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

Thiazolidinediones (TZDs) are peroxisomal proliferator-activated receptor (PPAR)-gamma agonists. They increase insulin action through several mechanisms including: stimulation of the expression of genes that increase fat oxidation and lower plasma free fatty acid levels; increased expression, synthesis and release of adiponectin; and stimulation of adipocyte differentiation resulting in more and smaller fat cells. TZDs lower blood sugar comparably to sulfonylureas and metformin. The clinical use of TZDs is limited due to the long duration of time required before they reach their full blood sugar-lowering action (3-4 months) and adverse effects such as fluid retention, resulting in excessive weight gain and occasionally in peripheral and/or pulmonary oedema and congestive heart failure. Troglitazone, a TZD that has since been removed from the market because of hepatoxicity, has been demonstrated to decrease the progression from normal or impaired glucose tolerance to overt Type 2 diabetes mellitus. Pioglitazone, another TZD, marginally decreased the incidence of cardiovascular complications in patients with Type 2 diabetes mellitus (PROactive trial). Other, as yet, unapproved uses of TZDs include: non-alcoholic fatty liver disease, in which TZDs reduced hepatic fat accumulation and improved liver function tests; polycystic ovary syndrome, where TZDs improved ovulation, hirsutism and endothelial dysfunction; and lipodystrophies, where TZDs increased body fat (marginally) and decrease liver size. Lastly, because PPAR-alpha and -gamma agonists improve atherosclerotic vascular disease and insulin sensitivity, respectively, dual PPAR-alpha/gamma agonists, which are currently undergoing clinical trials, may be useful in treating patients with the metabolic syndrome.
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PMID:Recent findings concerning thiazolidinediones in the treatment of diabetes. 1650 61

Diabetes is a major risk factor for stroke and is associated with an increase in overall stroke mortality. The metabolic syndrome associated with insulin resistance is also a significant risk factor for stroke. The etiology of stroke in diabetics is frequently microvascular disease from fibrinoid necrosis, which causes small subcortical infarcts designated as lacunar strokes. Diabetics also have an increased incidence of large vessel intracranial vascular disease. Although strict control of blood sugar has not been shown to reduce the overall incidence of stroke in diabetics, careful management of other associated risk factors, particularly hypercholesterolemia and hypertension, are imperative for the prevention of stroke in diabetic patients.
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PMID:Diabetes and stroke: part one--risk factors and pathophysiology. 1650 31

The insulin resistance syndrome, which presents among its many facets obesity and type 2 diabetes mellitus, is a major risk factor for cardiovascular events. Thus, therapeutic guidelines recommend multifactorial treatment programs including, especially in the presence of type 2 diabetes, antiplatelet drugs. Few data, however, are available about the protective effect of antiplatelet therapy in both obese and type 2 diabetic patients. Furthermore, some reports showed a decreased sensitivity to the platelet antiaggregating effect of acetylsalicylic acid in diabetic patients. In the first part of this review, we focused our attention to alterations of platelets from insulin resistant subjects with or without type 2 diabetes, underlining that platelet hyperactivation is explained, at least in part, by: i) a reduced sensitivity to agents exerting an inhibitory modulation of platelet responses, ii) an altered intracellular milieu with elevated cytosolic Ca2+, iii) an enhanced thromboxane A2 synthesis, and iv) an increased number and/or function of GPIIb/IIIa complexes on platelet membranes. Furthermore, oxidative stress, which increases isoprostane production from arachidonic acid, may be involved in platelet hyperactivation, since isoprostanes activate platelets by interplaying with thromboxane receptors. 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 carried out a critical overview of the clinical trials in subjects with metabolic syndrome and type 2 diabetes mellitus with or without macroangiopathy.
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PMID:Pathophysiology of platelet resistance to anti-aggregating agents in insulin resistance and type 2 diabetes: implications for anti-aggregating therapy. 1661 Oct 47

