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Query: UMLS:C0242339 (dyslipidemia)
 13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetes-related cardiovascular disease remains the leading cause of death in patients with type 2 diabetes. Hypertension is common among diabetics and has the same pathogenetic mechanisms as insulin resistance, in which the activated renin-angiotensin system contributes to the emerging high blood pressure and hyperglycemia. Hyperglycemia is one of the triggering factors for vascular dysfunction and clotting abnormalities and, therefore, for accelerated atherosclerosis in diabetes. Glycated hemoglobin levels, as a reflection of the degree of glycemia, are strongly associated with the risk of cardiovascular disease in diabetics and in the general population. Tight glycemic control, the treatment of dyslipidemia and raised blood pressure, in addition to the use of antiplatelet therapy, all powerfully reduce the risks associated with diabetes. Furthermore, angiotensin-converting enzyme inhibitors might offer additional cardioprotection to diabetics above that provided by blood pressure reduction.
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PMID:Diabetes mellitus and diabetes-associated vascular disease. 1139 48

Past and current drug therapies for weight loss are discussed. More than 50% of Americans can be categorized as overweight or obese. Obesity is associated with increased mortality and with comorbidities such as hypertension, hyperglycemia, dyslipidemia, coronary artery disease, and certain cancers. According to guidelines for identification, evaluation, and treatment of obesity, patients with a body mass index (BMI) of > or = 30 kg/m2 should attempt to lose weight. Patients with a BMI of > or = 25 kg/m2 plus two or more risk factors or patients with an excessive waist circumference plus two or more risk factors should also attempt to lose weight. The initial goal is a 10% weight reduction in six months achieved through lifestyle changes. If lifestyle changes alone are not effective, then drug therapy may be indicated. Pharmacotherapeutic options for obesity have decreased over the past few years. Fenfluramine, dexfenfluramine, and phenylpropanolamine have been withdrawn because of severe adverse effects, leaving only sympathomimetics, sibutramine, and orlistat as anorectics with FDA-approved labeling. Phentermine has been shown to cause a 5-15% weight loss if given daily or intermittently. Compared with sibutramine and orlistat, phentermine is cheaper, and specific formulations allow once-daily administration. However, phentermine is indicated only for short-term treatment, and tolerance often develops. Common adverse effects associated with phentermine are dry mouth, insomnia, increased blood pressure, and constipation. Sibutramine increases norepinephrine and serotonin levels in the CNS and should not be taken with many antidepressants because of the risk of increased norepinephrine and serotonin levels. Its use is also contraindicated in patients with cardiovascular disease. Orlistat is not systemically absorbed; therefore, it does not cause the systemic adverse effects or drug interactions of phentermine and sibutramine. Orlistat has a cholesterol-lowering effect not seen with other diet medications. However, the three-times-daily administration and frequent gastrointestinal effects limit its use. Sibutramine, phentermine, and orlistat have both positive and negative properties. Choosing among the medications will depend on concurrent disease states and medications, ease of administration, and cost.
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PMID:Pharmacologic options for the treatment of obesity. 1147 77

Type 2 diabetes is a complex metabolic disorder characterized by elevated blood glucose levels and a marked increase in the risk of cardiovascular disease (CVD). The increased CVD risk is caused by a unique cluster of metabolic abnormalities, including dyslipidemia, hypertension, insulin resistance, and hyperglycemia. To reduce the risk of cardiovascular complications in patients with type 2 diabetes, comprehensive management of risk factors is essential. Aggressive treatment of dyslipidemia and hypertension is known to benefit patients with type 2 diabetes. In addition, intensive glycemic control and targeted treatment of insulin resistance can further reduce the enormous burden of CVD in this high-risk population. Increasing evidence suggests that insulin resistance is one of the earliest markers of risk for both CVD and diabetes, and it is known that insulin resistance alone can significantly increase the risk of CVD. Type 2 diabetes and insulin resistance are both associated with disordered lipid metabolism, manifest in elevated triglyceride levels, low levels of high-density lipoprotein cholesterol, and small, dense low-density lipoprotein cholesterol particles. Patients with type 2 diabetes and insulin resistance have an increased risk of hypertension, which further contributes to their CVD risk. Each of these factors can also contribute to the risk of microvascular disease. To ensure that patients with type 2 diabetes receive comprehensive, high-quality care, specific standards have been developed. These standards can help providers establish clear treatment targets, identify specific priorities of care, and use therapies of known efficacy to reduce the risk of complications. This review summarizes the current standards of care for patients with type 2 diabetes, with an emphasis on treatments that reduce the cardiovascular risk factors. Using a case study approach, it reviews the essential components of diabetes care and proposes a rational approach to these complex cases--an approach that should result in consistent, high-quality care.
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PMID:Comprehensive management of patients with type 2 diabetes: establishing priorities of care. 1151 98

