas those serving in the navy were more likely to develop SLD. Serving in the army or the navy was negatively associated with SLD resolution, whereas serving in the air force was positively associated with SLD resolution. The prevalence of SLD, HTN, and hypertriglyceridemia decreased substantially during Korean military service.

Variational autoencoders for generative modeling of drug dosing determinants in renal, hepatic, metabolic, and cardiac disease states

AbstractPhysiological determinants of drug dosing (PDODD) are a promising approach for precision dosing. This study investigates the alterations of PDODD in diseases and evaluates a variational autoencoder (VAE) artificial intelligence model for PDODD. The PDODD panel contained 20 biomarkers, and 13 renal, hepatic, diabetes, and cardiac disease status variables. Demographic characteristics, anthropometric measurements (body weight, body surface area, waist circumference), blood (plasma volume, albumin), renal (creatinine, glomerular filtration rate, urine flow, and urine albumin to creatinine ratio), and hepatic (R‐value, hepatic steatosis index, drug‐induced liver injury index), blood cell (systemic inflammation index, red cell, lymphocyte, neutrophils, and platelet counts) biomarkers, and medical questionnaire responses from the National Health and Nutrition Examination Survey (NHANES) were included. The tabular VAE (TVAE) generative model was implemented with the Synthetic Data Vault Python library. The joint distributions of the generated data vs. test data were compared using graphical univariate, bivariate, and multidimensional projection methods and distribution proximity measures. The PDODD biomarkers related to disease progression were altered as expected in renal, hepatic, diabetes, and cardiac diseases. The continuous PDODD panel variables generated by the TVAE satisfactorily approximated the distribution in the test data. The TVAE‐generated distributions of some discrete variables deviated from the test data distribution. The age distribution of TVAE‐generated continuous variables was similar to the test data. The TVAE algorithm demonstrated potential as an AI model for continuous PDODD and could be useful for generating virtual populations for clinical trial simulations.

The Association of the Hepatic Steatosis Index With Pro/Anti-inflammatory Mediators in Adult Patients With NAFLD: A Cross-Sectional Study

The Association of the Hepatic Steatosis Index With Pro/Anti-inflammatory Mediators in Adult Patients With NAFLD: A Cross-Sectional Study

Influence of Adherence to the Mediterranean Diet and Level of Physical Activity with Liver Steatosis in People Aged > 50 Years and with a BMI > 25 kg/m2: Association with Biochemical Markers.

The main objective of this study is to determine the accuracy of different biochemical markers of hepatic steatosis and to correlate liver steatosis with adherence to the Mediterranean diet and level of physical activity. A cross-sectional study was carried out, including subjects over 50 years of age, with a BMI > 25 kg/m2, but excluding any patient with documented hepatic pathology other than hepatic steatosis. Participants were divided into two groups: patients with hepatic steatosis diagnosed by ultrasound (SG) and a control group of individuals without hepatic steatosis (CG). The level of physical activity was recorded by the IPAQ-SF questionnaire and the adherence to the Mediterranean diet was recorded using the PREDIMED questionnaire. Biochemical markers analyzed included the Hepatic steatosis index (HSI), AST-to-Platelet ratio (APRI) and Fibrosis-4 (FIB-4). A total of 116 patients were included, 71 belonging to the SG and 45 to the CG. A total of 58.6% of the patients showed low adherence to the Mediterranean diet, 35.4% moderate adherence and 6% high adherence. The median estimated physical activity was 495 METS, with most participants reporting light activity. In the SG, significantly higher HSI values were observed (p < 0.001). A cut-off point of a HSI of 40 was established, with a sensitivity of 73.2% and a specificity of 65.8%. Significantly higher FIB-4 values (p = 0.039) were also observed in the SG. A cut-off point of FIB-4 was set at 0.27, with a sensitivity of 69% and a specificity of 57.9%. Patients in the SG showed lower scores in the PREDIMED. Patients in the SG tended to show lower METS scores. However, the higher number of patients with intense activity in the CG group stands out (p = 0.008). The HSI and FIB-4 showed a significant correlation with liver steatosis. Hepatic steatosis is associated with low adherence to the Mediterranean diet and patients with hepatic steatosis tended to have lower METS scores.

