Fat Score Research Articles

Digital Twin-Enabled Personalized Nutrition Improves Metabolic Dysfunction-Associated Fatty Liver Disease in Type 2 Diabetes: Results of a 1-Year Randomized Controlled Study

ObjectivePostprandial hyperglycemia drives insulin resistance and inflammation, leading to metabolic dysfunction-associated fatty liver disease (MAFLD). Prediction of postprandial glycemic responses by digital twin (DT) technology can fashion a personalized nutrition, activity, and sleep to treat type 2 diabetes (T2D) and MAFLD. This study examines the effects of DT-enabled personalized nutrition, activity, and sleep on glycemic status, surrogate markers of MAFLD, and magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) in patients with T2D. MethodsIn an open-label randomized trial (2:1), 319 people with T2D were eligible to intervention (DT) or standard care (SC). DT patients followed personalized meal plans with foods suggested by artificial intelligence with least predicted postprandial glycemic response. The primary end point was to compare change in hemoglobin A1c (HbA1c) and medicine reduction between the DT and SC groups. Key secondary end points included remission to compare liver function test scores and visceral adiposity using MRI. ResultsHbA1C was significantly better for DT than for SC (−2.9 [1.8] vs −0.3 [1.2]; P < .001) at 1 year with 72.7% remission of T2D. In patients with abnormal baseline values, significant improvements were seen in DT vs SC patients from baseline to 1 year in nonalcoholic fatty liver disease liver fat score (mean [SD]; −2.5 [2.0] vs −0.1 [1.5]; P < .001) and nonalcoholic fatty liver disease fibrosis score (−1.20 [0.9] vs −0.1 [1.0]; P < .001), respectively. Improvements are seen with DT compared with SC in other liver fat, fibrosis score, and %liver fat by MRI-PDFF. ConclusionAt 1 year, DT-enabled personalized treatment significantly improved hyperglycemia and surrogate markers of MAFLD and MRI-PDFF.

Hepatic steatosis in women with polycystic ovary syndrome

BackgroundThis multi-center, cross-sectional study intended to explore the prevalence and risk factors of nonalcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated fatty liver disease (MAFLD) in patients with polycystic ovary syndrome (PCOS).MethodsPatients who met the PCOS Rotterdam diagnostic criteria were enrolled in 6 centers in China, and age-matched healthy volunteers were also recruited. Data were collected including medical history, physical characteristics, and blood tests (liver function, blood lipids, blood glucose and insulin, sex hormones, etc.). Transvaginal or transrectal ultrasound was employed to identify polycystic ovarian morphology (PCOM). The serological score Liver Fat Score (LFS) >-0.640 was used for the diagnosis of NAFLD, and the diagnosis of MAFLD was made according to the 2020 new definition.ResultsA total of 217 PCOS patients and 72 healthy controls were included. PCOS patients had impaired glucose and lipid metabolism, higher liver enzymes and LFS. Both NAFLD (33.6%) and MAFLD (42.8%) was more prevalent in PCOS patients than in controls (4.2%, P < 0.001). Logistic regression results showed that HOMA-IR ≥ 3.54 and ALT ≥ 18.2 were independently associated with NAFLD (P < 0.001) and MAFLD (P ≤ 0.001). The prevalence of NAFLD was significantly higher in PCOS patients with free androgen index (FAI) > 8 (53.8% versus 17.4%, P < 0.001) and BMI ≥ 24 kg/m2 (57.3%, 11.3%, P < 0.001).ConclusionThe prevalence of NAFLD/MAFLD in PCOS patients was significantly higher than that in healthy controls and was independently associated with HOMA-IR and ALT. PCOS patients with overweight and elevated FAI have a higher prevalence of fatty liver.

Uncovering genetic parameters and environmental influences on fertility, milk production, and quality in autochthonous Reggiana cattle

