Prevalence of Musculoskeletal and Metabolic Disorders in Kidney Transplant Recipients: A Systematic Review and Meta-Analysis.

Introduction: Musculoskeletal disorders could be associated with metabolic disorders that are common after kidney transplantation, which could reduce the quality of life of patients. The aim of this study was to assess the prevalence of both musculoskeletal and metabolic disorders in kidney transplant patients. Methods: MEDLINE, CINAHL, Cochrane Library, EMBASE and Web of Science were searched from their inception up to June 2023. DerSimonian and Laird random-effects method was used to calculate pooled prevalence estimates and their 95% confidence intervals (CIs). Results: 21,879 kidney transplant recipients from 38 studies were analysed. The overall proportion of kidney transplant patients with musculoskeletal disorders was 27.2% (95% CI: 18.4-36.0), with low muscle strength (64.5%; 95% CI: 43.1-81.3) being the most common disorder. Otherwise, the overall proportion of kidney transplant patients with metabolic disorders was 37.6% (95% CI: 21.9-53.2), with hypovitaminosis D (81.8%; 95% CI: 67.2-90.8) being the most prevalent disorder. Conclusion: The most common musculoskeletal disorders were low muscle strength, femoral osteopenia, and low muscle mass. Hypovitaminosis D, hyperparathyroidism, and hyperuricemia were also the most common metabolic disorders. These disorders could be associated with poorer quality of life in kidney transplant recipients. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier [CRD42023449171].

The potential association between metabolic disorders and pulmonary tuberculosis: a Mendelian randomization study.

BACKGROUND: Metabolic disorders (MetDs) have been demonstrated to be closely linked to numerous diseases. However, the precise association between MetDs and pulmonary tuberculosis (PTB) remains poorly understood. METHOD: Summary statistics for exposure and outcomes from genome-wide association studies (GWASs) for exposures and outcomes were obtained from the BioBank Japan Project (BBJ) Gene-exposure dataset. The 14 clinical factors were categorized into three groups: metabolic laboratory markers, blood pressure, and the MetS diagnostic factors. The causal relationship between metabolic factors and PTB were analyzed using two-sample Mendelian Randomization (MR). Additionally, the direct effects on the risk of PTB were investigated through multivariable MR. The primary method employed was the inverse variance-weighted (IVW) model. The sensitivity of this MR analysis was evaluated using MR-Egger regression and the MR-PRESSO global test. RESULTS: According to the two-sample MR, HDL-C, HbA1c, TP, and DM were positively correlated with the incidence of active TB. According to the multivariable MR, HDL-C (IVW: OR 2.798, 95% CI 1.484-5.274, P = 0.001), LDL (IVW: OR 4.027, 95% CI 1.140-14.219, P = 0.03) and TG (IVW: OR 2.548, 95% CI 1.269-5.115, P = 0.009) were positively correlated with the occurrence of PTB. TC (OR 0.131, 95% CI 0.028-0.607, P = 0.009) was negatively correlated with the occurrence of PTB. We selected BMI, DM, HDL-C, SBP, and TG as the diagnostic factors for metabolic syndrome. DM (IVW, OR 1.219, 95% CI 1.040-1.429 P = 0.014) and HDL-C (IVW, OR 1.380, 95% CI 1.035-1.841, P = 0.028) were directly correlated with the occurrence of PTB. CONCLUSIONS: This MR study demonstrated that metabolic disorders, mainly hyperglycemia, and dyslipidemia, are associated with the incidence of active pulmonary tuberculosis.

[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.

COVID-19 fatality and DALYs, and associated metabolic disorders and ambient air pollutants in pre-Omicron era of the pandemic: an international comparative study.

