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 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The prevalence of obesity has been increasing dramatically in the last decades in the whole world, not only in industrialized countries but also in developing areas. A major complication of obesity is insulin resistance and type 2 diabetes. Diabetes is also rapidly increasing world-wide--reaching a prevalence in adults of approx. 5-6% in Central Europe and in the US, and more than 50% in specific, genetically prone populations. This article reviews pathogenetic mechanisms linking obesity and type 2 diabetes. Emphasis is placed on the observation that excessive amounts of adipocytes are associated with an impairment of insulin sensitivity, a key feature of the "metabolic syndrome". This is a cluster of metabolic abnormalities such as type 2 diabetes, hypertension and dyslipidemia; all of them are enhanced by the presence of visceral (abdominal) obesity and all contribute to the increased cardiovascular risk observed in these patients. Besides release of free fatty acids, adipocytes secrete substances that contribute to peripheral insulin resistance, including adiponectin, resistin, TNF-alpha and interleukin 6. Increased turnover of free fatty acids interferes with intracellular metabolism of glucose in the muscle, and they exert lipotoxic effect on pancreatic beta-cells. The pre-receptor metabolism of cortisol is enhanced in visceral adipose tissue by activation of 11 beta-hydroxysteroid dehydrogenase type 1. A new class of anti-diabetic drugs (thiazolidinediones, or glitazones) bind to peroxisome proliferator activated receptor (PPAR-gamma) and lower thereby plasma free fatty acids and cytokine production in adipocytes, in addition to a decrease of resistin and an increase in adiponectin observed in animals, resulting in an overall increase in insulin sensitivity and in an improvement of glucose homeostasis. However, the first step to avoid insulin resistance and prevent the development of diabetes should be a reduction in body weight in overweight subjects, and an increase in physical activity. There are now three published randomized controlled trials demonstrating that in high risk individuals, life style changes with modest weight lost, associated with diminished fat intake and an increase in fruit and vegetable consumption result in marked inhibition of the transition from the prediabetic state to manifest type 2 diabetes.
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PMID:From obesity to diabetes. 1724 79

The increasing prevalence of obesity world-wide has an expected consequent increase in diabetes and cardiovascular disease. Less attention has been paid to the effect of obesity on dementia. This overview discusses methodological issues related to the epidemiologic study of obesity and dementia, reviews results of long-term prospective studies, and briefly considers possible mechanisms for an obesity-dementia association. At least six cohort studies of 18 to 32 years duration confirm that overweight middle-aged or older adults are at increased risk of dementia in later life. In many of these studies, the association persisted after adjusting for classical cardiovascular risk factors. A few epidemiologic studies (and more laboratory studies not reviewed here) suggest biomarkers such as C-reactive protein, interleukin 6, and leptin may explain part of the obesity-dementia connection. If any of these factors are in the causal pathway to dementia, their reversal or prevention by weight control would have huge public health importance.
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PMID:An introduction to obesity and dementia. 1743 Feb 30

Adrenal incidentalomas (AIs) have been associated with an increased incidence of several cardiovascular risk factors, similar to overt Cushing syndrome. Data about the involvement of the adipokines in the development of insulin resistance and atherosclerosis in AI are completely lacking. The aim of the present study was to evaluate plasma interleukin 6 (IL-6), adiponectin, resistin, tumor necrosis factor alpha (TNF-alpha), and monocyte chemoattractant protein 1 (MCP-1) levels in patients with AI. Plasma IL-6, adiponectin, resistin, TNF-alpha, and MCP-1 levels were measured in 20 healthy subjects (6 males; 14 females; age, 58.5 +/- 2.2 years; body mass index, 28.1 +/- 0.9 kg/m(2)) and in 20 patients (5 males; 15 females; age, 57.9 +/- 2.0 years; body mass index, 28.0 +/- 0.8 kg/m(2)) with AI and typical computed tomographic features of cortical adenoma, who were not affected by diabetes mellitus, hypertension, or other relevant diseases. All patients underwent anthropometric measurements and determination of basal corticotropin, cortisol, and urinary free cortisol excretion. Overnight dexamethasone test and 250-microg corticotropin test were performed in all cases. A subclinical Cushing syndrome was found in 3 patients, whereas the others had apparently nonfunctioning masses. Plasma IL-6, adiponectin, resistin, TNF-alpha, and MCP-1 levels were higher in patients than in controls (64.4 +/- 2.8 vs 5.5 +/- 0.6 pg/mL, 13.7 +/- 1.3 vs 3.6 +/- 0.5 microg/mL, 12.5 +/- 1.9 vs 5.1 +/- 0.2 ng/mL, 27.0 +/- 1.5 vs 22.2 +/- 1.5 pg/mL, 172.5 +/- 20.0 vs 104.4 +/- 19.5 pg/mL, respectively; P < .05) and apparently not affected by the presence of visceral obesity. Plasma IL-6 levels were negatively correlated with urinary free cortisol (r = -0.461, P < .05), and TNF-alpha levels were positively correlated with cortisol after the administration of 1 mg dexamethasone (r = 0.636, P < .01). In conclusion, patients with AI may show increased levels of adipokines (apparently not related to the presence of diabetes, hypertension, or obesity), which may be affected by the presence of the adrenal adenoma. For some adipokines, a direct production from the adrenal gland may be hypothesized even if other studies are needed to better investigate the role of adipokines in states of altered cortisol secretion.
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PMID:Adipokine levels and cardiovascular risk in patients with adrenal incidentaloma. 1744 45

