Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to determine the impact of the metabolic syndrome on vascular disease risk in patients with type-2 diabetes. A prospective cohort study was carried out. The main dependent variable was the combination of coronary disease, stroke and lower leg amputation. Cox regression modeling was used. In total, 317 patients were followed for a mean of 7.7 years. The prevalence of metabolic syndrome was 87%. Multivariate analysis identified the following as predictors of incident vascular disease: age (relative risk [RR] =1.06, 95% confidence interval [CI], 1.02-1.1; P=.0003), baseline cardiovascular disease (RR=1.8; 95% CI, 1.1-3.0; P=.017), and the simultaneous presence of four metabolic risk factors (RR=5.8; 95% CI, 1.8-18; P=.003). The most predictive factor was microalbuminuria (chi2=5.9; P=.015). Microalbuminuria accounts for the increased risk of vascular disease in patients with metabolic syndrome. In evaluating vascular disease risk in patients with type-2 diabetes, it is more important to consider the total number of metabolic risk factors than the presence of metabolic syndrome alone.
 ...
PMID:[Microalbuminuria accounts for the increased vascular disease risk in diabetic patients with metabolic syndrome]. 1799 82

" 'Diagnosis' of metabolic syndrome by any current criteria is not needed and adds little to clinical practice. Attention and resources should be focused on the major modifiable risk factors and more should be done to engender sustainable lifestyle changes in all with vascular disease."
 ...
PMID:Metabolic syndrome, dysglycaemia and vascular disease: making sense of the evidence. 1800 73

Insulin resistance is characterized by the systemic impairment of insulin action and is usually the result of aging, obesity, chronic inflammation, or another factor that may contribute to the inhibition of the insulin signaling pathway. Insulin resistance is accompanied by defects in lipid metabolism and blood coagulation, hypertension, obesity, and vascular inflammation in a syndrome called syndrome X or metabolic syndrome. Metabolic syndrome is involved in the development of atherosclerosis with consequent cardiovascular complications including acute myocardial infarction, stroke, and vascular disease. Recent data have shown that vitamin D acts as a negative regulator of the renin gene and that vitamin D deficiency is followed by increased renin-angiotensin II expression. The link between the insulin signaling pathway/insulin resistance and the renin-angiotensin system has been well documented in previous studies. The present review focuses on disorders characterized by a reduction in vitamin D concentration or its receptor function and the development of insulin resistance or metabolic syndrome, and discusses also possible therapeutic interventions.
 ...
PMID:Vitamin D, the renin-angiotensin system, and insulin resistance. 1819 90

Insulin resistance is a relevant risk factor for the major cardiovascular events, caused by severe atherosclerotic involvement of coronary, cerebral and lower limb blood vessels. One of the alterations accounting for this increased cardiovascular risk is the impairment of platelet function, explained, at least in part, by the reduced sensitivity to the physiological and pharmacological anti-aggregating agents. In the first part of this review, we will focus our attention on the physiological mechanisms involved in the attenuation of platelet response and on their impairment in insulin resistance, considering in particular: i) the reduced sensitivity to insulin and other substances acting via intracellular cyclic nucleotides; ii) the altered intracellular ionic milieu with elevated cytosolic Ca(2+), iii) the increase of oxidative stress, which elicits isoprostane production from arachidonic acid. Therapeutic guidelines recommend a multifactorial prevention including antiplatelet drugs, even though the protective effect of antiplatelet therapy in both obese and type 2 diabetic patients has not been completely clarified so far. Furthermore, some reports show a decreased sensitivity to the platelet antiaggregating effect of acetylsalicylic acid in obesity and type 2 diabetes mellitus. These defects explain why antiplatelet therapy for both chronic atherosclerotic vascular disease and acute coronary syndromes should be specifically tailored in obese, insulin resistant subjects, especially in the presence of type 2 diabetes mellitus. Thus, in the second part of this review we performed a critical overview of the clinical trials on anti-aggregating agents carried out in subjects with metabolic syndrome and type 2 diabetes mellitus.
 ...
PMID:Platelet resistance to the anti-aggregating agents in the insulin resistant states. 1822 Jun 45

