This study investigated the correlation between glucose time-in-range (TIR) and hepatic steatosis severity or liver fibrosis risk in Chinese adults with type 2 diabetes mellitus (T2DM) comorbid with metabolic dysfunction-associated steatotic liver disease (MASLD).

Participants with T2DM were evaluated for hepatic steatosis and fibrosis using vibration-controlled transient elastography. TIR was calculated based on data from a retrospective continuous glucose monitoring system.

A total of 184 T2DM patients with MASLD were enrolled. The controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) decreased with increasing TIR (p < 0.05). Spearman correlation showed negative correlations between CAP, LSM, and TIR (r = -0.824 and - 0.842, p < 0.05) and positive correlations with basal insulin resistance (HOMA-IR) (r = 0.205 and 0.208, p < 0.01). Multiple linear regression revealed TIR and HOMA-IR independently correlated with CAP (std. regression coefficients = -0.695 and 0.103, p < 0.05) and LSM (std. regression coefficients = -0.735 and 0.083, p < 0.05), wit0.34 h TIR having a stronger impact. Binary logistic regression showed TIR Groups 3 (70% ≥ TIR < 85%) and 4 (TIR ≥ 85%) were protective for MASLD (OR = 0.26 and 0.11, 95% CI 0.10-0.66 and 0.04-0.29, P = 0.005 and < 0.001) and liver fibrosis (OR = 0.29 and 0.13, 95% CI 0.12-0.74 and 0.05-0.36, P = 0.010 and < 0.001) compared to TIR Group 1 (lowest quartile).

In T2DM patients with coexisting MASLD, a significant and independent association existed between TIR and the severity of hepatic steatosis.

Not applicable.

It is widely believed that Silybum marianum (Silymarin) alleviates liver injury arising from various etiologies with different degrees of damage through its anti-inflammatory and antioxidant activities. This meta-analysis investigated the effects of silymarin administration on serum levels of liver enzymes including AST, ALT and ALP. From inception to November, 2023, a comprehensive literature search was conducted. Inclusion criteria for this study were randomized trials that provided sufficient data for each group at the beginning and end of the follow-up period. Ultimately, 55 studies with a total of 3545 patients were included. Comprehensive Meta-Analysis (CMA) V4 software was used for meta-analysis. Begg's funnel plot symmetry status, Begg's rank correlation, and Egger's weighted regression tests were used to examine potential publication bias. According to the findings of this meta-analysis silymarin administration showed a significant reduction in AST (SMD [95% CI]: - 0.670 [- 0.931, - 0.408], p-value = 0.000), and ALT (SMD [95% CI]: - 0.912 [- 1.177, - 0.646], p-value = 0.000) levels. While it had no statistically significant effect on ALP level (SMD [95% CI]: - 0.236 [- 1.929, 1.458], p-value = 0.159). Meta-regression analysis showed that there is no significant association between dose, age, BMI, treatment duration and hepatoprotective effects of silymarin. In subgroup analysis, a greater reduction in liver enzymes levels was observed in patients under 50 years old. The subgroup analysis was also showed significant decrease in AST and ALT levels for patients with BMI less than 30, while silymarin treatment had no significant effects on AST and ALT levels in patients with BMI ≥ 30. Silymarin at a dose of less than 400 mg and treatment duration ≤ 2 months showed greater decreasing effects on AST and ALT levels compared to its high doses and longer treatment duration. AST and ALT levels significantly decreased in patients with NAFLD and viral hepatitis, while it had no significant hepatoprotective effects in patients with drugs induced liver injury and alcohol-related liver disease. Modifying the dose and treatment duration with silymarin is recommended in patients with various causes of liver damage.

To comprehensively evaluate the therapeutic efficacy of pioglitazone and SGLT2 inhibitors (SGLT2i) in patients with MASLD and Type 2 Diabetes(T2DM).

Electronic databases, including Web of Science, PubMed, the Cochrane Library, China National Knowledge Internet (CNKI), Wan-Fang Digital Database, and China Science and Technology Journal Database (VIP) were searched from inception to December 2024. Two reviewers independently assessed study eligibility, performed continuous data extraction， and independently evaluated bias risks. Liver ultrasonography, computed tomography (CT), and biochemical indices were utilized to determine the impact of treatment in both groups. Improvement in liver biomarkers and fibrosis as primary outcome indicators; Improvement in body composition, metabolic parameters, glucose parameters, and incidence of adverse effects as a secondary outcome indicator. For continuous variables, mean and standard deviation (SD) were extracted. RevMan 5.4 software was used to systematically analyze the literature, including heterogeneity testing, odds ratios (OR) calculation, and 95 % confidence intervals (CI) for each influencing factor.

Nine randomly controlled trials with 755 Asian participants were included. Our research showed that SGLT2i was more effective than pioglitazone in improving fibrosis-4 score (SMD 0.41 [95%CI 0.18,0.64] p = 0.005), visceral fat area (SMD 0.34 [95%CI 0.14,0.54] p = 0.0007), BMI (SMD 0.29 [95%CI 0.03,0.56] p = 0.03), and low-density lipoprotein levels (SMD 0.21 [95%CI 0.04,0.38] p = 0.01). In contrast, no statistically significant differences were observed in other outcomes.

Our study demonstrated that in patients with MASLD and T2DM, SGLT2i was more effective overall in improving liver fibrosis, blood lipids, liver fat, and body composition in the short term. These findings establish a theoretical basis for safe and rational drug use in clinical practice. Additionally, they may contribute to new insights into the pathogenesis of MASLD and type 2 diabetes and drug discovery and development efforts.

To evaluate the prognostic impact of diabetes mellitus (DM) in patients who underwent resection for perihilar cholangiocarcinoma (PHCC) and the influence of remnant liver volumes on postoperative glycemic profiles and survival outcomes.

The impact of DM and extended hepatectomy on survival outcomes of patients with PHCC remains unclear.

A total of 184 patients who underwent hepatectomy with extrahepatic bile duct resection for PHCC between 2002 and 2020 were retrospectively analyzed and divided into groups based on DM and future liver remnant (FLR) ≥40% or <40%. Survival outcomes and glycemic profiles were analyzed.

Patients with DM (n = 34) had significantly worse overall survival compared with those without DM (n = 150; median survival time: 23.3 vs 46.7 months; P = 0.003) although cancer-specific survival was comparable (P = 0.894). Patients with DM had a higher incidence of death from infections (P < 0.001). Multivariate analysis identified DM as an independent prognostic factor (hazard ratio, 1.742; P = 0.021). DM with FLR <40% (n = 11) exhibited worse survival (median survival time: 13.7 vs 35.0 months; P = 0.026) and a higher incidence of death from infections (P = 0.016) compared with those with FLR ≥40% (n = 23). The median glucose fluctuation was larger in patients with DM and FLR <40% (80 vs 39 mg/dL; P = 0.023).

