MAFLD and glomerular hyperfiltration in subjects with normoglycemia, prediabetes and type 2 diabetes: A cross-sectional population study.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD, 2020 diagnostic criteria) and glomerular hyperfiltration share common risk factors, including obesity, insulin resistance, impaired glucose tolerance, diabetes, dyslipidemia, and hypertension. AIMS: To assess the prevalence of MAFLD and its association with glomerular hyperfiltration and age-related worsening of kidney function in subjects with normoglycemia, prediabetes and type 2 diabetes mellitus (T2DM). METHODS: We analysed data recorded during occupational health visits of 125,070 Spanish civil servants aged 18-65 years with a de-indexed glomerular filtration rate (GFR) estimated with the chronic-kidney-disease-epidemiological (CKD-EPI) equation (estimated glomerular filtration rate [eGFR]) ≥60 mL/min. Subjects were categorised according to fasting plasma glucose levels <100 mg/dL (normoglycemia), ≥100 and ≤ 125 mg/dL (prediabetes), or ≥126 mg/dL and/or antidiabetic treatment (T2DM). The association between MAFLD and glomerular hyperfiltration, defined as a de-indexed eGFR above the age- and gender-specific 95th percentile, was assessed by multivariable logistic regression. RESULTS: In the whole study group, MAFLD prevalence averaged 19.3%. The prevalence progressively increased from 14.7% to 33.2% and to 48.9% in subjects with normoglycemia, prediabetes and T2DM, respectively (p < 0.001 for trend). Adjusted odds ratio (95% CI) for the association between MAFLD and hyperfiltration was 9.06 (8.53-9.62) in the study group considered as a whole, and 8.60 (8.03-9.21), 9.52 (8.11-11.18) and 8.31 (6.70-10.30) in subjects with normoglycemia, prediabetes and T2DM considered separately. In stratified analyses, MAFLD amplified age-dependent eGFR decline in all groups (p < 0.001). CONCLUSIONS: MAFLD prevalence increases across the glycaemic spectrum. MAFLD is significantly associated with hyperfiltration and amplifies the age-related eGFR decline.

Nurse-led telephone intervention for lifestyle changes on glycaemic control in people with prediabetes: Study protocol for a randomized controlled trial.

AIM: To evaluate the effectiveness of a nurse-led personalized telephone lifestyle intervention versus automated SMSs in the reduction of fasting plasma glucose in adults with prediabetes. DESIGN: The PREDIPHONE is a randomized controlled, parallel, two arms, superiority trial with 15 months of follow-up. Participants will be randomized to either the intervention group (teleconsultations) or the active control group (SMSs). METHODS: A total of 428 participants will be randomized in a 1:1 ratio to one of the two arms and followed up during 9 months. The teleconsultations group will receive nurse-led personalized advice, while the SMSs group will receive 4-5 brief SMSs a week. Participants in both groups will receive evidence-based recommendations for diet and physical activity (PA). Outcome measures will be collected at baseline, months 4 and 9 and at month 15, to evaluate post-intervention effects. DISCUSSION: Prevention of diabetes through the implementation of lifestyle interventions remains an important priority. The current pandemic situation has magnified its urgency as it heavily affected the functionality of the healthcare system. Moreover, it created the need of remotely delivering preventative interventions. This study will provide insights on the effectiveness and feasibility of a telephone-based intervention led by nurses in the amelioration of risk factors associated with diabetes. IMPACT: Findings from this study will offer health services decision-makers sound evidence regarding an alternative method to face-to-face consultations that could be practical, acceptable and inexpensive, and that concretely answers the need for easily implementable prevention strategies. TRIAL REGISTRATION: NCT04735640 (ClinicalTrials.gov identifier). PROTOCOL VERSION: V1.0, 18/02/2021.

Metabolic Syndrome Features and Excess Weight Were Inversely Associated with Nut Consumption after 1-Year Follow-Up in the PREDIMED-Plus Study.

