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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was performed to compare concentrations of pro-inflammatory cytokines, such as interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha) as well as acute-phase protein, such as C-reactive protein (CRP) between subjects with normal glucose tolerance (NGT) and impaired glucose tolerance (IGT). The purpose of this study was to verify whether the pro-inflammatory cytokine-induced acute-phase response is a pathogenic mechanism in type 2 diabetes in elderly Korean women. A total of 1737 elderly subjects aged over 60 years participated in a population based study in Seoul, Korea (SWS Study 1999). Amongst them, a total of 232 non-smoking and non-diabetic female subjects aged 60-89 years was randomly selected and compared with each other. Higher serum high-sensitivity CRP (hs-CRP) concentrations were shown in subjects with IGT than those with normal glucose tolerance (median 1.2 versus 0.9, P < 0.05). Moreover, a relationship between serum hs-CRP concentrations and many components of the metabolic syndrome were detected. Serum pro-inflammatory cytokine IL-6 or TNF-alpha concentrations, however, were neither increased in subjects with IGT nor closely correlated with the components of the metabolic syndrome. In multiple regression analysis with stepwise selection method using hs-CRP as a dependent variable, it was found that white blood cell (WBC) counts, body mass index (BMI), fasting insulin, post-load 2h glucose, hematocrit and LDL cholesterol were significant independent variables. Our study confirms that increased acute-phase reaction is associated with impaired glucose tolerance and the metabolic syndrome in elderly Korean women. However, the hypothesis that pro-inflammatory cytokine-induced systemic inflammation is an early metabolic defect prior to onset of type 2 diabetes, is not supported in our study of elderly Korean women.
Diabetes Res Clin Pract 2004 May
PMID:Comparison of serum concentrations of C-reactive protein, TNF-alpha, and interleukin 6 between elderly Korean women with normal and impaired glucose tolerance. 1506 2

Numerous signals convey information about body fat status from the periphery to the brain areas that control energy homeostasis so that, throughout life, body weight remains nearly stable. These signals mainly originate, either from the adipose tissue, like leptin and to a lesser extent interleukin 6, or from the pancreas, like insulin and amylin. These factors circulate in proportion to body fat mass and they are referred to as "adiposity signals". It is well established, at least for leptin and insulin, that they enter the brain from the plasma where they induce/repress a network of important neuropeptide regulators of energy intake and expenditure. Beside these endocrine signals, a growing amount of literature show data relative to adipocyte-derived molecules, most of them belonging to the cytokine family, like IL6, TNFalpha, IL8, IL10 whose secretion also correlates with body fat mass and that may locally regulate fat mass expansion. Others, like adiponectin, are negatively correlated with body fat mass. These "adiposity molecules" have already been involved in insulin resistance associated with obesity and inflammatory process. They may participate to a complex inter organ dialogue. In this review, we will synthesize data relative to the role played by insulin, leptin and amylin, either alone or through a cross talk, in "energy level sensing" at the brain level. Furthermore, we will develop how "adiposity molecules" through their paracrin and/or autocrin action may contribute to maintain fat mass expansion, therefore representing new adiposity molecules per se. Lastly, since any distortion in the metabolic circuitry of energy homeostasis is susceptible to lead to a pathological status like obesity, the impact of known genetic polymorphisms in genes encoding the adiposity signals will be discussed.
Diabetes Metab 2004 06
PMID:Adiposity signals, genetic and body weight regulation in humans. 1522 73