DM was an independent prognostic factor in patients with PHCC undergoing hepatectomy. DM and FLR <40% were associated with worse survival and larger glucose fluctuation postoperatively.

Non-alcoholic steatohepatitis (NASH) is a serious end-stage spectrum of non-alcoholic fatty liver disease (NAFLD) with associated high risk of hepatic and extrahepatic complications. Several studies showed the significant beneficial effect of dapagliflozin on body composition, hepatic and metabolic parameters on NAFLD/NASH patients. The study aimed to investigate the efficacy and safety of dapagliflozin in both diabetic and non-diabetic biopsy-proven NASH patients; compared to pioglitazone.

This was a four-group, prospective, randomized, parallel, open label study in which 100 biopsy-proven NASH patients were selected, stratified to diabetics and non-diabetics and randomized with 1:1 allocation to either 30 mg pioglitazone or 10 mg dapagliflozin, once daily for 24 weeks. Histological evaluation, anthropometric measures, hepatic, metabolic biochemical markers, fibrosis non-invasive markers, quality of life (QOL) and medications adverse events were examined.

Dapagliflozin showed a comparable histological effect to pioglitazone in both diabetic and non-diabetic patients (P>0.05). As assessed by transient elastography, it also showed a comparable effect on liver fibrosis grade improvement from baseline in diabetics (P=0.287) versus a significant superiority in non-diabetics (P=0.018). Dapagliflozin showed a significant superiority in all anthropometric measures (P<0.001) and QOL (P<0.05) among both diabetics and non-diabetics. There was a significant interaction between interventions and diabetes status on change from baseline of hepatic and metabolic panel collectively (P=0.023) in favor to dapagliflozin among diabetics.

Compared to pioglitazone, dapagliflozin had a comparable effect histologically, superior effect biochemically among diabetics and superior effect on liver fibrosis, steatosis and insulin resistance among non-diabetics.

The study was registered on clinicaltrials.gov, identifier number NCT05254626.

The most prevalent chronic liver disease for which there is currently no proven treatment is non-alcoholic fatty liver disease (NAFLD). An incomplete understanding of the underlying mechanisms of NAFLD may be the cause. The onset and development of this illness appear to be influenced by problems with lipid metabolism, insulin resistance, oxidative stress, and inflammation. Considering the antioxidant properties of pomegranate peel extract, this study was conducted to determine the effects of pomegranate peel consumption on some metabolic features in patients with NAFLD. Our hypothesis is that pomegranate peel can improve the grade of fatty liver, liver enzymes, lipid profile, serum high-sensitivity C-reactive protein (hs-CRP), and anthropometric indices. The aim of this study was to investigate the efficacy of pomegranate peel extract in NAFLD patients. This double-blind randomized clinical trial was conducted on 46 patients with NAFLD. Patients were randomly assigned to intervention group (n = 23) and placebo group (n = 23). Patients in the pomegranate peel group consumed two capsules, each containing 500 mg pomegranate peel extract daily as a part of low-calorie diet (i.e., 500-deficit calorie diet) for 10 weeks. While patients in the control group followed the low calorie diet and two capsules containing 500 mg maltodextrin. At the beginning and end of the study, demographic information, anthropometric indices, food intake, physical activity level, grade of fatty liver, liver enzymes, lipid profile, and serum high-sensitivity C-reactive protein (hs-CRP) were measured. Food intake was measured by 24-h food recall questionnaires and physical activity was measured by the International Physical Activity Questionnaire (IPAQ). Analysis of food recall questionnaire was done using Nutritionist IV program. Statistical analysis was performed using SPSS software (version 22), and a p value < 0.05 was defined as statistically significant. Of 46 patients, 42 of them completed the trial. At the end of the trial, pomegranate peel group had significantly higher reduction in TG (triglycerides), ALT(alanine aminotransferase), AST(aspartate transferase), hs-CRP and also had higher significant increase in HDL-C(high-density lipoprotein cholesterol) compared to the control group (p = 0/02, p = 0/02, p = 0/01, p = 0/01, and p = 0/04, respectively). However, changes in LDL-C, TC, ALP, GGT, and fatty liver grade were not significantly different between the two groups at the end of the study. The current study indicates that pomegranate peel extract has a favorable effect on liver enzymes, lipid profile, and serum high-sensitivity C-reactive protein (hs-CRP) in patients with NAFLD. To support these results, trials examining various dosages over longer time periods are necessary.

Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are associated with a multifactorial complicated aetiology that is often coexisting and has a strong and distinct connection with cardiovascular diseases (CVDs). In order to accomplish effective and appropriate therapeutic strategies, a deeper understanding of the bidirectional interaction between NAFLD patients, NAFLD patients with T2DM, and NAFLD patients with CVDs is required to control the concomitant rise in prevalence of these conditions worldwide. This article also aims to shed light on the epidemiology and mechanisms behind the relationship between T2DM, NAFLD and the related cardiovascular consequences.

Literature was collected from PubMed, Medline, Embase, Web of Science and Google scholar from inception to June, 2024. For surveying literature different combinations and formats of terms including NAFLD, NASH, T2DM and CVDs were used.

In the recent decade, clinical and epidemiological studies have been conducted and provide strong evidence that NAFLD is closely linked with CVD progression along with associated morbidity and mortality in both patients with and without T2DM. Several mechanistic approaches contribute to cardiovascular consequences and abnormalities in cardiac biomarkers in T2DM and NAFLD patients, including adipose tissue malfunction, mitochondrial dysfunction, the microbiota, genetic and epigenetic alterations contributing to insulin resistance, glucotoxicity and lipotoxicity.

The study reveals a complex interplay between diabetes, hepatic and cardiovascular complications, leading to significant morbidity and mortality in diabetic and NAFLD patients. This pandemic necessitates further research to identify mitigating variables and develop effective treatment approaches.

Calorie restriction has been demonstrated to be effective in treating metabolic dysfunction-associated steatotic liver disease (MASLD). However, it has been limited by poor long-term adherence.

This study aimed to compare intermittent calorie restriction (ICR) with traditional continuous calorie restriction (CCR) for the treatment of MASLD.

We conducted a 12-wk, parallel-arm, randomized controlled trial that included 60 adults with MASLD and abnormal glucose metabolism. The participants were randomly assigned to either the ICR group (2 successive days of fasting [∼500 kcal/d] and 5 d of recovery per week) or the CCR group. The primary outcome was liver fat content (LFC) measured by 1H-proton magnetic resonance spectroscopy. The secondary and exploratory outcomes included weight, body composition, glucose, insulin, lipids, and liver stiffness.