Diagnostic performance of sixteen biomarkers for MASLD: A study in a Mexican cohort

Background and aimsMetabolic Dysfunction-associated Steatotic Liver Disease (MASLD) poses a heightened cardiovascular risk. Identifying efficient biomarkers for early MASLD detection in resource-limited Latin American regions is crucial. We aimed to evaluate the diagnostic efficacy of sixteen biomarkers for MASLD in Mexican individuals. MethodsIn this cross-sectional and analytical study, steatosis was assessed using vibration-controlled transient elastography. MASLD was defined according to international standards. Assessed biomarkers included: Visceral Fat (VF), Waist Circumference (WC), Waist-Height Ratio (WHtr), Waist-Hip Ratio (WHr), Visceral Adiposity Index (VAI), Hepatic Steatosis Index (HSI), Body Mass Index (BMI), Homeostatic Model Assessment (HOMA), Weight-Adjusted-Waist Index (WWI), Lipid Accumulation Product (LAP), Uric Acid-Creatinine Ratio (UACR), Triglyceride-Glucose Index (TyG) and its variants TyG-WC, TyG-HDL, TyG-BMI, TyG-WHtr. Results161 participants were included, of which 122 met MASLD criteria (56 % women, age 53.9 years [47.5–64]) and 39 were healthy controls (76 % women, age 52 [45–64]). The AUROCs of the biomarkers for MASLD were: TyG-WC (0.84), LAP (0.84), TyG-BMI (0.82), TyG-WHtr (0.80), WC (0.78), TyG (0.77), WHtr (0.75), BMI (0.76), VF (0.75), HSI (0.75), TyG-HDL (0.75), WHr (0.72), VAI (0.73), UA/CR (0.70), HOMA (0.71), and WWI (0.69). Sex-based differences were observed. After adjusting for sociodemographic variables, the TyG-WC index was the best predictor of MASLD. ConclusionsIn conclusion, our results underscore the potential of several noninvasive biomarkers for MASLD assessment in a Mexican population, highlighting variations in diagnostic efficacy and cut-off values between sexes. After adjusting, TyG-WC was the best MASLD predictor.

Precision Non-Alcoholic Fatty Liver Disease (NAFLD) Diagnosis: Leveraging Ensemble Machine Learning and Gender Insights for Cost-Effective Detection.

Non-Alcoholic Fatty Liver Disease (NAFLD) is characterized by the accumulation of excess fat in the liver. If left undiagnosed and untreated during the early stages, NAFLD can progress to more severe conditions such as inflammation, liver fibrosis, cirrhosis, and even liver failure. In this study, machine learning techniques were employed to predict NAFLD using affordable and accessible laboratory test data, while the conventional technique hepatic steatosis index (HSI)was calculated for comparison. Six algorithms (random forest, K-nearest Neighbors, Logistic Regression, Support Vector Machine, extreme gradient boosting, decision tree), along with an ensemble model, were utilized for dataset analysis. The objective was to develop a cost-effective tool for enabling early diagnosis, leading to better management of the condition. The issue of imbalanced data was addressed using the Synthetic Minority Oversampling Technique Edited Nearest Neighbors (SMOTEENN). Various evaluation metrics including the F1 score, precision, accuracy, recall, confusion matrix, the mean absolute error (MAE), receiver operating characteristics (ROC), and area under the curve (AUC) were employed to assess the suitability of each technique for disease prediction. Experimental results using the National Health and Nutrition Examination Survey (NHANES) dataset demonstrated that the ensemble model achieved the highest accuracy (0.99) and AUC (1.00) compared to the machine learning techniques that we used and HSI. These findings indicate that the ensemble model holds potential as a beneficial tool for healthcare professionals to predict NAFLD, leveraging accessible and cost-effective laboratory test data.

Precision nutrition impact on metabolic health and quality of life in aging population after a 3-month intervention: A randomized intervention