BACKGROUND: High nut consumption has been previously associated with decreased prevalence of metabolic syndrome (MetS) regardless of race and dietary patterns. OBJECTIVES: The aim of this study was to assess whether changes in nut consumption over a 1-y follow-up are associated with changes in features of MetS in a middle-aged and older Spanish population at high cardiovascular disease risk. METHODS: This prospective 1-y follow-up cohort study, conducted in the framework of the PREvención con DIeta MEDiterránea (PREDIMED)-Plus randomized trial, included 5800 men and women (55-75 y old) with overweight/obesity [BMI (in kg/m2) ≥27 and <40] and MetS. Nut consumption (almonds, pistachios, walnuts, and other nuts) was assessed using data from a validated FFQ. The primary outcome was the change from baseline to 1 y in features of MetS [waist circumference (WC), glycemia, HDL cholesterol, triglyceride (TG), and systolic and diastolic blood pressure] and excess weight (body weight and BMI) according to tertiles of change in nut consumption. Secondary outcomes included changes in dietary and lifestyle characteristics. A generalized linear model was used to compare 1-y changes in features of MetS, weight, dietary intakes, and lifestyle characteristics across tertiles of change in nut consumption. RESULTS: As nut consumption increased, between each tertile there was a significant decrease in WC, TG, systolic blood pressure, weight, and BMI (P < 0.05), and a significant increase in HDL cholesterol (only in women, P = 0.044). The interaction effect between time and group was significant for total energy intake (P < 0.001), adherence to the Mediterranean diet (MedDiet) (P < 0.001), and nut consumption (P < 0.001). Across tertiles of increasing nut consumption there was a significant increase in extra virgin olive oil intake and adherence to the MedDiet; change in energy intake, on the other hand, was inversely related to consumption of nuts. CONCLUSIONS: Features of MetS and excess weight were inversely associated with nut consumption after a 1-y follow-up in the PREDIMED-Plus study cohort. This trial was registered at isrctn.com as ISRCTN89898870.

Efficacy of dietary intervention or in combination with exercise on primary prevention of cardiovascular disease: A systematic review.

BACKGROUND AND AIM: Lifestyle factors heavily influence the development of cardiovascular disease (CVD); therefore, interventions delivering adequate lifestyle changes may improve the prognosis among patients at cardiovascular (CV) risk. Recently published research on the effectiveness of dietary and exercise intervention programmes, alone or combined, on reducing risk factors associated with CVD as well as preventing CV events have been now assessed. METHODS AND RESULTS: Using the Medline database via PubMed, we searched for prospective studies published between January 2000 and January 2020 assessing the efficacy of dietary interventions alone or in combination with exercise on reducing CV risk factors or events in human adults at risk. Study quality was assessed using the American Dietetic Association Quality Criteria Checklist. From 934 articles, 21 prospective experimental design studies (15 randomized controlled trials (RCTs), one cluster RCT, and five quasi-experimental intervention studies with a control group) met inclusion and exclusion criteria. Most interventions improved at least some markers of CV risk and the most improvement was time devoted to physical activity increased. A low-fat intervention diet seemed to be effective only when coupled with moderate intensity exercise and weight loss, while a Mediterranean diet (MedDiet) intervention without physical activity, decreased both systolic and diastolic blood pressure, major CV events rate and risk of developing type 2 diabetes. CONCLUSION: The MedDiet appears to have the most beneficial effect on CV events and increased hours of physical training are strongly related to greater improvement of risk factors; nevertheless, adherence to intervention is fundamental as it directly relates to health outcomes.

Mechanisms and treatment of obesity-related hypertension-Part 1: Mechanisms.

