Physical activity and metabolic syndrome severity among older adults at cardiovascular risk: 1-Year trends.

BACKGROUND AND AIMS: Modifiable lifestyle factors, such as physical activity (PA) and Mediterranean diet (MD), decrease metabolic syndrome (MetS). The aim was to assess 1-year changes of leisure-time physical activity (LTPA), sedentary behavior, and diet quality according to MetS severity in older population at high cardiovascular risk. METHODS AND RESULTS: Prospective analysis of 55-75-year-old 4359 overweight/obese participants with MetS (PREDIMED-Plus trial) categorized in tertiles according to 1-year changes of a validated MetS severity score (MetSSS). Anthropometrics, visceral adiposity index, triglycerides and glucose index, dietary nutrient intake, biochemical marker levels, dietary inflammatory index, and depression symptoms were measured. Diet quality was assessed by 17-item MD questionnaire. PAs were self-reported using the Minnesota-REGICOR Short Physical Activity Questionnaire and 30-s chair stand test. Sedentary behaviors were measured using the Spanish version of the Nurses' Health Study questionnaire. After 1-year follow-up, decreasing MetSSS was associated with an anti-inflammatory dietary pattern, high intake of vegetables, fruits, legumes, nuts, whole grain cereals, white fish, and bluefish and low intake of refined cereals, red and processed meat, cookies/sweets, and snacks/ready-to-eat-meals. It resulted in high intake of polyunsaturated fatty acids, omega-3 fatty acids, protein, fiber, vitamins B1, B6, B9, C, D, potassium, magnesium, and phosphorus and low glycemic index and saturated fatty acid, trans fatty acid, and carbohydrates intake. Regarding PA and sedentary behavior, decreasing MetSSS was associated with increased moderate-to-vigorous LTPA, chair stand test, and decreased sedentary and TV-viewing time. CONCLUSION: Decreasing MetSSS was associated with an anti-inflammatory dietary pattern, high LTPA, high MD adherence, low sedentary time, and low depression risk.

Isotemporal substitution of inactive time with physical activity and time in bed: cross-sectional associations with cardiometabolic health in the PREDIMED-Plus study.

BACKGROUND: This study explored the association between inactive time and measures of adiposity, clinical parameters, obesity, type 2 diabetes and metabolic syndrome components. It further examined the impact of reallocating inactive time to time in bed, light physical activity (LPA) or moderate-to-vigorous physical activity (MVPA) on cardio-metabolic risk factors, including measures of adiposity and body composition, biochemical parameters and blood pressure in older adults. METHODS: This is a cross-sectional analysis of baseline data from 2189 Caucasian men and women (age 55-75 years, BMI 27-40 Kg/m2) from the PREDIMED-Plus study (http://www.predimedplus.com/). All participants had ≥3 components of the metabolic syndrome. Inactive time, physical activity and time in bed were objectively determined using triaxial accelerometers GENEActiv during 7 days (ActivInsights Ltd., Kimbolton, United Kingdom). Multiple adjusted linear and logistic regression models were used. Isotemporal substitution regression modelling was performed to assess the relationship of replacing the amount of time spent in one activity for another, on each outcome, including measures of adiposity and body composition, biochemical parameters and blood pressure in older adults. RESULTS: Inactive time was associated with indicators of obesity and the metabolic syndrome. Reallocating 30 min per day of inactive time to 30 min per day of time in bed was associated with lower BMI, waist circumference and glycated hemoglobin (HbA1c) (all p-values < 0.05). Reallocating 30 min per day of inactive time with 30 min per day of LPA or MVPA was associated with lower BMI, waist circumference, total fat, visceral adipose tissue, HbA1c, glucose, triglycerides, and higher body muscle mass and HDL cholesterol (all p-values < 0.05). CONCLUSIONS: Inactive time was associated with a poor cardio-metabolic profile. Isotemporal substitution of inactive time with MVPA and LPA or time in bed could have beneficial impact on cardio-metabolic health. TRIAL REGISTRATION: The trial was registered at the International Standard Randomized Controlled Trial (ISRCTN: http://www.isrctn.com/ISRCTN89898870) with number 89898870 and registration date of 24 July 2014, retrospectively registered.