We show that high doses of salicylates reverse hyperglycemia, hyperinsulinemia, and dyslipidemia in obese rodents by sensitizing insulin signaling. Activation or overexpression of the IkappaB kinase beta (IKKbeta) attenuated insulin signaling in cultured cells, whereas IKKbeta inhibition reversed insulin resistance. Thus, IKKbeta, rather than the cyclooxygenases, appears to be the relevant molecular target. Heterozygous deletion (Ikkbeta+/-) protected against the development of insulin resistance during high-fat feeding and in obese Lep(ob/ob) mice. These findings implicate an inflammatory process in the pathogenesis of insulin resistance in obesity and type 2 diabetes mellitus and identify the IKKbeta pathway as a target for insulin sensitization.
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PMID:Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of Ikkbeta. 1153 94

Excess tissue glucocorticoid action may underlie the dyslipidemia, insulin resistance, and impaired glucose tolerance of the metabolic syndrome. 11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD-1) catalyzes conversion of circulating inert 11-dehydrocorticosterone into active corticosterone, thus amplifying local intracellular glucocorticoid action, particularly in liver. The importance of 11beta-HSD-1 in glucose homeostasis is suggested by the resistance of 11beta-HSD-1(-/-) mice to hyperglycemia upon stress or obesity, due to attenuated gluconeogenic responses. The present study further investigates the metabolic consequences of 11beta-HSD-1 deficiency, focusing on the lipid and lipoprotein profile. Ad lib fed 11beta-HSD-1(-/-) mice have markedly lower plasma triglyceride levels. This appears to be driven by increased hepatic expression of enzymes of fat catabolism (carnitine palmitoyltransferase-I, acyl-CoA oxidase, and uncoupling protein-2) and their coordinating transcription factor, peroxisome proliferator-activated receptor-alpha (PPARalpha). 11beta-HSD-1(-/-) mice also have increased HDL cholesterol, with elevated liver mRNA and serum levels of apolipoprotein AI. Conversely, liver Aalpha-fibrinogen mRNA levels are decreased. Upon fasting, the normal elevation of peroxisome proliferator-activated receptor-alpha mRNA is lost in 11beta-HSD-1(-/-) mice, consistent with attenuated glucocorticoid induction. Despite this, crucial oxidative responses to fasting are maintained; carnitine palmitoyltransferase-I induction and glucose levels are similar to wild type. Refeeding shows exaggerated induction of genes encoding lipogenic enzymes and a more marked suppression of genes for fat catabolism in 11beta-HSD-1(-/-) mice, implying increased liver insulin sensitivity. Concordant with this, 24-h refed 11beta-HSD-1(-/-) mice have higher triglyceride but lower glucose levels. Further, 11beta-HSD-1(-/-) mice have improved glucose tolerance. These data suggest that 11beta-HSD-1 deficiency produces an improved lipid profile, hepatic insulin sensitization, and a potentially atheroprotective phenotype.
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PMID:Improved lipid and lipoprotein profile, hepatic insulin sensitivity, and glucose tolerance in 11beta-hydroxysteroid dehydrogenase type 1 null mice. 1154 66

