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

A detailed overview of the various forms of hyperlipidemia/dyslipidemia that constitute a major risk factor for coronary heart disease and a detailed discussion of the various types of cholesterol-lowering drugs are presented. The importance of identifying the type of dyslipidemia with respect to the choice of treatment is emphasized, as is the use of nonpharmacologic intervention, i.e., diet, exercise, and weight loss. The appropriate use and benefits of bile acid sequestrants, nicotinic acid, fibric acids, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, and probucol are individually discussed, whereas nonpharmacologic approaches used in conjunction with the drugs are recommended emphatically.
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PMID:Cholesterol-lowering drugs as cardioprotective agents. 147 2

Patients with diabetes mellitus are at increased risk of morbidity and mortality from macrovascular disease manifesting as coronary heart disease, cerebrovascular accidents, and peripheral vascular disease. Increased frequency of dyslipidemia, hyperglycemia, obesity, hypertension, and associated nephropathy may contribute to accelerated atherogenesis in diabetic patients. Therefore, besides intensive control of hyperglycemia, management of dyslipidemia, hypertension, and obesity should also be emphasized in diabetic patients. Those who smoke should be strongly encouraged to quit smoking. Besides attempts to achieve normal levels of plasma lipoproteins, consideration also should be given to normalization of compositional abnormalities of various lipoproteins in patients with diabetes mellitus. The therapeutic goals for cholesterol reduction should be lower in diabetic patients than nondiabetic subjects. The first step is to achieve good metabolic control of diabetes mellitus by diet, exercise, and weight reduction and, if needed, with sulfonylureas or insulin therapy. Because most of the patients with insulin-dependent diabetes mellitus achieve normal levels of plasma lipoproteins with intensive insulin therapy, lipid-lowering medications are rarely needed. In patients with non-insulin-dependent diabetes mellitus, however, dyslipidemia often persists despite good glycemic control. Lipid-lowering medications should be considered in such patients. Because nicotinic acid can cause marked deterioration in glycemic control, and bile acid-binding resins may accentuate hypertriglyceridemia, these agents are less desirable for use by diabetic patients. Inhibitors of hydroxymethylglutaryl coenzyme A reductase may be preferred in patients with elevated LDL cholesterol and mld hypertriglyceridemia. For diabetic patients with marked hypertriglyceridemia, however, fibric acid derivatives should be the drug of choice.
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PMID:Lipid-lowering therapy and macrovascular disease in diabetes mellitus. 152 29

Cardiovascular disease, and in particular ischemic heart disease, is the principal cause of morbidity, functional disability, and mortality in patients with non-insulin-dependent (type II) diabetes. The main risk factors for the macrovascular complications of diabetes are dyslipidemia, hypertension, and cigarette smoking. Although degree of hyperglycemia is a risk factor for microvascular complications, it is not a prominent risk factor for macrovascular complications. Nevertheless, there are theoretical reasons for believing that glycemic control could lower cardiovascular risk. For example, glycemic control may both improve clearance and suppress hepatic overproduction of very-low-density lipoprotein. Moreover, there is direct empirical evidence that improved glycemic control can favorably alter lipid profiles in type II diabetic patients. Despite this, the only clinical trial that has assessed cardiovascular mortality as an end point in diabetic subjects (i.e., the University Group Diabetes Program) failed to demonstrate a benefit of glycemic control. In this study, the insulin-variable group, which achieved sustained glycemic control relative to the placebo group, had essentially the same cardiovascular mortality as the latter group. All of the conventional lipid-lowering agents have been shown to produce favorable changes in lipid profiles in diabetic subjects. However, the optimum regimen remains to be defined. Metabolic differences between diabetic and nondiabetic subjects mean that the optimum lipid-lowering regimens for the two categories of patients may differ. For example, nicotinic acid, which is a powerful lipid-altering drug, may worsen glucose intolerance. The characteristic lipid abnormalities in type II diabetic subjects are hypertriglyceridemia and low high-density lipoprotein cholesterol, not hypercholesterolemia. Although the role of hypertriglyceridemia as a cardiovascular risk factor in the general population has been questioned, there is evidence that this lipid abnormality may play a stronger role in diabetic subjects. For all of the above reasons, there is an urgent need for large-scale clinical trials assessing cardiovascular end points and testing various strategies of improving lipid profiles in diabetic subjects, particularly given the fact that all of the current generation of lipid-lowering trials have systematically excluded diabetic patients.
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PMID:Dyslipidemia in type II diabetes. Implications for therapeutic intervention. 177 1