Intrahepatic Fat Content and COVID-19 Lockdown in Adults with NAFLD and Metabolic Syndrome.

BACKGROUND: COVID-19 lockdowns had a significant impact on people's health, triggering levels of anxiety, perceived stress, and changes in food and nutritional status. OBJECTIVES: To assess the changes in dietary habits, metabolic syndrome (MetS) and liver parameters before and after the COVID-19 lockdown according to changes in intrahepatic fat content in adults with non-alcoholic fatty liver disease (NAFLD) and MetS. DESIGN: Pre- and post-lockdown observation of the COVID-19 lockdown on fifty-nine 40-60-year-old participants with MetS and NAFLD, in a parallel group, randomised experiment intended to treat NAFLD. METHODS: Anthropometrics, liver and MetS biochemical parameters, intrahepatic fat content by abdominal magnetic resonance imaging, and dietary assessment using a validated 148-item Food Frequency Questionnaire were collected pre-COVID-19 lockdown and post-lockdown. RESULTS: COVID-19 lockdown led to negative changes in the liver of patients with NAFLD and MetS, with weight gain and increases in glycemia, ALT and intrahepatic fat content post lockdown. Participants with worsened liver status had low consumption of fibre, cheese, nuts and coffee, and high consumption of sweets and pastries. Participants who improved liver status ameliorated ALT values, waist circumference, and intrahepatic fat content, assessed by magnetic resonance imaging post-lockdown. CONCLUSIONS: The maintenance of healthy lifestyle habits is vital, especially for populations with NAFLD and MetS, to reduce unhealthy lifestyle patterns displayed during lockdown.

Association between Stages of Hepatic Steatosis and Physical Activity Performance in Adults with Metabolic Syndrome: A Cross-Sectional Analysis in FLIPAN Study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease. The best treatment now is a healthy lifestyle with a Mediterranean diet and physical activity (PA). OBJECTIVE: To assess the association between stages of hepatic steatosis and physical activity performance in adults with metabolic syndrome. DESIGN: Cross-sectional study in 155 participants (40-60 years old) with MetS, a diagnosis of NAFLD by magnetic resonance imaging and BMI (body mass index) between 27 and 40 kg/m2. METHODS: Stages of hepatic steatosis were assessed and defined according to the percentage of intrahepatic fat contents: stage 0 ≤ 6.4% (control group); stage 1 = 6.4-17.4%; stage 2 ≥ 17.4%. Fitness was assessed through ALPHA-FIT test battery for adults, aerobic capacity by Chester-step test and PA by accelerometry and Minnesota questionnaire. RESULTS: Participants without NAFLD reported more years of education and major socioeconomic status than participants with NAFLD. A higher percentage of people in the most advanced stage of NAFLD were no smokers and no alcohol consumers. They also had higher stages of steatosis, lower sitting handgrip, standing handgrip, Chester step test values, sleep efficiency, and energy expenditure, and higher intensity of light and moderate physical activity, and self-reported physical activity. CONCLUSIONS: NAFLD patients showed lower fitness status, aerobic capacity, sleep efficiency and energy expenditure than non-NAFLD participants.

Effect of a Six-Month Lifestyle Intervention on the Physical Activity and Fitness Status of Adults with NAFLD and Metabolic Syndrome.

(1) Background: Physical inactivity has been linked to NAFLD, and exercise has been reported as useful to reduce intrahepatic fat content in NAFLD. (2) Objectives: To assess the physical activity (PA) and fitness status after a six-month lifestyle intervention (diet and PA) in adults with NAFLD and metabolic syndrome (MetS). (3) Design: Prospective cohort analysis of data obtained between baseline and six-year parallel-group randomized trial (n = 155, aged 40-60 years old, with MetS and NAFLD). Participants were randomized into three nutritional and PA intervention groups: Conventional diet (CD); MedDiet-high meal frequency (MD-HMF); MedDiet-physical activity (MD-PA). (4) Methods: PA and fitness status were assessed using a validated Minnesota questionnaire, ALPHA-FIT test battery, accelerometers, and functional fitness score. Information related to age, gender, education level, marital status, socioeconomic status, smoking habit, and alcohol consumption were also obtained. (5) Results: The CD group had higher improvement in standing handgrip than the MD-HMF group. The MD-PA group did more modified push-up repetitions than the CD group. The MD-PA and CD groups showed higher sitting handgrip than the MD-HMF group. The MD-HMF group showed the highest decrease in aerobic capacity. The MD-PA group showed lower light intensity PA/day than the CD and MD-HMF groups. The MD-PA group showed higher moderate intensity PA than the CD and MD-HMF groups. The CD group reported more METs per day than the MD-HMF group. (6) Conclusions: Lifestyle six-month intervention with diet and regular PA improved functional fitness in middle-aged patients with NAFLD and MetS. Aerobic capacity improved in patients who followed a Mediterranean diet and regular training sessions at six months.