Coronary artery, cerebrovascular and peripheral vascular disease, are the principal causes of morbidity and mortality in type 2 diabetes mellitus. The accelerated macrovascular disease in type 2 diabetes mellitus is due partly to the increased incidence of cardiovascular risk factors, such as hypertension, obesity and dyslipidemia. Advanced glycation end products, glycoxidised and oxidized low-density lipoproteins and reactive oxygen species linked to hyperglycemia have all been identified in type 2 diabetes mellitus and could accelerate macroangiopathy. Hence, the resistance to insulin is an additional independent risk factor, in association with oxidant stress, dyslipidemias, and prothrombic/hypofibrinolytic states. The endothelium is a major organ involved by cardiovascular risk factors, such as hypercholesterolemia, hypertension, inflammation, ageing, postmenopausal status, and smoking. Changes in endothelium function may lead to the coronary artery circulation being unable to cope with the increased metabolism of myocardial muscle independently of a reduced coronary artery diameter. The way endothelial function is altered in diabetic patients is not yet fully understood, but the loss of normal endothelial function could be involved in the pathogenesis of diabetic angiopathy, as endothelial dysfunction is associated with diabetic microangiopathy and macroangiopathy. Finally, recent reports indicate that an improved metabolic control in diabetic patients, whatever the treatment used, is associated with near normalization or restoration of normal endothelial function.
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PMID:Endothelial dysfunction and type 2 diabetes. Part 1: physiology and methods for exploring the endothelial function. 1154 16

Coronary artery, cerebrovascular and peripheral vascular disease, are the principal causes of morbidity and mortality in type 2 diabetes mellitus. The accelerated macrovascular disease in type 2 diabetes mellitus is due partly to the increased incidence of cardiovascular risk factors, such as hypertension, obesity and dyslipidemia. Advanced glycation end products, glycoxidised and oxidized low-density lipoproteins and reactive oxygen species linked to hyperglycemia have all been identified in type 2 diabetes mellitus and could accelerate macroangiopathy. Hence, the resistance to insulin is an additional independent risk factor, in association with oxidant stress, dyslipidemias, and prothrombic/hypofibrinolytic states. The endothelium is a major organ involved by cardiovascular risk factors, such as hypercholesterolemia, hypertension, inflammation, ageing, postmenopausal status, and smoking. Changes in endothelium function may lead to the coronary artery circulation being unable to cope with the increased metabolism of myocardial muscle independently of a reduced coronary artery diameter. The way endothelial function is altered in diabetic patients is not yet fully understood, but the loss of normal endothelial function could be involved in the pathogenesis of diabetic angiopathy, as endothelial dysfunction is associated with diabetic microangiopathy and macroangiopathy. Finally, recent reports indicate that an improved metabolic control in diabetic patients, whatever the treatment used, is associated with near normalization or restoration of normal endothelial function.
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PMID:Endothelial dysfunction and type 2 diabetes. Part 2: altered endothelial function and the effects of treatments in type 2 diabetes mellitus. 1154 17