Adiponectin can improve both glucose metabolism and insulin resistance via the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. Activated AMPK phosphorylates a variety of intracellular proteins, including acetyl coenzyme A carboxylase (ACC) that is involved in fatty acid oxidation. Adenosine monophosphate-activated protein kinase increases glucose transport by stimulating the translocation of glucose transporter 4 (GLUT4) to the sarcolemma in the heart. Adiponectin exerts its effect through adiponectin receptors, which are predominantly expressed in the liver and skeletal muscle. It is unknown whether the cardiac expression of adiponectin and its receptors is changed in diabetic rats. In the present study, we investigated the protein expression of adiponectin and its receptors in streptozotocin (STZ)-induced diabetic rat hearts. We also explored whether the levels of AMPK, ACC, and GLUT4 will be altered with the changed adiponectin and its receptors in STZ diabetic rat hearts. Plasma and cardiac adiponectin levels were measured by radioimmunoassay. Plasma and cardiac interleukin 6 and plasma tumor necrosis factor alpha (TNF-alpha) were assayed by enzyme-linked immunosorbent assay. Cardiac adiponectin receptors, AMPK-alpha, ACC, GLUT4, and TNF-alpha were analyzed by Western blot in control and STZ diabetic rats. The plasma adiponectin level was decreased, but the cardiac protein expression of adiponectin receptor 1 was increased in diabetic rats. There was no difference in the cardiac adiponectin level and the cardiac adiponectin receptor 2 protein expression between control and diabetic rats. The phosphorylation of AMPK-alpha and protein expression of GLUT4 were decreased, but the phosphorylation of ACC was unchanged in diabetic rat hearts. Plasma and cardiac levels of interleukin 6 and TNF-alpha were increased in diabetic rats. In conclusion, STZ-induced diabetes up-regulates adiponectin receptors in the heart. Despite an increase in cardiac adiponectin receptor 1 expression, there is an increased cardiac inflammatory response and a decreased GLUT4 protein expression associated with a reduction in circulating adiponectin.
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PMID:Cardiac expression of adiponectin and its receptors in streptozotocin-induced diabetic rats. 1788 46

Chronic kidney disease (CKD) has reached epidemic proportions in the last few years, generating an emergent public health problem. Common risk factors for CKD and cardiovascular disease (CVD) are now well known resulting in a high prevalence rate of cardiovascular events which are the main cause of death in CKD patients. Development of accelerated atherosclerosis is related to traditional risk factors such as diabetes mellitus, arterial hypertension, dislipidemia and smoking, but recently other non traditional factors were found to be significantly associated with cardiovascular mortality, including inflammation, oxidative stress, endothelial dysfunction and uremia, even at early stages of CKD. Inflammatory markers such as C-reactive protein, interleukin 6 and fibrinogen are all correlated with cardiovascular death. The MIA syndrome is characterized by the association between inflammation, malnutrition and accelerated atherosclerosis, a condition commonly found in uremic patients, which is related to the genesis of CVD. Other important factors are the high level of oxidative stress, expressed by oxidized lipids, proteins and carbohydrates (AGES) (Advanced Glycation End Products), which cause tissue damage and endothelial dysfunction, that is aggravated by the uremic environment and other factors. These alterations are the basis for the pathogenic process of atherosclerosis and CVD in CKD patients, contributing to their high morbidity/mortality. This article is an updated review of the mechanisms of inflammation and oxidative stress and their relation to atherosclerosis in CKD.
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PMID:[Chronic renal disease, inflammation and atherosclerosis: new concepts about an old problem]. 1795 55