ObjectivesInnovative precision dietary procedures are required to promote healthy aging. This study aimed to evaluate the effects of a personalised strategy based on the inclusion of individualised foods and digital tools on overall health status and quality of life within a follow-up of 3 months in older adults with overweight or obesity. Methods127 men and women aged between 50 and 80 years with overweight/obesity participated in the study—between January 2020 and September 2020 at the Center for Nutrition Research-University of Navarra and IMDEA-ALIMENTACIÓN—and were randomly assigned to a usual-care group (standard recommendations) or precision group (precision nutrition strategy based on the inclusion of individualised foods and a mobile application). Anthropometry, body fat percentage, biochemical parameters, diet, and quality of life (SF-36 Health Survey) were assessed at baseline and after 3 months. ResultsBoth strategies were found to improve overall metabolic health; however, the precision approach demonstrated significantly better outcomes. The precision strategy reduced body weight at 3 months (−4.3 kg; p < 0.001) with significant improvements in body fat percentage, blood pressure and general metabolic health (glycated haemoglobin; alanine aminotransferase; aspartate aminotransferase; hepatic steatosis index) in comparison with the standard recommendations. The precision approach significantly enhanced the quality of life (SF-36) of individuals, with additional improvements in emotional well-being (p = 0.024) and vitality (p = 0.008). Adherence to the Mediterranean diet was significantly associated with a higher quality of life and vitality. ConclusionThese results support the benefit of precision nutrition approaches for promoting healthy aging and emotional well-being, enhancing the quality of life in aging populations, during the COVID-19 pandemic.

Functional state of the liver and endothelium in patients with menopausal metabolic syndrome

Aim. To assess the functional state of the liver and endothelium in patients with menopausal metabolic syndrome, depending on the degree of obesity. Materials and methods. 70 patients with menopausal metabolic syndrome and obesity of varying degrees with an average age of 49.9±1.1 years and 30 practically healthy women without obesity and liver pathology with an average age of 47.3±2.6 years (comparison group) who were in the early postmenopausal period were examined. All women underwent biometric and laboratory-instrumental examination, including assessment of biometric indicators, determination of estradiol levels in the blood, biochemical markers of cytolysis and cholestasis, markers of endothelial dysfunction, assessment of microvascular tone reaction with calculation of the thermal vasodilation index, ultrasound examination of the liver and calculation of the Hepatic steatosis index (HSI). Results. All patients with menopausal metabolic syndrome had a genoid type of obesity and hypoestrogenism. The level of estradiol decreased more significantly during the transition to the 1st degree of obesity (p=0.001). According to ultrasound and the HSI index, signs of liver steatosis were found in all patients with menopausal metabolic syndrome. Functional liver tests were within the reference values, 13% had an increase in the level of alkaline phosphatase, more significant in the group with grade 3 obesity (p=0.034). Laboratory markers of endothelial dysfunction were significantly higher in patients with menopausal metabolic syndrome than in the comparison group. The muscular and neurogenic index of thermal vasodilation significantly decreased in women with grade 1 obesity compared to the group with “pre-obesity“ (p=0.041 and 0.047). The lowest endothelial response was observed at the transition to the 1st degree of obesity in comparison with women with excess body weight. Conclusion. For patients with menopausal metabolic syndrome to assess the condition of the liver, it is recommended to conduct a comprehensive instrumental laboratory examination, including ultrasound examination of the liver, biochemical parameters and calculation of the steatosis index.

Assessment of the appropriate cutoff points for anthropometric indices and their relationship with cardio-metabolic indices to predict the risk of metabolic associated fatty liver disease

BackgroundResearch on Metabolic Associated Fatty Liver Disease (MAFLD) is still in its early stages, with few studies available to identify and predict effective indicators of this disease. On the other hand, early diagnosis and intervention are crucial to reduce the burden of MAFLD. Therefore, the aim of this research was to investigate the effectiveness of eleven anthropometric indices and their appropriate cut-off values as a non-invasive method to predict and diagnose MAFLD in the Iranian population.MethodsIn this cross-sectional study, we analyzed baseline data from the Hoveyzeh Cohort Study, a prospective population-based study conducted in Iran that enrolled a total of 7836 subjects aged 35 to 70 years from May 2016 through August 2018.ResultsThe optimal cut-off values of anthropometric indices for predicting MAFLD risk were determined for waist circumference(WC) (102.25 cm for males and 101.45 cm for females), body mass index (BMI) (27.80 kg/m2 for males and 28.75 kg/m2 for females), waist-to-hip ratio (WHR) (0.96 for both males and females), waist-to-height ratio (WHtR) (0.56 for males and 0.63 for females), body adiposity index (BAI) (23.24 for males and 32.97 for females), visceral adiposity index (VAI) (1.64 for males and 1.88 for females), weight-adjusted waist index (WWI) (10.63 for males and 11.71 for females), conicity index (CI) (1.29 for males and 1.36 for females), body roundness index (BRI) (4.52 for males and 6.45 for females), relative fat mass (RFM) (28.18 for males and 44.91 for females) and abdominal volume index (AVI) (18.85 for males and for 21.37 females). VAI in males (sensitivity: 77%, specificity: 60%, Youden’s Index: 0.37) and RFM in females (sensitivity: 76%, specificity: 59%, Youden’s Index: 0.35) were found to have higher sensitivity and specificity compared to other anthropometric indices. Furthermore, anthropometric indices demonstrated statistically significant correlations with various hepatic and cardiometabolic indices. Among these, the strongest positive correlations were observed between WC, BMI, BAI, BRI, and AVI with the Hepatic Steatosis Index (HSI), TyG-BMI, and TyG-WC, as well as between VAI and the Atherogenic Index of Plasma (AIP), Lipid Accumulation Product (LAP), Cardiometabolic Index (CMI), and the Triglyceride and Glucose (TyG) Index.ConclusionAnthropometric indices are effective in predicting MAFLD risk among Iranian adults, with WWI, VAI, and RFM identified as the strongest predictors. The proposed cutoff values could serve as a straightforward and non-invasive methods for the early diagnosis of MAFLD.