Macrophage death in advanced atherosclerosis causes plaque necrosis, which promotes plaque rupture and acute atherothrombotic vascular events. Of interest, plaque necrosis and atherothrombotic disease are markedly increased in diabetes and metabolic syndrome. We discovered a novel 'multi-hit' macrophage apoptosis pathway that appears to be highly relevant to advanced atherosclerosis. The elements of the pathway include: (a) activation of the unfolded protein response (UPR) by cholesterol overloading of the endoplasmic reticulum or by other UPR activators known to exist in atheromata; and (b) pro-apoptotic signalling involving the type A scavenger receptor (SRA). The downstream apoptosis effectors include CHOP (GADD153) for the UPR and JNK for SRA signalling. Remarkably, components of this pathway are enhanced in macrophages with defective insulin signalling, including UPR activation and SRA expression. As a result, insulin-resistant macrophages show increased susceptibility to apoptosis when exposed to UPR activators and SRA ligands. Moreover, the advanced lesions of atherosclerosis-prone mice reconstituted with insulin-resistant macrophages show increased macrophage apoptosis and plaque necrosis. Based on these findings, we propose that one mechanism of increased plaque necrosis and atherothrombotic vascular disease in insulin resistant syndromes is up-regulation of a two-hit signal transduction pathway involved in advanced lesional macrophage death.
 ...
PMID:The impact of insulin resistance on macrophage death pathways in advanced atherosclerosis. 1826 77

Patients with hypertension and manifest vascular disease are at high risk for recurrent cardiovascular diseases. It is unknown if the metabolic syndrome further increases the risk in these patients. This study aims to quantify the effect of metabolic syndrome and type II diabetes on cardiovascular events in hypertensive patients with vascular disease. A total of 2,196 hypertensive patients with vascular disease (cerebrovascular disease (34%), coronary heart disease (50%), peripheral arterial disease (28%), abdominal aortic aneurysm (13%)) from the Second Manifestations of Arterial Disease study were followed for up to 10 years (mean 3.9 years) for death, stroke and myocardial infarction. Age and sex adjusted hazard ratios (HR) were calculated for hypertensive patients with metabolic syndrome but without diabetes (n=775) and for hypertensive patients with type II diabetes (n=381), compared to merely hypertensive patients (n=1,040). Forty-nine percent had metabolic syndrome (NCEP ATPIII definition) and 17% had type II diabetes. Metabolic syndrome predicted vascular death (HR 1.41, 95% confidence interval (CI) 1.01-1.98), stroke (HR 1.36, 95% CI 0.85-2.16) and myocardial infarction (HR 1.40, 95% CI 0.97-2.01). Type II diabetes accounted for even higher risks of vascular end points (HR 1.41-1.64). The effect of metabolic syndrome on future events could not be explained by the presence of type II diabetes. Even in high-risk patients with hypertension and vascular disease, presence of metabolic syndrome or type II diabetes identifies patients at high risk for future cardiovascular events. Identifying metabolic syndrome patients may direct therapy focusing on treatment of insulin resistance by reducing weight and increasing physical activity.
 ...
PMID:Effect of metabolic syndrome or type II diabetes mellitus on the occurrence of recurrent vascular events in hypertensive patients. 1827 39

Hyperhomocysteinemia is a well-established risk factor for cardiovascular disease. The association of hyperhomocysteinemia with diabetes mellitus is complex and may explain some of the risk of CVD in diabetics not explained by traditional risk factors. Both modifiable and non-modifiable factors interact with homocysteine metabolism and determine the plasma homocysteine concentrations. These include genetic abnormalities, age, sex, and various nutritional and hormonal determinants, all of which play a role in atherosclerosis and accelerated peripheral and cardio-vascular disease (CVD). Several medications modulate homocysteine metabolism and hence may play a role in the pathogenesis of CVD. Changes in renal function and interference with the homocysteine metabolism account for some of these drug effects. While a few of these drugs raise plasma homocysteine concentrations, others are beneficial and may counter some of the deleterious effects of hyperhomocysteinemia. Treatment of hyperhomocysteinemia with vitamins lowers plasma homocysteine concentrations and also reverses many of these drug effects. Little data is available on the effect of this intervention on cardiovascular outcomes. This review briefly outlines the effect of various medications used in the management of type 2 diabetes mellitus and metabolic syndrome.
 ...
PMID:Effect of pharmacological treatments for diabetes on homocysteine. 1837 Jun 36

