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 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Atherosclerosis is a chronic inflammatory disease associated with an elevation of inflammatory markers such as CRP -- a robust predictor of cardiovascular events. Inflammation also plays a pivotal role in the pathogenesis of osteoporosis. IL-6 proved to be the most important predictor of bone loss in the proximal femur. Adipocyte-produced inflammatory cytokines are the pathogenetic link between obesity and its metabolic consequences. The different components of the metabolic syndrome are at the same time well-established risk factors for osteoporosis. Physical training, weight loss, and a Mediterranean-style diet all have a proven cytokine-lowering effect. Contrary to muscle mass, adipose tissue if at all contributes only marginally to the preservation of bone. As a consequence, increasing lean body mass while reducing fat mass seems to be the most effective way to prevent both atherosclerosis and osteoporosis.
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PMID:[Obesity and osteoporosis]. 1591 26

Understanding the risk and pathogenesis of the numerous disorders including the insulin resistance/metabolic syndrome has changed meaningfully in the recent years. The remarkable similarity of the risk factors of cardiovascular disease, type 2 diabetes mellitus, obesity and atherogenic dyslipidemia induced to search for their pathophysiology. The aim of these examinations was to determine if the inflammatory state is a soil of the metabolic syndrome as in atherosclerosis? Increasing number of studies demonstrates a series of statistically significant correlations between the inflammatory markers and diseases present in the metabolic syndrome. It allows for the reasonable basis of hypothesis that chronic, mild inflammatory state underlies not only the cardiovascular disease, but also is the soil of the metabolic syndrome pathologies and its complications development. Both associations between the inflammatory mediators as CRP, fibrinogen, alpha1-glycoproteins, leptin, TNFalpha, PAI-1 and the metabolic syndrome variables, chiefly obesity, seem to suggest that both atherosclerosis and insulin resistance are the results of chronic activation of the nonspecific (innate) immune system. According to this hypothesis, daily stresses as traumas, infections and emotions would lead to primary immune and neuroendocrine systems alterations. By this manner, whole body metabolic disorders and metabolic syndrome component progressive reveal would approach. In this context, metabolic syndrome might be defined as an immunemetabolic disease.
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PMID:[Metabolic or immunometabolic syndrome?]. 1599 65

Type 2 diabetes is associated with a systemic low-grade inflammation. First data provided by cross-sectional studies from as early as the 1960s demonstrated elevated systemic levels of glycoproteins and acute-phase reactants and increased leukocyte counts in type 2 diabetes patients. Subsequently, prospective studies showed that elevated concentrations of several acute-phase proteins and cytokines are predictive of later type 2 diabetes. Immune gene variants in man and in animal models were found to affect insulin resistance and diabetes incidence. Antidiabetic treatment by medication, diet or physical activity results in a significant decrease of systemic immune mediator concentrations. Immunological analyses of the KORA Survey S4 (1999/2001) allowed us to show that levels of circulating acute-phase proteins like CRP and of IL-6 are highly correlated and associated not only with overt type 2 diabetes, but already with impaired glucose tolerance (IGT) pointing out a role of these mediators in the pathogenesis of type 2 diabetes. On the contrary, TNFalpha was neither coregulated with CRP nor associated with diabetes status. Our study therefore shows that type 2 diabetes is accompanied by a non-random and differential upregulation of components of the innate immunity and suggests that this inflammatory condition is involved in the aetiology of the disease. Future work will extend the range of analysed immune mediators to chemokines and will also investigate the association of immune markers with indices of obesity to elucidate the relevance of this traditional risk factor for low-grade inflammation.
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PMID:Inflammation and type 2 diabetes: results from KORA Augsburg. 1603 28

