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

Patients with diabetes mellitus have an increased risk for coronary artery disease due to hyperglycemia, hypertension, dyslipidemia, and other risk factors. The diabetic dyslipidemia in these patients is characterized by moderately high levels of (1) serum cholesterol and triglycerides; (2) small, dense low-density lipoprotein (LDL) particles; and (3) low high-density lipoprotein (HDL) cho-lesterol concentrations. Recent clinical trials have demonstrated the benefits of cholesterol-lowering therapy in both diabetic and nondiabetic patients, thus supporting aggressive treatment of diabetic dyslipidemia for coronary artery disease prevention. A 3-step approach is recommended for the treatment of diabetic dyslipidemia. First, modification of diet and lifestyle, including decreased intakes of cholesterol, cholesterol-raising fats, and total energy, and increased physical activity should be advised. Second, good glycemic control should be achieved with diet and hypoglycemic drugs, if needed. Third, lipid-lowering drugs should be used, if necessary. Non-HDL cholesterol levels, which include both very-low-density lipoprotein (VLDL) and LDL cholesterol, should be the target of cholesterol-lowering therapy. The use of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (the "statins") has become the first-line drug therapy for diabetic dyslipidemia. Bile acid sequestrants are effective cholesterol-lowering agents in normotriglyceridemic patients with non-insulin-dependent diabetes mellitus (NIDDM). Patients with severe hypertriglyceridemia may require fibric acids or n-3 polyunsaturated fatty acids. Nicotinic acid worsens hyperglycemia; therefore, it should be avoided in most cases. The efficacy and safety of estrogen-replacement therapy in postmenopausal women with diabetes needs to be determined. The combination of two lipid-lowering agents may be appropriate for some NIDDM patients but should be used judiciously.
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PMID:Treatment of diabetic dyslipidemia. 952 14

Subjects with diabetes have a greatly increased risk of CHD, which is only partially related to their elevated glucose. Other factors such as insulin resistance and dyslipidemia are likely to be important. The type of dyslipidemia that is most characteristic of type 2 diabetic subjects is elevated triglycerides and decreased HDL cholesterol levels, although all lipoproteins have compositional abnormalities. Surprisingly few good prospective studies of lipoprotein levels in relation to CHD have been done in diabetic subjects. Available studies suggest that low HDL cholesterol may be the most important risk factor for CHD in observational studies. In studies in which total cholesterol and triglyceride were done, cholesterol and triglycerides were risk factors for CHD, although triglycerides were often a stronger predictor. However, the strength of triglyceride as a risk factor for CHD may depend partially on its association with other variables (e.g., hypertension, plasminogen activator inhibitor 1 [PAI-1], etc.). In clinical trials in diabetic subjects, LDL reduction with statins has led to significant reductions in CHD incidence. In addition, overall mortality was reduced with statin therapy, although the results were not statistically significant. Gemfibrozil has led to reductions in CHD incidence in diabetic subjects, although the results were not statistically significant perhaps because of low sample size. Regarding lipoproteins and CHD risk in diabetic patients, the very positive results of statin trials point to LDL cholesterol being more important than previous realized. Apparently, having a borderline high LDL cholesterol (between 130 and 160 mg/dl) in a diabetic patient is equivalent to a much higher LDL cholesterol in terms of CHD risk for a nondiabetic subject. Therefore, the primary target of therapy in diabetic patients is lowering LDL cholesterol (or possibly, non-HDL cholesterol). Statins are the preferred pharmacological agent in this situation. Once LDL cholesterol levels have been lowered, attention can be given to treatment of residual hypertriglyceridemia and low HDL. The goal here is weight reduction and increased exercise. However, for selected patients, combining a fibric acid (or low-dose nicotinic acid) with a statin also can be considered. Reduction of LDL levels should take priority over reduction of triglycerides in combined hyperlipidemia because of the proven safety of the statin class of drugs as well as greater reduction in CHD incidence.
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PMID:Management of dyslipidemia in adults with diabetes. 953 88