Reggiana is a local cattle breed from northern Italy known for its rusticity and profitability, due to the production of branded Parmigiano Reggiano cheese. To ensure the persistence of such profitability in the long term, an adequate breeding program is required. To this aim, in the present study we estimate the genetic parameters of the main productive and reproductive traits, and we evaluate the effect of genotype by environment interaction (GxE) on these traits using 2 environmental covariates: (1) productivity and (2) temperature-humidity index (THI). Milk, fat, protein, and casein yield were considered as daily production traits, whereas protein, fat, casein percentage, casein index, and somatic cell score were considered as milk quality traits. Finally, reproductive traits such as the number of inseminations, days open, calving interval, and calving-to-first-insemination interval were evaluated. Reggiana cattle produce an average of 19 kg of milk per day with 3.7% fat and 3.4% protein content and have excellent fertility parameters. Compared with other breeds, they have slightly lower heritability for production and quality for production traits (e.g., 0.12 [0.09; 0.15] for milk yield), but similar heritability for fertility traits. Milk, protein, and fat daily yields are highly correlated but negatively correlated with the percentage of protein, fat, and casein, whereas fertility traits have an unfavorable genetic correlation with daily production traits. When considering productivity, a consistent amount of variability due to GxE was observed for all daily production traits, somatic cell count, and casein index. A modest amount of GxE was observed for fertility parameters, while the percentage of solid content showed almost no GxE effect. A similar situation occurred when considering the THI, but no GxE interaction was observed for reproduction traits. In conclusion, this study provides useful information for the implementation of accurate selection plans in this local breed, accounting for environmental plasticity measured through the consistent GxE interaction observed.

Comparisons of Insulin Resistance- and Steatosis-Based Scores in Monitoring Metabolic Associated Fatty Liver Disease Treatment Response

Background: Quantitative measurements of liver fat contents (LFCs) by magnetic resonance imaging derived-proton density fat fraction (MRI-PDFF) are accurate but limited by availability, convenience, and expense in the surveillance of metabolic associated fatty liver (MAFLD). Insulin resistance (IR) and steatosis-associated serum indices are useful in screening for MAFLD, but their value in monitoring MAFLD with or without chronic hepatitis B virus (CHB) infection remains unclear and we aimed to evaluate these scores in predicting changes in LFC. Methods: We conducted a prospective study between January 2015 and December 2021 with 620 consecutive participants with MAFLD (212 participants with CHB) who received a 24-week lifestyle intervention. The homeostasis model assessment of IR (HOMA-IR), HOMA2 index, glucose-insulin ratio, quantitative insulin sensitivity check index, fasting insulin resistance index, fatty liver index (FLI), hepatic steatosis index (HSI), liver fat score (LFS), visceral adiposity index, and triglycerides * glucose were calculated. Results: When using endpoints such as LFS improvements of ≥5% or 10% or escalations of ≥5%, LFS had the highest area under the curve (AUC) values at all endpoints for MAFLD alone (0.756, 95% CI: 0.707–0.805; 0.761, 95% CI: 0.705–0.818; 0.807, 95% CI: 0.713–0.901, all p < 0.05, respectively). With CHB, the FLI (AUC = 0.750) and HIS (AUC = 0.770) exhibited the highest AUCs between the former two outcomes, respectively, but no score could predict LFC escalation of ≥5%. Conclusion: Among IR and steatosis scores, changes in LFC through lifestyle interventions can be captured with LFS possessing moderate precision but not in those with CHB.

The Effect of Testosterone Replacement Therapy on Nonalcoholic Fatty Liver Disease in Older Hypogonadal Men.

Male hypogonadism is associated with visceral obesity and the metabolic syndrome: factors important for the development of nonalcoholic fatty liver disease (NAFLD). The Testosterone Trials (The T Trials) showed testosterone (T) treatment compared with placebo in older hypogonadal men was associated with decreases in cholesterol and insulin levels suggesting that T treatment may improve NAFLD. Compare effects of T vs placebo treatment on NAFLD scores and liver scans in elderly hypogonadal men. Secondary data analyses from 479 older hypogonadal men with total T < 275 ng/dL from The T Trials were performed. Three clinical liver fat scores-lipid accumulation product index, hepatic steatosis index, nonalcoholic fatty liver disease-metabolic syndrome score-and liver computed tomography (CT) Hounsfield units and liver to spleen ratio were evaluated at baseline and 12 months after treatment. There were no statistically significant differences of change in lipid accumulation product index (P = .98), hepatic steatosis index (P = .67), and nonalcoholic fatty liver disease-metabolic syndrome (P = .52) in 246 men treated with T compared with 233 treated with placebo for 12 months. Liver CT showed no statistically significant difference of change in Hounsfield units (P = .24; n = 71 for T, n = 69 for placebo) and liver to spleen ratio (P = .74; n = 55 for T, n = 62 for placebo) between the 2 groups. Our study did not show improvement of NAFLD in older hypogonadal men after 12 months of T vs placebo treatment, as assessed by 3 clinical scores and liver CT for hepatic steatosis. Future studies with longer treatment duration and additional NAFLD diagnostic modalities as primary outcome are warranted.

