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PubMed | Joan University Hospital, Hospital Universitari Of Girona Dr Josep Trueta, Research Center Biomedica En Red Of Diabetes fermedades Metabolicas Ciberdem and CIBER ISCIII
Type: Journal Article | Journal: International journal of obesity (2005) | Year: 2016

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome and is strongly associated with obesity, dyslipidaemia and altered glucose regulation. Previous data demonstrated that low circulating levels of tumour necrosis factor weak inducer of apoptosis (sTWEAK) were associated with obesity, diabetes and insulin resistance, all traits associated with an increased risk of NALFD. Circulating sTWEAK levels are expected to be reduced in the presence of NAFLD.We aimed to explore the relationship between NAFLD and circulating sTWEAK levels in obese patients, and to evaluate the effect of sTWEAK on hepatocyte triglyceride accumulation.Design setting and patients:This is an observational case-control study performed in n=112 severely obese patients evaluated for NAFLD by abdominal ultrasound and n=32 non-obese patients without steatosis. Serum sTWEAK concentrations were measured by ELISA. Multivariable analyses were performed to determine the independent predictors of NAFLD. We analysed TWEAK and Fn14 protein expression in liver biopsies by western blotting and immunohistochemistry. An immortalized primary human hepatocyte cell line (HHL) was used to evaluate the effect of sTWEAK on triglyceride accumulation.We observed a reduction in serum circulating sTWEAK concentrations with the presence of liver steatosis. On multivariable analysis, lower sTWEAK concentrations were independently associated with the presence of NAFLD (odds ratio (OR)=0.023; 95% confidence interval: 0.001-0.579; P<0.022). In human hepatocytes, sTWEAK administration reduced fat accumulation as demonstrated by the reduction in palmitic acid-induced accumulation of triglyceride and the decreased expression of cluster of differentiation 36 (CD36) and perilipin 1 and 2 (PLIN1 and PLIN2) genes.Decreased sTWEAK concentrations are independently associated with the presence of NAFLD. This is concordant with the observation that TWEAK reduces lipid accumulation in human liver cells.


Rojo-Martinez G.,Hospital Regional Universitario | Rojo-Martinez G.,Research Center Biomedica En Red Of Diabetes fermedades Metabolicas Ciberdem | Maymo-Masip E.,Research Center Biomedica En Red Of Diabetes fermedades Metabolicas Ciberdem | Maymo-Masip E.,Rovira i Virgili University | And 18 more authors.
PLoS ONE | Year: 2014

Objective: Serum levels of soluble TNF-like weak inducer of apoptosis (sTWEAK) and its scavenger receptor CD163 (sCD163) have been linked to insulin resistance. We analysed the usefulness of these cytokines as biomarkers of type 2 diabetes in a Spanish cohort, together with their relationship to food consumption in the setting of the Di@bet.es study. Research Design and Methods: This is a cross-sectional, matched case-control study of 514 type 2 diabetes subjects and 517 controls with a Normal Oral Glucose Tolerance Test (NOGTT), using data from the Di@bet.es study. Study variables included clinical and demographic structured survey, food frequency questionnaire and physical examination. Serum concentrations of sTWEAK and sCD163 were measured by ELISA. Linear regression analysis determined which variables were related to sTWEAK and sCD163 levels. Logistic regression analysis was used to estimate odd ratios of presenting type 2 diabetes. Results: sCD163 concentrations and sCD163/sTWEAK ratio were 11.0% and 15.0% higher, respectively, (P<0.001) in type 2 diabetes than in controls. Following adjustment for various confounders, the OR for presenting type 2 diabetes in subjects in the highest vs the lowest tertile of sCD163 was [(OR), 2,01 (95%CI, 1,46-2,97); P for trend <0.001]. Coffee and red wine consumption was negatively associated with serum levels of sCD163 (P = 0.0001 and; P = 0.002 for coffee and red wine intake, respectively). Conclusions: High circulating levels of sCD163 are associated with type 2 diabetes in the Spanish population. The association between coffee and red wine intake and these biomarkers deserves further study to confirm its potential role in type 2 diabetes. © 2014 Rojo-Martínez et al.


Ortega E.,Hospital Clinic iversitari Of Barcelona | Ortega E.,Research Center Biomedica En Red Of Diabetes fermedades Metabolicas Ciberdem | Amor A.J.,Hospital Clinic iversitari Of Barcelona | Rojo-Martinez G.,Research Center Biomedica En Red Of Diabetes fermedades Metabolicas Ciberdem | And 5 more authors.
Medicina Clinica | Year: 2015

Background and objective To describe the prevalence of cardiovascular disease (CVD) in type 1 diabetes (T1DM) and to compare it with that observed in type 2 diabetes (T2DM) and normal population in Spain. Patients and methods Cross-sectional study (18-70 years-old). Information on CVD was available from a nurse-administered questionnaire (Di@bet.es Study, NORMAL = 3,430, T2DM = 312) and from a physician reporting form (T1DM = 1,382). Differences in the crude and adjusted prevalence of coronary heart (CHD), cerebrovascular (CNSD), peripheral vascular (PVD) and overall CV (CVD) disease were investigated between T1DM vs. NORMAL, and T1DM vs. T2DM groups. Results We found differences in age, body mass index, proportion of women, dyslipemia and antihypertensive medication between T1DM vs. NORMAL and T1DM vs. T2DM (all P <.001). Smoking prevalence was not different between T1DM vs. T2DM and it was lower in T1DM compared to NORMAL (P <.0001). The percentage of CHD, CNSD, PVD, and overall CVD in T1DM vs. NORMAL was 3.0 vs. 2.5 (P =.31), 0.70 vs. 1.10 (P =.22), 2.61 vs. 0.20 (P <.0001), and 5.1 vs. 3.44 (P <.01), respectively. The prevalence in T2DM (vs. T1DM) was 11.3 (P <.0001), 3.5 (P <.0001), 4.2 (P =.13), and 17% (P <.0001), respectively. Multiple logistic regression adjusted models showed a higher prevalence of CHD (odds ratio [OR] 2.27, 95% confidence interval [95% CI] 1.41-3.67), PVD (OR 15.35, 95% CI 5.61-42.04), and overall CVD (OR 2.32, 95% CI 1.55-3.46), but not for CNSD (OR 0.49, 95% CI 0.19-1.27) in T1DM compared to NORMAL. No differences were found between T1DM and T2DM. Conclusions We found a higher prevalence of CVD in a Mediterranean population of T1DM individuals compared with non-diabetic subjects. This prevalence was similar to that observed in T2DM. © 2014 Elsevier España, S.L.U. All rights reserved.

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