Non-insulin-dependent diabetes mellitus (NIDDM) affects approximately 12 million people in the United States. NIDDM is frequently found to coexist with other conditions, such as obesity, dyslipidemia, atherosclerotic vascular disease, and hypertension, which contribute to morbidity and mortality. Although the major clinical objective in the management of NIDDM is to control hyperglycemia, the long-term objective is to prevent microvascular and macrovascular complications. Cardiovascular disease is the major cause of death in NIDDM patients. Although hyperglycemia may be adequately controlled, risk factors for coronary heart disease may remain unchanged. Treatment with metformin controls hyperglycemia and may have positive effects on cardiovascular risk factors. When used alone or in combination with sulfonylureas, metformin tends to stabilize or decrease weight, maintains or reduces insulin levels, has beneficial effects on plasma lipid profiles, and may also have beneficial effects on blood pressure and the fibrinolytic system.
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PMID:Metformin: effects on cardiovascular risk factors in patients with non-insulin-dependent diabetes mellitus. 955 89

Hyperglycemia and dyslipidemia are two biochemical markers of diabetes mellitus. Increased incidence of cardiovascular disease and impaired fibrinolytic activity have been found in diabetic subjects. Previous studies have demonstrated that low density lipoproteins (LDLs) stimulate the production of plasminogen activator inhibitor-1 (PAI-1) and reduce the generation of tissue plasminogen activator (tPA) in vascular endothelial cells (ECs). The present study investigated the effect of glycated LDL on the production of PAI-1 and tPA in cultured human umbilical vein ECs (HUVECs). Glycation increased the abundance of glucitollysine and conjugated dienes in LDL and amplified the overproduction of PAI-1 and the reduction in tPA generation from HUVECs induced by LDL. The steady-state levels of PAI-1 mRNA in glycated LDL-treated ECs were significantly higher than those in native LDL-treated cells. Actinomycin D blocked the increase in PAI-1 generation induced by glycated LDL. Glycated LDL did not significantly reduce the levels of tPA mRNA but attenuated de novo synthesis of tPA in ECs. Treatment with 25 mmol/L aminoguanidine, an antioxidant and inhibitor of the formation of advanced glycation end products, during glycation normalized glycated LDL-induced generation of PAI-1 and tPA in ECs. The results of the present study indicate that glycation enhances the production of PAI-1 and attenuates tPA synthesis in ECs induced by LDL, which may contribute to the increased incidence of cardiovascular complications in diabetes. Formation of advanced glycation end products or peroxidation may be involved in glycated LDL-induced alterations in the generation of fibrinolytic regulators from ECs.
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PMID:Influence of glycation on LDL-induced generation of fibrinolytic regulators in vascular endothelial cells. 967 75

Diabetic patients often develop hypertension, and the presence of both hypertension and diabetes doubles the risk of death from coronary heart disease (CHD). Moreover, the presence and importance of abnormalities such as high low-density lipoprotein (LDL) cholesterol and triglycerides levels as CHD risk factors in insulin-dependent diabetes mellitus type 1 have been downplayed, while increasing evidence suggests that the management of type 1 patients should include control of dyslipidemia and hyperglycemia and an effective antihypertensive treatment able also to reduce risk factors for coronary artery events. In this study we assessed the antihypertensive and metabolic effects of doxazosin in hypertensive patients with type 1 diabetes. We show that the drug normalizes blood pressure, and while no improvement in glucose control was observed, it reduced total cholesterol and increased HDL cholesterol as well as the HDL to total cholesterol ratio. The changes of the various parameters studied, including the calculated CHD risk score based on the Framingham equation, suggest that doxazosine can reduce the CHD risk for hypertensive type 1 patients.
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PMID:Effect of doxazosin in mild to moderate hypertensive patients with insulin-dependent diabetes mellitus. 974 62