Severe acture pancreatitis (SAP), a multisystem disease, is characterized by multiple organ system failure and additionally by local pancreatic complications such as necrosis, abscess, or pseudocyst. The rate of mortality in SAP, which is about 20% of all cases of acute pancreatitis (AP), may be as high as 25%, as in infected pancreatic necrosis. The factors that influence mortality in different degrees are various. Etiology for the episode, age, sex, race, ethnicity, genetic makeup, severity on admission, and the extent and nature of pancreatic necrosis (sterile vs. infected) influence the mortality. Other factors include treatment modalities such as administration of prophylactic antibiotics, the mode of feeding (TPN vs. enteral), ERCP with sphincterotomy, and surgery in selected cases. Epidemiological studies indicate that the incidence of AP is increasing along with an increase in obesity, a bad prognostic factor. Many studies have indicated a worse prognosis in idiopathic AP compared to pancreatitis induced by alcoholism or biliary stone. The risk for SAP after ERCP is the subject of extensive study. AP after trauma, organ transplant, or coronary artery bypass surgery is rare but may be serious. Since Ranson reported early prognostic criteria, a number of attempts have been made to simplify or add new clinical or laboratory studies in the early assessment of severity. Obesity, hemoconcentration on admission, presence of pleural effusion, increased fasting blood sugar, as well as creatinine, elevated CRP in serum, and urinary trypsinogen levels are some of the well-documented factors in the literature. The role of appropriate prophylactic antibiotic therapy although still is highly controversial, in properly chosen cases appears to be beneficial and well accepted in clinical practice. Early enteral nutrition has gained much support and jejunal feeding bypassing the pancreatic stimulatory effect of it in the duodenum is desirable in selected cases. The limited role for endoscopic sphincterotomy in patients with demonstrated dilated CBD with impacted stone and evidence of impending cholangitis is well documented. Surgery in AP other than for removal of the gallbladder is often limited to infected pancreatic necrosis, pseudocysts, and pancreatic abscess and in some cases of traumatic pancreatitis with a ruptured duct system. The progress in the understanding of the role of cytokines will over us opportunities to use immunomodulatory therapies to improve the outcome in SAP.
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PMID:Factors influencing mortality in acute pancreatitis: can we alter them? 1663 13

Abnormal glucose tolerance is associated with subclinical chronic inflammation in patients with type 2 diabetes. The aim of this study was to investigate whether plasma concentrations of inflammatory markers are associated with measures of obesity, insulin sensitivity, and hyperglycemia. IL-6, adiponectin, CRP, and IL-10 plasma concentrations were evaluated in 142 patients with a wide range of obesity, insulin sensitivity and glucose tolerance. In parallel with the impairment of glucose tolerance, there was a significant increase in IL-6, and CRP, and a significant decrease in adiponectin and IL-10 plasma concentrations. There were significant correlations between the plasma concentrations of all inflammatory markers and % body fat, insulin sensitivity, and fasting plasma glucose. However, multivariate linear regression analysis identified insulin sensitivity as determined by glucose infusion rate during the steady state of an euglycemic-hyperinsulinemic clamp as the strongest predictor of adiponectin, CRP, IL-6, and IL-10 plasma concentrations. In addition, fasting plasma glucose was a significant determinant of adiponectin, CRP, and IL-6 plasma concentrations, whereas body fat content was only a significant predictor of CRP plasma concentration. In conclusion, our data suggest that abnormal inflammatory markers in patients with type 2 diabetes are primarily related to decreased insulin sensitivity.
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PMID:Association of interleukin-6, C-reactive protein, interleukin-10 and adiponectin plasma concentrations with measures of obesity, insulin sensitivity and glucose metabolism. 1623 56

