[Analysis of non-alcoholic fatty liver disease differences from metabolic dysfunction-associated fatty liver disease based on clinical features].

Objective: To explore the clinical features of fatty liver disease (FLD) from non-alcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated fatty liver disease (MASLD), so as to elucidate its clinical application value under three renames. Methods: Patients who were hospitalized in the Department of Hepatology, Hospital of Traditional Chinese Medicine Affiliated to Xinjiang Medical University, from January 2020 to September 2023 and met the diagnosis of NAFLD, metabolic-associated fatty liver disease (MAFLD), or MASLD were selected as the research subjects. The clinical indicators differences among the three groups of patients were compared, mainly including general information (age, gender, body mass index, past history, etc.), serological indicators (liver and kidney function, blood lipids, blood sugar, coagulation function, etc.), non-invasive liver fibrosis indicators, fat attenuation parameters, etc. Measurement data were analyzed using ANOVA and the rank sum test, while count data were analyzed using the χ(2) test. Results: NAFLD, MAFLD, and MASLD prevalence rates among 536 cases were 64.0%, 93.7%, and 100%, respectively. 318 cases (59.3%) met the three fatty liver names at the same time among them. Male population proportions in NAFLD, MAFLD, and MASLD were 30.9%, 55.8%, and 53.9%, respectively. The alcohol consumption history proportion was 0, 36.7%, and 36.0%, respectively. The smoking history proportion was 7.0%, 31.9%, and 30.6%, respectively. The body mass index was (27.66 ± 3.97), (28.33 ± 3.63), and (27.90 ± 3.89) kg/m(2), respectively. The γ-glutamyltransferase levels were 26.6 (18.0, 47.0) U/L, 31.0 (20.0, 53.0) U/L, and 30.8 (19.8, 30.8) U/L, respectively. The high-density lipoprotein cholesterol levels were 1.07 (0.90, 1.23) mmol/L, 1.02 (0.86, 1.19) mmol/L, and 1.03 (0.87,1.21) mmol/L, respectively. Sequentially measured uric acid was (322.98 ± 84.51) µmol/L, (346.57 ± 89.49) µmol/L, and (344.89 ±89.67) µmol/L, respectively. Sequentially measured creatinine was 69.6 (62.9, 79.0) µmol/L, 73.0 (65.0, 83.5) µmol/L, and 73.0 (65.0, 83.0) µmol/L, respectively. The sequential analysis of obesity proportion was 74.3%, 81.7%, and 76.5%, respectively, with statistically significant differences (P<0.05). Conclusion: Compared with the NAFLD population, the MAFLD and MASLD populations were predominantly male, obese, and had a history of smoking and drinking. The levels of γ-glutamyltransferase, uric acid, and creatinine were slightly higher, while the levels of high-density lipoprotein cholesterol were lower. MASLD appeared in NAFLD and MAFLD on the basis of inheritance and progression, emphasizing once again the important role of metabolic factors in a fatty liver.

Comparison of all-cause mortality associated with non-alcoholic fatty liver disease and metabolic dysfunction-associated fatty liver disease in Taiwan MJ cohort.

OBJECTIVES: The global burden of non-alcoholic fatty liver disease (NAFLD) is rising. An alternative term, metabolic dysfunction-associated fatty liver disease (MAFLD), instead highlights the associated metabolic risks. This cohort study examined patient classifications under NAFLD and MAFLD criteria and their associations with all-cause mortality. METHODS: Participants who attended a paid health check-up (2012-2015) were included. Hepatic steatosis (HS) was diagnosed ultrasonographically. NAFLD was defined as HS without secondary causes, while MAFLD involved HS with overweight/obesity, type 2 diabetes mellitus, or ≥2 metabolic dysfunctions. Mortality was tracked via the Taiwan Death Registry until November 30, 2022. RESULTS: Of 118,915 participants, 36.9% had NAFLD, 40.2% had MAFLD, and 32.9% met both definitions. Participants with NAFLD alone had lower mortality, and those with MAFLD alone had higher mortality, than individuals with both conditions. After adjustment for potential confounders, the hazard ratios (HRs) for all-cause mortality were 1.08 (95% confidence interval [CI], 0.78 to 1.48) for NAFLD alone and 1.26 (95% CI, 1.09 to 1.47) for MAFLD alone, relative to both conditions. Advanced fibrosis conferred greater mortality risk, with HRs of 1.93 (95% CI, 1.44 to 2.58) and 2.08 (95% CI, 1.61 to 2.70) for advanced fibrotic NAFLD and MAFLD, respectively. Key mortality risk factors for NAFLD and MAFLD included older age, unmarried status, higher body mass index, smoking, diabetes mellitus, chronic kidney disease, and advanced fibrosis. CONCLUSIONS: All-cause mortality in NAFLD and/or MAFLD was linked to cardiometabolic covariates, with risk attenuated after multivariable adjustment. A high fibrosis-4 index score, indicating fibrosis, could identify fatty liver disease cases involving elevated mortality risk.