Coronary heart disease is the leading cause of death among patients with non-insulin-dependent diabetes mellitus (NIDDM). NIDDM patients have a high frequency of dyslipidemia, which along with obesity, hypertension, and hyperglycemia may contribute significantly to accelerated coronary atherosclerosis. Because risk factors for coronary heart disease are additive and perhaps multiplicative, even mild degrees of dyslipidemia may enhance coronary heart disease risk. Therefore, therapeutic strategies for management of NIDDM should give equal emphasis to controlling hyperglycemia and dyslipidemia. The National Cholesterol Education Program recently issued guidelines for treatment of hyperlipidemia in adults including diabetic patients. Because of the unique features of diabetic dyslipidemia, however, we suggest that certain modifications in these guidelines be made to meet specific needs of diabetic patients. For example, therapeutic goals for serum cholesterol reduction should be lower in diabetic patients than in nondiabetic subjects. Particular emphasis should be given to weight reduction in NIDDM patients. In some diabetic patients, monounsaturated fatty acids may be a better replacement for saturated fatty acids than carbohydrates. The target for cholesterol lowering should include both very-low-density lipoprotein and low-density lipoprotein (LDL) (non-high-density lipoprotein) rather than LDL alone. To obtain a substantial reduction of cholesterol levels, drug therapy may be required in many patients. However, first-line drugs for nondiabetic patients (nicotinic acid and bile acid sequestrants) may be less desirable in NIDDM patients than hydroxymethylglutaryl coenzyme A (HMG CoA) reductase inhibitors and even fibric acids. In fact, HMG CoA reductase inhibitors may be the drugs of choice for NIDDM patients with elevated LDL cholesterol and borderline hypertriglyceridemia, whereas gemfibrozil appears preferable for NIDDM patients with severe hypertriglyceridemia.
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PMID:Management of dyslipidemia in NIDDM. 219 Jul 70

Reasons for the current emphasis on cholesterol as coronary risk factor are multiple. On one hand current studies have shown that primary as well as secondary prevention of ischemic heart disease is a realistic possibility with lipid lowering measures. On the other hand new drugs are actually available which permit a potent and adapted therapy of hyperlipidemias. According to new guidelines of the Swiss "lipid task force" screening for hypercholesterolemia is recommended. A cholesterol value greater than 6.5 mmol/l should be investigated and treated. Because a great proportion of adult Swiss fall into this category (approximately 1/3) it is essential that all those are efficiently treated that have markedly abnormal cholesterol values or present with other risk factors such as smoking and hypertension or have a personal or familiar history of ischemic heart disease. Because progression is likely in patients with or after manifest ischemic heart disease even when hypercholesterolemia is mild (over 5.2 mmol/l) all patients presenting with an infarct should be investigated for dyslipidemia. Cholesterol, triglycerides and HDL should be determined. Dietary measures are the basis of every attempt to reduce hyperlipidemia. Most importantly intake of saturated fats prevailing in animal products should be restricted. The next important step is reduction of dietary cholesterol and in obese patients also caloric restriction. Lipid lowering agents are recommended in patients at risk who do not respond to or comply with dietary regimens. According to type of dyslipidemia bile-acid-binding resins, fibrates, nicotinic acid or HMG-CoA reductase inhibitors are available.
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PMID:[Lipid-lowering therapy in the prevention of coronary heart disease]. 221 47