The mean reduction in LFC was -20.5% [95% confidence interval (CI): -25.0, -15.9%] in the ICR group and -15.5% (95% CI: -20.3, -10.8%) in the CCR group. Changes in LFC were not significantly different between the 2 groups (P = 0.15), and were homogeneous among different liver segments. The analysis of exploratory endpoints provided clues that the ICR was associated with greater reductions in fat mass and glycosylated hemoglobin. There were no significant differences in changes of weight, lean mass, insulin resistance, triglyceride, and liver stiffness between the 2 groups. Participants showed high adherence to both the ICR and CCR schemes.

The ICR and CCR schemes had similar effects on reducing LFC, suggesting that the ICR 5:2 diet can be an effective alternative for treating MASLD with high adherence.

This trial was registered at clinicaltrials.gov as NCT04283942.

Modifiable risk factors associated with cognitive functioning are important for identifying potential targets for intervention development. Although there are a few recognized modifiable risk factors (e.g., diabetes mellitus, diet, physical activity), there are limitations in the conclusions that can be drawn due to limited data. Therefore, this study examined the relationship between modifiable liver disease-linked metabolic and behavioral factors in a sample of community dwelling adults who do not currently experience functional limitations due to cognitive abilities. Individuals aged 19 to 69 were recruited to participate in this cross-sectional study in the Washington, DC area. Participants were assessed using anthropometric measures, ultrasound of the liver, glycated hemoglobin A1C, self-reported fatigue, clinical history, and 7 domains of cognitive function: processing speed, short- and long-term visual memory, working memory, inhibition, shifting, and abstract reasoning. The study included 104 participants (44% female, 51.1 ± 13.5 years old). The modifiable factors that were most consistently related to cognitive performance were waist-to-height ratio, which was related to a decrease in performance in 4 of the domains (short-term and long-term visual memory, working memory, and abstract reasoning), and the presence of nonalcoholic fatty liver disease, which was related to an increase in performance in the same 4 domains. This study suggests that liver disease-linked modifiable factors are associated with cognitive performance, even in middle-aged individuals without self-reported cognitive dysfunction. Further research is needed to explore the mechanisms that impact cognitive performance in relation to these factors to establish early intervention targets for reducing future cognitive deficits.

Metformin was developed from an offshoot of Guanidine. It is known to be the first-line medication for type 2 diabetes mellitus, polycystic ovarian syndrome, and weight reduction. Metformin has also been shown to have effectiveness in the management of non-alcoholic fatty liver disease (NAFLD), liver cirrhosis, and various carcinomas like hepatocellular, colorectal, prostate, breast, urinary bladder, blood, melanoma, bone, skin, lung and so on. This narrative review focuses on the effect of metformin on non-alcoholic fatty liver disease, liver cirrhosis, and hepatocellular carcinoma. The search platforms for the topic were PubMed, Scopus, and Google search engine. Critical words for searching included 'Metformin,' AND 'Indications of Metformin,' AND 'Non-Alcoholic Fatty Liver Disease,' AND 'Metformin mechanism of action,' AND 'NAFLD management,' AND 'NAFLD and inflammation,' AND 'Metformin and insulin,' AND 'Metformin and inflammation,' AND 'Liver cirrhosis,' AND 'Hepatocellular carcinoma.' Lifestyle modification and the use of hypoglycemic agents can help improve liver conditions. Metformin has several mechanisms that enhance liver health, including reducing reactive oxygen species, nuclear factor kappa beta (NF-κB), liver enzymes, improving insulin sensitivity, and improving hepatic cell lipophagy. Long-term use of metformin may cause some adverse effects like lactic acidosis and gastrointestinal disturbance. Metformin long-term overdose may lead to a rise in hydrogen sulfide in liver cells, which calls for pharmacovigilance. Drug regulating authorities should provide approval for further research, and national and international guidelines need to be developed for liver diseases, perhaps with the inclusion of metformin as part of the management regime.

The prevalence of diabetes mellitus and diabetes-related complications is rapidly increasing worldwide, placing a substantial financial burden on healthcare systems. Approximately 537 million adults are currently diagnosed with type 1 or type 2 diabetes globally. However, interestingly, the increasing morbidity rate is primarily influenced by the effects of long-term hyperglycemia on vital organs such as the brain, the liver and the heart rather than the ability of the body to use glucose effectively. This can be attributed to the summation of the detrimental effects of excessive glucose on major vascular systems and the harmful side effects attributed to the current treatment associated with managing the disease. These drugs have been implicated in the onset and progression of cardiovascular disease, hepatocyte injury and cognitive dysfunction, thereby warranting extensive research into alternative treatment strategies. Literature has shown significant progress in utilizing metal-based compounds, specifically those containing transition metals such as zinc, magnesium and vanadium, in managing hyperglycaemia. Amongst these metals, research carried out on vanadium reflected the most promising anti-diabetic efficacy in cell culture and animal studies. This was attributed to the ability to improve glucose management in the bloodstream by enhancing its uptake and metabolism in the kidney, brain, skeletal muscle, heart and liver. Despite this, organic vanadium was considered toxic due to its accumulative characteristics. To alleviate vanadium's toxic nature while subsequently manipulating its therapeutic properties, vanadium complexes were synthesized using either vanadate or vanadyl as a base compound. This review attempts to evaluate organic vanadium salts' therapeutic and toxic effects, highlight vanadium complexes' research and provide insight into the novel dioxidovanadium complex synthesized in our laboratory to alleviate hyperglycaemia-associated macrovascular complications in the brain, heart and liver.

Patients with psoriasis are at increased risk of liver function abnormalities.

Explore rates of hepatic treatment-emergent adverse events (TEAEs) and changes in liver parameters in bimekizumab-treated patients with psoriasis.

Data are reported from 5 phase 3/3b trials over 2 years. Hepatic TEAEs, laboratory elevations in alanine aminotransferase (ALT) or aspartate aminotransferase (AST), and changes in clinical markers of liver fibrosis (Fibrosis-4 [FIB-4] Index and AST to Platelet Ratio Index [APRI]) are reported. TEAEs are presented using exposure-adjusted incidence rates (EAIRs) per 100 patient-years (PY).

2186 patients received ≥1 bimekizumab dose. Over 2 years, the EAIR of hepatic TEAEs was 3.5/100 PY and did not increase from first to second year. 2-year EAIRs of ALT/AST elevations >3x and >5x the upper limit of normal were 2.3 and 0.6/100 PY; rates were similar to placebo, adalimumab, secukinumab, and ustekinumab during controlled study periods. FIB-4 and APRI scores did not increase through 2 years, regardless of fibrosis risk at baseline.

Obesity, diabetes, dyslipidemia, chronic alcohol consumption, and medication changes are confounding factors for hepatic dysfunction.

Rates of hepatic adverse events (AEs) with bimekizumab were consistent through 2 years; incidences of transaminase elevations were similar to comparators during phase 3/3b controlled study periods.

Genetic factors contribute to the risk and severity of metabolic dysfunction-associated steatotic liver disease (MASLD). However, the utility of genetic testing in risk stratification remains poorly characterised.