BACKGROUND: Air pollution and a number of metabolic disorders have been reported to increase the risk of severe COVID-19 outcomes. This study explored the association between severe COVID-19 outcomes, metabolic disorders and environmental air pollutants, at regional level, across 38 countries. METHODS: We conducted an ecological study using COVID-19 data related to countries of the Organization for Economic Cooperation and Development (OECD), with an estimated population of 1.4 billion. They were divided into 3 regions: 1. Europe & Middle east; 2. Americas (north, central & south America); 3. East-Asia & West Pacific. The outcome variables were: COVID-19 case-fatality rate (CFR) and disability-adjusted life years (DALYs) at regional level. Freely accessible datasets related to regional DALYs, demographics and other environmental pollutants were obtained from OECD, WHO and the World in Data websites. Generalized linear model (GLM) was performed to determine the regional determinants of COVID-19 CFR and DALYs using the aggregate epidemiologic data (Dec. 2019-Dec. 2021). RESULTS: Overall cumulative deaths were 65,000 per million, for mean CFR and DALYs of 1.31 (1.2)% and 17.35 (2.3) years, respectively. Globally, GLM analysis with adjustment for elderly population rate, showed that COVID-19 CFR was positively associated with atmospheric PM2.5 level (beta = 0.64(0.0), 95%CI: 0.06-1.35; p < 0.05), diabetes prevalence (beta = 0.26(0.1), 95%CI: 0.12-0.41; p < 0.001). For COVID-19 DALYs, positive associations were observed with atmospheric NOx level (beta = 0.06(0.0), 95%CI: 0.02-0.82; p < 0.05) and diabetes prevalence (beta = 0.32(0.2), 95%CI: 0.04-0.69; p < 0.05). At regional level, adjusted GLM analysis showed that COVID-19 CFR was associated with atmospheric PM2.5 level in the Americas and East-Asia & Western Pacific region; it was associated with diabetes prevalence for countries of Europe & Middle east and East-Asia & Western Pacific region. Furthermore, COVID-19 DALYs were positively associated with atmospheric PM2.5 and diabetes prevalence for countries of the Americas only. CONCLUSION: These findings confirm that diabetes and air pollution increase the risk of disability and fatality due to COVID-19, with disparities in terms of their impact. They suggest that efficient preventive and management programs for diabetes and air pollution countermeasures would have curtailed severe COVID-19 outcome rates.

Understanding the Cardiovascular and Metabolic Health Effects of Air Pollution in the Context of Cumulative Exposomic Impacts.

Poor air quality accounts for more than 9 million deaths a year globally according to recent estimates. A large portion of these deaths are attributable to cardiovascular causes, with evidence indicating that air pollution may also play an important role in the genesis of key cardiometabolic risk factors. Air pollution is not experienced in isolation but is part of a complex system, influenced by a host of other external environmental exposures, and interacting with intrinsic biologic factors and susceptibility to ultimately determine cardiovascular and metabolic outcomes. Given that the same fossil fuel emission sources that cause climate change also result in air pollution, there is a need for robust approaches that can not only limit climate change but also eliminate air pollution health effects, with an emphasis of protecting the most susceptible but also targeting interventions at the most vulnerable populations. In this review, we summarize the current state of epidemiologic and mechanistic evidence underpinning the association of air pollution with cardiometabolic disease and how complex interactions with other exposures and individual characteristics may modify these associations. We identify gaps in the current literature and suggest emerging approaches for policy makers to holistically approach cardiometabolic health risk and impact assessment.

Relationship between hypocalcemia immediately after calving with metabolic disorders and body condition score in Holstein cows.

Background: Hypocalcemia is one of the most common transition period disorders that affects dairy cows and has been divided into clinical and subclinical types. Aim: This study aimed to investigate the relationship between postpartum serum calcium (Ca) concentrations with metabolic disorders and body condition score (BCS) in Holstein dairy cows. Methods: Two hundred and seventy-one Holstein cows were blocked from two commercial dairy herds based on parity (primiparous and multiparous) and serum Ca concentrations on calving day, 1 and 2 days postpartum were allocated to 1 of 3 groups: 1) Serum Ca concentration >8.5 mg/dl at the calving day, 1 and 2 days postpartum (normocalcemic); 2) serum Ca concentration ≤8.5 mg/dl on the calving day and 1 or 2 day postpartum (transient subclinical hypocalcemia (TSCH)); and 3) serum Ca concentration ≤8.5 mg/dl on the calving day, 1 and 2 days postpartum (persistent subclinical hypocalcemia (PSCH)). Results: The results showed that the primiparous and multiparous cows had the highest TSCH and PSCH percentages, respectively. Ca status after calving did not affect the BCS changes, incidence of milk fever, hypomagnesemia and hyperketonemia, and clinical and subclinical endometritis. The incidence of retained placenta, metritis, and subclinical mastitis was affected by Ca status after calving, so PSCH cows experienced 6.28, 6.43, and 5.9 times more retained placenta, metritis, and subclinical mastitis than normocalcemic cows, respectively. The culling rate within the first 60 days in milk for PSCH cows was 4.61 times more than for normocalcemic cows. Conclusion: Overall, the results of the study showed that cows with PSCH had a higher incidence of retained placenta; uterine infections, subclinical mastitis, and culling rate, but cows with TSCH were similar to healthy cows in terms of metabolic disorders and culling rate.