Little is known about the relationship between intramyocellular lipid (IMCL) and coronary artery disease (CAD)/non-insulin-dependent diabetes mellitus risk factors. The aim of the study was to examine the relationship between IMCL and CAD/non-insulin-dependent diabetes mellitus risk factors in healthy male (n = 9) and female (n = 10) subjects with similar norm-based aerobic fitness and body composition. Nineteen volunteers (21-36 years) completed health and physical activity questionnaires, cardiovascular and body composition evaluation, and assessment of thigh IMCL using proton magnetic resonance spectroscopy. Outcome measures were blood pressure, total cholesterol, high-density lipoprotein cholesterol, C-reactive protein, interleukin 6, tumor necrosis factor alpha (TNF-alpha), homocysteine, insulin resistance (IR), percentage of body fat, waist-to-hip ratio, physical activity levels, and cardiovascular fitness. Analysis of variance was used for group comparisons. Correlation analyses were used to determine association between variables, and stepwise regression was used to determine predictive variables of IR. Women had 2-fold higher IMCL and greater IR than men (P < .05). Men had greater plasma homocysteine and interleukin 6 concentration (P < .05) as well as stronger correlations with CAD risk factors than female subjects. Correlation analyses using all subjects revealed a significant relationship between IMCL and waist-to-hip ratio, body weight, percentage of body fat, and IR. In the regression analysis, age, IMCL, and TNF-alpha were the strongest predictors of IR (R2 = 0.62, P < .01). Our results suggest that female subjects, matched for age and fitness, have higher IMCL compared with their male counterparts. IMCL was correlated with several CAD and prediabetes markers in both male and female subjects. In the final regression model, age, IMCL, and TNF-alpha were the strongest predictors of IR. Future studies with larger sample sizes are warranted.
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PMID:Cardiovascular/non-insulin-dependent diabetes mellitus risk factors and intramyocellular lipid in healthy subjects: a sex comparison. 1632 31

Inflammation plays a central role in the pathogenesis of acute coronary syndromes, the prevalence of which is increased in individuals with diabetes. Monocytes and macrophages, T cells and mast cells contribute to the initiation, development and rupture of atherosclerotic plaques by synthesising a variety of pro-inflammatory cytokines, including interleukin 1beta, interleukin 6 and tumour necrosis factor alpha. Cytokines upregulate endothelial cell adhesion molecules, recruit leukocytes and induce smooth muscle cell migration and proliferation. Cytokines act systemically to initiate the acute phase response, up-regulating proteins involved in inflammation and haemostasis and resulting in a pro-inflammatory and pro-thrombotic state. Expression of tissue factor by inflammatory cells potently induces thrombus formation upon plaque rupture, leading to acute coronary syndromes. Inflammatory biomarkers, including C-reactive protein, complement proteins, interleukin 6 and white blood cell count, predict development of acute coronary syndromes. C-reactive protein has been widely studied and consistently predicts future acute coronary syndrome events.
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PMID:Inflammation, thrombosis and acute coronary syndromes. 1633 92

The aim of the present study was to investigate the factors contributing to the concentration of serum C-reactive protein in type 2 diabetic patients. One hundred and 48 Japanese type 2 diabetic patients were studied. In conjunction with C-reactive protein (CRP), BMI, systolic and diastolic blood pressure, glycosylated hemoglobin (HbA1c), fasting concentrations of plasma glucose, and serum lipids (triglycerides, HDL cholesterol, and total cholesterol), interleukin 6 (IL-6), and leptin were measured. Insulin resistance was also estimated by the insulin resistance index of homeostasis model assessment (HOMA-IR). With univariate analysis, serum CRP was positively correlated with BMI (r=0.281, P<0.001), diastolic blood pressure (r=0.176, P=0.048), triglycerides (r=0.293, P<0.001), HOMA-IR (r=0.294, P<0.001), IL-6 (r=0.323, P<0.001), and leptin (r=0.330, P<0.001), and negatively correlated with HDL cholesterol (r=-0.181, P=0.028). Multiple regression analyses showed that serum CRP was independently predicted by the level of IL-6 (P<0.001, F=4.04), leptin (P<0.001, F=7.09), and triglycerides (P<0.001, F=15.13), which explained 17.6% of the variability of serum CRP concentration in these patients. From these results, it can be concluded that along with IL-6 and triglycerides, leptin is another important independent factor that is associated with CRP in Japanese type 2 diabetic patients.
Diabetes Res Clin Pract 2007 Jan
PMID:Leptin, triglycerides, and interleukin 6 are independently associated with C-reactive protein in Japanese type 2 diabetic patients. 1676 62