Temporal relationship between inflammation and metabolic disorders and their impact on cancer risk.

Background: Inflammation and metabolic disorders are closely associated with cancer. Whether inflammation leads to metabolic disorders or vice versa during cancer initiation remains unclear. In this study, we explored this temporal relationship and the co-exposure effect on cancer risk. Methods: This prospective study had two phases. Initially, we examined the temporal relationship between inflammation (high-sensitivity C-reactive protein (CRP)) and metabolic disorders (metabolic syndrome severity Z-score (MetS-Z)) using a 3.98-year survey and cross-lagged analysis. Subsequently, we assessed the connection of co-exposure to inflammation and metabolic disorders, and the risks of overall cancer, as well as specific obesity-related, non-obesity-related, digestive system, lung, and other cancers using an 11.04-year survey and Cox proportional hazard models. Results: The cross-lagged analysis revealed that the path coefficient from baseline CRP to follow-up MetS-Z (ß2 = 0.032; 95% confidence interval (CI) = 0.026, 0.046) was more significant than the path coefficient from baseline MetS-Z to follow-up CRP (ß1 = 0.009; 95% CI = -0.001, 0.019). During the follow-up, 2304 cases of cancer occurred. Compared with the risk of cancer of patients with low average cumulative CRP and MetS-Z, patients with high value had a significantly increased risk (hazard ratio = 1.54, 95% CI = 1.30, 1.83). The mediation analysis showed that MetS-Z mediated the association between CRP levels and overall cancer (12.67%), digestive system cancer (10.16%), and obesity-related cancer risk (13.87%). Conclusions: Inflammation had a greater impact on metabolic disorders than vice versa. Co-exposure to inflammation and metabolic disorders significantly increased the risk of cancer, particularly digestive system and obesity-related cancers. Registration: Chinese Clinical Trial Registry: ChiCTR-TNRC-11001489.

From NAFLD to MASLD: When metabolic comorbidity matters.

INTRODUCTION AND OBJECTIVES: In a recent development, a cohort of hepatologists has proposed altering the nomenclature of non-alcoholic fatty liver disease (NAFLD) to metabolic-associated steatotic liver disease (MASLD), accompanied by modified diagnostic criteria. Our objective was to investigate the effect of the revised definition on identifying significant hepatic fibrosis. PATIENTS AND METHODS: From Jan 2009 to Dec 2022, a total of 428 patients with biopsy-proven hepatic steatosis were diagnosed with NAFLD. Patients were classified into subgroups according to MASLD and Cryptogenic-SLD diagnostic criteria. The clinical pathological features were compared between these two groups. Risk factors for significant fibrosis were analysed in the MASLD group. In total, 329 (76.9 %) patients were diagnosed with MASLD, and 99 (23.1 %) were diagnosed with Cryptogenic-SLD. RESULTS: Those with MASLD exhibited a higher degree of disease severity regarding histology features than Cryptogenic-SLD. The prevalence of significant fibrosis increased from 13 % to 26.6 % for one and two criteria present to 42.5 % for meeting three or more cardiometabolic risk factor (CMRF) criteria (p = 0.001). ALB (aOR:0.94,95 %CI:0.90-1.00; p = 0.030), lower levels of PLT (aOR:0.99, 95 %CI:0.99-1.00; p < 0.001), and more metabolic comorbidities (aOR:1.42,95 %CI:1.14-1.78; p = 0.012) were independent risk factors of significant fibrosis in MASLD. CONCLUSIONS: The new nomenclature of MASLD and SLD is more applicable to identifying significant fibrosis than NAFLD. Patients with three or more cardiometabolic risk factors are at higher risk of fibrosis.