To examine the influence of genetic risk on advanced fibrosis and cirrhosis in patients with type 2 diabetes mellitus (T2DM) and the utility of a polygenic risk score (PRS) in screening guidelines.

We prospectively enrolled adults aged ≥50 years with T2DM recruited from clinics. PRS was the sum of risk alleles in PNPLA3, TM6SF2 and SERPINA1 minus the protective variant in HSD17B13. We performed magnetic resonance elastography and vibration-controlled transient elastography to assess for advanced fibrosis and cirrhosis.

Of 382 included patients, the mean age and BMI were 64.8 (±8.4) years and 31.7 (±6.2) kg/m2 respectively. The prevalence of advanced fibrosis and cirrhosis were 12.3% and 5.2% respectively; higher PRS was associated with increased risk of cirrhosis (2.7% vs. 7.5%, p = 0.037). High PRS was associated with increased risk of advanced fibrosis among those with fibrosis-4 index (FIB-4) index <1.3 (9.6% vs. 2.3%, p = 0.036) but was not significantly different in other FIB-4 categories. Incorporating PRS determination into the American Gastroenterological Association and American Association for the Study of Liver Diseases screening guidelines prevented approximately 20% of all participants with advanced fibrosis from being inappropriately classified as low risk.

Utilising a well-phenotyped, prospective cohort of adults with T2DM, we found that adding an assessment of genetic risk to recommendations to screen at-risk populations may improve risk prediction.

Currently, steatohepatitis has been designated as metabolic dysfunction-associated steatohepatitis (MASLD). MASLD risk factors mainly include metabolic disorders but can also include genetic, epigenetic, and environmental factors. Disease entities such as obesity, diabetes, cardiovascular disease, and MASLD share similar pathomechanisms and risk factors. Moreover, a bidirectional relationship is observed between the occurrence of certain chronic diseases and MASLD. These conditions represent a global public health problem that is responsible for poor quality of life and high mortality. It seems that paying holistic attention to these problems will not only help increase the chances of reducing the incidence of these diseases but also assist in the prevention, treatment, and support of patients.

Obesity and metabolic syndrome are linked to steatotic liver disease (SLD), the most common form of chronic liver disease. Lifestyle modifications and dieting are strategies that can prevent metabolic dysfunction-associated steatotic liver disease (MASLD). The very low-calorie ketogenic diet (VLCKD) is a helpful treatment for MASLD and has been recommended for people affected by obesity; we evaluated the effect of gender on steatosis and fibrosis in a cohort of 112 overweight or obese patients undergoing an eight-week treatment with a VLCKD. Differences between the genders in terms of anthropometric measures, body composition, and metabolic indicators were examined before, during, and after the nutritional intervention. At baseline, there were significant differences between men and women in terms of anthropometric parameters, blood pressure, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), fasting insulin, hepatic markers, and lipid profile. Men had considerably higher levels of liver steatosis (measured by CAP) and liver stiffness (measured by E) under basal conditions than women. After the VLCKD, there were reductions in both genders of controlled attenuation parameter (CAP), body weight, body mass index (BMI), waist circumference, systolic and diastolic blood pressure, insulin resistance, fat mass (FM), free fat mass (FFM), and fasting blood glucose, insulin, glycated hemoglobin (HbA1c), triglycerides, total cholesterol, low-density lipoprotein (LDL) cholesterol, alanine transaminase (ALT), gamma-glutamyl transferase (γGT), and uric acid levels. Only in men, liver stiffness, aspartate aminotransferase (AST), creatinine, and C-reactive protein (CRP) levels significantly decreased. Moreover, men had significantly greater levels of liver steatosis: the male gender featured an increase of 23.96 points of the Fibroscan CAP. Men exhibited higher levels of steatosis and fibrosis than women, and these differences persist despite VLCKD. These gender-specific variations in steatosis and fibrosis levels could be caused by hormonal and metabolic factors, suggesting that different therapeutic strategies might be required depending on the gender.

Metabolic dysfunction-associated fatty liver disease (MAFLD) and type 2 diabetes (T2D) are interconnected metabolic disorders with significant health implications. However, a comprehensive understanding of the extent of their co-occurrence in Africa is lacking. The aim of this review was to determine the prevalence of MAFLD and its association with glycemic control (HbA1c) in persons with T2D in Africa. A systematic search was conducted on PubMed, Medline, Embase, Scopus, Global Health, and Web of Science from their inception to December 6, 2023. Data on MAFLD prevalence and correlation coefficients regarding its association with glycemic control were pooled through random effect meta-analyses. Potential sources of heterogeneity were investigated using subgroup analysis and meta-regression. A total of 10 studies were included in the meta-analysis of MAFLD prevalence, while 2 were incorporated in the analysis of the association between MAFLD and glycemic control. The pooled prevalence of MAFLD in persons with T2D was 48.1% (95% CI: 36.1-60.3). The subgroup analysis revealed regional variations in MAFLD prevalence, with rates of 44.7% (95% CI: 28.7-62.0) in sub-Saharan Africa and 55.3% (95% CI: 36.2-73.0) in Northern Africa. Additionally, we observed an increasing trend in MAFLD prevalence, recording 55.1% (95% CI: 43.6-66.1) in the recent five years. There was a weak positive correlation between MAFLD and HbA1c (r = 0.33, 95% CI: 0.18-0.47). The findings of this study highlight a high prevalence of MAFLD in persons with T2D in Africa, with a suggested link between MAFLD and suboptimal glycemic control. Therefore, healthcare providers should prioritize the screening and management of MAFLD in individuals with T2D to enhance their metabolic health.

The incidence and prevalence of metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) are rising globally. MetS and T2DM are associated with significant morbidity and mortality, which is partly related to liver and cardiovascular disease. Insulin resistance is central to MetS and T2DM pathophysiology, and drives ectopic fat deposition in the liver, also known as metabolic dysfunction-associated steatotic liver disease (MASLD). MetS and T2DM are not only risk factors for developing MASLD but are also independently associated with disease progression to steatohepatitis, cirrhosis, and hepatocellular carcinoma. In addition to the risk of liver disease, MetS and T2DM are independent risk factors for cardiovascular disease (CVD), including coronary artery disease (CAD) and heart failure (HF). Importantly, there is a bidirectional relationship between liver and CVD due to shared disease pathophysiology in patients with MetS and T2DM. In this review, we have described studies exploring the relationship of MetS and T2DM with MASLD and CVD, independently. Following this we discuss studies evaluating the interplay between liver and cardiovascular risk as well as pragmatic risk mitigation strategies in this patient population.