Chronic inflammation has been linked with an increased risk of type 2 diabetes and cardiovascular disease. As an endocrine and inflammatory organ, adipose tissue is an important source of circulating pro-inflammatory cytokines. Current evidence strongly supports that chronic inflammation is associated with enlarged body fat mass. Moreover, inflammation is independently linked with abdominal, especially visceral fat mass, possibly due to the regional variation in adipose tissue cytokine production. In addition to pharmacological approaches, lifestyle modifications have been advocated for the treatment of chronic inflammation. A number of studies have indicated that either weight loss via energy restriction, or energy restriction plus other strategies (aerobic exercise, behavioral counseling, and liposuction), could reduce chronic inflammation. While the amount of weight loss tends to be important, exercise and other strategies may have additional effects. A few studies have reported weight loss effects on adipose tissue cytokine production. Weight loss reduces subcutaneous adipose tissue production of pro-inflammatory cytokines (i.e. interleukin 6, tumor necrosis factor alpha) and increases adipose expression of anti-inflammatory cytokines (i.e. interleukin 10, interleukin 1 receptor antagonist). More studies are needed to investigate the role of regional adipose tissue cytokine production in regulation of inflammation and the modulating effects of weight loss.
Curr Diabetes Rev 2006 Feb
PMID:Chronic inflammation: role of adipose tissue and modulation by weight loss. 1822 Jun 15

The metabolic syndrome (MetS) is associated with an increased incidence of diabetes and coronary heart disease. Postprandial lipemia is a prominent feature of dyslipidemia in both type 2 diabetes mellitus and MetS and is also associated with coronary heart disease. Oxidative stress and inflammation are pivotal in all stages of atherosclerosis; however, there is a paucity of data on postprandial oxidative stress and inflammation in subjects with MetS. Thus, the primary aim of this study was to compare the postprandial effects of an energy-dense, high-fat, fast-food-style (FFS) meal with an American Heart Association (AHA)-recommended heart-healthy meal on biomarkers of oxidative stress and inflammation in subjects with MetS. A total of 11 subjects with MetS completed the study. Glucose levels were significantly increased 2 hours after both FFS and AHA diets (P < .0001), and high-density lipoprotein cholesterol levels significantly decreased in FFS diet but not in the AHA diet (P for interaction < .05). Total triglyceride levels significantly increased postprandially only in the FFS meal but not in the AHA meal (P for interaction = .03). Plasma thiobarbituric acid reactive substances and malondialdehyde + hydroxynonenal increased significantly with time in both dietary groups, and the postprandial increase was greater in the FFS diet compared to the AHA diet (P < .0005). Serum high-sensitivity C-reactive protein, interleukin 6, and tumor necrosis factor levels did not change with time or dietary treatment. The postprandial increase in interleukin 1b was significantly higher with the FFS meal, thus resulting in significant differences between both treatments (P for interaction = .03). Thus, in subjects with MetS, consumption of an energy-dense, fatty meal (FFS breakfast) results in increased postprandial oxidative stress compared to a heart-healthy meal (AHA).
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PMID:High-fat, energy-dense, fast-food-style breakfast results in an increase in oxidative stress in metabolic syndrome. 1850 72

Today, eggs with an increased content of -3 fatty acids are available but there are few publications on the effects of consumption of such eggs on the lipoproteins and acute phase markers in humans. The aim of the present study was to evaluate the effects of consumption of standard eggs and -3 enriched eggs on lipoproteins, glucose and inflammation markers. Nineteen healthy volunteers consumed one extra egg per day of either standard eggs or omega-3 enriched eggs in a double-blind, cross-over study. The duration of each period was 1 month. The effects of the different egg diets on apolipoprotein A1 and B (Apo A1 and B), lipoprotein (a), creatinine, cystatin C, C-reactive protein, serum amyloid protein A, interleukin 6, triglycerides, glucose, total-, high-density lipoprotein and low-density lipo-protein cholesterol concentrations were analyzed. Addition of one regular egg per day to the normal diet had no negative impact on blood lipids or inflammation markers. Consumption of omega-3 enriched eggs resulted in higher levels of ApoA1, lower ApoB/ApoA1 ratio and lower plasma glucose. These effects have been associated in previous studies with a reduced risk for cardiovascular mortality and diabetes.
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PMID:Biochemical effects of consumption of eggs containing omega-3 polyunsaturated fatty acids. 1899 Dec 44

