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Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Emerging scientific evidence suggests that increases in body iron represent a risk factor for the development of metabolic syndrome and diabetes. The aim of our study was to determine the body iron stores in patients with metabolic syndrome, and to evaluate the potential relationship of iron overload with specific features of the metabolic syndrome, such as fatty liver. A total of 490 individuals were enrolled. The diagnosis of metabolic syndrome was based on National Cholesterol Education Program-Adult Treatment Panel III (ATPIII) criteria. The metabolic syndrome group was consisted of 185 patients having three or more criteria, whereas individuals with less than three criteria constituted the control group. Metabolic syndrome patients displayed higher ferritin concentration as compared to control individuals. Ferritin levels were positively correlated with insulin concentration, as well as with Homeostasis Model Assessment (HOMA) index values. Multiple regression analysis revealed that ferritin was the most important independent determinant of insulin resistance indices. Patients with metabolic syndrome also exhibited increased concentrations of alanine aminotransferase and gamma-glutamyltranspeptidase compared to controls. Multiple regression analysis revealed that ferritin concentration was the most important determinant of gamma-glutamyltranspeptidase levels. Patients with the metabolic syndrome exhibit an increase in body iron stores as well as elevated concentrations of liver enzymes compared to the individuals who do not fulfill the criteria for the diagnosis of this syndrome. Our data support a direct role of increased body iron in the pathogenesis of insulin resistance, whereas iron overload may also contribute to the development of specific features of the metabolic syndrome, such as fatty liver.
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PMID:Increased serum ferritin concentrations and liver enzyme activities in patients with metabolic syndrome. 1837 Jul 38

The role of micronutrients in the etiology of type 2 diabetes is not well established. Several lines of evidence suggest that iron play may a role in the pathogenesis of type 2 diabetes. Iron is a strong pro-oxidant and high body iron levels are associated with increased level of oxidative stress that may elevate the risk of type 2 diabetes. Several epidemiological studies have reported a positive association between high body iron stores, as measured by circulating ferritin level, and the risk of type 2 diabetes and of other insulin resistant states such as the metabolic syndrome, gestational diabetes and polycystic ovarian syndrome. In addition, increased dietary intake of iron, especially that of heme iron, is associated with risk of type 2 diabetes in apparently healthy populations. Results from studies that have evaluated the association between genetic mutations related to iron metabolism have been inconsistent. Further, several clinical trials have suggested that phlebotomy induced reduction in body iron levels may improve insulin sensitivity in humans. However, no interventional studies have yet directly evaluated the effect of reducing iron intake or body iron levels on the risk of developing type 2 diabetes. Such studies are required to prove the causal relationship between moderate iron overload and diabetes risk.
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PMID:The role of iron in type 2 diabetes in humans. 1850 Nov 98

Hepcidin inhibits intestinal absorption of iron through internalisation of ferroportin. Its discovery helps to better understand the genetic iron overloads. The insulin resistance-hepatic iron overload (IR-HIO)--also coined as the dysmetabolic iron overload syndrome--is a common cause or iron overload. This article is a review about genetic iron overloads and IR-HIO. Type 1 haemochromatosis C282Y +/+ accounts for 95% of the haemochromatosis. Hepatic fibrosis may develop if serum ferritin is higher than 1000 microg/l but can be partially reversible with phlebotomies. Juvenile haemochromatosis (type 2) and type 3 haemochromatosis (mutation of the transferrin receptor 2) are very uncommon. Several mutations of the ferroportin gene can cause usually mild iron overload of autosomal dominant inheritance. Aceruleoplasminemia is an uncommon disorder involving cerebral iron overload. The causes and consequences of the IR-HIO are unknown. Treatment of IR-HIO is focused on metabolic syndrome and phlebotomies are questionable because the overload is moderate and intestinal absorption of iron seems to be low. MRI (or other non invasive methods) is needed to truly assess iron overload because serum ferritin overestimates it in metabolic syndrome. Several points have to be elucidated: how HFE interferes with hepcidin in type 1 haemochromatosis; the causes of variability of iron overload; the benefits of populations screening; the advantage of phlebotomies in IR-HIO; the use of new oral iron chelators.
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PMID:[Genetic iron overloads and hepatic insulin-resistance iron overload syndrome: an update]. 1858 23