Elevated plasma homocysteine has been reported in individuals with diseases of the metabolic syndrome including vascular disease and insulin resistance. As homocysteine exerts detrimental effects on endothelial and neuronal cells, this study investigated effects of acute homocysteine exposure on beta-cell function and insulin secretion using clonal BRIN-BD11 beta-cells. Acute insulin release studies in the presence of various test reagents were performed using monolayers of BRIN-BD11 cells and samples assayed by insulin radioimmunoassay. Cellular glucose metabolism was assessed by nuclear magnetic resonance (NMR) analysis following 60-min exposure of BRIN-BD11 cell monolayers to glucose in either the absence or presence of homocysteine. Homocysteine dose-dependently inhibited insulin release at moderate and stimulatory glucose concentrations. This inhibitory effect was reversible at all but the highest concentration of homocysteine. 13C-glucose NMR demonstrated decreased labelling of glutamate from glucose at positions C2, C3 and C4, indicating that the tricarboxylic acid (TCA) cycle-dependent glucose metabolism was reduced in the presence of homocysteine. Homocysteine also dose-dependently inhibited insulinotropic responses to a range of glucose-dependent secretagogues including nutrients (alanine, arginine, 2-ketoisocaproate), hormones (glucagon-like peptide-1 (7-36)amide, gastric inhibitory polypeptide and cholecystokinin-8), neurotransmitter (carbachol), drug (tolbutamide) as well as a depolarising concentration of KCl or elevated Ca2+. Insulin secretion induced by activation of adenylate cyclase and protein kinase C pathways with forskolin and phorbol 12-myristate 13-acetate were also inhibited by homocysteine. These effects were not associated with any adverse action on cellular insulin content or cell viability, and there was no increase in apoptosis/necrosis following exposure to homocysteine. These data indicate that homocysteine impairs insulin secretion through alterations in beta-cell glucose metabolism and generation of key stimulus-secretion coupling factors. The participation of homocysteine in possible beta-cell demise merits further investigation.
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PMID:Detrimental actions of metabolic syndrome risk factor, homocysteine, on pancreatic beta-cell glucose metabolism and insulin secretion. 1664 97

A number of dietary components modulate the inflammatory response in humans, thereby affecting cardiovascular risk. As basic research provides a better understanding of the molecular mechanisms of vascular function regulation by nutrients, clinical investigation and outcome studies demonstrate the relevance of dietary factors to the prevention and treatment of vascular disease. Benefits of dietary interventions may be attributable to weight loss or to more specialized mechanisms in which inflammation is targeted directly. Available evidence indicates that dietary intervention should be an integral part of therapeutic approaches for treating conditions such as the metabolic syndrome and, ultimately, for the prevention of cardiovascular disease.
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PMID:The emerging link between nutrition, inflammation and atherosclerosis. 1671 99

Our ability to assess individual patient cardiovascular risk is based on "traditional" risk factors including patient's characteristics (age, sex and body mass index), hypertension, diabetes, smoking, lipid profile and family history of premature coronary disease. These factors are important for the clinician in order to calculate risk and initiate treatment in both primary and secondary settings. As the morbidity and mortality from vascular disease in United Kingdom migrant populations of Indo Asian origin is significantly higher (approximately 50%) than the Western Europeans, an accurate assessment of risk and preventative therapies can reduce cardiovascular risk and improve clinical outcome. Indeed, scoring systems like the Framingham consistently underestimate risk in Indo Asians. This review assesses differences between traditional risk factors in Indo Asians and summarizes the relevance of more novel factors in a more comprehensive evaluation of cardiovascular risk in the Indo Asian population. Greater appreciation of these traditional risk factors for coronary atherosclerosis in Indo Asians--including hypertension and metabolic syndrome (of which hypertension is a key component)--suggests the need for a reappraisal to put these data in context of current management strategies.
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PMID:Traditional risk factors for coronary atherosclerosis in Indo Asians: the need for a reappraisal. 1672 73