Women with polycystic ovary syndrome (PCOS) often present for cosmetic and or reproductive symptoms; attention is generally not paid to the future risk of atherosclerosis for these women. Given that Asian Indians are insulin resistant and prone to metabolic syndrome at an earlier age, we assessed glucose/insulin ratio and intimal medial thickness (IMT) in young women with PCOS from south India. In this cross-sectional case control study, we assessed insulin resistance and carotid IMT in 40 women presenting with hyperandrogenic features of PCOS. Insulin resistance was assessed by fasting glucose/insulin ratio and IMT by the Doppler system with electrical linear transducer midfrequency of 12 MHz. Women with PCOS had higher fasting insulin levels (36.58 +/- 17.81 muU/mL, vs. 16.60 +/- 3.22 muU/mL in controls; p < 0.001), higher insulin resistance (glucose/insulin ratio 2.81 +/- 1.47 vs. 5.47 +/- 1.46 in controls; p < 0.001), and greater IMT (0.53 +/- 0.14 mm vs. 0.39 +/- 0.06 mm in controls; p < 0.001). Women with PCOS had a higher body mass index (BMI) (26.46 +/- 5.24 vs. 23.24 +/- 3.05 in controls; p < 0.001), and the differences between PCOS and controls persisted, even among those who had a BMI of less than 25. We concluded that South Indian women with the reproductive abnormalities of PCOS have greater insulin resistance and IMT, and therefore they must be advised about lowering the risk of future vascular disease.
 ...
PMID:Risk of atherosclerosis in women with polycystic ovary syndrome: a study from South India. 1837 Jun 51

Although elevated levels of C-reactive protein (CRP) independently predict increased risk of development of metabolic syndrome, diabetes, myocardial infarction, and stroke, comprehensive analysis of the influence of genetic variation on CRP is not available. To address this issue, we performed a genome-wide association study among 6345 apparently healthy women in which we evaluated 336,108 SNPs as potential determinants of plasma CRP concentration. Overall, seven loci that associate with plasma CRP at levels achieving genome-wide statistical significance were found (range of p values for lead SNPs within the seven loci: 1.9 x 10(-)(8) to 6.2 x 10(-)(28)). Two of these loci (GCKR and HNF1A) are suspected or known to be associated with maturity-onset diabetes of the young, one is a gene-desert region on 12q23.2, and the remaining four loci are in or near the leptin receptor protein gene, the apolipoprotein E gene, the interleukin-6 receptor protein gene, or the CRP gene itself. The protein products of six of these seven loci are directly involved in metabolic syndrome, insulin resistance, beta cell function, weight homeostasis, and/or premature atherothrombosis. Thus, common variation in several genes involved in metabolic and inflammatory regulation have significant effects on CRP levels, consistent with CRP's identification as a useful biomarker of risk for incident vascular disease and diabetes.
 ...
PMID:Loci related to metabolic-syndrome pathways including LEPR,HNF1A, IL6R, and GCKR associate with plasma C-reactive protein: the Women's Genome Health Study. 1843 48

After an initial attempt by the WHO to define metabolic syndrome (MS) on a pathophysiologically oriented approach requiring the assessment of insulin resistance markers, the NCEP-ATPIII and more recently the IDF proposed more clinically oriented criteria to help, toward a preventive medicine goal, to identify patients who are likely to have features of the MS and be at increased risk of type 2 diabetes and cardio vascular disease. The notion of MS is built around abnormalities of the metabolism of lipids and carbon hydrates, a rise of blood pressure, and visceral obesity of abdominal localization. These parameters report only partially on mechanisms leading to the development of the MS. The physiopathology of MS is partially understood even today and likely results from the combination of environmental, genetic and epigenetic factors. Abdominal visceral obesity, a state of low-grade chronic inflammation and insulin resistance are the main processes susceptible to explain the various constituents of this syndrome.
 ...
PMID:[Pathogenesis of the metabolic syndrome]. 1846 91


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>