Elevated levels of triglycerides and very low density lipoproteins (VLDL) are biochemical markers of metabolic syndrome and diabetes. VLDL from hypertriglyceridemic or diabetic patients increased the generation of plasminogen activator inhibitor-1 (PAI-1) from cultured vascular endothelial cells (EC). Susceptibility of VLDL to peroxidation was increased in diabetic patients. Heat shock factor-1 (HSF1) is implicated in the transcriptional regulation of PAI-1 induced by glycated low density lipoprotein (LDL). The present study examined the effects of oxidized VLDL (oxVLDL) on the expression of PAI-1 and HSF1 in cultured human EC and mouse embryo fibroblasts (MEF). OxVLDL modified by copper or iron ions increased the expression of PAI-1 and HSF1 in EC compared to VLDL or LDL. Butylated hydroxytulene inhibited oxVLDL-induced expression of PAI-1 and HSF1 in EC. OxVLDL increased the binding of HSF1 to PAI-1 promoter. Short interference RNA for HSF1 inhibited oxVLDL-induced PAI-1 expression in EC. OxVLDL stimulated the expression of PAI-1 from MEF of wild-type mice, but failed to increase PAI-1 expression in MEF of HSF1-knockout mice. The results indicate that oxVLDL increased PAI-1 expression, and HSF1 mediates the transcription of PAI-1 in cultured vascular EC or fibroblasts.
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PMID:Transcriptional regulation of plasminogen activator inhibitor-1 in vascular endothelial cells induced by oxidized very low density lipoproteins. 1859 60

We investigated the effect of body composition, nutrition, inflammation and iron status on insulin resistance in patients with long-term hemodialysis. We selected 43 stable end-stage chronic renal failure patients, on maintenance hemodialysis. We evaluated the nutritional status, body composition by subjective global assessment (SGA), anthropometric measurements (BMI and waist circumference), bioelectrical impedance analysis and biochemical parameters measurements [serum albumin, cholesterol, HDL-cholesterol, triglyceride, hematocrit, hemoglobin, iron, ferritin, calcium, phosphorus, intact parathormone (i-PTH), TNF-alpha, IL-6 and high sensitivity C-reactive protein]. All parameters were evaluated by comparisons between HOMA-IR tertiles, and after simple regression analysis, by backward multivariate regression analysis we identified independent variables for IR. As the tertile of HOMA-IR increased, serum level of glucose, insulin, and waist increascd, whereas HDL-cholesterol level decreased, or the prevalence of the metabolic syndrome increased across the tertiles of HOMA-IR. After adjustment for gender, age, hemodialysis duration, ferritin, phosphorus, waist and total fat percentages, multivariate regression analysis was performed and the association with HOMA-IR was still strong only for serum levels of iron and TNF-alpha. That explains 16% of the total variation in HOMA-IR. Our results suggest that the increase of IR in end-stage chronic renal failure patients on hemodialysis could be related to anemia and particularly to iron overload. Moreover, chronic inflammatory status with over-production of adipokine TNF-alpha participate in the pathogenesis of IR too. The present study demonstrated that adipokine TNF-alpha and serum iron participated as independent predictors in the pathogenesis of insulin resistance on long-term hemodialysis patients.
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PMID:The effect of nutritional status, body composition, inflammation and serum iron on the developement of insulin resistance among patients on long-term hemodialysis. 1892 54

C282Y homozygosity is the only common HFE genotype able to produce a complete hemochromatosis phenotype. However, its biochemical penetrance is incomplete (75% in men and 50% in women) and its clinical penetrance is low, especially in women (1 vs 25% in men). Environmental (e.g., diet, alcohol, drugs and metabolic syndrome) and genetic (digenism, common polymorphisms in the bone morphogenetic protein pathway involved in the regulation of hepcidin synthesis) explain a part of the variability of the C282Y homozygous phenotype. All other common HFE genotypes--including C282Y-H63D compound heterozygosity--are not associated with significant biochemical and clinical expression in the absence of comorbid factors (e.g., alcohol, diabetes or steatohepatitis). Better identification of acquired and genetic modifiers of iron burden and iron-related organ damage is needed to improve the preventive, diagnostic and therapeutic management of HFE hemochromatosis.
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PMID:Modifying factors of the HFE hemochromatosis phenotype. 1907 1

C282Y homozygosity is necessary (but insufficient in isolation) for the onset of hemochromatosis, as indicated by its low biochemical penetrance (75 % in men and 50 % in women) and clinical penetrance (25 % in men and 0 % in women). Factors modulating iron load may be acquired (diet, alcohol, metabolic syndrome, drugs, etc.) or, more importantly, genetic (digenism, polymorphism of genes involved in the regulation of hepcidin synthesis). Factors modulating iron-related organ damage include alcohol consumption, the metabolic syndrome, and the TGF-beta1 (hepatic fibrosis) and superoxide dismutase genes (cardiomyopathy). Further studies of these modifiers are needed to improve the management of C282Y homozygotes, at both the individual and the population levels.
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PMID:[Acquired and genetic factors influencing the penetrance of HFE haemochromatosis]. 1923 78