Association between Physical Activity and Non-Alcoholic Fatty Liver Disease in Adults with Metabolic Syndrome: The FLIPAN Study.

Background: A lifestyle with regular PA (physical activity) and Mediterranean diet has benefits on NAFLD (non-alcoholic fatty liver disease) and MetS (metabolic syndrome). Objectives: To assess the association between physical activity and NAFLD in adults with MetS. Design: Cross-sectional study in 155 participants (40−60 years old) from Balearic Islands and Navarra (Spain) with diagnosis of NAFLD and MetS, and BMI (body mass index) between 27 and 40 Kg/m2. Methods: PA level was categorized into two groups according to weekly METs (metabolic equivalents of tasks). PA was assessed using a validated Minnesota questionnaire and accelerometers. MetS parameters were assessed by blood collection analysis and NAFLD by abdominal MRI (magnetic resonance imaging). Results: Participants with high PA showed more energy expenditure and expended more calories than ingested (−143.9 Kcal/day; p < 0.001). PA was a risk factor for AST (aspartate aminotransferase) (adjusted OR: 7.26; 95% CI: 1.79−29.40) and a protective factor for ALT (alanine aminotransferase) (adjusted OR: 0.24; 95% CI: 0.12−0.48), GGT (gamma-glutamyl transferase) (adjusted OR: 0.52; 95% CI: 0.29−0.94) and IFC-NMR (intrahepatic fat content by nuclear magnetic resonance) (adjusted OR: 0.26; 95% CI: 0.12−0.56) when sociodemographic confounders were considered. Conclusions: NAFLD patients with high PA showed more positive relationship on MetS parameters and liver profile (ALT, GGT, IFC-NMR) than subjects with low PA, but not for AST. Difference between calories ingested and expended influenced this relationship.

A Greater Improvement of Intrahepatic Fat Contents after 6 Months of Lifestyle Intervention Is Related to a Better Oxidative Stress and Inflammatory Status in Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) is a disorder characterized by the excessive accumulation of lipids in the liver parenchyma. To date, there is no effective pharmacological treatment against NAFLD. Objective: To assess the relationship between the improvement of the intrahepatic fat content (IFC) in patients with NAFLD and metabolic syndrome and biomarkers of oxidative stress and inflammation after 6 months of lifestyle intervention. Patients diagnosed with NAFLD (n = 60 adults; 40-60 years old) residing in the Balearic Islands, Spain, were distributed in tertiles attending the improvement of IFC calculated by magnetic resonance imaging (MRI). Anthropometrics, blood pressure, maximal oxygen uptake, and pro/antioxidant and inflammatory biomarkers were determined in plasma before and after the lifestyle intervention. The improvement in IFC levels was higher in tertile 3 with respect to tertiles 2 and 1. The greatest improvement in IFC is related to cardiorespiratory fitness and adherence to the Mediterranean diet (ADM). Higher reductions in weight, body mass index (BMI), and alanine aminotransferase (ALT) were observed in tertile 3 with respect to tertile 1 after 6 months of intervention. The improvement in catalase, irisin, and cytokeratin 18 plasma levels were higher in tertile 3, whereas no differences were observed in superoxide dismutase activity. Malondialdehyde and protein carbonyl levels, as biomarkers of oxidative damage, remained unchanged in all groups. The present data show that the reduction of IFC is associated with an improvement in pro/antioxidant and pro-inflammatory status and a better cardiorespiratory fitness in NAFLD patients.