Efectos del ciclismo en la composición corporal e indicadores de riesgo metabólico / Effects of cycling on Body Composition and Metabolic Risk Indicators

Introducción: El ciclismo es una actividad física que se practica de forma recreativa y como actividad laboral, en base a esto los beneficios en la salud varían. Sus efectos pueden extenderse en la regulación de la expresión de citocinas proinflamatorias en la obesidad; sin embargo, se deben estudiar detalles en los indicadores clínicos asociados a otras enfermedades crónico-degenerativas. Objetivo: Identificar los cambios en los parámetros clínicos que sirven como indicadores de riesgo metabólico en personas que realizan ciclismo como ejercicio habitual y como actividad laboral. Métodos: Se realizó una investigación de diseño transversal, descriptivo en el Estado de México, México. Se formaron 3 grupos de 16 participantes provenientes de Toluca y municipios aledaños. Se realizaron mediciones de composición corporal y análisis bioquímicos para identificar las diferencias entre los grupos a través de la prueba t- student y el análisis de varianza ANOVA. Resultados: Los análisis estadísticos reportaron diferencias significativas en las concentraciones de lipoproteínas de alta densindad y triglicéridos. Para el grupo de los conductores de bicitaxi fue más favorable, se detalla como el tiempo de la actividad ayuda a mantener los parámetros de composición corporal como el porcentaje del tejido muscular y adiposo. Conclusiones: Los beneficios del ciclismo se presentaron con diferentes grados de eficiencia de acuerdo con la modalidad en la que se practican. Las variables no cambian de forma significativa en ningún grupo, pueden ser dependientes de otras variables como la alimentación(AU)

Introduction: Cycling is a physical activity, which is practiced recreationally and as a work activity. Its effects may extend to the regulation of the expression of proinflammatory cytokines in obesity; however, details should be studied in the clinical indicators associated with other chronic-degenerative diseases. Objective: To identify changes in clinical parameters that serve as indicators of metabolic risk in people who perform cycling as a regular exercise and as a work activity. Methods: A cross-sectional and descriptive design research was carried out in the State of Mexico, Mexico. Three groups of 16 participants were formed from Toluca and surrounding municipalities. Body composition measurements and biochemical analyzes were performed to identify differences between groups through Student's t test and ANOVA analysis of variance. Results: Statistical analyzes reported significant differences in HDL and triglyceride concentrations. For the group of pedicab drivers it was more favorable, it is detailed how the time of the activity helps to maintain body composition parameters such as the percentage of muscle and adipose tissue. Conclusions: The benefits of cycling were presented with different degrees of efficiency according to the modality in which they are practiced. The variables do not change significantly in any group and may be dependent on other variables such as diet(AU)

Metabolic diseases and healthy aging: identifying environmental and behavioral risk factors and promoting public health.

Aging is a progressive and irreversible pathophysiological process that manifests as the decline in tissue and cellular functions, along with a significant increase in the risk of various aging-related diseases, including metabolic diseases. While advances in modern medicine have significantly promoted human health and extended human lifespan, metabolic diseases such as obesity and type 2 diabetes among the older adults pose a major challenge to global public health as societies age. Therefore, understanding the complex interaction between risk factors and metabolic diseases is crucial for promoting well-being and healthy aging. This review article explores the environmental and behavioral risk factors associated with metabolic diseases and their impact on healthy aging. The environment, including an obesogenic environment and exposure to environmental toxins, is strongly correlated with the rising prevalence of obesity and its comorbidities. Behavioral factors, such as diet, physical activity, smoking, alcohol consumption, and sleep patterns, significantly influence the risk of metabolic diseases throughout aging. Public health interventions targeting modifiable risk factors can effectively promote healthier lifestyles and prevent metabolic diseases. Collaboration between government agencies, healthcare providers and community organizations is essential for implementing these interventions and creating supportive environments that foster healthy aging.

Diabetes and Metabolic Disorders: Their Impact on Cardiovascular Events in Liver Transplant Patients.