Usefulness of health checkup-based indices in identifying metabolic dysfunction-associated steatotic liver disease.

The application of indices in the context of metabolic dysfunction-associated steatotic liver disease (MASLD) remains unexplored. We aimed to validate the ability of alanine aminotransferase (ALT), fatty liver index (FLI), and hepatic steatosis index (HSI) to identify MASLD during health checkups. We recruited 627 participants and utilized their health checkup data and ultrasound to assess the potential of using ALT, FLI, and HSI as indices for MASLD; this was indicated by the area under the curve (AUC) and restricted cubic spline (RCS) model. The optimal, rule-out (sensitivity ≥90%), and rule-in (specificity ≥90%) cutoff values of each index for identifying MASLD were reported. Among participants with a median age of 46 years, the prevalence of MASLD was 28% in total (38% in males and 18% in females). RCS models confirmed a linear association between indices and MASLD. ROC analyses indicated that the AUC of ALT in identifying MASLD was 0.79 for the total cohort, 0.81 for males, and 0.69 for females. The optimal, rule-out, and rule-in cutoff values for ALT were 21, 13, and 29, respectively. Similarly, the AUC of FLI/HSI in identifying MASLD was 0.90/0.88 for the total cohort, 0.86/0.85 for males, and 0.93/0.90 for females. Considering the reference cutoff values, distinct cutoff values were observed between the sexes for FLI, while HSI had similar cutoff values. This study demonstrated that ALT > 30 IU/L is a reasonable cutoff value to rule-in MASLD. ALT, FLI, and HSI are reliable indices for identifying MASLD during health checkups.

Associations between neonicotinoids and liver function measures in US adults: National Health and Nutrition Examination Survey 2015–2016

Background: Toxicological studies indicate that neonicotinoids may be associated with disruptions in liver function due to an increase in oxidative stress. There are scant epidemiological studies investigating the chronic hepatotoxic effects of neonicotinoids. Objective: To examine the association between detectable concentrations of parent neonicotinoids and neonicotinoid metabolites with liver function markers among US adults, and whether sex modifies this association. Methods: National Health and Nutrition Examination Survey 2015–2016 data were used to estimate associations between detectable neonicotinoids and serum alkaline phosphatase (ALP), alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transaminase (GGT), albumin, total bilirubin, total protein, and Hepatic Steatosis Index (HSI) using multiple linear regression. Results: Detectable levels of N-desmethyl-acetamiprid were associated with a decrease in GGT (β = −3.54 unit/l; 95% confidence interval [CI] = −6.48, −0.61) and detectable levels of 5-hydroxy-imidacloprid were associated with a decrease in HSI (β = −1.11; 95% CI = −2.14, −0.07). Sex modified the association between any parent neonicotinoid and ALP (P int = 0.064) and the association between clothianidin and ALP (P int = 0.019), with a pattern of positive associations in males and inverse associations in females, though stratified associations did not reach statistical significance. Sex also modified the association between 5-hydroxy-imidacloprid and total protein (P int = 0.062), with a significant positive association in females (β = 0.14 g/dl; 95% CI = 0.03, 0.25) and a null association in males. Conclusion: Detectable concentrations of neonicotinoid metabolites were inversely associated with GGT and HSI in US adults. Evidence suggests neonicotinoids may influence liver function differently depending on sex. Future research is recommended to replicate the findings as the study was limited in its cross-sectional nature and inability to examine continuous neonicotinoid concentrations with liver function.

