Association between flavonoid and subclasses intake and metabolic associated fatty liver disease in U.S. adults: Results from National Health and Nutrition Examination Survey 2017-2018.

Background: Metabolic associated fatty liver disease (MAFLD) formerly known as non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Flavonoid is considered a promising candidate for metabolic disease prevention although few studies have explored the relationship between flavonoid intake and MAFLD. Purpose: To assess the relationship between flavonoid intake and MAFLD prevalence in the U.S. adult population. Materials and methods: The data of this cross-sectional study was obtained from National Health and Nutrition Examination Survey (NHANES) and Food and Nutrient Database for Dietary Studies (FNDDS) 2017-2018. Flavonoid and subclasses intake was assessed by two 24h recalls. MAFLD was diagnosed according to the consensus definitions. Multivariate logistic regression model was performed to examine the association between flavonoid intake and MAFLD with adjustments for confounders. Results: A total of 4,431 participants were included in this cross-sectional analysis. MAFLD had a weighted prevalence of 41.93% and was not associated with total flavonoid intake. A higher anthocyanin and isoflavone intake, on the other hand, was associated with a lower prevalence of MAFLD. The protective effect of higher anthocyanin intake was significant among male, Non-Hispanic White, and Non-Hispanic Asia participants. Higher isoflavone intake was associated with a lower risk of MAFLD in participants of younger (age < 50), Non-Hispanic Black, Non-Hispanic Asia, and higher HEI-2015 scores compared with the lowest quartile of isoflavone intake. Stratified analysis showed that compared with the lowest quartile of anthocyanin intake, the effect of anthocyanin intake on MAFLD varied by racial groups (P interaction = 0.02). A positive correlation existed between HDL and anthocyanidin intake (P = 0.03), whereas a negative correlation existed between FPG and isoflavone intake (P = 0.02). Conclusion: MAFLD was adversely linked with flavonoid subclasses, anthocyanin and isoflavone. This modifiable lifestyle provides a potential opportunity to prevent MAFLD. These findings promote future research into the links and mechanisms between anthocyanin and isoflavone intake and MAFLD.

Follistatin Alleviates Hepatic Steatosis in NAFLD via the mTOR Dependent Pathway.

Purpose: In this study, we aimed to investigate the effect of follistatin (FST) on hepatic steatosis in NAFLD and the underlying mechanism, which has rarely been reported before. Methods: Liver samples from NAFLD patients and normal liver samples (from liver donors) were collected to investigate hepatic FST expression in humans. Additionally, human liver cells (LO2) were treated with free fatty acid (FFA) to induce lipid accumulation. Furthermore, lentivirus with FST overexpression or knockdown vectors were used to generate stable cell lines, which were subsequently treated with FFA or FFA and rapamycin. In the animal experiments, male C57BL/6J mice were fed with a high-fat diet (HFD) to induce NAFLD, after which the adeno-associated virus (AAV) gene vectors for FST overexpression were administered. In both cell culture and mice, we evaluated morphological changes and the protein expression of sterol regulatory element-binding protein1 (SREBP1), acetyl-CoA carboxylase1 (ACC1), carbohydrate-responsive element-binding protein (ChREBP), fatty acid synthase (FASN), and Akt/mTOR signaling. The body weight and serum parameters of the mice were also measured. Results: Hepatic FST expression level was higher in NAFLD patients compared to normal samples. In LO2 cells, FST overexpression alleviated lipid accumulation and lipogenesis, whereas FST knockdown aggravated hepatic steatosis. FST could regulate Akt/mTOR signaling, and the mTOR inhibitor rapamycin abolished the effect of FST knockdown on hepatic de novo lipogenesis (DNL). Furthermore, FST expression was increased in HFD mice compared to the corresponding controls. FST overexpression in mice reduced body weight gain, hyperlipidemia, hepatic DNL, and suppressed Akt/mTOR signaling. Conclusion: Hepatic FST expression increases in NAFLD and plays a protective role in hepatic steatosis. FST overexpression gene therapy alleviates hepatic steatosis via the mTOR pathway.Therefore, gene therapy for FST is a promising treatment in NAFLD.

Diabetes patients with comorbidities had unfavorable outcomes following COVID-19: A retrospective study.