Cardiovascular diseases are currently one of the most important causes of morbidity and mortality in liver transplant patients over the long term. Therefore, evaluating prognostic factors for cardiovascular events (CVEs) in this population is essential for taking preventive measures. The aim of this study was to identify the impact of diabetes and other metabolic disorders on CVEs in liver transplant patients. Three hundred fifty-six liver transplant recipients who survived at least 6 months after surgery were enrolled. Patients were followed for a median time of 118 months (12-250 months). All cardiovascular events were carefully recorded and detailed in the patients' charts. Demographic data, diabetes, hypertension, dyslipidemia, weight changes, and a diagnosis of metabolic syndrome both before and after transplantation were noted to assess their possible relationship with CVE. The presence of a diagnosis of metabolic-associated fatty liver disease (MAFLD) was also evaluated. Immunosuppressive therapy was included in the analysis. Diabetes mellitus (DM), especially when present before transplantation, was strongly associated with CVEs (hazard risk HR 3.10; 95% confidence interval CI: 1.60-6.03). Metabolic syndrome was found to be associated with CVEs in univariate analysis (HR 3.24; 95% CI: 1.36-7.8), while pretransplantation and de novo MAFLD were not. Immunosuppressive therapy had no influence on predisposing transplanted patients to CVEs during follow-up. Further prospective studies may be useful in investigating the risk factors for CVEs after liver transplantation and improving the long-term survival of transplant patients.

Diet and physical activity and metabolic disorders in patients with schizophrenia and bipolar affective disorder in the Polish population.

Introduction: There are numerous reports of a higher prevalence of metabolic disorders in patients with schizophrenia and bipolar disorder (BD), yet its connections to diet and physical activity remain not fully explained. This article aimed to evaluate diet, physical activity and selected biochemical and anthropometric parameters associated with metabolism in patients with schizophrenia and BD and to analyse the relationships between these variables in the subjects. Materials and Methods: A total of 126 adults participated in the study: 47 patients with schizophrenia, 54 patients with BD and 25 patients in mental illness remission (reference group). Data were collected on the underlying illness and concomitant illnesses, and the severity of symptoms of the current episode was assessed using the following scales: PANSS, MADRS and YMRS. An assessment of the subjects' diet (KomPAN questionnaire) and their physical activity (International Physical Activity Questionnaire) was carried out. Anthropometric and blood pressure measurements were taken and BMI and WHR were calculated. Serum concentrations of fasting glucose, TSH, total cholesterol, LDL and HDL fractions, triglycerides and leptin, ghrelin and resistin were determined. For statistical analysis, the significance level was set at 0.05. For multiple comparisons one way ANOVA or Kruskal Wallis were used with post hoc Tukey and Dunn tests, respectively. To determine correlation of variables, Pearson's linear correlation coefficient or Spearman's rank correlation coefficient were used. Results: A total of 50.8% of the subjects had at least one metabolic disorder-most commonly excessive body weight (66.7%) and abdominal obesity (64.3%). Patients did not differ significantly in terms of physical activity, but they did differ in mean time spent sitting-with this being significantly longer for all groups than in the general population. The subjects differed in diet: patients with BD consumed less unhealthy foods than patients with schizophrenia. The highest correlations between physical activity, diet and variables defining metabolic disorders were found in patients with BD. Only in patients with schizophrenia were there significant correlations between the course of the disease and physical activity. Discussion: The results suggest the existence of associations between diet, physical activity, and metabolic disorders in both BD and schizophrenia patients. They also suggest a tendency among those patients to spend long periods of time sitting.

Association of Androgen Deprivation Therapy with Metabolic Disease in Prostate Cancer Patients: An Updated Meta-Analysis.

BACKGROUND: Androgen deprivation therapy (ADT), a backbone treatment for advanced prostate cancer (PC), is known to have a variety of metabolic side effects. We conducted an updated meta-analysis to quantify the metabolic risks of ADT. MATERIALS AND METHODS: We searched PubMed, Web of Science, and Scopus in May of 2022 for studies investigating the risk of metabolic syndrome (MetS), diabetes, and hypertension from ADT in PC patients using keywords. Only full-length studies with a control group of PC patients not on ADT were included. All results compatible with each outcome domain in each included study were sought. For included studies, relative risk (RR) was pooled using a random effects model and a trim-fill approach was used to adjust for publication bias. RESULTS: 1,846 records were screened, of which 19 were found suitable for data extraction. Five studies, including 891 patients, were evaluated for MetS as an outcome, with the random effects model showing a pooled RR of 1.60 ([95% Confidence Interval (CI), 1.06-2.42]; P=0.03) for patients on ADT while twelve studies, including 336,330 patients, examined diabetes as an outcome, and the random effects model showed a RR of 1.43 ([95% CI, 1.28-1.59]; P< 0.01). After adjustment for publication bias, ADT was associated with a 25% increased risk for diabetes but was not associated with MetS. 4 studies, including 7,051 patients, examined hypertension as an outcome, and the random effects model showed a RR of 1.30 ([95% CI, 1.08-1.55]; P=0.18) in ADT patients. CONCLUSION: In patients with PC, ADT was not associated with MetS and the association with diabetes was not as strong as previously reported. Our novel meta-analysis of hypertension showed that ADT increased the risk of hypertension by 30%. These results should be understood in the context of collaborating care between a patient's oncologist and primary care provider to optimize care.