There is increasing appreciation of the complex interaction between nonalcoholic fatty liver disease (NAFLD) with type 2 diabetes (T2D) and insulin resistance. Not only is the prevalence of NAFLD disease high among patients with T2D, the liver disease is also more progressive. Currently, the global prevalence of NAFLD in the general population (2016-2019) is 38 %. The prevalence of T2D among those with NAFLD is approximately 23 % while the prevalence of NAFLD among those with T2D can be as high as 70 %. The prevalence of nonalcoholic steatohepatitis (NASH) is approximately 7 % in the general population and 37 % among patients with T2D. Globally, the MENA and Latin America regions of the world appear to have the highest burden of both NAFLD and T2D. Compared to those with NAFLD but without T2D, those with NAFLD and T2D are at a much higher risk for disease progression to cirrhosis and for decompensated cirrhosis, hepatocellular carcinoma, and all-cause mortality. Given that highly effective new treatments are available for T2D, high risk NAFLD with T2D should be considered for these regimens. This requires implementation of risk stratification algorithms in the primary care and endocrinology practices to identify those patients at highest risk for adverse outcomes.

Liver fat storage, also called hepatic steatosis, is increasingly common and represents a very frequent diagnosis in the medical field. Excess fat is not without consequences. In fact, hepatic steatosis contributes to the progression toward liver fibrosis. There are two main types of fatty liver disease, alcoholic fatty liver disease (AFLD) and nonalcoholic fatty liver disease (NAFLD). Although AFLD and NAFLD are similar in their initial morphological features, both conditions involve the same evolutive forms. Moreover, there are various common mechanisms underlying both diseases, including alcoholic liver disease and NAFLD, which are commonalities. In this Review, the authors explore similar downstream signaling events involved in the onset and progression of the two entities but not completely different entities, predominantly focusing on the gut microbiome. Downstream molecular events, such as the roles of sirtuins, cytokeratins, adipokines and others, should be considered. Finally, to complete the feature, some new tendencies in the therapeutic approach are presented.

Fatty liver index (FLI) was developed as a simple and accurate marker of hepatic steatosis. FLI is derived from an algorithm based on body mass index, waist circumference, and levels of triglycerides and gamma-glutamyltransferase, and it is widely used in clinical and epidemiological studies as a screening tool for discriminating between healthy and nonalcoholic fatty liver disease (NAFLD) subjects. However, a systematic review of the literature regarding FLI revealed that this index has more extensive relationships with biochemical and physiological parameters. FLI is associated with key parameters of lipid, protein and carbohydrate metabolism, hormones, vitamins and markers of inflammation, or oxidative stress. FLI can be a predictor or risk factor for a number of metabolic and nonmetabolic diseases and mortality. FLI is also used as an indicator for determining the effects of health-related prevention interventions, medications, and toxic substances on humans. Although in most cases, the exact mechanisms underlying these associations have not been fully elucidated, they are most often assumed to be mediated by insulin resistance, inflammation, and oxidative stress. Thus, FLI may be a promising marker of metabolic health due to its multiple associations with parameters of physiological and pathological processes. In this context, the present review summarizes the data from currently available literature on the associations between FLI and biochemical variables and physiological functions. We believe that this review will be of interest to researchers working in this area and can provide new perspectives and directions for future studies on FLI.

Metabolic associated steatohepatitis (MASH) is metabolic disease that may progress to cirrhosis and hepatocellular carcinoma. Mouse models of diet-induced MASH, which is characterized by the high levels of fats, sugars, and cholesterol in diets, are commonly used in research. However, mouse models accurately reflecting the progression of MASH in humans remain to be established. Studies have explored the potential use of serological metabolites as biomarkers of MASH severity in relation to human MASH.

We performed a comparative analysis of three mouse models of diet-induced MASH in terms of phenotypic and metabolomic characteristics; MASH was induced using different diets: a high-fat diet; a Western diet; and a high-fat, high-cholesterol diet. Liver cirrhosis was diagnosed using standard clinical approaches (e.g., METAVIR score, hyaluronan level, and collagen deposition level). Mouse serum samples were subjected to nuclear magnetic resonance spectroscopy-based metabolomic profiling followed by bioinformatic analyses. Metabolomic analysis of a retrospective cohort of patients with hepatocellular carcinoma was performed; the corresponding cirrhosis scores were also evaluated.

Using clinically relevant quantitative diagnostic methods, the severity of MASH was evaluated. Regarding metabolomics, the number of lipoprotein metabolites increased with both diet and MASH progression. Notably, the levels of very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) significantly increased with fibrosis progression. During the development of diet-induced MASH in mice, the strongest upregulation of expression was noted for VLDL receptor. Metabolomic analysis of a retrospective cohort of patients with cirrhosis indicated lipoproteins (e.g., VLDL and LDL) as predominant biomarkers of cirrhosis.

Our findings provide insight into the pathophysiology and metabolomics of experimental MASH and its relevance to human MASH. The observed upregulation of lipoprotein expression reveals a feedforward mechanism for MASH development that may be targeted for the development of noninvasive diagnosis.

The prevalence of kidney disease is increasing rapidly worldwide, reflecting rising rates of obesity, diabetes, and associated metabolic syndrome (MetS). Chronic kidney disease and related comorbidities such as obesity, diabetes, and hypertension place a significant financial burden on healthcare systems. Despite the widespread use of RAAS inhibitors, intensive blood pressure and glycemic control, and newer therapeutic options consisting of sodium/glucose cotransporter-2 (SGLT-2) inhibitors or glucagon-like peptide-1 (GLP-1) receptor agonists, a significant risk of progression to end-stage renal disease remains in the high-risk obese and diabetic population. The MetS is a cluster of cardiovascular risk factors that adversely affect the development and progression of chronic kidney failure. According to the criteria of the World Health Organization, it is defined by visceral adiposity, impaired glucose tolerance or insulin resistance, atherogenic dyslipidemia, raised blood pressure, and microalbuminuria with a albumin-to-creatinine ratio ≥30 mg/g. At molecular level MetS is marked by a proinflammatory state and increased oxidative stress leading to various pathophysiological changes causing endothelial dysfunction and a hypercoagulable state. Because the kidney is a highly vascularized organ, it is especially susceptible for those microvascular changes. Therefore, the MetS and its individual components are associated with the premature development, acceleration, and progression of chronic kidney disease. Therefore, it is becoming increasingly important to elucidate the underlying mechanisms of MetS-associated chronic kidney disease in order to develop new strategies for preventing and slowing the progression of renal disease. In this review, we will elucidate (i) the renal structural, hemodynamic, and metabolic changes that occur in obesity and obesity-related kidney injury; (ii) the clinicopathological characteristics of obesity-related kidney injury, primarily focusing on obesity-associated glomerulopathy; (iii) the potential additional factors or predisposing factors that may turn patients more susceptible to renal structural or functional compensatory failure and subsequent injury.

Early screening may prevent fibrosis progression in metabolic-associated fatty liver disease (MAFLD).

We developed and validated MAFLD fibrosis score (MFS) for identifying advanced fibrosis (≥F3) among MAFLD patients.