The prevalence of obesity has tripled over the past five decades. Obesity, especially visceral obesity, is closely related to hypertension, increasing the risk of primary (essential) hypertension by 65%-75%. Hypertension is a major risk factor for cardiovascular disease, the leading cause of death worldwide, and its prevalence is rapidly increasing following the pandemic rise in obesity. Although the causal relationship between obesity and high blood pressure (BP) is well established, the detailed mechanisms for such association are still under research. For more than 30 years sympathetic nervous system (SNS) and kidney sodium reabsorption activation, secondary to insulin resistance and compensatory hyperinsulinemia, have been considered as primary mediators of elevated BP in obesity. However, experimental and clinical data show that severe insulin resistance and hyperinsulinemia can occur in the absence of elevated BP, challenging the causal relationship between insulin resistance and hyperinsulinemia as the key factor linking obesity to hypertension. The purpose of Part 1 of this review is to summarize the available data on recently emerging mechanisms believed to contribute to obesity-related hypertension through increased sodium reabsorption and volume expansion, such as: physical compression of the kidney by perirenal/intrarenal fat and overactivation of the systemic/renal SNS and the renin-angiotensin-aldosterone system. The role of hyperleptinemia, impaired chemoreceptor and baroreceptor reflexes, and increased perivascular fat is also discussed. Specifically targeting these mechanisms may pave the way for a new therapeutic intervention in the treatment of obesity-related hypertension in the context of 'precision medicine' principles, which will be discussed in Part 2.

Validity of nutrition screening tools for risk of malnutrition among hospitalized adult patients: A systematic review and meta-analysis.

BACKGROUNDS & AIMS: Malnutrition is prevalent among hospitalized patients in developed countries, contributing to negative health outcomes and increased healthcare costs. Timely identification and management of malnutrition are crucial. The lack of a universally accepted definition and standardized diagnostic criteria for malnutrition has led to the development of various screening tools, each with varying validity. This complicates early identification of malnutrition, hindering effective intervention strategies. This systematic review and meta-analysis aimed to identify the most valid and reliable nutritional screening tool for assessing the risk of malnutrition in hospitalized adults. METHODS: A systematic literature search was conducted to identify validation studies published from inception to November 2023, in the Pubmed/MEDLINE, Embase, and CINAHL databases. This systematic review was registered in INPLASY (INPLASY202090028). The risk of bias and quality of included studies were assessed using the Quality Assessment of Diagnostic Accuracy Studies version 2 (QUADAS-2). Meta-analyses were performed for screening tools accuracy using the symmetric hierarchical summary receiver operative characteristics models. RESULTS: Of the 1646 articles retrieved, 60 met the inclusion criteria and were included in the systematic review, and 21 were included in the meta-analysis. A total of 51 malnutrition risk screening tools and 9 reference standards were identified. The meta-analyses assessed four common malnutrition risk screening tools against two reference standards (Subjective Global Assessment [SGA] and European Society for Clinical Nutrition and Metabolism [ESPEN] criteria). The Malnutrition Universal Screening Tool (MUST) vs SGA had a sensitivity (95% Confidence Interval) of 0.84 (0.73-0.91), and specificity of 0.85 (0.75-0.91). The MUST vs ESPEN had a sensitivity of 0.97 (0.53-0.99) and specificity of 0.80 (0.50-0.94). The Malnutrition Screening Tool (MST) vs SGA had a sensitivity of 0.81 (0.67-0.90) and specificity of 0.79 (0.72-0.74). The Mini Nutritional Assessment-Short Form (MNA-SF) vs ESPEN had a sensitivity of 0.99 (0.41-0.99) and specificity of 0.60 (0.45-0.73). The Nutrition Universal Screening Tool-2002 (NRS-2002) vs SGA had a sensitivity of 0.76 (0.58-0.87) and specificity of 0.86 (0.76-0.93). CONCLUSIONS: The MUST demonstrated high accuracy in detecting malnutrition risk in hospitalized adults. However, the quality of the studies included varied greatly, possibly introducing bias in the results. Future research should compare tools within a specific patient population using a valid and universal gold standard to ensure improved patient care and outcomes.

Fatty Liver Disease in Patients with Prediabetes and Overweight or Obesity.