Increased risk of cardiometabolic disease in normal-weight individuals with non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is strongly associated with obesity, but there is increasing evidence that not all individuals who are overweight/obese also develop NAFLD. Currently, it is unclear whether normal-weight (Nw) individuals with NAFLD have a higher risk of cardiometabolic disease risk compared with individual sub-groups (Nw and Obesity [Ob]) of non-NAFLD. This study aimed to compare the cardiometabolic profiles, cardiovascular disease, and diabetes between Nw vs. Ob with non-NAFLD vs. NAFLD. This study utilized the Korea National Health and Nutrition Examination Surveys collected from 2019 to 2021. Individuals were stratified into Nw vs. Ob categories and further divided into non-NAFLD and NAFLD groups based on the hepatic steatosis index and liver fat score (N=6615). The prevalence of non-NAFLD Nw, non-NAFLD Ob, NAFLD Nw, and NAFLD Ob groups was 36%, 20%, 7%, and 37%, respectively. NAFLD Nw vs. non-NAFLD Ob manifests deteriorated cardiometabolic disease risk profiles and surrogate markers of insulin resistance despite having higher weight, waist circumference, and BMI. In addition, compared to non-NAFLD Nw, individuals with NAFLD Nw had a significantly higher risk of CVDs (738%, p<.001) and diabetes (408%, p<.001), with no difference between NAFLD Nw and NAFLD Ob groups. Cardiometabolic disease risk is more closely related to NAFLD developments than adiposity status. Therefore, not all overweight/obese individuals have a higher cardiometabolic disease risk, and NAFLD in Nw is an aggressive disease that is associated with cardiometabolic disease risk compared with Ob individuals without NAFLD.

Elevated Plasma Copeptin Levels Identify the Presence and Severity of Nonalcoholic Fatty Liver Disease in Obesity

Abstract Background Non-alcoholic fatty liver disease is characterized by excessive fat accumulation in the liver with unclear mechanism may be due to epigenetic changes which take place at the transcriptional level without altering the underlying DNA sequence. this epigenetic alternation are involved in regulation of hepatic lipid metabolism, insulin resistance, mitochondrial damage, oxidative stress response, and the release of inflammatory cytokines, all of which have been implicated in the development and progression of NAFLD. Elevated copeptin, a vasopressin marker, is linked to metabolic disease, and obese rats with lowvasopressin concentration had a decreased risk of liver steatosis. Aim and objectives To Detect the elevation of plasma copeptin in obese patients with nonalcoholic fatty liver disease in relation to general population. Subjects and Methods This is A randomized case control cross sectional study, was carried out at internal medicine and gastroenterology department, Ain Shams University hospitals, on 100 patients above 18 years old with Hepatic Steatosis Index (HSI) and NAFLD-Liver Fat Score (LFS), over a period of 6 months. Result There was high statistically significant difference between the studied groups as regard Serum plasma copeptin. Conclusion Our study demonstrates for the first time that copeptin levels predict the presence of biopsy-proven NAFLD in obese individuals, regardless of body adiposity and the coexistence of other metabolic disorders. Studies with longitudinal design are warranted for exploring the possible involvement of AVP/V1aR system in the development and progression of NAFLD.

Non-alcoholic fatty liver disease is associated with hyperandrogenism in women with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a highly complex reproductive metabolic disorder and women with PCOS have high prevalence of non-alcoholic fatty liver disease (NAFLD). Despite both hyperandrogenism and insulin resistance are common pathophysiologies in NAFLD and PCOS, this association is still controversial. Therefore, the aim of this study is to evaluate the relationship between hyperandrogenism and NAFLD in females diagnosed with PCOS. We recruited 667 women diagnosed with PCOS and 289 women with regular menstrual cycles as control. The PCOS diagnosis was made using National Institute of Child Health and Human Disease criteria. Total and free testosterone levels (TT and TF, respectively), and free androgen index (FAI) were used as measures of hyperandrogenism. Fatty liver index and liver fat score (FLI and LFS, respectively), and hepatic steatosis index (HSI) were used to assess NAFLD. The prevalence of NAFLD in PCOS women evaluated by LFS, FLI, and HIS were 19.9, 10.3, and 32.2%, respectively. In the control group, the incidence was 2.1, 0.7, and 4.2%, respectively. Both FT and FAI levels showed significant association with increased NAFLD-related indices, after adjusting for insulin resistance and other factors (LFS (OR 3.18 (95% CI 1.53–6.63) in FT; 1.12 (1.04–1.22) in FAI), FLI (OR 2.68 (95% CI 1.43–5.03) in FT; 1.13 (1.06–1.20) in FAI), and HSI (OR 3.29 (95% CI 2.08–5.21) in FT; 1.5 (1.09–1.21) in FAI). TT did not exhibit association with any NAFLD index. In women with PCOS, significantly higher rate of NAFLD was observed compared to the control women. The FT and FAI were independently associated with NAFLD in women with PCOS. The findings suggest the possibility of hyperandrogenism contributing to the progression and/or development of NAFLD in PCOS.