Adherence to Mediterranean Diet and NAFLD in Patients with Metabolic Syndrome: The FLIPAN Study.

Unhealthy diet is an important factor in the progression of non-alcoholic fatty liver disease (NAFLD). Previous studies showed the benefits of a Mediterranean diet (MedDiet) on Metabolic syndrome (MetS), type 2 diabetes mellitus (T2DM), and cardiovascular diseases, which usually have a pathophysiological relationship with NAFLD. To assess the effect of adherence to a MedDiet on NAFLD in MetS patients after lifestyle intervention, this multicentre (Mallorca and Navarra, Spain) prospective randomized trial, with personalized nutritional intervention based on a customized MedDiet, coupled with physical activity promotion was performed to prevent, and reverse NAFLD among patients with MetS. The current analysis included 138 patients aged 40 to 60 years old, Body Mass Index (BMI) 27-40 kg/m2, diagnosed with NAFLD using MRI, and MetS according to the International Diabetes Federation (IDF). A validated food frequency questionnaire was used to assess dietary intake. Adherence to Mediterranean diet by means of a 17-item validated questionnaire, anthropometrics, physical activity, blood pressure, blood biochemical parameters, and intrahepatic fat contents (IFC) were measured. The independent variable used was changes in MedDiet adherence, categorized in tertiles after 6 months follow-up. Subjects with high adherence to the MedDiet showed higher decreases in BMI, body weight, WC, SBP, DBP, and IFC. An association between improvement in adherence to the MedDiet and amelioration of IFC after 6-month follow-up was observed. High adherence to the MedDiet is associated with better status of MetS features, and better values of IFC.

Impact of Physical Activity Differences Due to COVID-19 Pandemic Lockdown on Non-Alcoholic Fatty Liver Parameters in Adults with Metabolic Syndrome.

BACKGROUND: A Mediterranean lifestyle with a Mediterranean diet and regular physical activity (PA) improves metabolic syndrome (MetS) characteristics and non-alcoholic fatty liver disease (NAFLD). The COVID-19 pandemic stopped healthy habits and increased NAFLD progression. OBJECTIVES: To assess how PA differences due to COVID-19 lockdown affected NAFLD parameters in adults with MetS. DESIGN: Longitudinal 2-year analysis of data obtained between COVID-19 pre- and post-lockdown in a parallel-group randomized trial (n = 57, aged 40-60 years old, with MetS and NAFLD). METHODS: NAFLD status and related parameters were assessed by magnetic resonance imaging (MRI), blood collection analysis and related indexes. PA and fitness status were assessed by an Alpha-Fit test battery, accelerometers, validated Minnesota questionnaire and functional fitness score. During lockdown, study personnel telephoned patients to motivate them. Participants were grouped according to PA levels. RESULTS: The low PA group improved its fitness score tests (0.2) after lockdown more than the medium PA group, and it decreased its sedentary activity (-48.7 min/day), increased light (20.9 min/day) and moderate (32.3 min/day) PA intensities and improved sleep efficiency (0.6%) in comparison with the medium and high PA groups. The high PA group increased its steps per day more than the other groups. The low PA group was the only group that decreased its gamma glutamyl transferase (GGT) levels (-17.0 U/L). All groups increased their fatty liver index (FLI) after lockdown, but the medium PA group increased its FLI more than the low PA group. Participants in the high PA group decreased their HDL-cholesterol levels more than participants in the medium PA group (-0.4 mg/dL). CONCLUSIONS: Stopping regular PA together with an unhealthy lifestyle leads to a worsening of MetS and NAFLD. COVID-19 lockdown induced a decrease in PA in more active people, but inactive people increased their PA levels. Motivation seemed to be very important during lockdown.

Increased Adherence to the Mediterranean Diet after Lifestyle Intervention Improves Oxidative and Inflammatory Status in Patients with Non-Alcoholic Fatty Liver Disease.