Histone H3 lysine 9 (H3K9) methylation is a crucial epigenetic mark of heterochromatin formation and transcriptional silencing. Recent studies demonstrated that most covalent histone lysine modifications are reversible and the jumonji C (JmjC)-domain-containing proteins have been shown to possess such demethylase activities. However, there is little information available on the biological roles of histone lysine demethylation in intact animal model systems. JHDM2A (JmjC-domain-containing histone demethylase 2A, also known as JMJD1A) catalyses removal of H3K9 mono- and dimethylation through iron and alpha-ketoglutarate dependent oxidative reactions. Here, we demonstrate that JHDM2a also regulates metabolic genes related to energy homeostasis including anti-adipogenesis, regulation of fat storage, glucose transport and type 2 diabetes. Mice deficient in JHDM2a (JHDM2a-/-) develop adult onset obesity, hypertriglyceridemia, hypercholesterolemia, hyperinsulinemia and hyperleptinemia, which are hallmarks of metabolic syndrome. JHDM2a-/- mice furthermore exhibit fasted induced hypothermia indicating reduced energy expenditure and also have a higher respiratory quotient indicating less fat utilization for energy production. These observations may explain the obesity phenotype in these mice. Thus, H3K9 demethylase JHDM2a is a crucial regulator of genes involved in energy expenditure and fat storage, which suggests it is a previously unrecognized key regulator of obesity and metabolic syndrome.
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PMID:Obesity and metabolic syndrome in histone demethylase JHDM2a-deficient mice. 1962 51

Environmental factors significantly influence the incidence and course of metabolic syndrome diseases such as diabetes and obesity. The content of elements in rainwater is an indirect indicator of their presence in dust suspended in the air. In this paper we present the relationships between the content of selected elements in rainwater and hospitalization frequencies due to diabetes (E10-E13) and obesity (E66). It was assumed that the hospitalization frequency could be taken as a measure of deterioration of the metabolic process in the course of diabetes and its complications. The observations concerned the population of Opole Voivodeship, Poland (one million inhabitants), distributed in small communities of 44,000 to 151,000 inhabitants during the years 2000-2002. In cases of diabetes E10-E13 for all subjects relevant correlation indicators were found for chromium (r = 0.71), cadmium (r = 0.65), and lead (r = 0.66). Borderline relevance was seen for copper (r = 0.57) and zinc (r = 056). For diabetic men the statistically relevant correlations were chromium (r = 0.79), lead (r = 0.77), cadmium (r = 0.74), copper (r = 0.70), chloride (r = 0.69), zinc (r = 0.68), and iron (r = 0.64). For women the only relevant correlations were chromium (r = 0.62) and cadmium (r = 0.55). No significant correlations were found in obese individuals of both sexes.
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PMID:The content of elements in rainwater and its relation to the frequency of hospitalization for diabetes and obesity in Opole Voivodship, Poland, during 2000-2002. 1980 27

Serum paraoxonase 1 (PON1) function has been associated with human cardiovascular disease. The projected mechanism postulates interaction of PON1 with lipoproteins and insulin signaling resulting in alterations in lipid homeostasis. Recently, PON2 was shown to directly regulate triglyceride accumulation in macrophages and PON1 was detected in the interstitial space of adipocytes. The aims of the present study were a) to examine the relationship of the PON1 function with serum parameters related to lipid homeostasis, and b) to examine a possible role of PON1 in the regulation of lipid composition in the human adipose tissue. Two important genetic variations with functional impact on PON1 activity in humans are the Q192R and the L55M. The present study evaluated the impact of the Q192R and the L55M polymorphisms in a cross-section of the population on the island of Crete, as regards to PON1 activity, plasma lipids/lipoproteins, parameters of the metabolic syndrome, and the fatty acid composition of the adipose tissue. We detected a significant association of the polymorphisms with blood pressure, fasting blood glucose, triglycerides, apolipoprotein B, serum iron, and homocysteine. Furthermore, a novel function is suggested for PON1 on the fatty acid composition in the adipose tissue through the positive association of the R allele with saturated fatty acid and of the Q allele with 20:5n3 fatty acid deposition.
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PMID:Paraoxonase 1 R/Q alleles are associated with differential accumulation of saturated versus 20:5n3 fatty acid in human adipose tissue. 2013 74


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