Is Metabolic Score for Visceral Fat (METS-VF) a Better Index Than Other Adiposity Indices for the Prediction of Visceral Adiposity.

Visceral adiposity is an important risk factor for cardiometabolic diseases. To determine whether the Metabolic Score for Visceral Fat (METS-VF) is more effective than other adiposity indices in predicting visceral fat area (VFA). In this single-center and cross-sectional study, we included patients aged 20-50 years, without diabetes and coronary artery disease, who underwent computed tomography (CT) including the third lumbar vertebra. Age, blood pressure, waist circumference (WC), hip circumference, fasting lipids, and glucose were assessed. VFA was measured by cross-sectional examination of CT. The correlation of WC, body mass index (BMI), waist-hip ratio (WHR), lipid accumulation product (LAP), visceral adiposity index (VAI), a body shape index (ABSI), body roundness index (BRI), and METS-VF with VFA was analyzed by correlation analysis. The cut-off values and area under the curve (AUC) for identifying increased VFA (>130 cm2) were determined. We included 185 individuals with mean age 38.2 ± 8 and female predominance (58.4%). There was a significant positive correlation between all indices and VFA (p<0.001). ROC analysis revealed that METS-VF and WC demonstrated the highest predictive value for identifying increased VFA. In both men (p=0.001) and women (p<0.001), METS-VF (AUC 0.922 and 0.939, respectively) showed a significant superiority over ABSI (AUC 0.702 and 0.658, respectively), and VAI (AUC 0.731 and 0.725, respectively). Additionally, in women, its superiority over WHR (AUC 0.807) was also statistically significant (p=0.003). We identified a METS-VF cut-off point >6.4 in males >6.5 in females and WC cut-off point >88 cm in males (AUC 0.922), >90.5 cm in females (AUC 0.938). METS-VF is strongly associated with visceral adiposity and better to predict increased VFA. However, its superiority over WC, BMI, BRI, and LAP was not significant. The results emphasize that WC is more appealing as screening indicator for visceral adiposity considering its easy use. Clinicaltrials.gov (http://www.clinicaltrials.gov). https://clinicaltrials.gov/ct2/show/NCT05648409. NCT05648409.

A vessel sealing device and an ultrasonic dissector are equally effective and safe for single port laparoscopic ovariectomy in dogs.

To evaluate ovary removal surgery times and intraoperative complication rates between a 5-mm Sonicision cordless ultrasonic dissector (SCUD) and 5-mm vessel sealing device (VSD) for laparoscopic ovariectomy in dogs. Client-owned, intact female dogs (n = 10) presented for elective laparoscopic ovariectomy. In each dog, 1 ovarian pedicle was randomly assigned to the SCUD group and 1 to the VSD group. In the SCUD group (n = 10), the ovariectomy was performed using the SCUD device; the ovariectomy in the VSD group (10) was performed using a VSD. The number of applications of each device during ovariectomy, surgery time required for each ovary removal, total surgery duration, ovarian pedicle fat score, and intraoperative complications were recorded. Both left and right ovaries had median pedicle fat scores of 2 (range, 1 to 3). To complete an ovariectomy, the median number of SCUD applications was 9 (range, 7 to 13) times; the VSD had a median of 10 (range, 5 to 18) times (P = .98). Median surgery times for the removal of 1 ovary with the SCUD and VSD were 96 seconds (range, 45 to 417 seconds) and 110 seconds (range, 42 to 164 seconds), respectively (P = 1). No intraoperative complications were associated with either device. Therefore, the VSD was not required for rescue in the SCUD group, and no conversions to open ovariectomy were necessary. A standard approach laparoscopic ovariectomy performed with the SCUD was successful in our population of dogs, making the 5-mm SCUD safe for laparoscopic ovariectomy in healthy dogs, which provides a more affordable option for practitioners and clients.