Comparative analysis of inherited metabolic diseases in normal newborns and high-risk children: Insights from a 10-year study in Shanghai.

BACKGROUND: Compare the differences between normal newborns and high-risk children with inherited metabolic diseases. The disease profile includes amino acidemias, fatty acid oxidation disorders, and organic acidemias. METHODS: Data was collected on newborns and children from high-risk populations in Shanghai from December 2010 to December 2020. RESULTS: 232,561 newborns were screened for disorders of organic, amino acid, and fatty acid metabolism. The initial positive rate was 0.66 % (1,526/232,561) and the positive recall rate was 77.85 %. The positive predictive value is 4.71 %. Among them, 56 cases were diagnosed as metabolic abnormalities. The total incidence rate is 1:4153. Hyperphenylalaninemia and short-chain acyl-CoA dehydrogenase are the most common diseases in newborns. In addition, in 56 children, 39 (69.42 %) were diagnosed by genetic sequencing. Some hotspot mutations in 14 IEMs have been observed, including PAH gene c.728G > A, c.611A > G, and ACADS gene c. 1031A > G, c.164C > T. A total of 49,860 symptomatic patients were screened, of which 185 were diagnosed with IEM, with a detection rate of 0.37 %. The most commonly diagnosed diseases in high-risk infants aremethylmalonic acidemia and hyperphenylalaninemia. CONCLUSION: There are more clinical cases of congenital metabolic errors diagnosed by tandem mass spectrometry than newborn screening. The spectrum of diseases, prevalence, and genetic characteristics of normal newborns and high-risk children are quite different.

Prevalence and risk factors of MAFLD and its metabolic comorbidities in community-based adults in China: A cross-sectional study.

AIMS: There is a growing interest in the co-management of metabolic dysfunction-associated fatty liver disease (MAFLD) and its metabolic comorbidities. However, there is insufficient epidemiological data regarding MAFLD and its metabolic comorbidities in China. This study aims to investigate the prevalence and risk factors of MAFLD and its metabolic comorbidities. METHODS: 9171 participants were recruited in this cross-sectional study, utilizing a multistage, stratified sampling method. All participants underwent a comprehensive assessment. The diagnosis of MAFLD was based on vibration-controlled transient elastography (VCTE). The prevalence of MAFLD and its metabolic comorbidities was calculated. Binary and ordinary logistic regressions were conducted. RESULTS: The overall weighted prevalence of MAFLD was 21.18%. Of the 2081 adults with MAFLD, 1866 (89.67%) had more than one metabolic comorbidity, and only 215 (10.33%) did not have comorbidity. Among the population with MAFLD, the prevalence of dyslipidemia, hypertension, hyperuricemia, and diabetes was 67.47%, 43.73%, 39.10%, and 33.88%, respectively. Advanced age, male gender, overweight/obesity, excessive alcohol consumption, and elevated HOMA-IR levels were positively correlated with the number of MAFLD-related metabolic comorbidities. CONCLUSIONS: A significant proportion of individuals diagnosed with MAFLD presented with metabolic comorbidities. Therefore, engaging in the co-management of MAFLD and its metabolic comorbidities is imperative.

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.

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.

The association between atherogenic index of plasma and metabolic dysfunction-associated fatty liver disease as detected by FibroScan.

Introduction: Objectives: this study aimed to explore the potential of the atherogenic index of plasma (AIP) as a predictor of metabolic dysfunction-associated fatty liver disease (MAFLD). Methods: a cross-sectional study, including data from 4473 participants in the National Health and Nutrition Examination Survey (NHANES) 2017-2018, was performed. A control attenuation parameter (CAP) ≥ 285 dB/m was used to confirm hepatic steatosis. Degrees of liver stiffness were confirmed according to liver stiffness measurement (LSM). Weighted multivariate logistic regression models were used to assess the association between AIP and the risk for MAFLD and liver fibrosis. Finally, receiver operating characteristic (ROC) curve analysis was used to test the accuracy of AIP in predicting MAFLD. Results: the association between AIP and the prevalence of MAFLD was positive in all three multivariate logistic regression models (model 1, odds ratio (OR), 18.2 (95 % confidence interval (CI), 14.4-23.1); model 2, OR, 17.0 (95 % CI, 13.3-21.8); model 3, OR, 5.2 (95 % CI, 3.9-7.0)). Moreover, this positive relationship was found to be significant in patients of different sexes and whether they had diabetes. However, no significant differences were observed between AIP and significant fibrosis or cirrhosis as assessed by different liver fibrosis indices. Finally, ROC curve analysis demonstrated that the AIP index also demonstrated positive diagnostic utility (area under the ROC curve, 0.733 (95 % CI, 0.718-0.747); p < 0.001). Conclusion: This study revealed a positive association between AIP and MAFLD among American adults. Furthermore, this association persisted in different sexes and whether they had diabetes.