This paper outlines the rationale and design of the Study of the Effects of Diet on Metabolism and Nutrition (STEDMAN) weight loss project, in which detailed biologic profiling of three hundred and fifty obese individuals (body mass index (BMI): 30-50 kg/m(2)) will be conducted as they lose weight via seven distinct interventions. These profiles will be compared to those of fifty normal, healthy, control participants (BMI: 18.5-24.9 kg/m(2)). The interventions include the following: Roux-en-Y gastric bypass surgery, dietary interventions of differing macronutrient composition and diverse pharmacologic interventions. Outcome variables include eight conventional metabolites and CRP measured by standard clinical chemistry techniques, twenty hormones of energy balance and fuel homeostasis measured by radioimmunoassay (RIA) or by enzyme-linked Immunosorbent assay (ELISA), ten pro- and anti-inflammatory cytokines measured using Luminex xMAP technology, one hundred and one intermediary metabolites measured by targeted mass-spectrometry-based methods, and physiologic variables such as body composition measured by dual energy X-ray absorptiometry (DEXA), air displacement plethysmography, and abdominal computerized tomography (CT), insulin sensitivity measured by intravenous glucose tolerance test (IV-GTT) and metabolic rate measured by indirect calorimetry. Results from this study will expand our knowledge of the biology of obesity and weight regulation and may lead to targeted strategies for its treatment and control.
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PMID:The Study of the Effects of Diet on Metabolism and Nutrition (STEDMAN) weight loss project: Rationale and design. 1623 28

It now appears that, in most obese patients, obesity is associated with a low-grade inflammation of white adipose tissue (WAT) resulting from chronic activation of the innate immune system and which can subsequently lead to insulin resistance, impaired glucose tolerance and even diabetes. WAT is the physiological site of energy storage as lipids. In addition, it has been more recently recognized as an active participant in numerous physiological and pathophysiological processes. In obesity, WAT is characterized by an increased production and secretion of a wide range of inflammatory molecules including TNF-alpha and interleukin-6 (IL-6), which may have local effects on WAT physiology but also systemic effects on other organs. Recent data indicate that obese WAT is infiltrated by macrophages, which may be a major source of locally-produced pro-inflammatory cytokines. Interestingly, weight loss is associated with a reduction in the macrophage infiltration of WAT and an improvement of the inflammatory profile of gene expression. Several factors derived not only from adipocytes but also from infiltrated macrophages probably contribute to the pathogenesis of insulin resistance. Most of them are overproduced during obesity, including leptin, TNF-alpha, IL-6 and resistin. Conversely, expression and plasma levels of adiponectin, an insulin-sensitising effector, are down-regulated during obesity. Leptin could modulate TNF-alpha production and macrophage activation. TNF-alpha is overproduced in adipose tissue of several rodent models of obesity and has an important role in the pathogenesis of insulin resistance in these species. However, its actual involvement in glucose metabolism disorders in humans remains controversial. IL-6 production by human adipose tissue increases during obesity. It may induce hepatic CRP synthesis and may promote the onset of cardiovascular complications. Both TNF-alpha and IL-6 can alter insulin sensitivity by triggering different key steps in the insulin signalling pathway. In rodents, resistin can induce insulin resistance, while its implication in the control of insulin sensitivity is still a matter of debate in humans. Adiponectin is highly expressed in WAT, and circulating adiponectin levels are decreased in subjects with obesity-related insulin resistance, type 2 diabetes and coronary heart disease. Adiponectin inhibits liver neoglucogenesis and promotes fatty acid oxidation in skeletal muscle. In addition, adiponectin counteracts the pro-inflammatory effects of TNF-alpha on the arterial wall and probably protects against the development of arteriosclerosis. In obesity, the pro-inflammatory effects of cytokines through intracellular signalling pathways involve the NF-kappaB and JNK systems. Genetic or pharmacological manipulations of these effectors of the inflammatory response have been shown to modulate insulin sensitivity in different animal models. In humans, it has been suggested that the improved glucose tolerance observed in the presence of thiazolidinediones or statins is likely related to their anti-inflammatory properties. Thus, it can be considered that obesity corresponds to a sub-clinical inflammatory condition that promotes the production of pro-inflammatory factors involved in the pathogenesis of insulin resistance.
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PMID:Recent advances in the relationship between obesity, inflammation, and insulin resistance. 1661 57