Effects of a multicomponent lifestyle modification intervention on liver function, lipid profile, and body composition in adults with elevated hepatic steatosis index

Parallel to the escalating burden of obesity is the steadily increasing prevalence of metabolic dysfunction associated steatotic liver diseases (MASLD), a chronic condition that progresses from simple steatosis to advanced stages of steatohepatitis, fibrosis, and cirrhosis (1-2). MASLD, regarded as the hepatic manifestation of metabolic syndrome is known to be exacerbated by unhealthy lifestyle choices and the presence of comorbidities such as diabetes, dyslipidemia, and obesity (3-4). Therefore, early identification of the general population at risk of MASLD and the development of multicomponent interventions that can prevent the progression of liver damage and mitigate associated adverse cardiometabolic health outcomes are important. Our study aimed to evaluate the effects of a lifestyle modification program on glucose levels, lipid profile, liver function, and body composition measures in community-living adults with elevated hepatic steatosis index in Mumbai, India.Adults (n= 231, mean age 46.1(13.7) years), 58.6% men) were screened for risk of MASLD using a non-invasive screening tool, Hepatic Steatosis Index (HSI) (calculated as (HSI)= 8 x (ALT/AST ratio) +BMI (+2, if female; +2, if diabetes mellitus) (5). Eligible participants with HSI &gt;36 (predictive of the presence of MASLD) were randomized to receive either a multicomponent lifestyle intervention (experimental group, EG) comprising weekly sessions of individualized dietary counseling (Participants having BMI &gt;23kg/m2 (n = 36) received hypocaloric diets with 40% carbohydrates, 40% fat and 30% proteins (WLD) and those having BMI &lt;22.9kg/m2 (n= 22) received weight maintenance diet (WMD) plans including 55% carbohydrates, 15% protein and 30% fats) and fortnightly group sessions of structured exercise and nutrition education or a standard of care package (control group, CG, n= 43) including general healthy eating and activity guidelines for the 8- week study duration. Paired t test and independent sample t tests were used to determine within and between group changes in variables from baseline to endline.Trial Registration: This study is registered as CTRI/2022/05/042927.Overall, the prevalence of MASLD was 52.2%, 32.8% were hypertensive, and 26.7% and 15.4% had diabetes and hypertriglyceridemia respectively. The intervention (WLD) resulted in decreased weight (mean (M)= 3.4 kg, standard error (SE) = 1.88 k, p = 0.02), body fat percent (M = 2.2%, SE = 1.1%, p= 0.042), serum triglycerides (M=28.8mg/dL, SE 8.5mg/dL, p&lt;0.001) and AST (M= 3.8 U/L, SE= 2.2U/L, p &lt;0.05) values. The WMD group reported improvements in serum cholesterol levels, and ALT/ AST ratio as compared to CG (p &lt;0.001). In WMD, HDL-C increased from 45.8 mg/dl to 47.2 mg/dl and the mean AST values reduced from 28.8 (10.6) U/L to 25.6 (9.9) U/L, but these changes were not statistically significant.Multicomponent lifestyle modification programs integrating diet, physical activity and education are effective strategies to improve liver outcomes and optimize cardiometabolic health in people with MASLD.

Enzyme-Treated Zizania latifolia Ethanol Extract Improves Liver-Related Outcomes and Fatigability.