This cross-sectional, multicentre study consecutively recruited MAFLD patients receiving tertiary care (Malaysia as training cohort [n = 276] and Hong Kong and Wenzhou as validation cohort [n = 431]). Patients completed liver biopsy, vibration-controlled transient elastography (VCTE), and clinical and laboratory assessment within 1 week. We used machine learning to select 'highly important' predictors of advanced fibrosis, followed by backward stepwise regression to construct MFS formula.

MFS was composed of seven variables: age, body mass index, international normalised ratio, aspartate aminotransferase, gamma-glutamyl transpeptidase, platelet count, and history of type 2 diabetes. MFS demonstrated an area under the receiver-operating characteristic curve of 0.848 [95% CI 0.800-898] and 0.823 [0.760-0.886] in training and validation cohorts, significantly higher than aminotransferase-to-platelet ratio index (0.684 [0.603-0.765], 0.663 [0.588-0.738]), Fibrosis-4 index (0.793 [0.735-0.854], 0.737 [0.660-0.814]), and non-alcoholic fatty liver disease fibrosis score (0.785 [0.731-0.844], 0.750 [0.674-0.827]) (DeLong's test p < 0.05). MFS could include 92.3% of patients using dual cut-offs of 14 and 15, with a correct prediction rate of 90.4%, resulting in a larger number of patients with correct diagnosis compared to other scores. A two-step MFS-VCTE screening algorithm demonstrated positive and negative predictive values and overall diagnostic accuracy of 93.4%, 89.5%, and 93.2%, respectively, with only 4.0% of patients classified into grey zone.

MFS outperforms conventional non-invasive scores in predicting advanced fibrosis, contributing to screening in MAFLD patients.

Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease, with type 2 diabetes mellitus (T2DM) as a major predictor. Insulin resistance and chronic inflammation are key pathways in the pathogenesis of T2DM leading to NAFLD and vice versa, with the synergistic effect of NAFLD and T2DM increasing morbidity and mortality risks. This meta-analysis aims to quantify the prevalence of NAFLD and the prevalence of clinically significant and advanced fibrosis in people with T2DM.

MEDLINE and Embase databases were searched from inception until 13 February 2023. The primary outcomes were the prevalence of NAFLD, non-alcoholic steatohepatitis (NASH) and fibrosis in people with T2DM. A generalised linear mixed model with Clopper-Pearson intervals was used for the analysis of proportions with sensitivity analysis conducted to explore heterogeneity between studies.

156 studies met the inclusion criteria, and a pooled analysis of 1 832 125 patients determined that the prevalence rates of NAFLD and NASH in T2DM were 65.04% (95% CI 61.79% to 68.15%, I2=99.90%) and 31.55% (95% CI 17.12% to 50.70%, I2=97.70%), respectively. 35.54% (95% CI 19.56% to 55.56%, I2=100.00%) of individuals with T2DM with NAFLD had clinically significant fibrosis (F2-F4), while 14.95% (95% CI 11.03% to 19.95%, I2=99.00%) had advanced fibrosis (F3-F4).

This study determined a high prevalence of NAFLD, NASH and fibrosis in people with T2DM. Increased efforts are required to prevent T2DM to combat the rising burden of NAFLD.

CRD42022360251.

We aimed to compare the risk of incident diabetes according to fatty liver disease (FLD) definition, focusing on the comparison between those who met criteria for either metabolic dysfunction-associated fatty liver disease (MAFLD) or nonalcoholic fatty liver disease (NAFLD) but not the other. This was a 5.0-year (interquartile range, 2.4-8.2) retrospective longitudinal cohort study of 21,178 adults who underwent at least two serial health checkup examinations. The presence of hepatic steatosis was determined by abdominal ultrasonography at the first health examination. Cox proportional hazard analyses were used to compare the risk of incident diabetes among five groups. Incident diabetes cases occurred in 1296 participants (6.1%). When non-FLD without metabolic dysfunction (MD) group was set as a reference, the risk of incident diabetes increased in the order of NAFLD-only, non-FLD with MD, both FLD, and MAFLD-only groups. The presence of excessive alcohol consumption and/or hepatitis B virus (HBV)/hepatitis C virus (HCV) infection, FLD, and MD synergistically increased the risk of incident diabetes. MAFLD-only group showed a greater increase in incidence of diabetes than non-FLD with MD and NAFLD-only groups. The interaction among excessive alcohol consumption, HBV/HCV infection, MD, and hepatic steatosis on the development of diabetes should not be overlooked.

This network meta-analysis aims to compare the efficacy and safety of new anti-diabetic medications for the treatment of non-alcoholic fatty liver disease (NAFLD).

PubMed and Scopus were searched from inception to 27th March 2022 to identify all randomized controlled trials (RCTs) in NAFLD patients. Outcomes included reductions in intrahepatic steatosis (IHS) and liver enzyme levels. The efficacy and safety of DPP-4 inhibitors, GLP-1 agonists, SGLT-2 inhibitors, and other therapies were indirectly compared using a NMA approach. Unstandardized mean difference (USMD) with 95% confidence intervals (CI) were calculated.

2,252 patients from 31 RCTs were included. "Add-on" GLP-1 agonists with standard of care (SoC) treatment showed significantly reduced IHS compared to SoC alone [USMD (95%CI) -3.93% (-6.54%, -1.33%)]. Surface under the cumulative ranking curve (SUCRA) identified GLP-1 receptor agonists with the highest probability to reduce IHS (SUCRA 88.5%), followed by DPP-4 inhibitors (SUCRA 69.6%) and pioglitazone (SUCRA 62.2%). "Add-on" GLP-1 receptor agonists were also the most effective treatment for reducing liver enzyme levels; AST [USMD of -5.04 (-8.46, -1.62)], ALT [USMD of -9.84 (-16.84, -2.85)] and GGT [USMD of -15.53 (-22.09, -8.97)] compared to SoC alone. However, GLP-1 agonists were most likely to be associated with an adverse event compared to other interventions.

GLP-1 agonists may represent the most promising anti-diabetic treatment to reduce hepatic steatosis and liver enzyme activity in T2DM and NAFLD patients. Nevertheless, longer-term studies are required to determine whether this delays progression of liver cirrhosis in patients with NAFLD and T2DM.

https://www.crd.york.ac.uk/prospero/, identifier CRD42021259336.1.