Non-alcoholic fatty liver disease (NAFLD) is a global health problem associated with liver morbimortality, obesity, and type 2 diabetes mellitus. This study aimed to analyze the prevalence of NAFLD (defined as a fatty liver index [FLI] ≥ 60) and its association with other cardiovascular risk (CVR) factors in patients with prediabetes and overweight/obesity. The present cross-sectional analysis uses baseline data from an ongoing randomized clinical trial. Sociodemographic and anthropometric characteristics, CVR (assessed by the REGICOR-Framingham risk equation), metabolic syndrome (MetS), and FLI-defined NAFLD (cut-off value of ≥60) were assessed. The prevalence of FLI-defined NAFLD was 78% overall. Men exhibited a worse cardiometabolic profile as compared to women, specifically, with higher values of systolic blood pressure (137.02 ± 13.48 vs. 131.22 ± 14.77 mmHg), diastolic blood pressure (85.33 ± 9.27 vs. 82.3 ± 9.12 mmHg), aspartate aminotransferase (AST) (27.23 ± 12.15 vs. 21.23 ± 10.05 IU/L), alanine aminotransferase (ALT) (34.03 ± 23.31 vs. 21.73 ± 10.80 IU/L), and higher CVR (5.58 ± 3.16 vs. 3.60 ± 1.68). FLI-defined NAFLD was associated with elevated AST, ALT, and the presence of MetS (73.7%) and CVR for the whole sample. People with prediabetes present a high burden of comorbidities related to CVR, despite clinical follow-up, and it is recommended to actively begin working with them to reduce their risks.

MAFLD and glomerular hyperfiltration in subjects with prediabetes, visceral obesity and "preserved" kidney function: A cross-sectional study.

AIMS: To investigate the prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) in prediabetes, visceral obesity, and preserved kidney function, and explore whether MAFLD is associated with hyperfiltration. METHODS: We analyzed data from 6697 Spanish civil servants, aged 18-65 years, with fasting plasma glucose ≥ 100 and ≤ 125 mg/dL (prediabetes, ADA), waist circumference ≥ 94 cm in men and ≥ 80 cm in women (visceral obesity, IDF) and de-indexed estimated glomerular filtration rate (eGFR) ≥ 60 ml/min, collected during occupational health visits. The association between MAFLD and hyperfiltration (eGFR > age- and sex-specific 95th percentile) was tested by multivariable logistic regression analyses. RESULTS: Overall, 4213 patients (62.9%) had MAFLD, and 330 (4.9%) were hyperfiltering. MAFLD was more frequent in hyperfiltering than in non-hyperfiltering subjects (86.4% vs 61.7%, P < 0.001). BMI, waist circumference, systolic, diastolic, mean arterial pressure, and prevalence of hypertension were higher in hyperfiltering than in non-hyperfiltering subjects (P < 0.05). MAFLD was independently associated with hyperfiltration, even after adjusting for common confounders [OR (95% CI): 3.36 (2.33-4.84), P < 0.001]. In stratified analyses MAFLD potentiated age-related eGFR decline vs. non-MAFLD (P < 0.001). CONCLUSIONS: More than half of subjects with prediabetes, visceral obesity and eGFR ≥ 60 ml/min presented MAFLD that was associated with hyperfiltration and potentiated the age-related eGFR decline.

Sex and age differences in the association of fatty liver index-defined non-alcoholic fatty liver disease with cardiometabolic risk factors: a cross-sectional study.

