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Up to 80% of diabetic patients die of macrovascular complications, including CAD, stroke, and peripheral vascular disease. Because of the growing numbers of diabetic patients and the increased mortality after their first cardiovascular event, it is critical to identify and treat risk factors early and aggressively in these patients. Numerous studies in patients with type 2 diabetes have shown the benefits of aggressive treatment of blood pressure and lipids to levels that 10 years ago would have seemed abnormally low. The downward changes in "normal" limits can be frustrating to primary care physicians, but advances in treatment are redefining "normal" levels required to avoid complications in this high-risk population.
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PMID:Reducing cardiovascular risk in diabetes. Which factors to modify first? 1131 67

It has been conclusively established that treatment of hypertension in patients with type 2 (non-insulin-dependent) diabetes mellitus will significantly reduce the incidence of stroke, heart failure and progression of diabetic complications. Beta-blockers are effective antihypertensive agents which, in long term studies, have proven beneficial in reducing important clinical end-points. However nonselective beta-blockers may have a negative effect on lipid profiles and contribute to hypoglycaemic unawareness, thus preventing their use in some patients with diabetes mellitus. The development of newer and more selective beta-blockers has overcome many of these problems. In addition, some of the newer agents have novel properties such as release of nitric oxide, which theoretically would make them more attractive in patients with diabetes mellitus. Overall, the adverse metabolic effects of beta-blockers do not appear to be important in clinical practice and these agents should no longer be contraindicated in patients with type 2 diabetes mellitus. Their proven cardiovascular benefits would seem to easily tip the balance in favour of their use.
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PMID:Beta-blockers in the management of hypertension in patients with type 2 diabetes mellitus: is there a role? 1155 36

Stroke is a major cause of morbidity and mortality. Risk factors for stroke have been determined through prospective epidemiologic study. Control of risk factors has been demonstrated to reduce stroke incidence, either through controlled trials or inferred from observational studies. In the past few years, new approaches to the treatment of established risk factors have been discovered. These include aggressive control of hypertension in diabetes patients, prevention of type 2 diabetes through lifestyle modification, carotid endarterectomy for moderate symptomatic carotid stenosis, encouragement of a high level of physical activity, and control of abdominal obesity and elevated body mass index. In addition, new strategies for stroke prevention have been identified, including encouragement of a diet high in fruits, vegetables, whole grains, and omega-3 fatty acids, the use of vitamins B12, B6, and folic acid in hyperhomocysteinemia, and moderate alcohol consumption. Clinical trial data support the use of hydroxy-methyl-coenzyme A inhibitors in patients with coronary artery disease, and ramipril in high-risk patients with coronary artery disease and diabetes, for the primary prevention of stroke. New risk factors for stroke are being investigated, including the role of chronic inflammation and infection, and these may provide future strategies for stroke prevention.
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PMID:Prevention of strokes. 1138 98

Uncontrolled hypertension leads to an increased risk of cardiovascular disease and stroke. Hypertensive patients with concomitant type 2 diabetes are at even greater risk of cardiovascular complications; also, this high-risk patient population is at increased risk of renal disease and, ultimately, renal failure. Prospective morbidity and mortality trials have demonstrated that tight blood pressure control improves the cardiovascular prognosis and provides target organ protection. Current treatment guidelines recommend a target blood pressure of < 130/85 mm Hg for patients with hypertension and diabetes. Angiotensin II (A-II), a major component of the renin-angiotensin system, plays an essential role in the pathophysiology of hypertension and diabetes-related renal disease. Currently, the treatment of choice for hypertensive patients with diabetes is angiotensin-converting enzyme (ACE) inhibition, but most of the data are limited to patients with type 1 diabetes. Although ACE inhibition is clearly a mechanism for blocking A-II formation, inhibition at this site may not be complete, as alternate pathways exist for A-II formation. Thus, for interrupting the renin-angiotensin system, A-II receptor antagonists theoretically provide advantages over ACE inhibitors in that they directly inhibit A-II by binding to the AT(1) receptor subtype. The objectives of this review are to: 1) provide an overview of the associated risk of cardiovascular complications with concomitant hypertension and diabetes; 2) demonstrate the cardiovascular benefits of effective blood pressure control in this patient population; 3) review the current treatment guidelines for managing high-risk hypertensive patients; and 4) discuss major, ongoing clinical studies with A-II receptor antagonists in patients with concomitant hypertension, type 2 diabetes, and renal disease. (c)2001 Le Jacq Communications, Inc.
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PMID:Management of high-risk hypertensive patients with diabetes: potential role of angiotensin II receptor antagonists. 1149 50

