The global increase in chronic kidney disease (CKD) parallels the obesity epidemic. Obesity conveys a gradual but independent risk of progression of CKD that seems irrespective of the underlying ...nephropathy. Obesity has been associated with a secondary focal segmental glomerulosclerosis coined obesity-related glomerulopathy (ORG). Pathways through which obesity might cause renal disease are not well understood, and early clinical biomarkers for incipient ORG or renal relevant obesity are currently lacking. Recent human and experimental studies have associated ectopic lipid accumulation in the kidney (fatty kidney) with obesity-related renal disease. There is enough growing insight that ectopic lipid--the accumulation of lipid in non-adipose tissue--is associated with structural and functional changes of mesangial cells, podocytes, and proximal tubular cells to propose the development of ORG as a maladaptive response to hyperfiltration and albuminuria. Recent advances in metabolic imaging might validate ectopic lipid as a biomarker and research aid, to help translate novel therapeutics from experimental models to patients.
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.
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.
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).
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).
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.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Largely on the basis of data from patients with type 1 diabetes, the natural history of diabetic renal disease has been classified as a sequence of three stages: normoalbuminuria, microalbuminuria, ...and macroalbuminuria. Progressive decline of glomerular filtration rate (GFR) was thought to parallel the onset of macroalbuminuria (overt nephropathy), whereas glomerular hyperfiltration was deemed a hallmark of early disease. However, researchers have since shown that albuminuria is a continuum and that GFR can start to decline before progression to overt nephropathy. In addition to proteinuria, other risk factors might contribute to GFR deterioration including female sex, obesity, dyslipidaemia (in particular hypertriglyceridaemia), hypertension, and glomerular hyperfiltration, at least in a subgroup of patients. This phenomenon could explain why patients with type 2 diabetes can have renal insufficiency even before the onset of overt nephropathy, and might also suggest why the heterogeneous phenotype of type 2 diabetic renal disease does not necessarily associate with typical histological lesions of diabetic renal disease, unlike in type 1 diabetic renal disease. Patients with renal insufficiency but without albuminuria are usually excluded from randomised clinical trials in overt nephropathy, thus optimum treatment for this group of patients is unknown. The wide inter-patient variability of the disease probably needs individually tailored intervention.
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 greater than or equal to 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 greater than or equal to 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. Keywords: Fatty liver index, Non-alcoholic fatty liver disease, Cardiometabolic risk factors, Metabolic syndrome, Sex, Age
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.
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 (R
= 0.248,
= 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.
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 IL1β) 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.
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 (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.
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).
To assess the relationship between NAFLD and kidney glomerular hyperfiltration in adults with MetS.
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.
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.
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.
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