Associations between metabolic score for visceral fat and the risk of cardiovascular disease and all-cause mortality among populations with different glucose tolerance statuses

AimsTo investigate the associations between metabolic score for visceral fat (METS-VF) and clinical outcomes among populations with different glucose tolerance statuses. MethodsWe analysed 6827 participants aged ≥ 40 years with different glucose tolerance statuses from a cohort study. The associations between METS-VF and cardiovascular disease (CVD) events and all-cause mortality were assessed using Cox regression, restricted cubic spline and receiver operating characteristic curves. ResultsDuring a follow-up of 5.00 years, there were 338 CVD events and 307 subjects experienced all-cause death. The METS-VF quartile (Quartile 4 versus 1) was significantly related to CVD events [adjusted HRs and 95% CIs: 5.75 (2.67–12.42), 2.80 (1.76–4.48), and 3.31 (1.28–8.54) for subjects with normal glucose tolerance, prediabetes and diabetes, respectively] and all-cause mortality [adjusted HRs and 95% CIs: 2.80 (1.43–5.49), 4.15 (2.45–7.01), and 4.03 (1.72–9.42), respectively]. Restricted cubic spline suggested a dose–response association of METS-VF with the risk of CVD events and all-cause mortality. The area under curve for CVD events and all-cause mortality was higher for METS-VF than for the other obesity and IR indexes in subjects with different glucose tolerance statuses. ConclusionsThe METS-VF was associated with an increased risk of CVD events and all-cause mortality and could be used as a predictive index of the risk of CVD events and all-cause mortality among populations with different glucose tolerance statuses.

Assessing the usefulness of a newly proposed metabolic score for visceral fat in predicting future diabetes: results from the NAGALA cohort study.

Visceral adipose tissue assessment holds significant importance in diabetes prevention. This study aimed to explore the association between the newly proposed Metabolic Score for Visceral Fat (METS-VF) and diabetes risk and to further assess the predictive power of the baseline METS-VF for the occurrence of diabetes in different future periods. This longitudinal cohort study included 15,464 subjects who underwent health screenings. The METS-VF, calculated using the formula developed by Bello-Chavolla etal., served as a surrogate marker for visceral fat obesity. The primary outcome of interest was the occurrence of diabetes during the follow-up period. Established multivariate Cox regression models and restricted cubic spline (RCS) regression models to assess the association between METS-VF and diabetes risk and its shape. Receiver operating characteristic (ROC) curves were used to compare the predictive power of METS-VF with body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), and visceral adiposity index (VAI) for diabetes, and time-dependent ROC analysis was conducted to assess the predictive capability of METS-VF for the occurrence of diabetes in various future periods. During a maximum follow-up period of 13 years, with a mean of 6.13 years, we observed that the cumulative risk of developing diabetes increased with increasing METS-VF quintiles. Multivariable-adjusted Cox regression analysis showed that each unit increase in METS-VF would increase the risk of diabetes by 68% (HR 1.68, 95% CI 1.13, 2.50), and further RCS regression analysis revealed a possible non-linear association between METS-VF and diabetes risk (P for non-linearity=0.002). In addition, after comparison by ROC analysis, we found that METS-VF had significantly higher predictive power for diabetes than other general/visceral adiposity indicators, and in time-dependent ROC analysis, we further considered the time-dependence of diabetes status and METS-VF and found that METS-VF had the highest predictive value for predicting medium- and long-term (6-10 years) diabetes risk. METS-VF, a novel indicator for assessing visceral adiposity, showed a significantly positive correlation with diabetes risk. It proved to be a superior risk marker in predicting the future onset of diabetes compared to other general/visceral adiposity indicators, particularly in forecasting medium- and long-term diabetes risk.

Evaluation of Steaming and Drying of Black Sesame Seeds for Nine Cycles Using Grey-Correlation Analysis Based on Variation-Coefficient Weight.