Dyslipidemia in patients with diabetes constitutes quantitative and qualitative abnormalities in all classes of lipoproteins and may be a significant contributor to the high risk of atherosclerosis in these patients. A step-care approach to therapy of diabetic dyslipidemia, including hygienic measures (diet and increased physical activity), hypoglycemic drugs, and lipid-lowering drugs, is recommended. The choice of lipid-lowering drugs depends on severity of hypertriglyceridemia. Statins and bile-acid-binding resins are the choice of therapy for diabetic dyslipidemia; however, for severely hypertriglyceridemic patients, fibric acid derivatives should be used. Nicotinic acid worsens hyperglycemia and, therefore, should be avoided. The value of estrogen replacement therapy in postmenopausal women with diabetes has not been established.
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PMID:Dyslipoproteinemia and diabetes. 978 56

Several observational studies document a considerably increased risk of advanced renal disease, cardiovascular disease, and early mortality in persons with diabetes. Both epidemiologic and observational studies indicate that progression of cardiovascular disease and renal disease is associated not only with high blood glucose levels, but also with hypertension and dyslipidemia. In persons with type 1 diabetes, hypoglycemic and antihypertensive therapy are important in the prevention of cardiovascular and renal disease. In those with type 2 diabetes, hypoglycemic therapy can help to prevent microvascular disease in the retina and in the kidney, and recent studies show that antihypertensive treatment is important in preventing cardiovascular disease. Thus, a multifactorial intervention program is key to preventing complications of hyperglycemia and, equally important, elevated blood pressure and dyslipidemia.
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PMID:Natural history of cardiovascular and renal disease in patients with type 2 diabetes: effect of therapeutic interventions and risk modification. 982 36

Women with polycystic ovary syndrome come to the gynecologist with a variety of symptoms, including menstrual irregularities, hirsutism, acne, weight gain, obesity, and infertility. An accurate diagnosis requires both confirmation of signs and symptoms of polycystic ovary syndrome and exclusion of other disorders. Once the diagnosis of polycystic ovary syndrome has been established, the presence of concomitant conditions, such as hypertension, dyslipidemia, and diabetes, must be assessed. Because the cause of polycystic ovary syndrome is not clear, treatment options have focused on symptom management. Such treatment options include oral contraceptives, gonadotropin-releasing hormone analogs with "add-back" hormone regimens, antiandrogens, ovulation-inducing agents, electrolysis, nutritional and weight loss counseling, exercise, laparoscopic ovarian drilling, and glucocorticoids. Pathogenic considerations, risk factor assessments, and treatment objectives combine to determine the choice of therapies. It is not clear whether insulin resistance is clinically important or causal in polycystic ovary syndrome symptom complex in all affected women. Polycystic ovary syndrome may be the final common expression of a variety of metabolic or neuroendocrine perturbations. If insulin resistance is a universal feature, it would make sense to treat with an insulin-sensitizing agent in the expectation that symptoms would resolve or improve. If insulin resistance is not the main etiologic factor, however, then insulin-sensitizing agents would be useful as adjunctive agents only for women with clinically important insulin resistance (eg, patients with polycystic ovary syndrome in whom insulin resistance causes hyperglycemia). In such cases an insulin-sensitizing agent could be instituted along with a program of weight loss and exercise.
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PMID:The obstetrician-gynecologist's role in the practical management of polycystic ovary syndrome. 985 17