BACKGROUND: A Mediterranean diet (MedDiet) is recommended as a therapy for non-alcoholic fatty liver disease (NAFLD) because there is no specific pharmacological treatment for this disease. OBJECTIVE: To assess the relationship between the adherence to the Mediterranean diet and the intrahepatic fat content (IFC), levels of oxidative stress, and inflammation biomarkers after a 6-month lifestyle intervention in NAFLD patients. METHODS: Patients diagnosed with NAFLD (n = 60 adults; 40-60 years old) living in the Balearic Islands, Spain, were classified into two groups, according to the adherence to the MedDiet after 6 months of lifestyle intervention. Anthropometry, blood pressure, IFC, maximal oxygen uptake, and pro/antioxidant and inflammatory biomarkers were measured in plasma and in PBMCs before and after the intervention. RESULTS: Reductions in weight, body mass index, IFC, blood pressure levels, circulating glucose, glycosylated hemoglobin, and markers of liver damage-aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), and cytokeratin 18 (CK-18)-were observed after the intervention. The highest reductions were observed in the group with the best adherence to the MedDiet. A significant improvement in cardiorespiratory fitness was also observed in the group with a higher adherence. The activities of catalase in plasma and catalase and superoxide dismutase in blood mononuclear cells increased only in the group with a higher adherence, as well as the catalase gene expression in the blood mononuclear cells. The plasma levels of malondialdehyde and myeloperoxidase decreased, and resolvin-D1 increased in both groups after the intervention, whereas interleukin-6 levels decreased only in the group with a higher adherence to the MedDiet. CONCLUSIONS: A greater adherence to the MedDiet is related to greater improvements in IFC, cardiorespiratory fitness, and pro-oxidative and proinflammatory status in NAFLD patients after a 6-month nutritional intervention based on the MedDiet.

Effect of Dietary and Lifestyle Interventions on the Amelioration of NAFLD in Patients with Metabolic Syndrome: The FLIPAN Study.

BACKGROUND: Adults with fatty liver present unusual glycaemia and lipid metabolism; as a result, non-alcoholic fatty liver disease (NAFLD) is now considered as part of the metabolic syndrome (MetS). OBJECTIVE: To assess the 6- and 12-month effects of customized hypocaloric dietary and enhanced physical activity intervention on intrahepatic fat contents and progression of NAFLD, in patients with MetS. DESIGN: Cross-sectional study in 155 participants (40-60 years old) from Balearic Islands and Navarra (Spain) with a diagnosis of NAFLD and MetS, and BMI (body mass index) between 27 and 40 kg/m2; patients were randomized in a 1:1:1 ratio to either Conventional Diet, Mediterranean diet (MD)-high meal frequency, and MD-physical activity groups. METHODS: Dietary intake was assessed using a validated food frequency questionnaire. Adherence to Mediterranean diet, anthropometrics, physical activity, and biochemical parameters (fasting glucose, glycated hemoglobin, bilirubin, aspartate aminotransferase, alanine aminotransferase-ALT-, gamma-glutamyl transferase, uric acid, urea, creatinine, albumin, total cholesterol, high-density lipoprotein cholesterol-HDL-cholesterol-, and triglycerides) were also assessed. RESULTS: Subjects with NAFLD and MetS had reduced intrahepatic fat contents, and liver stiffness, despite the intervention the participants went through. All participants ameliorated BMI, insulin, Hb1Ac, diastolic blood pressure, HDL-cholesterol, and ALT, and improved consumption of total energy, fish, and legumes. Participants in the MD-HMF group improved waist circumference. CONCLUSIONS: Customized hypocaloric dietary and enhanced physical activity interventions may be useful to ameliorate NAFLD.

Association between Non-Alcoholic Fatty Liver Disease and Mediterranean Lifestyle: A Systematic Review.

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is an excessive accumulation of fat in the liver without alcohol abuse. It is linked to metabolic syndrome (MetS) and no pharmacological treatment exists. This systematic review aims to assess evidence about the effect of Mediterranean lifestyle on the prevention and reversion of NAFLD. METHODS: A systematic literature search was performed in MEDLINE via Pubmed. MeSH terms used were: non-alcoholic fatty liver disease [MeSH Major Topic] AND metabolic syndrome [MeSH Term] AND (Diet, Mediterranean [MeSH Term]) OR (Exercise [MeSH Term]). (PROSPERO ID: 2021 CRD42021289495). RESULTS: Thirteen articles were selected and divided into two categories (four focused on Mediterranean diet and NAFLD and nine focused on Mediterranean diet, physical activity, and NAFLD). Information of clinical endpoints was based on NAFLD, as well as MetS, body mass index, fasting glycemia, obesity, cholesterol, triglycerides, transaminases, albuminuria, and hepatic steatosis, among others. All studies found beneficial associations between the clinical parameters of NAFLD/MetS and following a Mediterranean diet and regular physical activity. CONCLUSIONS: An effective treatment that prevents, and even reverses, NAFLD is to adapt lifestyle to the Mediterranean one, based on a Mediterranean diet and regular physical activity.