This study aimed to improve the steaming process of black sesame seeds. A comprehensive evaluation was conducted using the grey-correlation method based on the variation-coefficient weight to observe the treatments of normal-pressure (NPS) and high-pressure (HPS) steaming (with/without soaking in water) for nine cycles. Their effects on the contents of water, protein, fat, ash, melanin, sesamin, and sesamolin of black sesame seeds, as well as the sensory score of the black sesame pill, were determined. We found that with varied steaming methods and increased steaming cycles, the contents of the nutritional and functional components of black sesame seeds and the sensory score of the black sesame pill differed. The results of the variation-coefficient method showed that water, protein, fat, ash, melanin, sesamin, sesamolin, and sensory score had different effects on the quality of black sesame seeds with weighting factors of 34.4%, 5.3%, 12.5%, 11.3%, 13.9%, 11.3%, 7.8%, and 3.5%, respectively. The results of two-factor analysis of variance without repeated observations indicated that the grey-correlation degree of HPS was the largest among the different steaming treatments, and the following sequence was HPS after soaking in water (SNPS), NPS, and SNPS. There was no significant difference between NPS and SNPS (p < 0.05). Moreover, with increased cycles, the value of the grey-correlation degree increased. The comprehensive score of the procedure repeated nine times was significantly higher than other cycles (p < 0.05). The results of the grey-correlation degree and grade analysis showed that the best steaming process of black sesame seeds was HPS for nine cycles, followed by HPS for eight cycles and NPS after soaking in water (SNPS) for nine cycles. These findings could provide a scientific basis for replacing SNPS with HPS to simplify steaming and realize the parametric steaming of black sesame seeds, and thus, ensure the quality of black-sesame products.

Pamrevlumab, a Fully Human Monoclonal Antibody Targeting Connective Tissue Growth Factor, for Non-Ambulatory Patients with Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy (DMD) is a neuromuscular disease stemming from dystrophin gene mutations. Lack of dystrophin leads to progressive muscle damage and replacement of muscle with fibrotic and adipose tissue. Pamrevlumab (FG-3019), a fully human monoclonal antibody that binds to connective tissue growth factor (CTGF), is in Phase III development for treatment of DMD and other diseases. MISSION (Study 079; NCT02606136) was an open-label, Phase II, single-arm trial of pamrevlumab in 21 non-ambulatory patients with DMD (aged≥12 years, receiving corticosteroids) who received 35-mg/kg intravenous infusions every 2 weeks for 2 years. The primary endpoint was change from baseline in percent predicted forced vital capacity (ppFVC). Secondary endpoints included other pulmonary function tests, upper limb function and strength assessments, and changes in upper arm fat and fibrosis scores on magnetic resonance imaging. Fifteen patients completed the trial. Annual change from baseline (SE) in ppFVC was -4.2 (0.7) (95% CI -5.5, -2.8). Rate of decline in ppFVC in pamrevlumab-treated patients was slower than observed in historical published trials of non-ambulatory patients. MISSION participants experienced slower-than-anticipated muscle function declines compared with natural history and historical published trials of non-ambulatory patients with DMD. Pamrevlumab was well-tolerated. Treatment-emergent adverse events were mild to moderate, and none led to study discontinuation. nti-CTGF therapy with pamrevlumab represents a potential treatment for DMD. The lack of internal control group limits the results.

Association of non-high-density lipoprotein cholesterol trajectories with the development of non-alcoholic fatty liver disease: an epidemiological and genome-wide association study

BackgroundNon-alcoholic fatty liver disease (NAFLD) shares common risk factors with cardiovascular diseases. Effects of longitudinal trends in non-high-density lipoprotein (non-HDL) cholesterol on NAFLD development are not understood. This study aimed to assess the relationship between non-HDL cholesterol trajectories and the incidence of NAFLD and to identify genetic differences contributing to NAFLD development between non-HDL cholesterol trajectory groups.MethodsWe analyzed data from 2203 adults (aged 40–69 years) who participated in the Korean Genome and Epidemiology Study. During the 6-year exposure periods, participants were classified into an increasing non-HDL cholesterol trajectory group (n = 934) or a stable group (n = 1269). NAFLD was defined using a NAFLD-liver fat score > -0.640. Multiple Cox proportional hazard regression analysis estimated the hazard ratio (HR) and the 95% confidence interval (CI) for the incidence of NAFLD in the increasing group compared with the stable group.ResultsA genome-wide association study identified significant single-nucleotide polymorphisms (SNPs) associated with NAFLD. During the median 7.8-year of event accrual period, 666 (30.2%) newly developed NAFLD cases were collected. Compared with the stable non-HDL group, the adjusted HR (95% CI) for the incidence of NAFLD in the increasing non-HDL cholesterol group was 1.46 (1.25–1.71). Although there were no significant SNPs, the polygenic risk score was highest in the increasing group, followed by the stable and control groups.ConclusionOur study indicates that lifestyle or environmental factors have a greater effect size than genetic factors in NAFLD progression risk. Lifestyle modification could be an effective prevention strategy for NAFLD for people with elevated non-HDL cholesterol.