Endothelial dysfunction is associated with several vascular conditions as atherosclerosis, hypertension, hyperlipidemia and diabetes mellitus. In all these conditions insulin resistance (IR) is present. Cytokines are low molecular weight proteins with several endocrine and metabolic functions that participate of inflammation and immune response. Several of these cytokines are independent risk factors for cerebrovascular and coronary artery disease. The major sources of cytokines (adipokines) are the visceral and subcutaneous adipose tissues. Thus, increased adipose tissue mass is associated with alteration in adipokine production as over expression of tumor necrosis factor alpha, interleukin 6, plasminogen activator inhibitor 1, and under expression of adiponectin in adipocite tissue. The pro-inflammatory status associated with these changes provides a potential link between IR and endothelial dysfunction, the early stage in the atherosclerotic process, in obese individuals, and type 2 diabetic patients. Reduction of adipose tissue mass through weight reduction in association with exercise reduces TNF-alpha, IL-6, and PAI-1, increases adiponectin, and is associated with improved insulin sensitivity and endothelial function. This review will focus on the evidence for regulation of endothelial function by insulin and the adypokines such as adyponectin, leptin, resistin, IL-6 and TNF-alpha. Interaction between insulin signaling and adypokines will be discussed, as well as the concept that aberrant adypokine secretion in IR and/or obesity impairs endothelial function and contributes further to reduce insulin sensitivity.
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PMID:[Cytokines, endothelial dysfunction, and insulin resistance]. 1676 96

Inflammation is frequently present in the visceral fat and vasculature in certain patients with cardiovascular disease (CVD) and/or adult onset Diabetes Mellitus Type II (NIDDM). An hypothesis is presented which argues that repeated acute or chronic psychologically stressful states may cause this inflammatory process. The mediators are the major stress hormones norepinephrine (NE) and epinephrine (E) and cortisol together with components of the renin-angiotensin system (RAS), the proinflammatory cytokines (PIC), as well as free fatty acids (ffa), the latter as a result of lipolysis of neutral fat. NE/E commence this process by activation of NF(kappa)B in macrophages, visceral fat, and endothelial cells which induces the production of toll-like receptors which, when engaged, produce a cascade of inflammatory reactions comprising the acute phase response (APR) of the innate immune system (IIS). The inflammatory process is most marked in the visceral fat depot as well as the vasculature, and is involved in the metabolic events which culminate in the insulin resistance/metabolic syndromes (IRS/MS), the components of which precede and comprise the major risk factors for CVD and NIDDM. The visceral fat has both the proclivity and capacity to undergo inflammation. It contains a rich blood and nerve supply as well as proinflammatory molecules such as interleukin 6 (IL-6), tumor necrosis factor alpha (TNFalpha), leptin, and resistin, the adipocytokines, and acute phase proteins (APP) which are activated from adipocytes and/or macrophages by sympathetic signaling. The inflammation is linked to fat accumulation. Cortisol, IL-6, angiotensin II (angio II), the enzyme 11(beta) hydroxysteroid dehydrogenase-1 and positive energy balance, the latter due to increased appetite induced by the major stress hormones, are factors which promote fat accumulation and are linked to obesity. There is also the capacity of the host to limit fat expansion. Sympathetic signaling induces TNF which stimulates the production of IL-6 and leptin from adipocytes; these molecules promote lipolysis and ffa fluxes from adipocytes. Moreover, catecholamines and certain PIC inhibit lipoprotein lipase, a fat synthesizing enzyme. The brain also participates in the regulation of fat cell mass; it is informed of fat depot mass by molecules such as leptin and ffa. Leptin stimulates corticotrophin releasing hormone in the brain which stimulates the SNS and HPA axes, i.e. the stress response. Also, ffa through portal signaling from the liver evoke a similar stress response which, like the response to psychologic stress, evokes an innate immune response (IIR), tending to limit fat expansion, which culminates in inflammatory cascades, the IRS-MS, obesity and disease if prolonged. Thus, the brain also has the capacity to limit fat expansion. A competition apparently exists between fat expansion and fat loss. In "western" cultures, with excessive food ingestion, obesity frequently results. The linkage of inflammation to fat metabolism is apparent since weight loss diminishes the concentration of inflammatory mediators. The linkage of stress to inflammation is all the more apparent since the efferent pathways from the brain in response to fat signals, which results in inflammation to decrease and limit fat cell mass, is the same as the response to psychologic stress, which strengthens the hypothesis presented herein.
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PMID:The inflammatory consequences of psychologic stress: relationship to insulin resistance, obesity, atherosclerosis and diabetes mellitus, type II. 1678 Oct 84