The impact of metabolic diseases and their comorbidities for stroke in a middle-income area of China: a case-control study.

BACKGROUND: There are few studies on the comorbidity of hypertension (HTN), diabetes mellitus (DM) and dyslipidemia (DLP) associated with stroke. We aimed to explore the relationship between the number of metabolic diseases and stroke and its different subtypes, and to reveal whether metabolic diseases alone or coexist can significantly increase the risk of stroke. METHODS: We completed a multi-center case-control study in Jiangxi Province, China. Neuroimaging examination was done in all cases. Controls were stroke-free adults recruited from the community in the case concentration area and matched with the cases in 1:1 ratio by age and sex. Odds ratios (OR) were calculated by conditional logistic regression. RESULTS: We enrolled 11,729 case-control pairs. The estimated ORs among patients with 1, 2 and 3 metabolic diseases were 3.16 (2.78-3.60), 7.11 (6.16-8.20), 12.22 (9.73-15.36), respectively after adjusting age, body mass index, urban-rural areas, cardiac disease, smoking, alcohol intake, physically active, high intake of salt, meat-biased diet, high homocysteine. The coexistence of HTN and DM (OR: 7.67), the coexistence of HTN and DLP (OR:7.58), and the coexistence of DM and DLP (OR:3.64) can all significantly increase the risk of stroke. HTN alone or combined other metabolic diseases were significantly more strongly associated with intracerebral haemorrhage than ischemic stroke. CONCLUSIONS: The risk of stroke increased with the number of chronic metabolic diseases. It is necessary to regularly monitor blood pressure, blood sugar and blood lipids and strengthen lifestyle management and take appropriate drug interventions to prevent exposure to multiple metabolic diseases based on existing conditions.

Liver Inflammation Is Common and Linked to Metabolic Derangements in Persons With Treated Human Immunodeficiency Virus (HIV).

BACKGROUND: We sought to characterize in people with human immunodeficiency virus (PWH) the potential etiologies of elevated alanine aminotransferase (ALT) levels, which are common and often unexplained. METHODS: Participants from the longitudinal observational AIDS Clinical Trials Group HAILO cohort without a history of hepatitis C virus (HCV) or hepatitis B virus (HBV) infection nor reported heavy alcohol use were included. Clinical and demographic characteristics, including medication use, the hepatic steatosis index (HSI), and metabolic syndrome (MetS) were compared between participants with and without ALT elevation. RESULTS: Six hundred sixty-two participants were included; 444 (67%) had ≥1 and 229 (35%) ≥2 consecutive ALT elevations during a median of 4.0 years of follow-up. HSI and Hispanic or other (non-White or Black) race/ethnicity were consistently associated with higher odds of abnormal ALT (odds ratio [OR] 1.1 for HSI as a continuous variable, OR 1.9-2.8 for Hispanic/other race/ethnicity for ≥1 or ≥2 ALT elevations); older age and current smoking were associated with lower odds of abnormal ALT. Associations with metabolic disease, as well as with incident HBV and HCV infection, were strengthened by restricting outcomes to persistent and higher degrees of ALT elevation. CONCLUSIONS: ALT elevation was common in this cohort of PWH and associated with metabolic disease and hepatic steatosis markers. Nonalcoholic fatty liver disease is likely a common cause of liver inflammation in PWH receiving suppressive antiretrovirals, deserving targeted diagnosis and intervention.