Introduction: Non-alcoholic fatty liver disease (NAFLD) is one of the metabolic disorders related to the pathophysiology of type 2 diabetes mellitus (T2DM). Therapeutic strategies are focused on the improvement of energy balance and lifestyle modification. Additionally, the derivative of the bioactive fungal metabolite is of interest to provide health benefits, especially in obese and pre-diabetic conditions. In our screening of anti-diabetic compounds from fungal metabolites and semisynthetic derivatives, a depsidone derivative, namely pyridylnidulin (PN), showed potent glucose uptake-inducing activity. The present study aimed to investigate the liver lipid metabolism and anti-diabetic properties of PN in diet-induced obesity mice. Methods: Male C57BL/6 mice were induced obesity and pre-diabetic conditions by dietary intervention with a high-fat diet (HFD) for 6 weeks. These obese mice were orally administered with PN (40 or 120 mg/kg), metformin (150 mg/kg), or vehicle for 4 weeks. Glucose tolerance, plasma adipocytokines, hepatic gene and protein expressions were assessed after treatment. Results: Improved glucose tolerance and reduced fasting blood glucose levels were found in the PN and metformin-treated mice. Additionally, hepatic triglyceride levels were consistent with the histopathological steatosis score regarding hepatocellular hypertrophy in the PN and metformin groups. The levels of plasma adipocytokines such as tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1) were reduced in the PN (120 mg/kg) and metformin-treated mice. In addition, hepatic gene expression involved in lipid metabolism, including lipogenic enzymes was significantly reduced in the PN (120 mg/kg) and metformin-treated mice. The increased protein expression levels of phosphorylated AMP-activated protein kinase (p-AMPK) was also found in PN and metformin-treated mice. Discussion: Considering the increased p-AMPK protein expression levels in PN and metformin-treated mice were revealed as the underlying mechanisms to improve metabolic parameters. These results suggested that PN provided the health benefit to slow the progression of NAFLD and T2DM in obese and pre-diabetic conditions.

Introduction Brightness mode ultrasound (B-mode US) and FibroScan (Echosens, Paris, France) are the two ultrasound methods often recommended for screening non-alcoholic fatty liver disease (NAFLD) in persons with type 2 diabetes mellitus (T2DM). This study assessed the diagnostic performance of B-mode US using FibroScan as the reference standard. Methods Persons with a known history of T2DM were invited to screen for NAFLD using B-mode US and FibroScan on separate days within a one-month period. Assessors of B-mode US and FibroScan were blinded to each other's findings. Both B-mode US and FibroScan independently assessed and graded each participant for the presence of NAFLD. Using the diagnostic test findings of FibroScan as a reference standard, the sensitivity and specificity of B-mode US were analyzed. The area under the receiver operating characteristic curve (AUROC) was analyzed using Jamovi (version 2.3.21). A multinomial logistic regression of the B-mode US and FibroScan in predicting NAFLD grade was also analyzed. Results A total of 171 participants were assessed. B-mode US detected NAFLD in T2DM patients with 63.6% sensitivity, 65.6% specificity, and 0.646 AUROC. Sensitivity and specificity in overweight and obese participants were 36-43% and 76-85%, respectively. Multinomial logistic regression demonstrated an insignificant statistical relationship between FibroScan and B-mode US in predicting grade 1 steatosis (p-value = 0.397), which was significantly affected by a higher BMI (p-value = 0.034) rather than a higher liver fibrosis level (p-value = 0.941). The logistic regression further showed a significant relationship between B-mode US and FibroScan in predicting steatosis grade 2 (p-value = 0.045) and grade 3 (p-value < 0.001), which was not significantly affected by BMI (p-value = 0.091). Conclusion B-mode US can replace FibroScan for severe steatosis; however, it cannot be used to screen for NAFLD in T2DM patients due to lower sensitivity for early detection in the overweight.

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by hyperglycemia, insulin resistance, and pancreatic islet cell dysfunction. T2DM is associated with non-alcoholic fatty liver disease (NAFLD) because of impaired glucose metabolism in both conditions. However, it is widely assumed that people with T2DM in sub-Saharan Africa (SSA) have a lower prevalence of NAFLD than in other parts of the world. With our recent access to transient elastography, we aimed to investigate the prevalence of, severity of, and contributing factors to NAFLD in persons with T2DM in Ghana. We performed a cross-sectional study recruiting 218 individuals with T2DM at the Kwadaso Seventh-Day Adventist and Mount Sinai Hospitals in the Ashanti region of Ghana using a simple randomized sampling technique. A structured questionnaire was used to obtain socio-demographic information, clinical history, exercise and other lifestyle factors, and anthropometric measurements. Transient elastography was performed using a FibroScan® machine to obtain the Controlled Attenuation Parameter (CAP) score and liver fibrosis score. The prevalence of NAFLD among Ghanaian T2DM participants was 51.4% (112/218), of whom 11.6% had significant liver fibrosis. An evaluation of the NAFLD group (n = 112) versus the non-NAFLD group (n = 106) revealed a higher BMI (28.7 vs. 25.2 kg/m2, p = 0.001), waist circumference (106.0 vs. 98.0 cm, p = 0.001), hip circumference (107.0 vs. 100.5 cm, p = 0.003), and waist-to-height ratio (0.66 vs. 0.62, p = 0.001) in T2DM patients with NAFLD compared to those without NAFLD. Being obese was an independent predictor of NAFLD in persons with T2DM than known history of hypertension and dyslipidaemia.

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.

Non-alcoholic fatty liver disease (NAFLD) associated with type 2 diabetes may more easily progress towards severe forms of non-alcoholic steatohepatitis (NASH) and cirrhosis. Although the Wnt effector transcription factor 7-like 2 (TCF7L2) is closely associated with type 2 diabetes risk, the role of TCF7L2 in NAFLD development remains unclear. Here, we investigated how changes in TCF7L2 expression in the liver affects hepatic lipid metabolism based on the major risk factors of NAFLD development.

Tcf7l2 was selectively ablated in the liver of C57BL/6N mice by inducing the albumin (Alb) promoter to recombine Tcf7l2 alleles floxed at exon 5 (liver-specific Tcf7l2-knockout [KO] mice: Alb-Cre;Tcf7l2f/f). Alb-Cre;Tcf7l2f/f and their wild-type (Tcf7l2f/f) littermates were fed a high-fat diet (HFD) or a high-carbohydrate diet (HCD) for 22 weeks to reproduce NAFLD/NASH. Mice were refed a standard chow diet or an HCD to stimulate de novo lipogenesis (DNL) or fed an HFD to provide exogenous fatty acids. We analysed glucose and insulin sensitivity, metabolic respiration, mRNA expression profiles, hepatic triglyceride (TG), hepatic DNL, selected hepatic metabolites, selected plasma metabolites and liver histology.

Alb-Cre;Tcf7l2f/f essentially exhibited increased lipogenic genes, but there were no changes in hepatic lipid content in mice fed a normal chow diet. However, following 22 weeks of diet-induced NAFLD/NASH conditions, liver steatosis was exacerbated owing to preferential metabolism of carbohydrate over fat. Indeed, hepatic Tcf7l2 deficiency enhanced liver lipid content in a manner that was dependent on the duration and amount of exposure to carbohydrates, owing to cell-autonomous increases in hepatic DNL. Mechanistically, TCF7L2 regulated the transcriptional activity of Mlxipl (also known as ChREBP) by modulating O-GlcNAcylation and protein content of carbohydrate response element binding protein (ChREBP), and targeted Srebf1 (also called SREBP1) via miRNA (miR)-33-5p in hepatocytes. Eventually, restoring TCF7L2 expression at the physiological level in the liver of Alb-Cre;Tcf7l2f/f mice alleviated liver steatosis without altering body composition under both acute and chronic HCD conditions.

