Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0242339 (dyslipidemia)
 13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

BACKGROUND AND THERAPY: The metabolic syndrome comprises a virulent and lethal group of atherosclerotic risk factors, including dyslipidemia, obesity, systemic hypertension and insulin resistance. The prevalence of the metabolic syndrome has continuously grown in industrialized and developing countries during the last decades, and affects tens of millions of people in Germany and Europe. Particularly prominent as a risk factor for the development of insulin resistance is central obesity, which is causally involved in the pathogenesis of insulin resistance in addition to genetic predisposition. The metabolic syndrome can easily be diagnosed in clinical practice (guidelines of the WHO and ATP III panel), and immediate treatment of the metabolic syndrome is mandatory because those patients are at increased risk to develop overt diabetes mellitus, coronary artery disease and stroke. The high risk for cardiovascular diseases is supported by findings that the risk for myocardial infarction in patients with insulin resistance is as high as the risk of patients after their first myocardial infarction. Intentional weight reduction reduces abdominal obesity and beneficially modulates all features of the metabolic syndrome, while the benefits of aerobic exercise training are discussed controversially. Thus, weight reduction causally undoes essential features of the metabolic syndrome, but effects are often not enduring. Therefore, the treatment of cardiovascular risk factors such as hypertension and dislipidemia is essential. Of note, antihypertensive treatment is more effective than tight glucose control to reduce cardiovascular events. Diuretics, ACE-inhibitors and angiotensin II type 1 receptor antagonists are suggested as first line therapeutics. However, at least two antihypertensives are usually necessary to achieve the suggested goals of blood pressure reduction. In conclusion, the prevalence of the metabolic syndrome is continuously growing. Due to its adverse impact on cardiovascular disease, early detection and aggressive treatment is mandatory to ensure longlasting benefits for affected patients.
 ...
PMID:[Arterial hypertension and metabolic syndrome]. 1468 1

Type 2 diabetes mellitus (DM) is associated with an increased risk for both micro-and macrovascular complications, and cardiovascular diseases (CVD) are the most common causes of death in these patients, accounting for almost 70% of the deaths. Given the high prevalence of the condition and the expected global increase in the prevalence of type 2 DM, a case is made for prevention of these serious complications in order to reduce the individual morbidity and the economic burden on society. In this review we present the knowledge of how macrovascular disease in patients with type 2 DM may be prevented, and suggest possible strategies for doing so.A thorough search of the published literature was conducted and we first present relevant epidemiological studies demonstrating the impact of important risk factors for CVD in DM, such as dyslipidemia, hyperglycemia, hypertension, smoking, familial premature coronary heart disease and some non-classical risk factors such as hyperinsulinemia, insulin resistance, endothelial dysfunction and inflammation. Secondly, we review the results from published randomized controlled clinical trials and meta-analysis of these, evaluate the findings and suggest strategies for preventing CVD in patients with type 2 DM using non-pharmacological and pharmacological approaches. Present knowledge indicates that most patients with type 2 DM either have manifest CVD or have a high risk for future cardiovascular events, men with DM have a 2- to 4-fold; and women with DM a 3- to 5-fold increased risk for cardiovascular death compared with non-diabetic individuals. Care of patients with type 2 DM should include yearly risk assessment by the use of published risk equations or risk charts. On the background of this assessment, an individual risk reducing strategy should be tailored to each patient's need, including the treatment of hyperglycemia, hypertension and dyslipidemia together with the use of aspirin (acetylsalicylic acid) and ACE inhibitors. Such measures can reduce the risk of cardiovascular events in patients with type 2 DM.
 ...
PMID:Preventing macrovascular disease in patients with type 2 diabetes mellitus. 1472 81

Heart failure affects nearly 5 million Americans and is associated with high morbidity and mortality rates. It is now recognized that activation of multiple neurohormonal systems is intrinsic in the pathophysiology of heart failure. Patients with diabetes mellitus are at high risk for heart failure, and some of the complications of diabetes (e.g., insulin resistance) contribute to the development and progression of heart failure, partly because of their effects on neurohormonal systems. Pharmacologic intervention directed toward these systems (i.e., angiotensin-converting enzyme [ACE] inhibition, use of aldosterone antagonists, and beta-adrenergic blockade) has been shown to decrease the morbidity and mortality associated with heart failure. Despite this knowledge, ACE inhibitors, aldosterone antagonists, and beta-blockers are grossly underused, and deaths and hospitalizations due to heart failure have steadily increased. Guidelines for the management of heart failure recommend the use of ACE inhibitors and beta-blockers in patients with mild, moderate, or severe disease. Aldosterone antagonists are recommended in severe heart failure, and recent data also support their use in mild to moderate heart failure. Concerns about the increased incidence of hypoglycemia, worsening dyslipidemia, and decreased insulin sensitivity with beta-blocker use may be preventing physicians from prescribing these agents for patients with diabetes with heart failure. Although evidence from earlier clinical trials justifies some of these concerns, newer vasodilating beta-blockers (e.g., carvedilol) have been shown to have a neutral or positive effect on dyslipidemia and insulin resistance. beta-Blockade in conjunction with ACE inhibition should be standard therapy for all patients with diabetes who have heart failure. Furthermore, early in-hospital initiation of neurohormonal intervention can provide earlier benefit to these patients.
 ...
PMID:Managing the patient with diabetes mellitus and heart failure: issues and considerations. 1501 65