Albuminuria Is Associated with Hepatic Iron Load in Patients with Non-Alcoholic Fatty Liver Disease and Metabolic Syndrome.

BACKGROUND: Increased albuminuria is associated with increased serum ferritin, insulin resistance, and non-alcoholic fatty liver disease (NAFLD). Liver iron accumulation is also related to hyperferritinemia, insulin resistance, and NAFLD; however, there is no evidence on its relationship with albuminuria. AIMS: To assess the relationship between hepatic iron load and urine albumin-to-creatinine ratio (UACR) in patients with metabolic syndrome (MetS) and NAFLD. METHODS: In total, 75 MetS and NAFLD patients (aged 40-60 years, BMI 27-40 kg/m2) were selected from a cohort according to available data on hepatic iron load (HepFe) by magnetic resonance imaging (MRI). Subjects underwent anthropometric measurements, biochemistry testing, and liver MRI. Increased albuminuria was defined by UACR. RESULTS: UACR correlated with NAFLD, HepFe, triglycerides, serum ferritin, fasting insulin, insulin resistance (calculated using the homeostatic model assessment for insulin resistance-HOMA-IR- formula), and platelets (p < 0.05). Multiple regression analysis adjusted for gender, age, eGFR, HbA1c, T2DM, and stages of NAFLD, found that HepFe (p = 0.02), serum ferritin (p = 0.04), fasting insulin (p = 0.049), and platelets (p = 0.009) were associated with UACR (R2 = 0.370; p = 0.007). UACR, liver fat accumulation, serum ferritin, and HOMA-IR increased across stages of HepFe (p < 0.05). Patients with severe NAFLD presented higher HepFe, fasting insulin, HOMA-IR, and systolic blood pressure as compared to patients in NAFLD stage 1 (p < 0.05). CONCLUSION: Hepatic iron load, serum ferritin, fasting insulin, and platelets were independently associated with albuminuria. In the context of MetS, increased stages of NAFLD presented higher levels of HepFe. Higher levels of HepFe were accompanied by increased serum ferritin, insulin resistance, and UACR. The association between iron accumulation, MetS, and NAFLD may represent a risk factor for the development of increased albuminuria.

Animal Fat Intake Is Associated with Albuminuria in Patients with Non-Alcoholic Fatty Liver Disease and Metabolic Syndrome.

Non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS) are associated with chronic kidney disease (CKD). Diet could play a predisposing role in the development of increased albuminuria in patients with NAFLD and MetS; however, published evidence is still limited. The aim of this cross-sectional analysis was to assess whether dietary fats are associated with changes in urinary albumin-to-creatinine ratio (UACR) in 146 patients aged 40-60-years with NAFLD and MetS. Dietary data were collected by food frequency questionnaire; UACR was measured in a single first morning void. Sources and types of dietary fats used in the analysis were total fat, fats from animal and vegetable sources, saturated, monounsaturated, polyunsaturated, and trans fats. One-way analysis of variance was performed to assess differences in dietary fats intakes across stages of UACR. The association between dietary fats and UACR was assessed by Pearson's correlation coefficient and multivariable linear regression. Patients with increased UACR showed a worse cardiometabolic profile and higher intakes of animal fat, as compared to patients with normal levels of albuminuria. Animal fat intake was associated with mean UACR, independent of potential covariates.