The current study was initiated to evaluate the ability of insulin resistance to predict a variety of age-related diseases. Baseline measurements of insulin resistance and related variables were made between 1988-1995 in 208 apparently healthy, nonobese (body mass index < 30 kg/m2) individuals, who were then evaluated 4-11 yr later (mean +/- SEM = 6.3 +/- 0.2 yr) for the appearance of the following age-related diseases: hypertension, coronary heart disease, stroke, cancer, and type 2 diabetes. The effect of insulin resistance on the development of clinical events was evaluated by dividing the study group into tertiles of insulin resistance at baseline and comparing the events in these 3 groups. Clinical endpoints (n = 40) were identified in 37 individuals (18%) of those evaluated, including 12 with hypertension, 3 with hypertension + type 2 diabetes, 9 with cancer, 7 with coronary heart disease, 4 with stroke, and 2 with type 2 diabetes. Twenty-eight out of the total 40 clinical events were seen in 25 individuals (36%) in the most insulin-resistant tertile, with the other 12 occurring in the group with an intermediate degree of insulin resistance. Furthermore, insulin resistance was an independent predictor of all clinical events, using both multiple logistic regression and Cox's proportional hazards analysis. The fact that an age-related clinical event developed in approximately 1 out of 3 healthy individuals in the upper tertile of insulin resistance at baseline, followed for an average of 6 yr, whereas no clinical events were observed in the most insulin-sensitive tertile, should serve as a strong stimulus to further efforts to define the role of insulin resistance in the genesis of age-related diseases.
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PMID:Insulin resistance as a predictor of age-related diseases. 1150 81

The number of mammalian calpain protease family members has grown to 14 on last count. Overactivation of calpain 1 and calpain 2 (and their small subunit) has long been tied to acute neurological disorders (e.g. stroke and traumatic brain injury) and recently to Alzheimer's disease. Loss-of-function mutations of the calpain 3 gene have now been identified as the cause of limb-girdle muscular dystrophy 2A. Calpain 10 was recently identified as a susceptibility gene for type 2 diabetes, whereas calpain 9 appears to be a gastric cancer suppressor. This review describes our current understanding of the calpain family members and their mechanistic linkages to the aforementioned diseases as well as other emerging pathological conditions.
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PMID:The calpain family and human disease. 1151 96

In adults, abdominal visceral adiposity is related to an increased risk of cardiovascular diseases, Type 2 diabetes mellitus, and stroke. The antecedents of these conditions likely begin with the alterations in body fat distribution during childhood and adolescence. The sexually dimorphic alterations in fat distribution are influenced by sex differences in hormone concentrations, anatomical differences in the number and density of specific hormone receptors, capillary blood flow, and the activity of enzymes promoting lipid synthesis or degradation. Hormones influencing the amount and regional distribution of adipose tissue during puberty include cortisol, insulin, growth hormone, and the sex steroids. Cortisol and insulin promote fat deposition while the sex steroids and GH stimulate lipolysis. An overly sensitive hypothalamic-pituitary-adrenal axis may exist in obesity and disrupt the balance between the lipogenic effects of cortisol and insulin and the lipolytic effects of sex steroids and growth hormone. Leptin is released from the adipocytes and may act as a metabolic signal to the hypothalamic areas controlling satiety, energy expenditure, and the regulation of cortisol, insulin, sex steroid and growth hormone release. The complex issues of the hormonal control of alterations in body fat distribution during puberty are developed and a working model is proposed. Am. J. Hum. Biol. 11:209-224, 1999. Copyright 1999 Wiley-Liss, Inc.
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PMID:Hormonal changes during puberty and their relationship to fat distribution. 1153 45