This article describes the relationship between CVD and CKD, the current state of knowledge regarding medical interventions, and underscores the importance of attending to both CVD and kidney disease aspects in each individual. The burden of cardiac disease in CKD patients is high with severe LVH, dilated cardiomyopathy and coronary artery disease occurring frequently. This predisposes to congestive heart failure, angina, myocardial infarction, and death. Multiple risk factors for cardiac disease exist and include hypertension, diabetes, smoking, anemia, abnormal calcium and phosphate metabolism, inflammation, and LVH. The efficacy of risk factor intervention has not been established in these populations, although there is good evidence for good blood pressure control, partial correction of anemia, treatment of dyslipidemia, cessation of tobacco use, correction of divalent abnormalities, and aspirin us. Appropriate use of ACE inhibitors, beta-blockers, and statins should be encouraged.
 ...
PMID:Multiple risk factor intervention in chronic kidney disease: management of cardiac disease in chronic kidney disease patients. 1575 65

The basis for accelerated atherosclerosis in diabetes is unclear. Diabetes is associated with loss of heparan sulfate (HS) from the liver, which may impede lipoprotein clearance and thereby worsen atherosclerosis. To study hepatic HS loss in diabetes, we examined regulation of HS N-deacetylase/N-sulfotransferase-1 (NDST), a key enzyme in hepatic HS biosynthesis. Hepatic NDST mRNA, protein, and enzymatic activity were suppressed by >50% 2 weeks after induction of type 1 diabetes in rats. Treatment of diabetic rats with enalapril, an ACE inhibitor, had no effect on hyperglycemia or hepatic NDST mRNA levels, yet increased hepatic NDST protein and enzymatic activity. Similar results were obtained in diabetic animals treated with losartan, which blocks the type 1 receptor for angiotensin II (AngII). Consistent with these findings, diabetic livers exhibited increased ACE expression, and addition of AngII to cultured hepatoma cells reduced NDST activity and protein. We conclude that diabetes substantially suppresses hepatic NDST mRNA, protein, and enzymatic activity. AngII contributes to suppression of NDST protein and enzymatic activity, whereas mRNA suppression occurs independently. Suppression of hepatic NDST may contribute to diabetic dyslipidemia, and stimulation of NDST activity by AngII inhibitors may provide cardiovascular protection.
 ...
PMID:Loss of heparan N-sulfotransferase in diabetic liver: role of angiotensin II. 1579 51

America is experiencing a major obesity epidemic. The ramifications of this epidemic are immense since obesity is associated with chronic metabolic abnormalities such as insulin resistance, dyslipidemia, and heart disease. Reduced physical activity and/or increased energy intakes are important factors in this epidemic. Additionally, a genetic susceptibility to obesity is associated with gene polymorphisms affecting biochemical pathways that regulate fat oxidation, energy expenditure, or energy intake. However, these pathways are also impacted by specific foods and nutrients. Vitamin C status is inversely related to body mass. Individuals with adequate vitamin C status oxidize 30% more fat during a moderate exercise bout than individuals with low vitamin C status; thus, vitamin C depleted individuals may be more resistant to fat mass loss. Food choices can impact post-meal satiety and hunger. High-protein foods promote postprandial thermogenesis and greater satiety as compared to high-carbohydrate, low-fat foods; thus, diet regimens high in protein foods may improve diet compliance and diet effectiveness. Vinegar and peanut ingestion can reduce the glycemic effect of a meal, a phenomenon that has been related to satiety and reduced food consumption. Thus, the effectiveness of regular exercise and a prudent diet for weight loss may be enhanced by attention to specific diet details.
 ...
PMID:Strategies for healthy weight loss: from vitamin C to the glycemic response. 1703 Oct 14

High-fructose diet stimulates hepatic de novo lipogenesis (DNL) and causes hypertriglyceridemia and insulin resistance in rodents. Fructose-induced insulin resistance may be secondary to alterations of lipid metabolism. In contrast, fish oil supplementation decreases triglycerides and may improve insulin resistance. Therefore, we studied the effect of high-fructose diet and fish oil on DNL and VLDL triglycerides and their impact on insulin resistance. Seven normal men were studied on four occasions: after fish oil (7.2 g/day) for 28 days; a 6-day high-fructose diet (corresponding to an extra 25% of total calories); fish oil plus high-fructose diet; and control conditions. Following each condition, fasting fractional DNL and endogenous glucose production (EGP) were evaluated using [1-13C]sodium acetate and 6,6-2H2 glucose and a two-step hyperinsulinemic-euglycemic clamp was performed to assess insulin sensitivity. High-fructose diet significantly increased fasting glycemia (7 +/- 2%), triglycerides (79 +/- 22%), fractional DNL (sixfold), and EGP (14 +/- 3%, all P < 0.05). It also impaired insulin-induced suppression of adipose tissue lipolysis and EGP (P < 0.05) but had no effect on whole- body insulin-mediated glucose disposal. Fish oil significantly decreased triglycerides (37%, P < 0.05) after high-fructose diet compared with high-fructose diet without fish oil and tended to reduce DNL but had no other significant effect. In conclusion, high-fructose diet induced dyslipidemia and hepatic and adipose tissue insulin resistance. Fish oil reversed dyslipidemia but not insulin resistance.
 ...
PMID:Effect of fructose overfeeding and fish oil administration on hepatic de novo lipogenesis and insulin sensitivity in healthy men. 1598 89