Tendencia de consejerías en actividad física y enfermedades cardiometabólicas en el Maule, Chile: estudio previo a pandemia por COVID-19 entre 2012 y 2019 / Trend in Physical Activity Counseling and Cardiometabolic Diseases in Maule, Chile: COVID-19 Pre-Pandemic Study between 2012 and 2019

BACKGROUND: Physical activity (PA) practice reduces the adverse effects of COVID-19. PA counseling promotes healthy lifestyles and prevents cardiometabolic diseases. AIM: To assess the trend in cases of PA counseling and the cardiometabolic disease between 2012 and 2019 (before COVID-19) in a southern Chilean region. MATERIAL AND METHODS: Records of Maule Region Health Service for 731.163 men, and 829.097 women aged < 10 to ≥ 65 years were analyzed. The average annual percentage change (AAPC) during the study period and the annual percentage change (APC) during intermediate periods, were calculated. RESULTS: There was a significant decrease in PA counseling in women in the study period (AAPC: −13.6%). In the 2012-2017 period a significant decrease in counseling for total, men and women were observed (APC: −18.1, −16.5 and −19.1%, respectively). Obesity increased significantly in total, men and women in the 2012-2019 period (AAPC: 10.1, 8.5 and 10.7%, respectively). The same trend was observed for hypertension (AAPC: 8.1, 8.5 and 7.6% respectively) and elevated blood glucose (AAPC: 10, 11.5 and 9.6%, respectively). CONCLUSIONS: In the study period PA counseling decreased along with an increase in obesity, hypertension and high blood glucose. Increasing PA counseling is a mainstay in the prevention of cardiometabolic diseases and probably to prevent contagion and complement the treatment of COVID-19.

Polycystic ovary syndrome and metabolic disorders: A review of the literature.

Polycystic ovarian syndrome (PCOS) is one of the most common female endocrinopathies and is a leading cause of infertility. The syndrome derives its name from the pathological appearance of the ovary in women with menstrual irregularities and hyperandrogenism. Its symptoms appear as early as adolescence in the form of amenorrhea, hirsutism and obesity. The majority of patients are overweight, obese or of normal weight, but metabolically obese. The prevalence of PCOS is on the increase and is associated with a significantly higher risk of various metabolic disorders including cardiovascular disease (CVD), Type2 diabetes (T2DM), gestational diabetes, hypercholesterolemia and different types of cancer, including endometrial and possibly ovarian cancer, especially if associated with hyperinsulinaemia. In contrast, in women with PCOS who have normal insulin levels, it is likely that genetics, inflammation, oxidative stress and possible interaction with environmental factors are present that link these women to metabolic disorders. The mechanism of PCOS is not well understood and this review aims to provide a detailed description of the mechanism underlying the development of PCOS and associated metabolic disorders with a full description of all possible scenarios associating PCOS to metabolic disorders, as well as an epidemiological overview regarding the relationship between these metabolic disorders and PCOS.

Distinct contributions of metabolic dysfunction and genetic risk factors in the pathogenesis of non-alcoholic fatty liver disease.

BACKGROUND & AIMS: There is substantial inter-individual variability in the risk of non-alcoholic fatty liver disease (NAFLD). Part of which is explained by insulin resistance (IR) ('MetComp') and part by common modifiers of genetic risk ('GenComp'). We examined how IR on the one hand and genetic risk on the other contribute to the pathogenesis of NAFLD. METHODS: We studied 846 individuals: 492 were obese patients with liver histology and 354 were individuals who underwent intrahepatic triglyceride measurement by proton magnetic resonance spectroscopy. A genetic risk score was calculated using the number of risk alleles in PNPLA3, TM6SF2, MBOAT7, HSD17B13 and MARC1. Substrate concentrations were assessed by serum NMR metabolomics. In subsets of participants, non-esterified fatty acids (NEFAs) and their flux were assessed by D5-glycerol and hyperinsulinemic-euglycemic clamp (n = 41), and hepatic de novo lipogenesis (DNL) was measured by D2O (n = 61). RESULTS: We found that substrate surplus (increased concentrations of 28 serum metabolites including glucose, glycolytic intermediates, and amino acids; increased NEFAs and their flux; increased DNL) characterized the 'MetComp'. In contrast, the 'GenComp' was not accompanied by any substrate excess but was characterized by an increased hepatic mitochondrial redox state, as determined by serum ß-hydroxybutyrate/acetoacetate ratio, and inhibition of hepatic pathways dependent on tricarboxylic acid cycle activity, such as DNL. Serum ß-hydroxybutyrate/acetoacetate ratio correlated strongly with all histological features of NAFLD. IR and hepatic mitochondrial redox state conferred additive increases in histological features of NAFLD. CONCLUSIONS: These data show that the mechanisms underlying 'Metabolic' and 'Genetic' components of NAFLD are fundamentally different. These findings may have implications with respect to the diagnosis and treatment of NAFLD. LAY SUMMARY: The pathogenesis of non-alcoholic fatty liver disease can be explained in part by a metabolic component, including obesity, and in part by a genetic component. Herein, we demonstrate that the mechanisms underlying these components are fundamentally different: the metabolic component is characterized by hepatic oversupply of substrates, such as sugars, lipids and amino acids. In contrast, the genetic component is characterized by impaired hepatic mitochondrial function, making the liver less able to metabolize these substrates.