Non-Alcoholic Fatty Liver Disease Is Associated with Kidney Glomerular Hyperfiltration in Adults with Metabolic Syndrome.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a risk factor for the development of chronic kidney disease (CKD), which is early marked by kidney glomerular hyperfiltration. However, the association of NAFLD with kidney glomerular hyperfiltration has not been tested so far in adults with metabolic syndrome (MetS). AIMS: To assess the relationship between NAFLD and kidney glomerular hyperfiltration in adults with MetS. METHODS: The study included 154 participants aged 40-60 years with MetS and NAFLD diagnosed by ultrasound. NAFLD was confirmed by MRI in 109 subjects. Participants underwent anthropometric measurements, and biochemistry testing. Estimated GFR (eGFR) was calculated using the CKD-Epidemiology Collaboration (CKD-EPI) formula; hyperfiltration was defined as eGFR ≥ 120 mL/min. RESULTS: Participants with MRI-proven NAFLD showed a worse metabolic profile and higher levels of eGFR than those with no NAFLD. Presence of NAFLD and increased weight were independently associated with an increased probability of presenting hyperfiltration. CONCLUSIONS: The present study shows an association between kidney glomerular hyperfiltration and NAFLD in adults with MetS. Establishing an association between NAFLD and kidney glomerular hyperfiltration would help to earlier identify those patients at increased risk of CKD, who would benefit from an early intervention.

Energy Expenditure Improved Risk Factors Associated with Renal Function Loss in NAFLD and MetS Patients.

To assess the efficacy of three lifestyle interventions on the reduction of liver fat content and metabolic syndrome (MetS), and whether such reductions would influence renal outcomes, we conducted a randomized controlled trial on 128 participants with MetS and non-alcoholic fatty liver disease (NAFLD), as well as available data on estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatine ratio (UACR). Patients were randomized in 1:1:1 ratio to either Conventional Diet, Mediterranean diet (MD)-high meal frequency, and MD-physical activity groups. Each intervention aimed at reducing caloric intake by 25%-30% of baseline intake and increase energy expenditure by 400 kcal/70 kg. Patients attended regular visits and were followed-up for 6 months. Increased albuminuria was present in 13.3% of patients, while 32.8% showed hyperfiltration. UACR reduction was associated with higher levels of UACR at baseline but not with changes in liver fat. eGFR decreased in patients presenting hyperfiltration at baseline and was associated with reduction in liver fat and insulin resistance, as well as with increase in energy expenditure (R2 = 0.248, p = 0.006). No significant differences were observed between the three treatment groups. In patients with NAFLD and MetS, energy expenditure significantly reduced hepatic fat accumulation and insulin resistance, which reduced glomerular hyperfiltration. Increased albuminuria was reduced, but it was not associated with reduced liver fat.

Oxidative Stress and Pro-Inflammatory Status in Patients with Non-Alcoholic Fatty Liver Disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive fat accumulation, especially triglycerides, in hepatocytes. If the pathology is not properly treated, it can progress to nonalcoholic steatohepatitis (NASH) and continue to fibrosis, cirrhosis or hepatocarcinoma. OBJECTIVE: The aim of the current research was to identify the plasma biomarkers of liver damage, oxidative stress and inflammation that facilitate the early diagnosis of the disease and control its progression. METHODS: Antioxidant and inflammatory biomarkers were measured in the plasma of patients diagnosed with NAFLD (n = 100 adults; 40-60 years old) living in the Balearic Islands, Spain. Patients were classified according to the intrahepatic fat content (IFC) measured by magnetic resonance imaging (MRI). RESULTS: Circulating glucose, glycosylated haemoglobin, triglycerides, low-density lipoprotein-cholesterol, aspartate aminotransferase and alanine aminotransferase were higher in patients with an IFC ≥ 2 of NAFLD in comparison to patients with an IFC of 0 and 1. The plasma levels of catalase, irisin, interleukin-6, malondialdehyde, and cytokeratin 18 were higher in stage ≥2 subjects, whereas the resolvin D1 levels were lower. No differences were observed in xanthine oxidase, myeloperoxidase, protein carbonyl and fibroblast growth factor 21 depending on liver status. CONCLUSION: The current available data show that the severity of NAFLD is associated with an increase in oxidative stress and proinflammatory status. It may be also useful as diagnostic purpose in clinical practice.

Relationship of visceral adipose tissue with surrogate insulin resistance and liver markers in individuals with metabolic syndrome chronic complications.