Diabetic patients are at increased risk for adverse outcomes of surgery. These adverse outcomes are related to pre-existing complications of diabetes, especially atherosclerotic disease, nephropathy (and perhaps increased susceptibility to other renal toxins), and peripheral and autonomic neuropathy. Hyperglycemia is associated with likely risks for poorer wound healing, increased susceptibility to infection, and probable loss of administered nutrients through glycosuria. Insulin use has the flexibility of timing and dose in the postoperative management of most diabetic patients. The combinations of intermediate-acting and long-acting insulins and short-acting insulins usually are related to the experience and preferences of the treating physicians and allied health professionals. Intravenous insulin (always R) may be limited to administration in the ICU because of the need for frequent blood glucose monitoring and rapidity of glucose response to intravenous insulin. The use of short-acting insulin analogues has been shown to work well as premeal insulin or for rapidly treating marked hyperglycemia in the outpatient setting. Meal delivery in the hospitalized patient may not be timed as precisely as in the home situation. Nurses may be responsible for many patients. The rapid-acting analogues may be associated with increased risk for hypoglycemia in the hospitalized patient if insulin cannot be given immediately before a meal. These rapid-acting insulin analogues usually are limited to circumstances in which the patient can determine the dose and self-administer just before ingestion of the meal. The long-acting insulin analogues may not afford enough flexibility in many situations in which daily dosages changes are occurring in intermediate-acting and long-acting insulins. Oral glucose-lowering agent use in the postoperative state usually is limited to selected patients, including patients who have been on such agents before surgery, who have only mild elevations of blood glucose, who are able to ingest oral medications, and who do not have significant comorbid conditions (or significant risk for such conditions) that may be contraindications to use of such agents (see Table 3). Sulfonylureas and other insulin secretagogues (e.g., meglitinide, nateglinide) lower glucoses acutely. The risk for hypoglycemia is slightly less with the nonsulfonylurea agents. Efficacy and side effects limit the use of carbohydrase inhibitors for hospitalized patients. The glucose-lowering effects of biguanides and thiazolidinediones usually are not rapid enough for hospitalized patients who have never taken these medications. For patients who have been on a biguanide or thiazolidinedione before admission, these agents often are restarted in the postoperative period when oral intake of medications is possible and hepatic and renal function are stable. The hospital period affords an opportunity to review long-term management issues related to diabetes and its complications. Instruction on the importance of medical nutrition therapy, glycemic control, management of hypertension, dyslipidemia, and aspirin use as well as basic guidelines for foot care should be carried out during the hospitalization and at the time of discharge. Similarly, appropriate arrangements for medical nutrition therapy, general diabetes education (especially for newly diagnosed diabetic patients), and regular medical follow-up are important to ensure long-term, excellent surgical and medical outcomes.
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PMID:Postoperative management of the diabetic patient. 1156 95

Patients with type 2 diabetes mellitus have an elevated risk of morbidity and mortality from cardiovascular disease. This risk is partly attributable to an increased prevalence of classic coronary artery disease risk factors and partly because of hyperglycemia itself and a highly atherogenic lipid profile. The altered composition of lipoproteins and lipids in type 2 diabetic patients, termed diabetic dyslipidemia, is characterized by: (1) elevated levels of triglyceride; (2) normal levels of total and low-density lipoprotein cholesterol (LDL-C); (3) reduced levels of high-density lipoprotein cholesterol (HDL-C); (4) elevated levels of apolipoprotein B; (5) a preponderance of small, dense LDL particles; and (6) increased levels of cholesterol-rich very-low-density lipoprotein. In most cases, diabetic dyslipidemia is preceded by hyperinsulinemia resulting from insulin resistance. Because patients with type 2 diabetes and insulin resistance are at a markedly increased risk of atherosclerosis, and because strict control of glycemia has proved beneficial in reducing microangiopathy but not macroangiopathy, treatment of diabetic dyslipidemia should be aggressive. Target levels have, therefore, been set at <2.6 mmol/L (100 mg/dL) for LDL-C, <2.3 mmol/L [200 mg/dL] for triglycerides, and >1.15 mmol/L (45 mg/dL) for HDL-C. Trial data suggest that these target levels are likely to be achieved with statins, if necessary, in combination with fibrates or nicotinic acid derivatives. Furthermore, in large-scale clinical trials (eg, Scandinavian Simvastatin Survival Study [4S] and the Cholesterol and Recurrent Events [CARE] study), it has been demonstrated that lipid lowering can appreciably reduce cardiovascular events in diabetic patients.
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PMID:Insulin resistance syndrome and type 2 diabetes mellitus. 1159 98

The rapidly growing number of patients with coexisting diabetes and hypertension must be intensively treated to protect them from their very high risk for premature cardiovascular morbidity and mortality. After careful ascertainment of their out-of-the-office blood pressure, and testing for postural hypotension, therapy should consist of both lifestyle modifications and antihypertensive drugs. Usually, two or more such drugs are needed to bring blood pressure below the 130/85 mm Hg level. In addition, control of hyperglycemia and dyslipidemia is usually required. Despite the costs and difficulties of achieving adequate control of these diseases, such patients can be protected from the debilities of diabetes and hypertension.
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PMID:Treatment of coexisting diabetes and hypertension. 1160 81


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