100 years of inherited metabolic disorders in Austria-A national registry of minimal birth prevalence, diagnosis, and clinical outcome of inborn errors of metabolism in Austria between 1921 and 2021.

Inherited metabolic disorders (IMDs) are a heterogeneous group of rare disorders characterized by disruption of metabolic pathways. To date, data on incidence and prevalence of IMDs are limited. Taking advantage of a functioning network within the Austrian metabolic group, our registry research aimed to update the data of the "Registry for Inherited Metabolic Disorders" started between 1985 and 1995 with retrospectively retrieved data on patients with IMDs according to the Society for the Study of Inborn Errors of Metabolism International Classification of Diseases 11 (SSIEM ICD11) catalogue. Included in this retrospective register were 2631 patients with an IMD according to the SSIEM ICD11 Classification, who were treated in Austria. Thus, a prevalence of 1.8/10 000 for 2020 and a median minimal birth prevalence of 16.9/100 000 (range 0.7/100 000-113/100 000) were calculated for the period 1921 to February 2021. We detected a male predominance (m:f = 1.2:1) and a mean age of currently alive patients of 17.6 years (range 5.16 months-100 years). Most common diagnoses were phenylketonuria (17.7%), classical galactosaemia (6.6%), and biotinidase deficiency (4.2%). The most common diagnosis categories were disorders of amino acid and peptide metabolism (819/2631; 31.1%), disorders of energy metabolism (396/2631; 15.1%), and lysosomal disorders (395/2631; 15.0%). In addition to its epidemiological relevance, the "Registry for Inherited Metabolic Disorders" is an important tool for enhancing an exchange between care providers. Moreover, by pooling expertise it prospectively improves patient treatment, similar to pediatric oncology protocols. A substantial requirement for ful filling this goal is to regularly update the registry and provide nationwide coverage with inclusion of all medical specialties.

Post-treatment heterogeneity of cardiometabolic risk in patients with acromegaly: The impact of GH and IGF-1.

BACKGROUND: Metabolic abnormalities are frequently seen in patients with acromegaly. However, it is not clear to what extent growth hormone/insulin-like growth factor-1 (GH/IGF-1) contributes to the development of these abnormalities. OBJECTIVE: This study aimed to explore the impact of postoperative GH/IGF-1 on different aspects of metabolic abnormalities in patients with acromegaly. METHODS: This retrospective, registry-based study conducted on 102 patients with acromegaly. The impact of GH/IGF-1 on the cardiometabolic risk factors at 3-12 months after surgery has been investigated using linear and logistic regression models. RESULTS: In this study, each 1 ng/ml increase in the level of GH was significantly associated with a 2 mg/dl increase in the level of fasting blood glucose (FBG), a 0.5 mmHg increase in the level of systolic blood pressure (SBP), and a 0.9 mmHg increase in the level of diastolic blood pressure (DBP). Upon multivariate analysis, GH, but not IGF-1, significantly increased the odds of diabetes mellitus (DM) (OR; 1.2, 95% CI; 1.0-1.4, p = .025). CONCLUSIONS: Our findings indicated at early postoperative stage, GH is significantly associated with the levels of FBG, SBP, and DBP. Moreover, GH, but not IGF-1, appears as a predictive factor for the presence of DM. However, neither GH nor IGF-1 could predict the presence of hypertension HTN, or dyslipidemia in this study. ABBREVIATIONS: CVD: Cardiovascular disease; GH: Growth hormone; IGF-1: Insulin-like growth factor 1; BMI: Body mass index; HTN: hypertension; IPTR: Iran Pituitary Tumor Registry; WC: Waist circumference; MRI: Magnetic resonance imaging; FBG: Fasting blood glucose; HbA1C: Glycated hemoglobin; TG: Triglyceride; LDL: Low density lipoprotein; HDL: High density lipoprotein; SBP: Systolic blood pressure; DBP: Diastolic blood pressure.