BACKGROUND: Despite the extensive scientific evidence accumulating on the epidemiological risk factors for non-alcoholic fatty liver disease (NAFLD), evidence exploring sex- and age-related differences remains insufficient. The present cross-sectional study aims to investigate possible sex differences in the prevalence of FLI-defined NAFLD as well as in its association with common risk factors across different age groups, in a large sample of Spanish working adults. METHODS: This cross-sectional study included data from 33,216 Spanish adult workers (18-65 years) randomly selected during voluntary routine occupational medical examinations. Sociodemographic characteristics (age and social class), anthropometric (height, weight, and waist circumference) and clinical parameters (blood pressure and serum parameters) were collected. NAFLD was determined by the validated fatty liver index (FLI) with a cut-off value of ≥ 60. The presence of metabolic syndrome (MetS) was assessed according to the diagnostic criteria of the International Diabetes Federation. Cardiovascular risk was determined using the REGICOR-Framingham equation. The association between FLI-defined NAFLD and risk factors by sex and age was evaluated by multivariate logistic regression. RESULTS: The prevalence of FLI-defined NAFLD (FLI ≥ 60) was 19.1% overall, 27.9% (95% CI 23.3-28.5%) for men and 6.8% (95% CI 6.4-7.3%) for women and increasing across age intervals. As compared to women, men presented worse cardiometabolic and anthropometric profiles. The multivariate analysis model showed that hepatic steatosis assessed by FLI was strongly associated with age, HDL-cholesterol, social class, prediabetes, diabetes, prehypertension, hypertension, and smoking status for both men and women. The association between diabetes and hypertension with FLI-defined NAFLD was stronger in women than in men at both univariate and multivariate analyses. CONCLUSIONS: Men presented a higher prevalence of NAFLD than women across all age intervals, as well as a worse cardiometabolic profile and a higher cardiovascular risk. Nevertheless, the association between FLI-defined NAFLD and diabetes or hypertension was significantly stronger in women than in men, possibly indicating that the presence of a dysmetabolic state might affect women more than men with regard to liver outcomes.

Occupational and Leisure Physical Activity on Cardiovascular Risk and Body Composition Among Courier Workers.

OBJECTIVE: There is some controversy about the beneficial effects of occupational physical activity (OPA) on cardiovascular risk (CVR). The main aim of this study was to explore the effect of the combination of different frequencies of leisure-time physical activity (LTPA) and two types of OPA on CVR and body composition, and whether the association between physical activity (PA) and CVR was mediated by visceral adipose tissue (VAT). METHODS: This cross-sectional study included data from 2516 couriers living in Spain, delivering either by motorbike or foot, and practicing LTPA never, occasionally, or regularly. Couriers were classified into six categories according to LTPA and OPA; body composition was assessed by Bioelectrical Impedance, and CVR by the Framingham equation. General linear models were performed to explore the association between different categories with each outcome (CVR and body composition) and the possible role of VAT as a mediator between PA and CVR. RESULTS: Compared with the most sedentary group (motorbike couriers that never practice PA), walking couriers who practice regular PA presented the lowest CVR [ß -1.58 (95% CI -2.31; -0.85)] and the lowest VAT [ß -2.86 (95% CI -3.74; -1.98) followed by the motorbike couriers who practiced regular PA [ß -0.51 (95% CI -1.00; -0.03) for CVR and ß -2.33 (95% CI -2.91; -1.75) for VAT]. The association between PA and CVR was partially mediated by VAT. CONCLUSION: The present results indicated that both OPA and LTPA are protective factors for CVR and play an important role on VAT accumulation.

Long-term kidney and systemic effects of calorie restriction in overweight or obese type 2 diabetic patients (C.Re.S.O. 2 randomized controlled trial).