Introducción: Objetivos: este estudio tuvo como objetivo explorar el potencial del índice aterogénico del plasma (AIP) como predictor de enfermedad hepática grasa asociada a disfunción metabólica (MAFLD). Métodos: se realizó un estudio transversal que incluyó datos de 4473 participantes de la encuesta nacional de exémenes de salud y nutrición (NHANES) 2017-2018. Se utilizó un parámetro de atenuación de control (CAP) ≥ 285 dB/m para confirmar la esteatosis hepática. Los grados de rigidez hepática se confirmaron de acuerdo con la medición de rigidez hepática (LSM). Se utilizaron modelos de regresión logística multivariponderponderados para evaluar la asociación entre AIP y el riesgo de MAFLD y fibrosis hepática. Por último, se utilizó el análisis de la curva ROC para probar la precisión de la AIP en la predicción de la MAFLD. Resultados: la asociación entre AIP y prevalencia de MAFLD fue positiva en los tres modelos de regresión logística multivariable (modelo 1, odds ratio (OR): 18,2 (intervalo de confianza (IC) del 95 %: 14,4-23,1); Modelo 2, OR: 17,0 (IC del 95 %: 13,3-21,8); Modelo 3, OR: 5,2 (IC del 95 %: 3,9-7,0)). Además, esta relación positiva se encontró significativa en pacientes de diferentes sexos ya tuvieran o no diabetes. Sin embargo, no se observaron diferencias significativas entre la AIP y la fibrosis o cirrosis significativa evaluada por diferentes índices de fibrosis hepática. Finalmente, el análisis de la curva ROC demostró que el índice AIP también demostró utilidad diagnóstica positiva (área bajo la curva ROC = 0,733 (IC del 95 %: 0,718-0,747); p < 0,001). Conclusión: este estudio reveló una asociación positiva entre AIP y MAFLD en los adultos estadounidenses. Además, esta asociación persistió en los diferentes sexos ya tuvieran o no diabetes.

Offspring cardiometabolic outcomes and postnatal growth trajectories after exposure to maternal SARS-CoV-2 infection.

OBJECTIVE: The objective of this study is to determine whether in utero exposure to SARS-CoV-2 is associated with increased risk for a cardiometabolic diagnosis by 18 months of age. METHODS: This retrospective electronic health record (EHR)-based cohort study included the live-born offspring of all individuals who delivered during the COVID-19 pandemic (April 1, 2020-December 31, 2021) at eight hospitals in Massachusetts. Offspring exposure was defined as a positive maternal SARS-CoV-2 polymerase chain reaction test during pregnancy. The primary outcome was presence of an ICD-10 code for a cardiometabolic disorder in offspring EHR by 18 months. Weight-, length-, and BMI-for-age z scores were calculated and compared at 6-month intervals from birth to 18 months. RESULTS: A total of 29,510 offspring (1599 exposed and 27,911 unexposed) were included. By 18 months, 6.7% of exposed and 4.4% of unexposed offspring had received a cardiometabolic diagnosis (crude odds ratio [OR] 1.47 [95% CI: 1.10 to 1.94], p = 0.007; adjusted OR 1.38 [1.06 to 1.77], p = 0.01). Exposed offspring had a significantly greater mean BMI-for-age z score versus unexposed offspring at 6 months (z score difference 0.19 [95% CI: 0.10 to 0.29], p < 0.001; adjusted difference 0.04 [-0.06 to 0.13], p = 0.4). CONCLUSIONS: Exposure to maternal SARS-CoV-2 infection was associated with an increased risk of receiving a cardiometabolic diagnosis by 18 months preceded by greater BMI-for-age at 6 months.

Metabolic effects of milk fatty acids: A literature review.

