Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a nuclear transcription factor that comprises the primary molecular target for thiazolidinedione (TZD) insulin-sensitizing drugs. Whilst expressed in many tissues in humans, its abundant expression in adipose tissue is believed to be the focal point through which TZDs regulate genes involved in glucose and lipid metabolism and via which these agents ultimately improve the hyperglycemia of type 2 diabetes. However, TZDs exhibit many additional properties, not least an array of effects which suggest a broad attack on the inflammatory process. Thus, TZDs have been shown to reduce plasma levels of the chemokine, monocyte chemotactic protein-1 (MCP-1), the anti-fibrinolytic protein, plasminogen activator inhibitor-1 (PAI-1), the endothelial cell adhesion molecules, e-selectin and inter-cellular adhesion molecule-1 (ICAM-1), the leucocyte-activating molecule, CD40L, and the tissue-remodeling enzyme, matrix metalloproteinase-9 (MMP-9). Further tangible evidence of a reduction by TZDs of systemic inflammation in patients with the classical metabolic syndrome stems from falls in the white blood cell count, P-selectin-positive platelets and in the acute-phase inflammatory proteins, C-reactive protein, serum amyloid A and fibrinogen. At the tissue level, TZDs improve vascular endothelial function, and reduce the rate of progression of intimal-medial thickening of the carotid artery and the microalbuminuria of type 2 diabetes. Further, TZDs have been shown to be efficacious in inflammatory diseases as wide-ranging as psoriasis, ulcerative colitis and non-alcoholic steatohepatitis (NASH). In the case of the latter, a broad spectrum of TZD-related properties is visible. Here, these drugs improve insulin sensitivity for glucose metabolism, reduce hyperinsulinemia, hepatic steatosis, inflammation and fibrosis, and lower the circulating levels of liver transaminases (ALT, AST), alkaline phosphatase and gamma glutamyl transferase. These effects in humans are also well-supported by investigative animal and in vitro studies. The ameliorative effects on liver fibrosis are of particular interest since they suggest that TZDs are able to activate a program of corrective tissue-remodeling. The basis for this action may be partly an ability to inhibit matrix protein secretion by hepatic stellate cells. An analogous action has also been seen in kidney mesangial cells. In conclusion, TZDs are important new drugs, presently indicated for the treatment of type 2 diabetes but with a spectrum of properties which suggests their potential for treating a number of degenerative inflammatory diseases, including NASH. However, full-scale, long-term clinical trials are needed with TZDs to test their potential to treat NASH, not least because of the (hepatotoxic) legacy of the prototype TZD, troglitazone, but also in view of the escalating burden of liver disease which is accompanying the increasing global prevalence of clinical obesity and type 2 diabetes.
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PMID:Thiazolidinediones: Pleiotropic drugs with potent anti-inflammatory properties for tissue protection. 1619 19

The role of chronic inflammation causing metabolic and vascular disorders is increasingly recognized. It is hypothesized that proinflammatory cytokines contribute to atherogenesis, peripheral insulin resistance, and the development of hypertension and type II diabetes. Psoriasis as a chronic inflammatory skin disorder is characterized by a variety of immunologic and inflammatory changes and may similarly predispose for those disorders. The objective of this study was to elucidate the association of psoriasis with chronic vascular and metabolic disorders. We investigated a total of 581 adult patients hospitalised for plaque type psoriasis as compared to 1,044 hospital-based controls. A distinct pattern of chronic disorders was found to be significantly associated with psoriasis, including diabetes mellitus type II [odds ratio (OR)=2.48], arterial hypertension (OR = 3.27), hyperlipidemia (OR = 2.09), and coronary heart disease (OR = 1.95). The combined presence of these conditions together with obesity, known as the metabolic syndrome, was clearly more prevalent in psoriasis patients (OR = 5.29). In addition, psoriasis patients were significantly more likely to be smokers (OR = 2.96) and to have a regular or heavy consumption of alcohol (OR = 3.33 and 3.61, respectively). In conclusion, psoriasis patients appear to be at higher risk for diabetes mellitus and cardiovascular disease. This could likely be due to the effects of chronic inflammatory changes, in particular the secretion of proinflammatory cytokines. The risk of late term cardiovascular complications might support the use of systemic treatment in psoriasis.
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PMID:Increased prevalence of the metabolic syndrome in patients with moderate to severe psoriasis. 1702 63