Long-term hepatic damage is associated with human morbidity and mortality owing to numerous pathogenic factors. A variety of studies have focused on improving liver health using natural products and herbal medicines. We aimed to investigate the effect of enzyme-treated Zizania latifolia ethanol extract (ETZL), which increases the content of tricin via enzymatic hydrolysis, for 8 weeks on liver-related outcomes, lipid metabolism, antioxidant activity, and fatigue compared to a placebo. Healthy Korean adult males aged 19-60 years were randomized into ETZL treatment and placebo groups, and alcohol consumption was 24.96 and 28.64 units/week, respectively. Alanine transaminase, a blood marker associated with liver cell injury, significantly decreased after 8 weeks compared to the baseline in the ETZL treatment group (p = 0.004). After 8 weeks, the treatment group showed significant changes in the levels of high-density lipoprotein and hepatic steatosis index compared to the baseline (p = 0.028 and p = 0.004, respectively). ETZL treatment tended to reduce antioxidant-activity-related factors, total antioxidant status, and malondialdehyde, but there was no significant difference. In the multidimensional fatigue scale, ETZL treatment showed a significant reduction in general fatigue and total-fatigue-related values after 8 weeks compared to the baseline (p = 0.012 and p = 0.032, respectively). Taken together, the 8-week treatment of enzyme-treated Zizania latifolia ethanol extract demonstrated positive effects on liver-related outcomes, lipid metabolism, and mental fatigue without adverse effects on safety-related parameters.

Circulating levels of amyloid-beta (1-40) peptide associate with cardiometabolic traits and risk for metabolic dysfunction-associated steatotic liver disease

Abstract Funding Acknowledgements None. Background and Aims The ageing-associated amyloid-beta 1-40 peptide (Αbeta40) has recently emerged as a blood-based biomarker of cardiovascular disease (CVD). Its levels predict future cardiovascular death and major adverse cardiovascular events in patients with established CVD. The value of Abeta40 in patients with metabolic syndrome who do not concomitantly have clinically overt CVD or other end-organ damage remains poorly understood. At the present study we investigated the value of plasma Αbeta40 in patients with pre- or established metabolic syndrome who are at risk for metabolic dysfunction-associated steatotic liver disease (MASLD). Methods Αbeta40 was measured in plasma by enzyme-linked immunosorbent assay and cardiometabolic traits were determined in a mixed population (n=888) of patients with established (n=243) and pre- or without metabolic syndrome (n=645) who did not have clinical signs of established cardiometabolic disease. The endpoint of the study was the association of Abeta40 with cardiometabolic indices and risk (BARD score) for MASLD. Odds ratio (OR) was calculated by ordinal regression analysis for the increasing incidence of metabolic syndrome components per increasing Abeta40 (1-SD) after adjustment for age, sex, smoking status and hyperlipidemia. Results Abeta40 levels are associated with the presence of metabolic syndrome and with higher odds for increasing incidence of metabolic syndrome components (prediabetes, low HDL-C levels, high triglyceride levels, increased waist circumference and high-risk for MASLD) after adjustment for sex, age, smoking status, hypertension and dyslipidemia. Increased Abeta40 plasma levels were associated with decreased HDL-C levels and increased triglyceride levels after adjustment for traditional cardiovascular risk factors (age, sex, smoking status, hypertension and hyperlipidemia). Among the total population (n=888), we identified n=473 subjects with increased MASLD risk if any of the following was present: hepatic steatosis index≥36 or fatty liver index≥60 or Fib-4 index≥2.67 or NAFLD score≥0.675. Among patients with high-risk for MASLD, patients with increased BARD score had significantly higher Abeta40 levels (median Abeta40 concentration in patients with BARD score≥2 vs. patients with BARD score&amp;lt;2: 54.9 pg/ml (IQR=38.25) vs. 41.9 pg/m (IQR=30.35), P=0.012). Increased Abeta40 levels were associated with increased odds for AST/ALT≥0.8 ratio (OR:1.017, 95% CI: 1.006-1.028, P=0.003) and increased odds for BARD score≥2 after adjustment for age, sex, smoking status, hypertension and hyperlipidemia. Conclusion Our findings suggest that Abeta40 peptide is associated with cardiometabolic traits and risk for MASLD. Whether Abeta40 may emerge as an early cardiometabolic prognostic biomarker, future longitudinal studies are warranted to determine the prognostic value of Abeta40 for the development of cardiometabolic diseases in patients with metabolic syndrome.