AIMS: In type 2 diabetic patients with obesity, hyperfiltration is a risk factor for accelerated glomerular filtration rate (GFR) decline and is ameliorated by calorie restriction (CR). We assessed whether CR-induced amelioration of hyperfiltration could translate into slower long-term GFR decline in this population. METHODS: In this academic, single-center, parallel-group, prospective, randomized, open-label, blinded endpoint trial, consenting >40-year-old patients with type 2 diabetes, BMI ≥27 kg/m2, creatinine <1.2 mg/dL and albuminuria ≤300 mg/24 h were randomized (1:1) to two-year 25% CR (n = 53) or standard diet (SD, n = 50). Primary outcome was 6-month measured GFR. Analyses were by modified intention-to-treat. RESULTS: At 6 months GFR decreased by 5.16 ± 10.03 mL/min (P = 0.001) with CR, and by 0.98 ± 9.71 mL/min (P = 0.497) with SD. Between-group difference was significant (P = 0.044). GFR decline from 6 to 24 months was significant with SD (P < 0.01), but not with CR (P = 0.075). Between-group difference, however, was not significant (P = 0.414). Body weight, BMI, waist circumference, systolic blood pressure, HbA1c, blood glucose, serum triglycerides decreased and ApoA-I concentration increased with CR. No changes were observed with SD. Between-group differences were significant. CR was tolerated well. CONCLUSIONS: In obese type 2 diabetic patients, CR ameliorated glomerular hyperfiltration and several cardiovascular risk factors, and blunted long-term GFR decline. TRIAL REGISTRATION: NCT01930136.

Utility of Fatty Liver Index to predict reversion to normoglycemia in people with prediabetes.

BACKGROUND: Fatty Liver Index (FLI) is strongly associated with changes in glycemic status and incident Type 2 Diabetes (T2D). The probability of reverting to normoglycemia from a state prediabetes could be determined by FLI, however such relationship remains poorly understood. AIM: To determine the clinical interest of using FLI to estimate prediabetes reversion at 5 years in patients with impaired fasting plasma glucose at baseline, and identify those factors associated with changes in FLI, that could contribute to the reversion of prediabetes. METHODS: This 5-year cohort study included 16,648 Spanish working adults with prediabetes. Prediabetes was defined as fasting plasma glucose (FPG) between 100 and 125 mg/dl according to the ADA criteria, while prediabetes reversion was defined as a FPG <100 mg/dL. The population was classified as: FLI <30 (no hepatic steatosis), FLI 30-59 (intermediate status), and FLI ≥60 (hepatic steatosis). RESULTS: At 5 years follow-up, 33.7% of subjects reverted to normoglycemia (annual rate of 6.7%). The adjusted binomial logistic regression model showed that scoring FLI <30 (OR 1.544; 95% CI 1.355-1.759), performing at least 150 min/week of physical activity (OR 4.600; 95% CI 4.088-5.177) and consuming fruits and vegetables daily (OR 1.682; 95% CI 1.526-1.855) were associated with the probability of reverting form prediabetes to normoglycemia. The ROC curve for prediction of reversion showed that FLI (AUC 0.774;95% CI 0.767-0.781) was a better predictor than FPG (AUC 0.656; 95% CI 0.648-0.664). CONCLUSIONS: Regular physical activity, healthy dietary habits and absence of hepatic steatosis are independently associated with the probability of reversion to normoglycemia in adult workers with prediabetes at baseline. Low FLI values (especially FLI< 30) may be useful to predict the probability of prediabetes reversion, especially in active subjects with healthy eating habits, and thus identify those who might benefit from early lifestyle intervention.

Socioeconomic Inequalities in Metabolic Syndrome by Age and Gender in a Spanish Working Population.

Lower socio-economic status (SES) is significantly associated with metabolic syndrome (MS) prevalence, possibly affecting women more than men, although evidence in Spain is still limited. The present cross-sectional study analyzed the association between MS and SES by age and gender among 42,146 working adults living in the Balearic Islands (Spain). Prevalence was higher in men (9.4% by ATP-III; 12.3% by IDF) than women (3.8% by ATP-III; 5.7% by IDF) and in the lower social class (7.9% by ATP-III; 10.7% by IDF) than the higher (4.1% by ATP-III; 5.9% by IDF). The SES gradient in MS prevalence was larger in women (PR 95% CI: 3.38, 2.50-4.58 by ATP-III; 3.06, 2.43-3.86 by IDF) than in men (1.23, 1.06-1.41 by ATP-III; 1.15, 1.03-1.30 by IDF) and was already evident from early adulthood, reaching the highest ratio at the late stages of middle adulthood (4.34, 1.11-16.98). Among men, it was significant during the late stages of early adulthood only (1.80, 1.19-2.73). Lower SES influenced MS prevalence in both genders, however, women seemed more affected than men. From a public health perspective, SES could be strongly associated with the burden of MS; in an effort to reduce its prevalence, public health policies should focus on gender differences in socio-economic inequality and consider women with low socio-economic resources as a priority.