Milk and dairy products are known to have a significant role in human development and tissue maintenance due to their high nutritional value. With the higher incidence of obesity and metabolic diseases, nutrition and public health authorities have recommended the intake of fat-free or low-fat dairy due to the saturated fatty acid content of whole-fat products and their effect on serum cholesterol levels. However, recent studies have questioned the association between milk fat consumption and cardiometabolic risk. This literature review aims to compile the scientific evidence of the metabolic effects of milk fatty acids in clinical and basic research studies, as well as their relationship with metabolic disorders and gut microbiota composition. Research shows that various milk fatty acids exert effects on metabolic alterations (obesity, type 2 diabetes and cardiovascular diseases) by modifying glucose homeostasis, inflammation and lipid profile-related factors. Additionally, recent studies have associated the consumption of milk fatty acids with the production of metabolites and the promotion of healthy gut microbiota. From mainly observational studies, evidence suggests that milk and dairy fatty acids are not directly linked to cardiometabolic risk, but further controlled research is necessary to clarify such findings and to assess whether dietary recommendations to choose low-fat dairy foods are necessary for the population for the prevention of obesity and cardiometabolic disease.

The potential causal association between systemic lupus erythematosus and endocrine and metabolic disorders in the East Asian population: A bidirectional two-sample Mendelian randomization study.

OBJECTIVES: Observational studies indicate a significant correlation between systemic lupus erythematosus (SLE) and endocrine and metabolic disorders, but the causal association between SLE and endocrine and metabolic disorders remains unclear due to the reverse causality and confounding biases commonly presented in conventional observational research. This study endeavors to uncover the causal association between SLE and three common endocrine and metabolic disorders, including Graves' disease (GD), type 2 diabetes mellitus (T2DM), and osteoporosis (OP). METHODS: We used genome-wide association study data for SLE and three endocrine and metabolic disorders in an East Asian population, employing bidirectional two-sample Mendelian randomization (MR) analysis and sensitivity analysis to ascertain the causal association between SLE and endocrine and metabolic disorders. RESULTS: A multiplicative random-effect inverse-variance weighted approach revealed a significant positive correlation between SLE and an elevated risk of GD with an odds ratio (OR) of 1.12 (95% CI: 1.04-1.22, p < .01), and inverse-variance weighted (IVW) analysis also indicated that SLE increased the risk of OP with an OR of 1.035 (95% CI: 1.003-1.068, p < .05). Additionally, GD causally affected SLE in an IVW analysis after Bonferroni correction, with an OR of 1.33 (95% CI: 1.19-1.49, p < .05/3), but the application of multivariable MR analysis resulted in the absence of a causal association of GD on SLE (OR 1.047, 95% CI: 0.952-1.151, p > .05). Lastly, the robustness and validity of the findings were verified through a sensitivity analysis. CONCLUSIONS: We confirmed that SLE has a causal effect on GD as well as OP, but no evidence exists to substantiate a causal link between SLE and T2DM. Our study offers valuable contributions for uncovering the etiology of SLE and endocrine and metabolic disorders and furthering disease risk research while providing potential targets for disease monitoring and therapeutic intervention.

Mortality in metabolic dysfunction-associated steatotic liver disease: A nationwide population-based cohort study.

BACKGROUND: A new fatty liver disease nomenclature, steatotic liver disease (SLD) has been proposed; however, there are no data on clinical outcomes. We investigated the impact of SLD with metabolic dysfunction (MD; SLD-MD) on all-cause mortality. METHODS: We evaluated nationally representative participants aged ≥19 years using data from the Korea National Health and Nutrition Examination Survey 2007-2015 and their linked death data through 2019. The presence of fatty liver disease was assessed by liver fat score, fatty liver index and significant liver fibrosis was evaluated by the Fibrosis-4 Index, and fibrosis score. SLD-MD was categorized into three groups: metabolic dysfunction-associated steatotic liver disease (MASLD); metabolic alcoholic liver disease (MetALD); and SLD with other combination etiologies. RESULTS: Among 26734 individuals (11561 men and 15173 women, mean age 48.8 years), 1833 (6.9 %) died during a mean follow-up period of 110.6 ± 33.9 months. Mortality risk was significantly higher in individuals with SLD-MD (hazard ratio [HR] = 1.35) than in those without (P < 0.001). Among the three groups, MASLD (HR = 1.32) and SLD with other combination etiologies (HR = 2.06) independently increased mortality risk (all P < 0.001). When individuals with SLD-MD had significant liver fibrosis or diabetes, mortality risk increased further (HR = 1.68 and 1.85, respectively; all P < 0.001). SLD-MD with both significant liver fibrosis and diabetes showed the highest mortality risk (HR = 2.29, P < 0.001). When applied fatty liver index and fibrosis score, similar results were observed. CONCLUSIONS: SLD-MD is associated with a higher mortality risk. When SLD-MD was combined with significant liver fibrosis or diabetes, the mortality risk became much higher. Treatment strategies to reduce fibrotic burden and improve glycemic control in individuals with MASLD are needed.