In mice, loss of hepatic Tcf7l2 contributes to liver steatosis by inducing preferential metabolism of carbohydrates via DNL activation. Therefore, TCF7L2 could be a promising regulator of the NAFLD associated with high-carbohydrate diets and diabetes since TCF7L2 deficiency may lead to development of NAFLD by promoting utilisation of excess glucose pools through activating DNL.

RNA-sequencing data have been deposited into the NCBI GEO under the accession number GSE162449 ( www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE162449 ).

The aim of this study was to identify characteristics of non-alcoholic fatty liver disease (NAFLD) in adults with HFE p.C282Y/p.C282Y.

We retrospectively studied non-Hispanic white hemochromatosis probands with iron overload (serum ferritin (SF) > 300 µg/L (M), > 200 µg/L (F)) and p.C282Y/p.C282Y at non-screening diagnosis who did not report alcohol consumption > 14 g/d, have cirrhosis or other non-NAFLD liver disorders, use steatogenic medication, or have diagnoses of heritable disorders that increase NAFLD risk. We identified NAFLD-associated characteristics using univariate and multivariable analyses.

There were 66 probands (31 men, 35 women), mean age 49 ± 14 (SD) y, of whom 16 (24.2%) had NAFLD. The following characteristics were higher in probands with NAFLD: median SF (1118 µg/L (range 259, 2663) vs. 567 µg/L (247, 2385); p = 0.0192); prevalence of elevated ALT/AST (alanine/aspartate aminotransferase) (43.8% vs. 10.0%; p = 0.0056); and prevalence of type 2 diabetes (T2DM) (31.3% vs. 10.0%; p = 0.0427). Mean age, sex, and prevalences of human leukocyte antigen-A*03 positivity, body mass index ≥ 30.0 kg/m², hyperlipidemia, hypertension, and metabolic syndrome in probands with/without NAFLD did not differ significantly. Logistic regression on NAFLD using variables SF, elevated ALT/AST, and T2DM revealed: SF (p = 0.0318; odds ratio 1.0-1.0) and T2DM (p = 0.0342; 1.1-22.3). Median iron removed to achieve iron depletion (QFe) in probands with/without NAFLD did not differ significantly (3.6 g (1.4-7.2 g) vs. 2.8 g (0.7-11.0 g), respectively; p = 0.6862).

NAFLD in hemochromatosis probands with p.C282Y/p.C282Y is associated with higher median SF and greater T2DM prevalence, after adjustment for other factors. NAFLD does not influence QFe significantly.

Nonalcoholic fatty liver disease (NAFLD) represents the most common chronic liver disease worldwide, reaching one of the highest prevalences in patients with type 2 diabetes mellitus (T2DM). For now, no specific pharmacologic therapies are approved to prevent or treat NAFLD. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are currently evaluated as potential candidates for NAFLD treatment in patients with T2DM. Some representatives of this class of antihyperglycemic agents emerged as potentially beneficial in patients with NAFLD after several research studies suggested they reduce hepatic steatosis, ameliorate lesions of nonalcoholic steatohepatitis (NASH), or delay the progression of fibrosis in this population. The aim of this review is to summarize the body of evidence supporting the effectiveness of GLP-1RA therapy in the management of T2DM complicated with NAFLD, describing the studies that evaluated the effects of these glucose-lowering agents in fatty liver disease and fibrosis, their possible mechanistic justification, current evidence-based recommendations, and the next steps to be developed in the field of pharmacological innovation.

This Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) is intended to provide clinicians an overview of type 2 diabetes mellitus (T2DM), an obesity-related cardiometabolic risk factor.

The scientific support for this CPS is based upon published citations and clinical perspectives of OMA authors.

Topics include T2DM and obesity as cardiometabolic risk factors, definitions of obesity and adiposopathy, and mechanisms for how obesity causes insulin resistance and beta cell dysfunction. Adipose tissue is an active immune and endocrine organ, whose adiposopathic obesity-mediated dysfunction contributes to metabolic abnormalities often encountered in clinical practice, including hyperglycemia (e.g., pre-diabetes mellitus and T2DM). The determination as to whether adiposopathy ultimately leads to clinical metabolic disease depends on crosstalk interactions and biometabolic responses of non-adipose tissue organs such as liver, muscle, pancreas, kidney, and brain.

This review is intended to assist clinicians in the care of patients with the disease of obesity and T2DM. This CPS provides a simplified overview of how obesity may cause insulin resistance, pre-diabetes, and T2DM. It also provides an algorithmic approach towards treatment of a patient with obesity and T2DM, with "treat obesity first" as a priority. Finally, treatment of obesity and T2DM might best focus upon therapies that not only improve the weight of patients, but also improve the health outcomes of patients (e.g., cardiovascular disease and cancer).

Aim: Non-alcoholic fatty liver disease (NAFLD) exhibits a racial disparity. We examined the prevalence and the association between race, gender, and NAFLD among prediabetes and diabetes populations among adults in the United States. Methods: We analyzed data for 3,190 individuals ≥18 years old from the National Health and Nutrition Examination Survey (NHANES) 2017-2018. NAFLD was diagnosed by FibroScan® using controlled attenuation parameter (CAP) values: S0 (none) < 238, S1 (mild) = 238-259, S2 (moderate) = 260-290, S3 (severe) > 290. Data were analyzed using Chi-square test and multinomial logistic regression, adjusting for confounding variables and considering the design and sample weights. Results: Of the 3,190 subjects, the prevalence of NAFLD was 82.6%, 56.4%, and 30.5% (p < 0.0001) among diabetes, prediabetes and normoglycemia populations respectively. Mexican American males with prediabetes or diabetes had the highest prevalence of severe NAFLD relative to other racial/ethnic groups (p < 0.05). In the adjusted model, among the total, prediabetes, and diabetes populations, a one unit increase in HbA1c was associated with higher odds of severe NAFLD [adjusted odds ratio (AOR) = 1.8, 95% confidence level (CI) = 1.4-2.3, p < 0.0001; AOR = 2.2, 95% CI = 1.1-4.4, p = 0.033; and AOR = 1.5, 95% CI = 1.1-1.9, p = 0.003 respectively]. Conclusion: We found that prediabetes and diabetes populations had a high prevalence and higher odds of NAFLD relative to the normoglycemic population and HbA1c is an independent predictor of NAFLD severity in prediabetes and diabetes populations. Healthcare providers should screen prediabetes and diabetes populations for early detection of NAFLD and initiate treatments including lifestyle modification to prevent the progression to non-alcoholic steatohepatitis or liver cancer.