Prolonged hyperglycemia, dyslipidemia and oxidative stress in diabetes result in the production and accumulation of AGEs. It is now clear that AGEs contribute to the development and progression of cardiovascular disease in diabetes, as well as other complications. AGEs are thought to act through receptor-independent and dependent mechanisms to promote vascular damage, fibrosis and inflammation associated with accelerated atherogenesis. As a result, novel therapeutic agents to reduce the accumulation of AGEs in diabetes have gained interest as potential cardioprotective approaches. A variety of agents have been developed which are examined in detail in this review. These include aminoguanidine, ALT-946, pyridoxamine, benfotiamine, OPB-9195, alagebrium chloride, N-phenacylthiazolium bromide and LR-90. In addition, it has been demonstrated that a number of established therapies have the ability to reduce the accumulation of AGEs in diabetes including ACE inhibitors, angiotensin receptor antagonists, metformin, peroxisome proliferators receptor agonists, metal chelators and some antioxidants. The fact that many of these inhibitors of AGEs are effective in experimental models, despite their disparate mechanisms of action, supports the keystone role of AGEs in diabetic vascular damage. Nonetheless, the clinical utility of AGE inhibition remains to be firmly established. Optimal metabolic and blood pressure control, that is achieved early and sustained indefinitely, remains the best recourse for inhibition of AGEs until more specific interventions become a clinical reality.
 ...
PMID:The role of AGEs and AGE inhibitors in diabetic cardiovascular disease. 1602 65

Diabetes mellitus is a chronic progressive disease that results in microvascular and macrovascular complications. Diabetes is a significant independent risk factor for heart failure, and there are a substantial number of patients with diabetes and heart failure. Neurohormonal activation plays an important pathophysiologic role in insulin resistance, diabetes, cardiovascular events, and progression of heart failure. Pharmacologic intervention in these neurohormonal systems (ie, angiotensin-converting enzyme [ACE] inhibition, aldosterone antagonism, and beta-adrenergic blockade) has been shown to decrease the morbidity and mortality of diabetes and of heart failure. Despite this knowledge, ACE inhibitors, aldosterone antagonists, and beta-blockers are grossly underutilized, and deaths and hospitalizations due to heart failure have steadily increased. Guidelines for the management of heart failure recommend the use of ACE inhibitors and beta-blockers in patients with mild, moderate, and severe heart failure with or without diabetes. Aldosterone antagonists are recommended in severe heart failure and recent data also support their use in mild to moderate heart failure. Concerns about increased incidence of hypoglycemia, worsening dyslipidemia, and decreased insulin sensitivity with beta-blockers may be preventing physicians from prescribing these agents for their patients with diabetes who have heart failure. Beta-blockade, in conjunction with ACE inhibition and aldosterone antagonism, should be standard therapy for all patients with diabetes and heart failure. Furthermore, every effort should be made to ensure that eligible patients are treated with these evidence-based, guideline-recommended, life-prolonging therapies.
 ...
PMID:An approach to heart failure and diabetes mellitus. 1609 44

Cardiac artery disease and heart failure are major causes for morbidity and mortality in diabetes in general and in those with chronic kidney disease (CKD) in particular. Hypertension and dyslipidemia are more common in diabetes and the prevalence of coronary artery disease in diabetics is two-fold to four-fold higher than in nondiabetics. In those with CKD the incidence of cardiovascular complications is nearly two-fold higher than those without CKD. Recent studies suggest that the pathophysiology of cardiac disease is complex process involving both microvascular and macrovascular disease. In addition, myocardial lipotoxicity may be a novel contributing factor particularly in type 2 diabetics. Compelling evidence from cardiovascular outcomes trials indicates that treatment with drugs that block the renin-angiotensin system are cardioprotective in diabetics with microalbuminuria and early stages of kidney disease. Multiple risk factor intervention aimed at optimal blood pressure control (BP <130/<80 mmHG), lowering LDL cholesterol below 100 mg/dl, lowering triglyceride level to 150 mg/dl, A1C <6.5%, treatment with an ACE inhibitor or an angiotensin II receptor blocker, administration of once daily low-dose aspirin and smoking cessation together reduce cardiovascular morbidity and mortality in type 2 diabetics. Novel studies including diabetics with nephropathy aimed at improving outcomes in diabetics by treatment of anemia and optimal control of dyslipidemia are now underway. These and other clinical trials should provide important new insights into improving the quality of life in diabetics and ultimately preventing cardiac disease.
 ...
PMID:Heart disease in diabetic patients. 1629 58


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