A secondary analysis of indices of hepatic and beta cell function following 12 weeks of carbohydrate and energy restriction vs. free-living control in adults with type 2 diabetes

BackgroundSubstantial weight loss in people living with type 2 diabetes (T2D) can reduce the need for glucose-lowering medications while concurrently lowering glycemia below the diagnostic threshold for the disease. Furthermore, weight-loss interventions have also been demonstrated to improve aspects of underlying T2D pathophysiology related to ectopic fat in the liver and pancreatic beta-cell function. As such, the purpose of this secondary analysis was to explore the extent to which a low-carbohydrate and energy-restricted (LCER) diet intervention improves markers of beta-cell stress/function, liver fat accumulation, and metabolic related liver function in people with type 2 diabetes.MethodsWe conducted secondary analyses of blood samples from a larger pragmatic community-based parallel-group randomized controlled trial involving a 12-week pharmacist implemented LCER diet (Pharm-TCR: <50 g carbohydrates; ~850–1100 kcal/day; n = 20) versus treatment-as-usual (TAU; n = 16). Participants were people with T2D, using ≥ 1 glucose-lowering medication, and a body mass index of ≥ 30 kg/m2. Main outcomes were C-peptide to proinsulin ratio, circulating microRNA 375 (miR375), homeostatic model assessment (HOMA) beta-cell function (B), fatty liver index (FLI), hepatic steatosis index (HSI), HOMA insulin resistance (IR), and circulating fetuin-A and fibroblast growth factor 21 (FGF21). Data were analysed using linear regression with baseline as a covariate.ResultsThere was no observed change in miR375 (p = 0.42), C-peptide to proinsulin ratio (p = 0.17) or HOMA B (p = 0.15). FLI and HSI were reduced by -25.1 (p < 0.0001) and − 4.9 (p < 0.0001), respectively. HOMA IR was reduced by -46.5% (p = 0.011). FGF21 was reduced by -161.2pg/mL (p = 0.035) with a similar tendency found for fetuin-A (mean difference: -16.7ng/mL; p = 0.11). These improvements in markers of hepatic function were accompanied by reductions in circulating metabolites linked to hepatic insulin resistance (e.g., diacylglycerols, ceramides) in the Pharm TCR group.ConclusionsThe Pharm-TCR intervention did not improve fasting indices of beta-cell stress; however, markers of liver fat accumulation and and liver function were improved, suggesting that a LCER diet can improve some aspects of the underlying pathophysiology of T2D.Trial registrationClinicaltrials.gov (NCT03181165).

Effect of sustained decreases in sedentary time and increases in physical activity on liver enzymes and indices in type 2 diabetes.

Current guidelines for nonalcoholic fatty liver disease (NAFLD) recommend high volumes and/or intensities of physical activity (PA), the achievement of which generally requires participation in supervised exercise training programs that however are difficult to implement in routine clinical practice. Conversely, counselling interventions may be more suitable, but result in only modest increases in moderate-to-vigorous-intensity PA (MVPA). This study assessed whether a counseling intervention for increasing PA and decreasing sedentary time (SED-time) is effective in improving NAFLD markers in people with type 2 diabetes. Three-hundred physically inactive and sedentary patients were randomized 1:1 to receive one-month theoretical and practical counseling once-a-year (intervention group) or standard care (control group) for 3 years. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and γ-glutamyltranspeptidase (γGT) levels were measured and fatty liver index (FLI), hepatic steatosis index (HSI), and visceral adiposity index (VAI) were calculated. Total PA volume, light-intensity PA (LPA), moderate-to-vigorous-intensity PA (MVPA), and SED-time were objectively measured by an accelerometer. Throughout the 3-year period, NAFLD markers did not change in the control group, whereas ALT, γGT, FLI, and HSI decreased in the intervention group, with significant between-group differences, despite modest MVPA increases, which however were associated with larger decrements in SED-time and reciprocal increments in LPA. Mean changes in NAFLD markers varied according to quartiles of (and correlated with) changes in MVPA (all markers) and SED-time, LPA, and PA volume (ALT, γGT, and HSI). Mean changes in MVPA or PA volume were independent predictors of changes in NAFLD markers. When included in the models, change in cardiorespiratory fitness and lower body muscle strength were independently associated with some NAFLD markers. A behavior change involving all domains of PA lifestyle, even if insufficient to achieve the recommended MVPA target, may provide beneficial effects on NAFLD markers in people with type 2 diabetes.