Usual risk factors for coronary artery disease account for only 25-50% of increased atherosclerotic risk in diabetes mellitus. Other obvious risk factors are hyperglycemia and dyslipidemia. However, hyperglycemia is a very late stage in the sequence of events from insulin resistance to frank diabetes, whereas lipoprotein abnormalities are manifested during the largely asymptomatic diabetic prodrome and contribute substantially to the increased risk of macrovascular disease. The insulin-resistant diabetes course affects virtually all lipids and lipoproteins. Chylomicron and very-low-density lipoprotein (VLDL) remnants accumulate, and triglycerides enrich high-density lipoprotein (HDL) and low-density lipoprotein (LDL), leading to high levels of potentially atherogenic particles and low levels of HDL cholesterol. Hyperglycemia eventually impairs removal of triglyceride-rich lipoproteins, the accumulation of which accentuates hypertriglyceridemia. As triglycerides increase-still within the so-called normal range-abnormalities in HDL and LDL became more apparent. Thus, when triglycerides are >200 mg/dL, LDL particles are small and dense (when they are <90 mg/dL, the particles are of the large, buoyant variety). The atherogenicity of small, dense LDL particles is attributed to their increased susceptibility to oxidation, but in many patients they may be a marker for insulin resistance or the presence of atherogenic VLDL. Hypertriglyceridemia is associated with atherosclerosis because (1) it is a marker for insulin resistance and atherogenic metabolic abnormalities; and (2) the small size of triglyceride-enriched lipoproteins enables them to infiltrate the blood vessel wall where they are oxidized, bind to receptors on macrophages, and ingested, leading to the development of the atherosclerotic lesion. Various studies (primary prevention with gemfibrozil: Helsinki Heart Study; secondary prevention with simvastatin and pravastatin: Scandinavian Simvastatin Survival Study [4S] and Cholesterol and Recurrent Events [CARE], respectively) have demonstrated that lipid-lowering therapy in type 2 diabetes is effective in decreasing the number of cardiac events. Risk reduction was 22% to 50% (statins) and approximately 65% (fibrate) relative to placebo. It was also noted (in 4S and CARE) that the risk of major coronary events in untreated diabetic patients was 1.5-1.7-fold greater than in untreated nondiabetic patients. Although gemfibrozil (fibric acid derivative) is more effective in decreasing triglycerides and increasing HDL cholesterol in diabetic patients than the statins, it does not change and may even increase LDL-cholesterol levels (fenofibrate may be an exception, decreasing LDL cholesterol by 20-25% in some studies). However, gemfibrozil does increase LDL particle size. Nevertheless, the statins are the current lipid-lowering drugs of choice because the change in LDL-cholesterol-to-HDL-cholesterol ratio is better than with gemfibrozil. Moreover, the diabetic patient may be more likely to benefit from statin therapy than the nondiabetic patient. It should be noted that, in theory, nicotinic acid can correct or improve all lipid or lipoprotein abnormalities in patients with type 2 diabetes. Unfortunately, it is relatively contraindicated because it causes insulin resistance and may precipitate or aggravate hyperglycemia (in addition to its other well-known side effects such as flushing, gastric irritation, development of hepatotoxicity, and hyperuricemia). It is unknown at present whether newer formulations such as once-daily Niaspan may be better tolerated in diabetes. In any case, most patients with type 2 diabetes have risk factors for coronary artery disease and qualify for aggressive LDL cholesterol-lowering therapy. At the same time, it is presently unknown whether improved glycemic control decreases coronary artery disease risk in such patients.
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PMID:Diabetic dyslipidemia. 991 65

Prevalence of atherosclerotic vascular disease is markedly increased among individuals with diabetes-mellitus and hypertension. Its major clinical manifestations are consequences of atherosclerosis of coronary arteries, cerebral arteries and large arteries of lower extremities. Thus, atherosclerotic vascular disease is the major cause of mortality and significant morbidity in diabetes and hypertension. Dyslipidemia, hyperinsulinemia, and central obesity seem to be associated with increased risk of atherosclerosis, along with the development of hypertension and diabetes (NIDDM). Insulin resistance is the fundamental factor in this situation which has strong genetic predisposition. Accelerated atherosclerosis in diabetes due to mechanism unique to diabetes like non-enzymatic glycation of proteins, oxidative modification of lipoproteins, formation of lipoproteins immune complexes, lipoproteins aggregation, disturbances of cell replication and growth factors and propensity to thrombosis are clearly established. Therapeutic implication for the prevention of atherosclerosis in diabetes and hypertension clearly emphasizes the need to achieve tight control of hyperglycemia, hypertension, and hyperlipidemia in addition to avoiding cigarette smoking and developing obesity.
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PMID:Pathogenesis of atherosclerosis in diabetes and hypertension. 1005 43


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