Efeito do estresse calórico e da insolação sobre consumo, indicadores bioquímicos, produção e qualidade do leite de vacas Holandês e Jersey

ABSTRACT The objective of this work was to compare the dry matter intake, milk yield and quality, physiological and biochemical parameters in Holstein (n=10) and Jersey (n=10) cows under heat stress and insolation, in two treatments: CL - cooling by ventilation and sprinkling and HS - heat stress and insolation. Data were submitted to ANOVA. There was an interaction between treatment and breed and day effect for dry matter intake. For consumption in % of body weight, CL and Jersey cows consumed more. CL cows produced more milk and 3.5% fat-corrected milk. Feed efficiency was similar between treatments and breeds. Fat, lactose, total solids, and somatic cell score did not differ. The concentration of milk urea nitrogen was higher for CL cows. Milk from Holstein cows had greater stability to alcohol, and from HT cows had a greater freezing point of milk. HT cows had higher respiratory rates in the morning and surface temperatures in the afternoon. There were no differences in beta-hydroxybutyrate and glucose concentrations. Heat stress, with insulation, reduces intake, especially in Holstein cows, as well as milk production and increases the freezing point of milk, respiratory rate, and surface temperature.

Gender Differences in the Risk for Incident Non-Alcoholic Fatty Liver Disease According to the Transition of Abdominal Obesity Status: A 16-Year Cohort Study.

Waist circumference (WC) is an important predictor of long-term adverse outcomes. We aimed at assessing the correlation between abdominal obesity (AO) patterns and non-alcoholic fatty liver disease (NAFLD). Data from 4467 adults aged 40-69 years and without NAFLD who participated in the Korean Genome and Epidemiology Study were analyzed. Participants were classified according to two-year WC pattern into four groups: persistent lean WC, improved AO, progressed to AO, and persistent AO. NAFLD was defined as NAFLD-liver fat score >-0.640. Multiple Cox proportional hazards regression analysis revealed that the fully adjusted hazard ratio (HR) (95% confidence intervals (CIs)) for NAFLD in persistent AO, progressed to AO, and improved AO groups compared to the persistent lean WC group was 1.33 (1.13-1.57), 1.73 (1.48-2.02), and 1.06 (0.84-1.33), respectively. Women in persistent AO or progressed to AO groups had significantly higher risk for NAFLD than those in persistent lean WC or improved AO groups. Men who had progressed to an AO event over two years had significantly higher risk for NAFLD than those without any AO event over two years. Maintaining lean WC and improving AO would be successful strategies for preventing NAFLD in women, while maintaining lean WC would be more effective in men.

1472-P: Polygenic Risk Score for Liver Fat Predicts Earlier Onset of Type 2 Diabetes in an East Asian Population

Liver, pancreas fat deposition and volume have been associated with type 2 diabetes (T2D) risk by Mendelian randomization study. However, it is unknown whether genetic variation in these traits impact on T2D onset, insulin resistance and drug use. We hypothesized that (1) genetic predisposition to smaller pancreas would be associated with earlier onset of T2D and earlier need for insulin; (2) genetic predisposition to higher pancreas and liver fat would be associated with greater insulin resistance, earlier onset of T2D and earlier need for insulin. This study utilized three Chinese cohorts of genotyped T2D patients in Hong Kong: Hong Kong Diabetes Register (HKDR, n=6011), Hong Kong Diabetes Biobank Phase 1 (HKDB-P1, n=6662) and Hong Kong Diabetes Biobank Phase 2 (HKDB-P2, n= 5899). We used lead SNPs (single nucleotide polymorphisms) associated with pancreas volume (13 SNPs), fat (7 SNPs) and liver fat (8 SNPs) from UK Biobank (n&amp;gt;32,000) to construct PRS (Polygenic risk score) in these cohorts. Linear regression models were employed to examine the associations between PRS and age of T2D onset and insulin resistance. Multivariable cox regression models were employed to examine association with time to insulin use. All models included age (except for age of T2D onset), sex and top 4 genetic principal components as covariates. To assess the confounding effects of BMI, we also performed BMI subgroup analysis by stratifying individuals into underweight, normal and overweight groups. Our analyses found that higher PRS for liver fat, but not pancreatic size or fat predicts earlier onset of T2D in HKDB-P1 (p&amp;lt;0.001, t=−3.43). The direction of association in HKDB-P2 was consistent though not significant. When stratified by BMI, higher PRS for liver fat predicts earlier onset of T2D in HKDB-P1 (p= 0.002, t=−3.14) and HKDB-P2 (p=0.029, t=−2.19) among the overweight group. Our results highlighted a PRS of liver fat as a potential biomarker for age of T2D onset, which needs further validation. Disclosure G.Yu: None. C.Huang: None. A.Luk: Research Support; Novo Nordisk, Boehringer-Ingelheim, Bayer Inc., Speaker's Bureau; Eli Lilly and Company. E.S.H.Lau: None. Hong kong diabetes biobank study group: n/a. R.C.Ma: Advisory Panel; AstraZeneca, Merck &amp; Co., Inc., Other Relationship; Bayer Inc., Boehringer-Ingelheim, Research Support; Tricida, Inc., Roche Diagnostics, Novo Nordisk. C.H.Tam: None. M.Shi: None. B.Fan: None. C.K.Lim: Stock/Shareholder; GemVCare Ltd. J.C.Chan: Board Member; Asia Diabetes Foundation, Consultant; Bayer Inc., Celltrion, Boehringer Ingelheim and Eli Lilly Alliance, Sanofi, Research Support; AstraZeneca, Servier Laboratories, Viatris Inc., Hua Medicine, Merck KGaA, Applied Therapeutics Inc., Lee Powder, Pfizer Inc., Speaker's Bureau; Novartis, Stock/Shareholder; GemVCare Ltd. M.N.Weedon: None. R.A.Oram: Consultant; Janssen Research &amp; Development, LLC, Research Support; Randox R &amp; D. Funding Research Grants Council of the Hong Kong Special Administrative Region (CU-R4012-18); Croucher Foundation