Experts on psoriasis convened with authorities from other medical specialties to discuss the recently described association between psoriasis, obesity and subsequent cardiovascular comorbidity. Similar to other diseases of increased systemic inflammation, psoriasis has been linked to a heightened risk of myocardial infarction, especially in the more severely affected, younger patients. However, unlike in other inflammatory diseases - such as rheumatoid arthritis - more severely affected patients with psoriasis are much more likely to be obese. Importantly, the pathophysiology of both psoriasis and obesity shows many shared cytokines that are known to contribute to features of the metabolic syndrome, such as hypertension, dyslipidaemia and insulin resistance. The strong association between psoriasis and obesity potentially makes psoriasis an important healthcare issue that requires an update in its standard of care. This meeting reviewed the evidence-based literature and addressed how, moving forward, dermatologists and other specialists may redefine the magnitude of health risk associated with more severe psoriasis and its comorbidities, while clarifying both the epidemiology and pathophysiology of the association with obesity.
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PMID:Obesity in psoriasis: the metabolic, clinical and therapeutic implications. Report of an interdisciplinary conference and review. 1762 91

It has long been recognized the epidemiological association of psoriasis, especially the most severe forms, with several diseases that share a common pathogenic substrate involving TNF-alpha and different target organs (arthritis and Crohn's disease, for example), as well as an increased risk of coronary heart disease and occlusive cardiovascular disease. In the patient with severe psoriasis there is also an increased prevalence of obesity, dyslipemia, adult diabetes mellitus, alcohol abuse and tobacco habit which contribute to the increased risk of mortality associated with atherosclerosis. Recently it has been identified the so-called metabolic syndrome, characterized by the association of abdominal obesity, atherogenic dyslipemia, hypertension, insulin resistance with or without glucose intolerance and a proinflammatory and prothrombotic state as a risk factor for cardiovascular disease. There is evidence that in rheumatoid arthritis as well as in psoriasis, chronic inflammation has a pathogenic role in the metabolic syndrome and associated comorbidities, and its adequate treatment may contribute to revert it. The dermatologist should recognize the elements of the metabolic syndrome and propose the patient with psoriasis, in addition to the optimal dermatologic treatment, changes in life habits and appropriate drug therapy to reduce the risk of cardiovascular morbi-mortality.
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PMID:[Psoriasis, a systemic disease?]. 1766 29

Previous reports have shown a possible association between psoriasis and obesity, ischaemic heart disease, hypertension or diabetes mellitus. However, most of these studies were uncontrolled and were based on small sample sizes. We therefore investigated the association between psoriasis and the metabolic syndrome in a case control study. Case patients were defined as patients with a diagnosis of psoriasis vulgaris. Control patients were subjects who underwent hernioplasty or appendectomy. We used data mining techniques utilizing the database of the southern district of Clalit Health Services. The proportions of patients with diseases that belong to the metabolic syndrome were compared between case and control patients by univariate analyses. chi2 tests were used to compare categorical parameters between the groups. Logistic regression models were used to measure the association between psoriasis and the metabolic syndrome. A total of 340 patients with psoriasis and 6643 controls were included in the study. The mean age of case patients was 47.7 years (SD 10.7 years). There were 50.3% men and 49.7% women. Ischaemic heart disease was present in 23.5% of the patients with psoriasis, compared with 17.2% of the controls (p=0.003). Diabetes mellitus was present in 27.9% of the patients with psoriasis, compared with 19.5% of the controls (p <0.001). Hypertension was present in 44.4% of the patients with psoriasis, compared with 37.2% of the controls (p=0.007). Obesity was present in 29.4% of the patients with psoriasis, compared with 23.5% of the controls (p=0.012). Dyslipidaemia was present in 50.9% of the patients with psoriasis, compared with 44.2% of the controls (p=0.015). The association between psoriasis and the metabolic syndrome was pronounced after the age of 50 years and in men. Multivariate models adjusting for age and gender demonstrated that psoriasis was associated with an increased risk for ischaemic heart disease (odds ratio (OR) 1.4 95% confidence interval (CI) 1.0-1.8), diabetes mellitus (OR 1.5 95% CI 1.2-2.0), hypertension (OR 1.3 95% CI 1.0-1.7), obesity (OR 1.3 95% CI 1.0-1.7) and dyslipidaemia (OR 1.2 95% CI 1.0-1.6). Our findings demonstrate a possible association between psoriasis and the metabolic syndrome. Further studies are needed to establish this observation.
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PMID:Psoriasis and the metabolic syndrome. 1798 88