Microglia, activated when physiological homeostasis is threatened, play an important role as immune cells in the CNS. Activated microglia show a progressive series of changes in morphology, gene expression, function and number, and produce and release various chemical mediators, including proinflammatory cytokines that can produce immunological actions and modify neuronal function. Recently, accumulating evidence has indicated an important role for ATP receptors of activated microglia in neuropathic pain. Neuropathic pain is often a consequence of nerve injury through surgery, bone compression, cancer, diabetes or infection. The expression of the P2X4 receptor, a subtype of ATP receptors, is enhanced in spinal microglia in a peripheral nerve injury model, and blocking pharmacologically and suppressing molecularly P2X4 receptors produces a reduction of the neuropathic pain. Several cytokines such as interleukin 6 (IL6) and tumour necrosis factor alpha (TNFalpha) in the dorsal horn are also increased after nerve lesion and have been implicated in contributing to nerve-injury pain. ATP can activate mitogen-activated protein kinase (MAPK) leading to the release of bioactive substances including cytokines from microglia. Thus, diffusible factors released from activated microglia by the stimulation of purinergic receptors may have an important role in the development of neuropathic pain.
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PMID:ATP receptors of microglia involved in pain. 1680 36

Definitions of the metabolic syndrome (MetS) include obesity, dyslipidemia, elevated levels of fasting blood glucose, and blood pressure as criteria, but it is also known that the MetS is associated with chronic, subclinical inflammation. Hyperglycemia (fasting and postprandial) may be important in exacerbating this proinflammatory state. We aimed to assess the impact of oral glucose challenge and in vitro glucose-stimulation on gene expression and secretion of inflammatory parameters in peripheral blood leukocytes and to investigate whether presence of the MetS could "prime" leukocytes to up-regulate proinflammatory markers in response to glucose. Using quantitative real-time PCR, we could show that the expression of intercellular adhesion molecule 1 (ICAM-1), tumor necrosis factor alpha (TNF-alpha), and interleukin 6 (IL-6) significantly increased in peripheral blood leukocytes from "MetS" subjects (n=39) compared to "no MetS" subjects (n=35) 2 h after an oral glucose tolerance test (ICAM-1 +52%, TNF-alpha +107%, and IL-6 +38%) and also in vitro after 72 h cultivation in high-glucose medium (ICAM-1 +74%, TNF-alpha +71%, and IL-6 +44%). Using ELISA and Luminex technique, we further observed a trend towards increased immune mediator concentrations in the corresponding cell culture supernatants from MetS patients (ICAM-1 +21%, TNF-alpha +31%, and IL-6 +175%). Thus, the MetS may support peripheral inflammation by sensitizing leukocytes to up-regulate proinflammatory markers in response to glucose, which in turn increases the risk for type-2 diabetes mellitus and cardiovascular disease.
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PMID:The metabolic syndrome sensitizes leukocytes for glucose-induced immune gene expression. 1716 Jun 70

Increasing evidence implicates periodontitis, a chronic inflammatory disease of the tooth-supporting structures, as a potential risk factor for increased morbidity or mortality for several systemic conditions including cardiovascular disease (atherosclerosis, heart attack, and stroke), pregnancy complications (spontaneous preterm birth [SPB]), and diabetes mellitus. Cross-sectional, case-control, and cohort studies indicate that periodontitis may confer two- and up to sevenfold increase in the risk for cardiovascular disease and premature birth, respectively. Given the recently acquired knowledge that systemic inflammation may contribute in the pathogenesis of atherosclerosis and may predispose to premature birth, research in the field of periodontics has focused on the potential of this chronic low-grade inflammatory condition to contribute to the generation of a systemic inflammatory phenotype. Consistent with this hypothesis clinical studies demonstrate that periodontitis patients have elevated markers of systemic inflammation, such as C-reactive protein (CRP), interleukin 6 (IL-6), haptoglobin, and fibrinogen. These are higher in periodontal patients with acute myocardial infarction (AMI) than in patients with AMI alone, supporting the notion that periodontal disease is an independent contributor to systemic inflammation. In the case of adverse pregnancy outcomes, studies on fetal cord blood from SBP babies indicate a strong in utero IgM antibody response specific to several oral periodontal pathogens, which induces an inflammatory response at the fetal-placental unit, leading to prematurity. The importance of periodontal infections to systemic health is further strengthened by pilot intervention trials indicating that periodontal therapy may improve surrogate cardiovascular outcomes, such as endothelial function, and may reduce four- to fivefold the incidence of premature birth. Nevertheless, further research is needed to fully discern the underlying mechanisms by which local chronic infections can have an impact on systemic health, and in this endeavor periodontal disease may serve as an ideal disease model.
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PMID:Low-grade inflammation in chronic infectious diseases: paradigm of periodontal infections. 1719 71


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