1698-P: The Effect of Ectopic Fat on Brain Structure and Cognitive Function—A Meta-analysis from Observational Studies of 1,003,593 Individuals

Abstract Purpose: To investigate the effects of ectopic fat on brain structure and cognitive function. Methods: Data extraction and meta-analysis of eligible clinical studies were performed. Results: The results showed ectopic fat was associated with the decreased total brain volume, posterior cingulate cortex volume, semioval center volume, sensorimotor cortex volume, and the increased lateral ventricle volume. Subcutaneous fat significantly was associated with the reduced risk of cerebral white matter hyperintensities (OR = 0.86, 95% CI: 0.74 to 1.00). Ectopic fat was associated with the decreased cognitive function. Visceral fat was significantly associated with poor cognitive outcomes (OR=1.42, 95% CI: 1.11 to 1.81). Conclusion: Visceral ectopic fat was associated with the increased risk of brain structural changes and cognitive impairment. A new strategy identifying patients at risk of developing cognitive decline may be implemented timely and personalized treatment. Fig.1 The relationship between ectopic fat and cognitive scores (WMD) Disclosure Z.Song: None. J.Liu: None. Z.Zhang: None. J.Zhou: None.

Tofacitinib Reduces Spinal Inflammation in Vertebral Bodies and Posterolateral Elements in Ankylosing Spondylitis: Results from a Phase 2 Trial.

This post hoc analysis of phase 2 trial data assessed the efficacy of tofacitinib on magnetic resonance imaging (MRI) outcomes with the detailed anatomy-based Canada-Denmark (CANDEN) MRI scoring system and evaluated tofacitinib suppression of spinal inflammation in patients with active ankylosing spondylitis (AS). Patients with active AS (per modified New York criteria) were randomized 1:1:1:1 to receive tofacitinib 2, 5, or 10mg twice daily (BID), or placebo, in a 16-week, phase 2, double-blind clinical trial. Spine MRI assessments were performed at baseline and week 12. For post hoc analysis, MRI images from patients receiving tofacitinib 5 or 10mg BID, or placebo, were re-evaluated by two readers blinded to time point/treatment and assessed by the CANDEN MRI scoring system. Least squares mean changes from baseline to week 12 were reported for CANDEN-specific MRI outcomes, with analysis of covariance used for comparisons of pooled tofacitinib and tofacitinib 5 or 10mg BID versus placebo. p values without multiplicity adjustment were reported. MRI data from 137 patients were analyzed. At week 12, CANDEN spine inflammation score and vertebral body, posterior elements, corner, non-corner, facet joint, and posterolateral inflammation subscores were significantly reduced with pooled tofacitinib versus placebo (p < 0.0001; except non-corner subscore, p < 0.05). Total spine fat score was numerically increased with pooled tofacitinib versus placebo. In patients with AS, tofacitinib treatment was associated with significant reductions in MRI scores of spinal inflammation versus placebo, as assessed by the CANDEN MRI scoring system. Tofacitinib reduced inflammation in posterolateral elements of the spine and facet joints, which has not been described previously. ClinicalTrials.gov registry (NCT01786668).