Type 2 diabetes and atherosclerotic vascular disease develop in parallel. Prospective epidemiologic studies have shown a striking communality of major risk factors for both diseases. This raises the question of a "common soil". The traits of the metabolic syndrome including dyslipidemia, visceral obesity and hypertension are predictors of type 2 diabetes as well as coronary heart disease. The same applies to the environmental factors: overnutrition, physical inertia and smoking. Visceral obesity, insulin resistance and low-grade inflammation are known as major components of the common soil for metabolic syndrome and coronary heart disease. Depending on the quality of metabolic control diabetes will accelerate the progression of atherosclerosis via unstable plaque formation. The "common soil" concept provides a paradigm for an integrated therapeutic approach. This applies to a lifestyle intervention as well as a rational use of drugs in diseases of the metabolic syndrome. The medication should consider coexisting disorders of the metabolic syndrome to use pleiotropic effects. On the other hand, side effect such as the worsening of blood glucose levels caused by beta-blockers and diuretics should be avoided. The following medication should be preferred in context of the metabolic syndrome: oral antidiabetics such as acarbose, metformin and thiazolidinediones, antihypertensives such as ACE inhibitors and ARBs (angiotensin receptor blockers) and lipid-lowering drugs such as atorvastatin, rosuvastatin, and the modern nicotinic acid derivative Niaspan, respectively. The strategy using synergies in drug treatment can reduce polypharmacy and costs and improve the patients' compliance.
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PMID:[Metabolic syndrome: "common soil" for diabetes and atherosclerosis. Novel approaches to an integrated therapy]. 1677 May 62

Cardiovascular diseases (CVDs) may have their origin before birth: the combination of being small at birth and having an overly rich post-natal diet increases the likelihood of obesity and of acquiring a specific metabolic syndrome in adulthood that carries an increased risk of CVD. The incidence of CVD and mortality is very low in women of reproductive age but rises to a significant level in older women. In this article, we discuss CVD in relation to hormonal contraception, pregnancy and polycystic ovarian syndrome (PCOS) in younger women and menopause in older women. Women with PCOS have a higher risk of diabetes and hypertension, but studies to date have not shown an effect on CVD events. Use of combined hormonal contraception has only small effects on CVD because of the low baseline incidence of myocardial infarction (MI), stroke and venous thromboembolism (VTE) among young women. Women with existing risk factors or existing CVD, however, should consider alternative contraception. In pregnancy, CVD is rare, although, in the West, it now accounts for a significant proportion of maternal mortality as the frequency of obstetrical causes of mortality has substantially declined. The frequency of VTE is 15 per 10,000 during pregnancy and the post-partum period. In older women, menopause causes a slightly higher risk of MI after allowing for age, although there is substantial heterogeneity in the results of studies on menopause and age at menopause and MI. A larger effect might have been expected, because estrogen reduces the risk of developing atherosclerosis in premenopausal women, whereas in post-menopausal women who may have established atherosclerotic disease, estrogen increases the risk of myocardial disease through the effects on plaque stability and clot formation. Recent trial results indicate that hormone treatment in menopause does not favourably affect the risk of MI, stroke or other vascular disease. Thus, prevention of CVD should rely on diet and fitness, low-dose aspirin and treatment of hypertension, hyperglycaemia and hyperlipidaemia.
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PMID:Hormones and cardiovascular health in women. 1680 76

Considerable evidence supports the association between insulin resistance and vascular disease, and this has led to wide acceptance of the clustering of hyperlipidemia, glucose intolerance, hypertension, and obesity as a clinical entity, the metabolic syndrome. While insulin resistance, by promoting dyslipidemia and other metabolic abnormalities, is part of the proatherogenic milieu, it is possible that insulin resistance itself in the vascular wall does not promote atherosclerosis. Recent findings suggest that insulin resistance and atherosclerosis could represent independent and ultimately maladaptive responses to the disruption of cellular homeostasis caused by the excess delivery of fuel.
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PMID:Insulin resistance and atherosclerosis. 1682 79

A popular hypothesis for the greater prevalence of type 2 diabetes and cardiovascular disease in UK south Asians is that they have an increased susceptibility of developing insulin resistance in response to certain environmental factors, including obesity and adoption of a sedentary lifestyle. Insulin resistance is postulated as a central feature of the metabolic syndrome, culminating in type 2 diabetes, atherosclerotic vascular disease and CHD; a pathway potentially accelerated by migration/urbanisation. We describe and compare the prevalence of type 2 diabetes, cardiovascular disease and their associated risk factors in UK south Asian and white Caucasian populations to determine possible reasons for the increased preponderance of these diseases in south Asians, and highlight key evidence for optimal risk factor management. Finally, we describe a UK community-based programme that attempts to reduce the morbidity and mortality from type 2 diabetes and cardiovascular disease in south Asians through a new approach to management.
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PMID:Type 2 diabetes and cardiovascular risk in the UK south Asian community. 1684 1


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