Four hepatic steatosis indices in predicting quantitative computed tomography-based metabolic dysfunction-associated fatty liver disease

Aim: To evaluate the prediction ability for quantitative computed tomography (QCT)-based metabolic dysfunction-associated fatty liver disease (MAFLD) of four widely known hepatic steatosis algorithms, namely the fatty liver index (FLI), the hepatic steatosis index (HSI), the Framingham Steatosis index (FSI) and the Zhejiang University index (ZJU index). Methods: From July 2020 to June 2022, health checkup subjects who accepted liver fat quantification with QCT at the Health Management Center of the Second Affiliated Hospital of Chongqing Medical University were recruited in this study. MAFLD was diagnosed by using QCT-based liver fat quantification. The prediction performance of FLI, HSI, FSI, and ZJU index on MAFLD was evaluated using the area under the receiver operating characteristic curve (AUC). Results: Of a total of 4,566 subjects enrolled in this study, 48.7% were diagnosed with MAFLD. The AUC values of FLI, HSI, FSI, and ZJU index were 0.819, 0.792, 0.822 and 0.826, respectively. FLI exhibited the highest sensitivity (SN) of 79.42%, while the ZJU index demonstrated the highest specificity (SP) of 75.35%. Conclusions: All four indices (FLI, HSI, FSI, and ZJU index) have acceptable predictive performance for patients with QCT-based MAFLD. Our study suggests that the above indices have a stable ability for detecting MAFLD.

The prognostic value of metabolic dysfunction-associated steatotic liver disease in acute myocardial infarction: A propensity score-matched analysis.

Patients with metabolic dysfunction-associated steatotic liver disease (MASLD) are at increased risk of incident cardiovascular disease. However, the clinical characteristics and prognostic importance of MASLD in patients presenting with acute myocardial infarction (AMI) have yet to be examined. This study compared the characteristics and outcomes of patients with and without MASLD presenting with AMI at a tertiary centre in Singapore. MASLD was defined as hepatic steatosis, with at least one of five metabolic criteria. Hepatic steatosis was determined using the Hepatic Steatosis Index. Propensity score matching was performed to adjust for age and sex. The Kaplan-Meier curve was constructed for long-term all-cause mortality. Cox regression analysis was used to investigate independent predictors of long-term all-cause mortality. In this study of 4446 patients with AMI, 2223 patients with MASLD were matched with patients without MASLD using propensity scores. The mean follow-up duration was 3.4 ± 2.4 years. The MASLD group had higher rates of obesity, diabetes and chronic kidney disease than their counterparts. Patients with MASLD had early excess all-cause mortality (6.8% vs. 3.6%, p < .001) at 30 days, with unfavourable mortality rates sustained in the long-term (18.3% vs. 14.5%, p = .001) compared with those without MASLD. After adjustment, MASLD remained independently associated with higher long-term all-cause mortality (hazard ratio 1.330, 95% confidence interval 1.106-1.598, p = .002). MASLD embodies a higher burden of metabolic dysfunction and is an independent predictor of long-term mortality in the AMI population. Its early identification may be beneficial for risk stratification and provide therapeutic targets for secondary preventive strategies in AMI.

The associations of maternal liver biomarkers in early pregnancy with the risk of gestational diabetes mellitus: a prospective cohort study and Mendelian randomization analysis.

Associations of liver function with the risk of gestational diabetes mellitus (GDM) remain unclear. This study aimed to examine the relationship and the potential causality between maternal liver biomarkers and the risk of subsequent GDM, as well as to evaluate the interaction between liver biomarkers and lipids on GDM risk. In an ongoing Zhoushan Pregnant Women Cohort, pregnant women who finished the first prenatal follow-up record, underwent liver function tests in early pregnancy, and completed the GDM screening were included in this study. Logistic regression models were used to investigate the association, and the inverse-variance weighted method supplemented with other methods of two-sample Mendelian randomization (MR) analysis was applied to deduce the causality. Among 9,148 pregnant women, 1,668 (18.2%) developed GDM. In general, the highest quartile of liver function index (LFI), including ALT, AST, GGT, ALP, and hepatic steatosis index, was significantly associated with an increased risk of GDM (OR ranging from 1.29 to 3.15), especially an elevated risk of abnormal postprandial blood glucose level. Moreover, the causal link between ALT and GDM was confirmed by the MR analysis (OR=1.28, 95%CI:1.05-1.54). A significant interaction between AST/ALT and TG on GDM risk was observed (P interaction = 0.026). Elevated levels of LFI in early pregnancy were remarkably associated with an increased risk of GDM in our prospective cohort. Besides, a positive causal link between ALT and GDM was suggested.