BACKGROUND: Visceral adipose tissue (VAT) has a hazardous influence on systemic inflammation, insulin resistance and an adverse metabolic profile, which increases the risk of developing non-alcoholic fatty liver disease (NAFLD) and chronic complications of diabetes. In our study we aimed to evaluate the association of VAT and the triglyceride glucose (TyG) as a proxy of insulin resistance surrogated with metabolic and liver risk factors among subjects diagnosed with metabolic syndrome (MetS). METHODS: A cross-sectional study was performed including 326 participants with MetS (55-75 years) from the PREDIMED-Plus study. Liver-status markers, VAT and TyG were assessed. Participants were stratified by tertiles according to VAT (n = 254) and TyG (n = 326). A receiver operating characteristic curve was used to analyse the efficiency of TyG for VAT. RESULTS: Subjects with greater visceral fat depots showed worse lipid profile, higher homeostatic model assessment for insulin resistance (HOMA-IR), TyG, alanine transaminase (ALT), fibroblast growth factor-21 (FGF-21), fatty liver index (FLI) and hepatic steatosis index (HSI) compared with participants in the first tertile. The multi-adjusted linear-regression analyses indicated that individuals in the third tertile of TyG (>9.1-10.7) had a positive association with HOMA-IR [ß = 3.07 (95% confidence interval (CI) 2.28-3.86; p trend < 0.001)], ALT [ß = 7.43 (95% CI 2.23-12.63; p trend = 0.005)], gamma glutamyl transferase (GGT) [ß = 14.12 (95% CI 3.64-24.61; p trend = 0.008)], FGF-21 [ß = 190.69 (95% CI 93.13-288.25; p trend < 0.001)], FLI [ß = 18.65 (95% CI 14.97-22.23; p trend < 0.001)] and HSI [ß = 3.46 (95% CI, 2.23-4.68; p trend < 0.001)] versus participants from the first tertile. Interestingly, the TyG showed the largest area under the receiver operating curve (AUC) for women (AUC = 0.713; 95% CI 0.62-0.79) compared with men (AUC = 0.570; 95% CI 0.48-0.66). CONCLUSIONS: A disrupted VAT enlargement and impairment of TyG are strongly associated with liver status and cardiometabolic risk factors linked with NAFLD in individuals diagnosed with MetS. Moreover, the TyG could be used as a suitable and reliable marker estimator of VAT.

Leisure-Time Physical Activity, Sedentary Behaviour and Diet Quality are Associated with Metabolic Syndrome Severity: The PREDIMED-Plus Study.

Healthy lifestyle factors, such as physical activity (PA) and Mediterranean diet (MD), decrease the likelihood of developing metabolic syndrome (MetS). The aim of this study was to report main lifestyle components and related factors according to the MetS severity. Cross-sectional analysis was done of baseline lifestyle factors from 5739 participants with overweight/obesity and MetS features (aged 55-75 years) included in the PREDIMED-PLUS primary cardiovascular prevention randomized trial. Participants were categorized in tertiles according to a validated MetS severity score (MetSSS). Anthropometrics, visceral adiposity index, dietary nutrient intake, biochemical marker levels, as well as a Dietary Inflammatory Index and depression symptoms (Beck Depression Inventory-II) were measured. Diet quality was assessed using a 17-item energy-restricted MD questionnaire. Duration and intensity of PA was self-reported using the Minnesota-REGICOR Short Physical Activity Questionnaire. Sedentary behaviours were measured using the Spanish version of the Nurses' Health Study questionnaire. The 30 s chair stand test was also assessed. Participants with highest MetSSS showed higher values of cardiovascular risk factors (except for total cholesterol and LDL cholesterol), depression risk, sedentary and TV viewing time, and lower moderate and vigorous leisure-time physical activity (LTPA). Highest MetSSS participants tended to a pro-inflammatory dietary pattern and tended to lower MD adherence. In addition, they showed lower carbohydrate and nut intake and higher intake of protein, saturated and trans fatty acids, cholesterol, iodine, sodium, red and processed meat products, other oils different from olive oil and spirit alcoholic drinks. The highest MetS severity score was associated with lower moderate and vigorous LTPA and higher sedentary time and depression risk, as they tended to a pro-inflammatory dietary pattern and lower MD adherence.