Metabolic Disease Incidence After Allogeneic Stem Cell Transplantation: A Nationwide Korean Case-Control Study.

CONTEXT: There have been no large-scale reports elucidating the relative risks of developing metabolic diseases in adult allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients compared to the general population. OBJECTIVE: This work aimed to investigate the relative risk of developing metabolic diseases and cerebrovascular or cardiovascular disease (CVA) in allo-HSCT recipients compared to the general population in a real-world setting, using a large Korean cohort under long-term observation. METHODS: We conducted a population-based case-control study and analyzed data of 8230 adult allo-HSCT recipients and 32 920 healthy individuals matched for age, sex, and index date in a 1:4 ratio, using a nationwide database of the Korean National Health Insurance Service. Thereafter, we established 4 substudies to investigate the relative risks of metabolic disease development following allo-HSCT: hypertension (cohort A study), diabetes (cohort B study), dyslipidemia (cohort C study), and CVA (cohort D study). RESULTS: The 10-year cumulative incidence of metabolic disease in each experimental cohort was statistically significantly higher than that in the control cohort (overall P value < .001 for all): cohort A study, 17.6% vs 11.8%; cohort B study, 23.5% vs 14.4%; cohort C study for dyslipidemia, 44.5% vs 32.1%; and cohort D study for CVA, 4.2% vs 3.2%. In comparison to the incidence of metabolic diseases in the general population, allo-HSCT recipients presented adjusted hazard ratios of 1.58 for hypertension, 2.06 for diabetes, 1.62 for dyslipidemia, and 1.45 for CVA. CONCLUSION: Recipients of allo-HSCT need to be rigorously monitored for the development of metabolic diseases, including hypertension, diabetes, dyslipidemia, and CVA, based on an enhanced lifelong health care policy including a robust screening program compared to the general population.

Effects of Positive Hepatitis B Core Antibody and Metabolic Disorders in Hepatocellular Carcinoma in an Endemic Area of Hepatitis B Virus.

BACKGROUND AND AIMS: This retrospective study aimed to investigate the impact of positive hepatitis B core antibody (anti-HBc) and metabolic disorders on clinical characteristics of hepatocellular carcinoma (HCC) patients in an HBV-endemic area. METHODS: A total of 1950 consecutive patients newly diagnosed with HCC between 2002 and 2015 were included. Patient records were reviewed. We compared non-viral and non-alcoholic HCC patients with other etiological groups for HCC. In addition, we compared HCC patients with negative hepatitis B surface antigen (HBsAg) and positive anti-HBc to those with negative HBsAg and negative anti-HBc, and to those with HBV. RESULTS: The prevalence of non-viral and non-alcoholic HCC increased from 7% in 2002-2011 to 12% in 2012-2015. The proportion of non-viral and non-alcoholic HCC gradually increased with age. Patients with non-viral and non-alcoholic HCC exhibited higher rates of metabolic disorders and preserved liver function. The rate of anti-HBc positivity was similarly high in all HCC etiological groups. The clinical features of HCC patients with negative HBsAg and positive anti-HBc were similar to those with negative HBsAg and negative anti-HBc, but significantly different from those with HBV HCC. Regarding tumor characteristics, patients in the non-viral and non-alcoholic HCC group had more advanced stages of tumors (mUICC stage III-V and BCLC stage C/D). There was no significant difference in overall survival among the patient groups. The presence of anti-HBc did not affect patient survival. CONCLUSION: Patients with non-viral and non-alcoholic HCC had a relatively high prevalence of metabolic disorders and preserved liver function. However, they had advanced tumor stage compared to patients from other etiological groups. Anti-HBc positivity did not affect the clinical characteristics or prognosis of non-HBV HCC patients in this study.