The aim of this study was to provide an overview of diabetes management and complication status in Taiwan. A cohort of 2446 patients (from 25 diabetic centers) with more than 12 months of diabetes management participated and data were collected by interviews and reviewing the medical records. Overall, 97% were diagnosed as type 2 diabetes, with a mean age (+/-S.D.) of 61.6+/-11.3 years, duration of diabetes of 10.3+/-7.3 years and age at onset of diabetes of 51.5+/-11.8 years. Mean BMI was 25.1+/-3.6 kg/m(2) and about 50% had BMI>25 kg/m(2). Majority (75%) were treated with oral hypoglycemic agents (OHAs), 14% with insulin and 10% with combination of insulin and OHA. Mean HbA(1c) was 8.1+/-1.6% and 59% had HbA(1c) >7.4% (1% above the upper limit of normal range, 4.7-6.4%). Mean FBG was 9.0+/-3.3 mmol/l and 59% had FBG>7.8 mmol/l. Of all the patients who had screening for complications, cataract (38%), neuropathy (30%), proteinuria (17%) and stroke (6%) were the most frequently reported eye, feet, kidney and late complications. We conclude that the majority of patients involved in this study had unsatisfactory glycaemic control which may lead to diabetes complications.
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PMID:The current state of diabetes management in Taiwan. 1158 Sep 70

Platelet glycoprotein receptors play a role in the pathogenesis of chronic diabetic complications. Genetic polymorphisms of the alpha2beta1 integrin and glycoprotein IIIa (GPIIIa) have been associated with myocardial infarction, stroke, and diabetic retinopathy. To identify risk factors for their development in a cohort of patients with type 2 diabetes, we evaluated clinical variables and genetic polymorphisms in the alpha2beta1 integrin and GPIIIa genes. Two hundred thirty-four subjects with type 2 diabetes (126 patients with and 108 patients without diabetic nephropathy), as well as 217 nondiabetic healthy subjects, were recruited for this study. Clinical factors for investigation included sex, age at diagnosis, duration of diabetes, body mass index (BMI), and fasting plasma glucose, hemoglobin A(1c) (HbA(1c)), total cholesterol, and triglyceride levels. Genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism analyses. No difference in the Bgl II polymorphism of the alpha2beta1 integrin gene was found between patients with type 2 diabetes with or without nephropathy (11 [8.7%], 47 [37.3%], and 68 patients [54.0%] versus 10 [9.3%], 32 [29.6%], and 66 patients [61.1%] for Bgl II+/+, Bgl II+/-, and Bgl II-/-, respectively; P = 0.271). Multiple logistic regression analyses showed that duration of diabetes, BMI, hypertension, and poor glycemic control were four independent predictors for the development of diabetic nephropathy. No contribution of the Bgl II+ allele of the alpha2beta1 integrin was found for the risk for nephropathy (odds ratio, 1.258; 95% confidence interval, 0.655 to 2.418; P = 0.490). The Pl(A2) allele genotype was not found among our studied subjects. In conclusion, age, duration of diabetes, BMI, and HbA(1c) level are strong predictors for nephropathy in patients with type 2 diabetes. However, the Bgl II polymorphism of the alpha2beta1 integrin gene and the Apa I polymorphism of the platelet GPIIIa gene do not have a major role in the development of diabetic nephropathy in our population.
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PMID:Platelet collagen receptor alpha2beta1 integrin and glycoprotein IIIa Pl(A1/A2) polymorphisms are not associated with nephropathy in type 2 diabetes. 1172 49

Several recent comparative trials in hypertension have reported that similar blood pressure reductions may not necessarily translate into similar reductions in risk for cardiovascular complications. Thus, the method used to lower blood pressure may be important. In the Antihypertensive and Lipid-Lowering Treatment To Prevent Heart Attack Trial (ALLHAT), low-dose chlorthalidone as the first-line drug was superior to doxazosin. The 25% higher risk for major cardiovascular events associated with doxazosin was attributed primarily to a doubling in the risk for heart failure. A meta-analysis of patients with type 2 diabetes mellitus suggested that despite achieving similar blood pressure reductions, angiotensin-converting enzyme inhibitors are superior to other antihypertensive drugs in reducing the risk for acute myocardial infarction and cardiovascular events, but not stroke. Although individual comparative trials have failed to show conclusively that calcium-channel blockers differ from other antihypertensive drugs, a meta-analysis that included all published trials concluded that calcium-channel blockers are inferior to other classes of drugs in reducing the risk for acute myocardial infarction and heart failure. These observations suggest not only that antihypertensive drugs may have important mechanisms of action apart from blood pressure lowering but also that effective treatment is not a matter of simply lowering blood pressure. These findings have potential implications for the regulatory approval of antihypertensive agents, revisions of treatment guidelines, the design of future randomized trials comparing different antihypertensive drugs and, most important, the selection of drugs for the treatment of hypertensive patients.
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PMID:Clinical Implications of Recent Findings from the Antihypertensive and Lipid-Lowering Treatment To Prevent Heart Attack Trial (ALLHAT) and Other Studies of Hypertension. 1174 86


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