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.

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.

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.

Nutrient adequacy and diet quality in a Mediterranean population with metabolic syndrome: A cross-sectional study.

BACKGROUND & AIMS: Few studies have compared micronutrient intake and fulfilment of average requirements (EAR) in non-diabetic, pre-diabetic and diabetic adults at high cardiovascular risk. We assessed these variables in a large sample of participants in the PREDIMED-PLUS randomized trial of primary cardiovascular prevention with diet and physical activity. DESIGN: Baseline assessment of nutritional adequacy in n = 5792 men and women, aged 55-75 years, with overweight/obesity and some metabolic syndrome features. METHODS: Participants were categorised as non-diabetic (n = 2390), pre-diabetic (n = 1322) or diabetic (n = 2080) by standard criteria. Food and nutrient intake were assessed using a validated food frequency questionnaire. Micronutrients examined were vitamins B1, B2, B3, B6, B12, A, C, D, E and folic acid; Ca, K, P, Mg, Fe, Se, Cr, Zn, and iodine. The proportion of micronutrient inadequacy was evaluated using the EAR or adequate intake (AI) cut-offs. Diet quality was also determined using a 17-item energy-restricted Mediterranean diet (MedDiet) questionnaire. RESULTS: Compared to non-diabetic participants, those with pre-diabetes had lower intakes of total carbohydrates (CHO) and higher intakes of total fat and saturated fatty acids (SFA) and were more likely to be below EAR for folic, while diabetic participants had lower intakes of total CHO and higher intakes of protein, total fat, monounsaturated fatty acids, SFA and cholesterol and were less likely to be below EAR for vitamins B2, and B6, Ca, Zn and iodine. Diabetic participants disclosed higher adherence to the MedDiet than the other two groups. CONCLUSIONS: Older Mediterranean individuals with metabolic syndrome and diabetes had better nutrient adequacy and adherence to the MedDiet than those with pre-diabetes or no diabetes.

Effects of Millimolar Steady-State Hydrogen Peroxide Exposure on Inflammatory and Redox Gene Expression in Immune Cells from Humans with Metabolic Syndrome.

Reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) can exert opposed effects depending on the dosage: low levels can be involved in signalling and adaptive processes, while higher levels can exert deleterious effects in cells and tissues. Our aim was to emulate a chronic ex vivo oxidative stress situation through a 2 h exposure of immune cells to sustained H2O2 produced by glucose oxidase (GOX), at high or low production rate, in order to determine dissimilar responses of peripheral blood mononuclear cells (PBMCs) and neutrophils on ROS and cytokine production, and mitochondrial dynamics-related proteins, pro/anti-inflammatory and anti-oxidant gene expression. Immune cells were obtained from subjects with metabolic syndrome. H2O2 at low concentrations can trigger a transient anti-inflammatory adiponectin secretion and reduced gene expression of toll-like receptors (TLRs) in PBMCs but may act as a stimulator of proinflammatory genes (IL6, IL8) and mitochondrial dynamics-related proteins (Mtf2, NRF2, Tfam). H2O2 at a high concentration enhances the expression of pro-inflammatory genes (TLR2 and IL1ß) and diminishes the expression of mitochondrial dynamics-related proteins (Mtf1, Tfam) and antioxidant enzymes (Cu/Zn SOD) in PBMCs. The GOX treatments produce dissimilar changes in immune cells: Neutrophils were more resistant to H2O2 effects and exhibited a more constant response in terms of gene expression than PBMCs. We observe emerging roles of H2O2 in mitochondrial dynamics and redox and inflammation processes in immune cells.