Elevated plasma concentration of C-reactive protein has emerged as an important predictor of future cardiovascular diseases and metabolic abnormalities in apparently healthy individuals. Obese individuals tend to have elevated C-reactive protein concentrations. Weight loss induces a change in this protein, and single nucleotide polymorphisms in regulating genes might affect this change, since C-reactive protein concentration is known to be approximately 40-50% heritable. Our aim was to study the association between the IL6 -174(G/C), IL1B +3,954(C/T) and CRP +1,059(G/C) single nucleotide polymorphisms, and CRP concentrations in obese men during a weight reduction program. We genotyped 72 obese men who had participated in a weight reduction program. Their C-reactive protein concentrations, interleukin-6 levels and fat mass were determined at two time points: at baseline and after weight reduction (after 2 months). After weight reduction, the mean weight loss was 14.3 kg. Median C-reactive protein concentrations decreased, after weight reduction, from 1.72 to 1.22 mg/l (p < 0.02). The baseline C-reactive protein concentration did not differ between the IL6-174(G/C) genotypes, but after weight loss, concentrations differed (p = 0.03 Kruskal-Wallis test); the highest concentration was found in the CC genotype (CC 1.01 versus GG 1.93 mg/l, p = 0.007 ANOVA post-hoc test). This change in concentration was associated with the IL6-174(G/C) genotype (p = 0.01, Kruskal-Wallis test), being least in the CC genotype. The other single nucleotide polymorphisms studied were not associated with CRP concentrations. Our results show that, at baseline, there is no difference in C-reactive protein concentrations among the different IL6-174(G/C) genotypes, but after weight loss the CC genotype is associated with highest C-reactive protein concentrations, resulting from the fact that C-reactive protein seems not to decrease with weight loss in this genotype.
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PMID:Association of the IL6-174(G/C) polymorphism with C-reactive protein concentration after weight loss in obese men. 1684 32

The metabolic syndrome (MS) is a cluster of metabolic abnormalities leading to increased risk for cardiovascular diseases and diabetes type 2. Its prevalence is increasing with aging. There exists actually an epidemic of MS. Visceral obesity and the resulting insulin resistance (IR) are the major determinant in the development of the MS. Abdominal obesity results in a low grade inflammation via the adipose tissue and macrophages secreted adipokines. This inflammation, via the generated pro-inflammatory molecules, interferes with the normal insulin signalling and thus contributes to the etiopathogenesis of the MS. Large clinical studies showed that CRP is increased in obese subjects and concomitantly to the number of existing component of the MS. Treatment of the MS is aimed to improve the IR by lifestyle changes including exercise and diet alone or in combination with medication targeting the individual components but having also anti-inflammatory actions. More research is needed to bring new therapies to be able to decrease the incidence and prevalence of the MS among the population and thus increasing their quality of life.
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PMID:The metabolic syndrome. 1690 49

The discovery of leptin in 1994 led to research into the participation of that hormone in the development of many pathologic states. This article presents current knowledge on the role of leptin, in the pathogenesis of cardiovascular diseases. Leptin is a circulating peptide hormone produced by adipose cells which plays the main role in the regulation of metabolism in humans. Leptin, in the physiological range of plasma levels, is a regulator of cardiovascular function. In fact, higher plasma leptin levels as well as insulin resistance are directly correlated with adiposity. Hyperleptinemia accompanying obesity leads to many pathologic states: stimulation in platelets aggregation, tachycardia, hypertension, increases in plasma levels of pro-thrombotic factors and in levels of CRP and ET-1. In a multicenter study, hyperleptinemia turned out to be the main risk factor responsible for the ischemic disease, especially acute myocardial infarction. Elevated plasma leptin levels play a key role in increased incidence of cardiovascular mortality in obese.
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PMID:[Leptin--adipose tissue hormone and its role in cardiovascular diseases]. 1700 77


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