Epidemiological studies have shown that, in psoriasis patients, associated disorders may occur more frequently than expected. Such comorbidities include psoriatic arthritis, psoriatic pustular diseases, Crohn disease, and signs of metabolic syndrome, which leads to atherosclerosis with coronary heart disease. Although the disorders represent separate entities, they appear to follow overlapping pathogenic pathways. Comorbidities often become clinically manifest years after onset of psoriasis and are frequently seen in severe disease. Persistent low-grade inflammation with secretion of proinflammatory cytokines (eg, tumor necrosis factor alpha) favors the development of insulin resistance and metabolic syndrome. In addition, biochemical and immunologic observations point toward an inflammatory immune mechanism that uses tools of the innate defense armamentarium.
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PMID:Comorbidities in psoriasis. 1802 89

Metabolic syndrome is associated to chronic low grade inflammation, characterized by increased levels of inflammatory cytokines, such as Tumor Necrosis Factor-alpha (TNF-alpha) and Interleukin-6 (IL-6). In particular, TNF-alpha causes a decrease in the insulin-stimulated kinases related to the early phases of the insulin cascade, thereby leading to insulin resistance. Etanercept is a human fusion protein used in the treatment of psoriasis and inflammatory arthritis. It blocks inflammatory response by interfering in the binding of TNF-alpha to its receptors. The aim of this case report study is to verify the effect of Etanercept on insulin sensitivity, lipid profile and inflammatory status in psoriatic patients. Nine psoriatic patients with stable, active, plaque type psoriasis were enrolled and treated with Etanercept for 24 weeks. We found an improvement in the metabolic assessment with a significant reduction of insulin plasma levels. In particular, this treatment allows to maintain their euglycemic state with lower insulin plasma levels, as confirmed by the improved Homeostasis Model Assessment (HOMA) index. We conclude that Etanercept, probably acting on inflammation, improves insulin sensitivity in psoriatic subjects.
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PMID:Effect of etanercept on insulin sensitivity in nine patients with psoriasis. 1817 45

Psoriasis is a chronic and debilitating inflammatory disease associated with serious comorbidities. Psoriasis can have a significant impact on a patient's quality of life and is associated with loss of productivity, depression, and an increased prevalence of malignancy. Emerging comorbidities of psoriasis include cardiovascular disease and metabolic syndrome. Psoriasis patients have an increased prevalence of the core components of metabolic syndrome, including obesity, dyslipidemia, and insulin resistance. The relationship between psoriasis and comorbidities such as metabolic syndrome and cardiovascular disease is likely linked to the underlying chronic inflammatory nature of psoriasis. The molecular mechanisms involved in psoriasis-associated dysregulation of metabolic function are believed to be due, in large part, to the action of increased levels of proinflammatory factors, such as tumor necrosis factor-alpha, that are central to the pathogenesis of psoriasis. Recent studies investigating the effects of tumor necrosis factor antagonists on the treatment of cardiovascular disease and metabolic syndrome support this concept.
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PMID:Psoriasis comorbidities. 1827 20

Psoriasis is an immune mediated, inflammatory skin condition affecting approximately 1.43% of Spanish population. In clinical practice, physicians use PASI index to assess the severity. Psoriasis causes physical and mental disability comparable to other chronic diseases and affects seriously the patients quality of life. For treatment we have different options. Conventional systemic treatment such as methotrexate, cyclosporine and acitretin may be associated with relevant side effects, and organ toxicity that avoid long term therapy. Several psoriasis patients have other comorbid disorders like obesity, diabetes, dyslipemia, hypertension and an increased rate of cardiovascular disease and metabolic syndrome and these patients need safer treatments. The accumulating clinical experience with new therapies consistent on biological agents like efalizumab indicates that are effective therapies, with safety profile and no evidence of cumulative toxicity that allows a long term use. A better control of psoriasis improves patients quality of life.
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PMID:[Long-term control of psoriasis is necessary]. 1834 51

Psoriasis is associated with comorbidities that include metabolic syndrome and increased cardiovascular risk. These conditions share etiologic features and health consequences that directly correlate with the severity of psoriatic disease. This disease, in both its skin and joint manifestations, may represent a relevant healthcare issue as an indicator of a broader, underlying disorder of systemic inflammation, and warrants more comprehensive study and multidisciplinary collaboration on its pathophysiology, epidemiology, and treatment in relation to its comorbid conditions.
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PMID:Psoriasis as the marker of underlying systemic disease. 1835 63


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