BACKGROUND: Previous studies have shown that diabetes mellitus is a common comorbidity of coronavirus disease 2019 (COVID-19), but the effects of diabetes or anti-diabetic medication on the mortality of COVID-19 have not been well described. AIM: To investigate the outcome of different statuses (with or without comorbidity) and anti-diabetic medication use before admission of diabetic after COVID-19. METHODS: In this multicenter and retrospective study, we enrolled 1422 consecutive hospitalized patients from January 21, 2020, to March 25, 2020, at six hospitals in Hubei Province, China. The primary endpoint was in-hospital mortality. Epidemiological material, demographic information, clinical data, laboratory parameters, radiographic characteristics, treatment and outcome were extracted from electronic medical records using a standardized data collection form. Most of the laboratory data except fasting plasma glucose (FPG) were obtained in first hospitalization, and FPG was collected in the next day morning. Major clinical symptoms, vital signs at admission and comorbidities were collected. The treatment data included not only COVID-19 but also diabetes mellitus. The duration from the onset of symptoms to admission, illness severity, intensive care unit (ICU) admission, and length of hospital stay were also recorded. All data were checked by a team of sophisticated physicians. RESULTS: Patients with diabetes were 10 years older than non-diabetic patients [(39 - 64) vs (56 - 70), P < 0.001] and had a higher prevalence of comorbidities such as hypertension (55.5% vs 21.4%, P < 0.001), coronary heart disease (CHD) (9.9% vs 3.5%, P < 0.001), cerebrovascular disease (CVD) (3% vs 2.2%, P < 0.001), and chronic kidney disease (CKD) (4.7% vs 1.5%, P = 0.007). Mortality (13.6% vs 7.2%, P = 0.003) was more prevalent among the diabetes group. Further analysis revealed that patients with diabetes who took acarbose had a lower mortality rate (2.2% vs 26.1, P < 0.01). Multivariable Cox regression showed that male sex [hazard ratio (HR) 2.59 (1.68 - 3.99), P < 0.001], hypertension [HR 1.75 (1.18 - 2.60), P = 0.006), CKD [HR 4.55 (2.52-8.20), P < 0.001], CVD [HR 2.35 (1.27 - 4.33), P = 0.006], and age were risk factors for the COVID-19 mortality. Higher HRs were noted in those aged ≥ 65 (HR 11.8 [4.6 - 30.2], P < 0.001) vs 50-64 years (HR 5.86 [2.27 - 15.12], P < 0.001). The survival curve revealed that, compared with the diabetes only group, the mortality was increased in the diabetes with comorbidities group (P = 0.009) but was not significantly different from the non-comorbidity group (P = 0.59). CONCLUSION: Patients with diabetes had worse outcomes when suffering from COVID-19; however, the outcome was not associated with diabetes itself but with comorbidities. Furthermore, acarbose could reduce the mortality in diabetic.

Chronic Cardio-Metabolic Disease Increases the Risk of Worse Outcomes Among Hospitalized Patients With COVID-19: A Multicenter, Retrospective, and Real-World Study.

Background Although chronic cardio-metabolic disease is a common comorbidity among patients with COVID-19, its effects on the clinical characteristics and outcome are not well known. Methods and Results This study aimed to explore the association between underlying cardio-metabolic disease and mortality with COVID-19 among hospitalized patients. This multicenter, retrospective, and real-world study was conducted from January 22, 2020 to March 25, 2020 in China. Data between patients with and without 5 main cardio-metabolic diseases including hypertension, diabetes mellitus, coronary heart disease, cerebrovascular disease, and hyperlipidemia were compared. A total of 1303 hospitalized patients were included in the final analysis. Of them, 520 patients (39.9%) had cardio-metabolic disease. Compared with patients without cardio-metabolic disease, more patients with cardio-metabolic disease had COVID-related complications including acute respiratory distress syndrome (9.81% versus 3.32%; P<0.001), acute kidney injury (4.23% versus 1.40%; P=0.001), secondary infection (13.9% versus 9.8%; P=0.026), hypoproteinemia (12.1% versus 5.75%; P<0.001), and coagulopathy (19.4% versus 10.3%; P<0.001), had higher incidences of the severe type of COVID-19 (32.9% versus 16.7%; P<0.001), more were admitted to the intensive care unit (11.7% versus 7.92%; P=0.021), and required mechanical ventilation (9.8% versus 4.3%; P<0.001). When the number of the patients' cardio-metabolic diseases was 0, 1, and >2, the mortality was 4.2%, 11.1%, and 19.8%, respectively. The multivariable-adjusted hazard ratio of mortality among patients with cardio-metabolic disease was 1.80 (95% CI, 1.17-2.77). Conclusions Cardio-metabolic disease was a common condition among hospitalized patients with COVID-19, and it was associated with higher risks of in-hospital mortality.

Elevated Lactate Dehydrogenase (LDH) level as an independent risk factor for the severity and mortality of COVID-19.

Early identification of severe patients with coronavirus disease 2019 (COVID-19) is very important for individual treatment. We included 203 patients with COVID-19 by propensity score matching in this retrospective, case-control study. The effects of serum lactate dehydrogenase (LDH) at admission on patients with COVID-19 were evaluated. We found that serum LDH levels had a 58.7% sensitivity and 82.0% specificity, based on a best cut-off of 277.00 U/L, for predicting severe COVID-19. And a cut-off of 359.50 U/L of the serum LDH levels resulted in a 93.8% sensitivity, 88.2% specificity for predicting death of COVID-19. Additionally, logistic regression analysis and Cox proportional hazards model respectively indicated that elevated LDH level was an independent risk factor for the severity (HR: 2.73, 95% CI: 1.25-5.97; P=0.012) and mortality (HR: 40.50, 95% CI: 3.65-449.28; P=0.003) of COVID-19. Therefore, elevated LDH level at admission is an independent risk factor for the severity and mortality of COVID-19. LDH can assist in the early evaluating of COVID-19. Clinicians should pay attention to the serum LDH level at admission for patients with COVID-19.