Matrix metalloproteinases (MMPs) play a key role in periodontal disease. Although it is known that macrophages and fibroblasts are co-localized and express MMPs in the diseased periodontal tissue, the effect of interaction between these two cell types on MMP expression has not been well elucidated. Furthermore although it is known that diabetes is associated with accelerated periodontal tissue destruction, it remains unknown whether hyperglycemia, a major metabolic abnormality in diabetes, regulates MMP expression by affecting the cross-talking between fibroblasts and macrophages. In this study, human gingival fibroblasts and U937 macrophages were cocultured in a two-compartment transwell culture system, and the cells were treated with normal or high glucose. We found that coculture of fibroblasts and U937 macrophages led to an augmentation of MMP-1 expression by U937 macrophages, and high glucose further enhanced this augmentation. Similar observations were also made in the coculture of fibroblasts and human primary monocytes. We also found that interleukin 6 (IL-6) released by fibroblasts was essential for the augmentation of MMP-1 expression by U937 macrophages. Furthermore our results showed that high glucose, IL-6, and lipopolysaccharide had a synergistic effect on MMP-1 expression. Finally our study indicated that MAPK pathways and activator protein-1 transcription factor were involved in the coculture- and high glucose-augmented MMP-1 expression. In conclusion, this study demonstrates that IL-6 derived from fibroblasts is essential for MMP-1 up-regulation by cross-talking between fibroblasts and U937 macrophages exposed to high glucose, revealing an IL-6-dependent mechanism in MMP-1 up-regulation.
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PMID:Interleukin-6 released from fibroblasts is essential for up-regulation of matrix metalloproteinase-1 expression by U937 macrophages in coculture: cross-talking between fibroblasts and U937 macrophages exposed to high glucose. 1930 87

Both insulin resistance and decreased insulin secretion are major features of the pathophysiology of type 2 diabetes. Inflammatory pathways are found to be critical in mechanisms underlying insulin resistance, which is a major determinant of increased risk of cardiovascular complications in type 2 diabetes, and so, it is a potential therapeutic target. Thiazolidinediones (e.g., rosiglitazone) act primarily as insulin sensitizers and were discovered to have anti-inflammatory effects leading to reevaluation of their potential use in treatment of diabetes. Acetyl salicylic acid (aspirin), which is currently recommended for cardiovascular disease (CVD) or even CVD risk factors, is shown to ameliorate diabetic process. This work aimed to study correlation between homeostasis model assessment estimate of insulin resistance (HOMA-IR) with serum levels of inflammatory markers tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), C-reactive protein (CRP), and free fatty acids (FFAs) in experimental model of induced type 2 diabetes in rats, with evaluation of effects of rosiglitazone and aspirin (low or high dose), alone or in combination. There is significant elevation of insulin resistance and serum levels of fasting glucose, insulin, TNF-alpha, IL-6, CRP, and FFAs in the diabetic group when compared to the normal group, with positive significant correlation between levels of each of TNF-alpha, IL-6, CRP, and FFAs with insulin resistance (HOMA-IR). Administration of rosiglitazone, low-dose aspirin, or high-dose aspirin to diabetic rats caused nonsignificant lowering in insulin level with significant reduction of levels of other parameters when compared to the diabetic group. Also, there is no significant difference in the measured parameters between diabetic rats administered a combination of rosiglitazone with high-dose aspirin and those administered a combination of rosiglitazone with low-dose aspirin. It was concluded that aspirin and rosiglitazone offer unique approaches for treatment of type 2 diabetes due to their insulin-sensitizing and anti-inflammatory properties, and their combination was found to provide augmented beneficial effects. Also, in view of the potential dose-dependent adverse effects of aspirin, with no achievement of further benefit by high dose in this study, it is strongly recommended to use low-dose aspirin as a safe and effective medication for diabetes.
J Diabetes Complications
PMID:Effects of rosiglitazone and aspirin on experimental model of induced type 2 diabetes in rats: focus on insulin resistance and inflammatory markers. 1932 14


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