Long-term exposure to PM1 is associated with increased prevalence of metabolic diseases: evidence from a nationwide study in 123 Chinese cities.

Exposure to particulate matter (PM) has been linked to metabolic diseases. However, the effects of PM with an aerodynamic diameter ≤ 1.0 µm (PM1) on metabolic diseases remain unclear. This study is aimed at assessing the associations of PM1 with metabolic disease risk and quantifying the concentration-response (C-R) relationship of PM1 with metabolic disease risk. A national cross-sectional study was conducted, including 12,495 middle-aged and older adults in 123 Chinese cities. The two-year average concentration of PM1 was evaluated using satellite-based spatiotemporal models. Metabolic diseases, including abdominal obesity, diabetes, hypertension, dyslipidemia, and metabolic syndrome, were identified based on physical examination, blood standard biochemistry examination, and self-reported disease histories. Generalized linear models and C-R curves were used to evaluate the associations of PM1 with metabolic diseases. A total of 12,495 participants were included in this study, with a prevalence of 45.73% for abdominal obesity, 20.22% for diabetes, 42.46% for hypertension, 41.01% for dyslipidemia, and 33.78% for metabolic syndrome. The mean ± standard deviation age of participants was 58.79 ± 13.14 years. In addition to dyslipidemia, exposure to PM1 was associated with increased risks of abdominal obesity, diabetes, hypertension, and metabolic syndrome. Each 10 µg/m3 increase in PM1 concentrations was associated with 39% (odds ratio (OR) = 1.39, 95% confidence interval (CI) 1.33, 1.46) increase in abdominal obesity, 18% (OR = 1.18, 95%CI 1.12, 1.25) increase in diabetes, 11% (OR = 1.11, 95%CI 1.06, 1.16) increase in hypertension, and 25% (OR = 1.25, 95%CI 1.19, 1.31) in metabolic syndrome, respectively. C-R curves showed that the OR values of abdominal obesity, diabetes, hypertension, and metabolic syndrome were increased gradually with the increase of PM1 concentrations. Subgroup analysis indicated that exposure to PM1 was associated with increased metabolic disease risks among participants with different lifestyles and found that solid fuel users were more susceptible to PM1 than clean fuel users. This national cross-sectional study indicated that exposure to higher PM1 might increase abdominal obesity, diabetes, hypertension, and metabolic syndrome risk, and solid fuel use might accelerate the adverse effects of PM1 on metabolic syndrome risk. Further longitudinal cohort studies are warranted to establish a causal inference between PM1 exposure and metabolic disease risk.

Metabolic dysfunction-associated steatotic liver disease and risk of cardiovascular disease.

OBJECTIVE: We explored clinical implications of the new definition of metabolic dysfunction-associated steatotic liver disease (MASLD) by assessing its prevalence and associated cardiovascular disease (CVD) risk. DESIGN: From nationwide health screening data, we identified 9 775 066 adults aged 20-79 who underwent health examination in 2009. Participants were categorised into four mutually exclusive groups: (1) MASLD; (2) MASLD with increased alcohol intake (MetALD); (3) MASLD with other combined aetiology (the three collectively referred to as MASLD/related steatotic liver disease (SLD)); and (4) no MASLD/related SLD. SLD was determined by fatty liver index ≥30. The primary outcome was CVD event, defined as a composite of myocardial infarction, ischaemic stroke, heart failure or cardiovascular death. RESULTS: The prevalence of MASLD, MetALD and MASLD with other combined aetiology was 27.5%, 4.4% and 1.5%, respectively. A total of 8 808 494 participants without prior CVD were followed up for a median of 12.3 years, during which 272 863 CVD events occurred. The cumulative incidence and multivariable-adjusted risk of CVD were higher in participants with MASLD/related SLD than in those without (HR 1.38 (95% CI 1.37 to 1.39)). Multivariable-adjusted HR (95% CI) of CVD events was 1.39 (1.38 to 1.40) for MASLD, 1.28 (1.26 to 1.30) for MetALD and 1.30 (1.26 to 1.34) for MASLD with other combined aetiology compared to the absence of any of these conditions. CVD risk was also higher in participants with metabolic dysfunction-associated fatty liver disease or non-alcoholic fatty liver disease than in those without the respective condition. CONCLUSION: Over one-third of Korean adults have MASLD/related SLD and bear a high CVD risk.

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.