Recently, nicotinic acid has been recommended as a first-line hypolipidemic drug. To determine the effectiveness of nicotinic acid in dyslipidemic patients with non-insulin-dependent diabetes mellitus, 13 patients were treated in a randomized crossover trial. Patients received either nicotinic acid (1.5 g three times daily) or no therapy (control period) for 8 weeks each. Compared with the control period, nicotinic acid therapy reduced the plasma total cholesterol level by 24%, plasma triglyceride level by 45%, very-low-density lipoprotein cholesterol level by 58%, and low-density lipoprotein cholesterol level by 15%, and it increased the high-density lipoprotein cholesterol level by 34%. However, nicotinic acid therapy resulted in the deterioration of glycemic control, as evidenced by a 16% increase in mean plasma glucose concentrations, a 21% increase in glycosylated hemoglobin levels, and the induction of marked glycosuria in some patients. Furthermore, a consistent increase in plasma uric acid levels was observed. Therefore, despite improvement in lipid and lipoprotein concentrations, because of worsening hyperglycemia and the development of hyperuricemia, nicotinic acid must be used with caution in patients with non-insulin-dependent diabetes mellitus with dyslipidemia. We suggest that the drug not be used as a first-line hypolipidemic drug in patients with non-insulin-dependent diabetes mellitus.
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PMID:Nicotinic acid as therapy for dyslipidemia in non-insulin-dependent diabetes mellitus. 228 21

Niacin (nicotinic acid) in large doses (> 2 g) has been increasingly the choice of lipid-lowering agent by clinicians. However, the potential risks of the use of high doses of the vitamin have not been critically considered in the same way as has the use of other lipid-lowering drugs. The present study provides evidence that pharmacological levels of niacin interfere with the metabolism of methionine, leading to hyperhomocysteinemia and hypocysteinemia. Male Sprague-Dawley rats were fed a semisynthetic diet supplemented with either 400 or 4000 mg niacin/kg (compared with 47 mg/kg diet in the control diet). In Experiment 1, feeding these diets for 3 wk resulted in a dose-related increase in the plasma and urine methionine concentrations while cysteine levels were decreased. This altered methionine metabolism was accompanied by a lower plasma vitamin B-6 concentration in niacin-supplemented rats compared with controls. In Experiment 2, the methionine and cysteine levels in plasma and urine were normalized when vitamin B-6 (10 mg/kg diet) was added to the diet containing 4000 mg niacin/kg and fed for 6 wk. This experiment also showed that plasma and urine homocysteine concentrations were increased by niacin and normalized by vitamin B-6. The hypolipidemic action of niacin was unaffected by the presence of vitamin B-6. These results indicate that niacin at large dosages interferes with methionine metabolism by affecting vitamin B-6 status. The treatment of dyslipidemia with simultaneous administration of niacin and vitamin B-6 could be a better therapy than the use of niacin alone.
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PMID:Vitamin B-6 normalizes the altered sulfur amino acid status of rats fed diets containing pharmacological levels of niacin without reducing niacin's hypolipidemic effects. 904 May 54

Non-insulin-dependent diabetes mellitus (NIDDM) is associated with approximately two fold increase in coronary heart disease (CHD) in men and fourfold increase in CHD in women. In most studies, the duration of diabetes and severity of glycemia are only weakly related to CHD in NIDDM, suggesting that the prediabetic period may be important for the increased CHD in NIDDM subjects. Both hyperinsulinemia and/or insulin resistance predict the development of NIDDM. A number of studies have shown that increased cardiovascular risk factors (especially high triglyceride, blood pressure, and small dense low-density lipoprotein (LDL) and low high-density liproprotein (HDL) cholesterol) precede the onset of NIDDM. Recent data from the San Antonio Heart Study suggest that the atherogenic pattern of cardiovascular risk factors is more marked in prediabetic women than in prediabetic men, thus partially explaining the higher risk of CHD in prediabetic women than in prediabetic men. The atherogenic changes in cardiovascular risk factors appear to be mainly due to increased hyperinsulinemia and insulin resistance in nondiabetic subjects. Interventions to reduce cardiovascular disease in NIDDM subjects should emphasize the primary prevention of NIDDM and very aggressive treatment of traditional cardiovascular risk factors in prediabetic subjects. Treatment of hypertension and dyslipidemia in high-risk patients for NIDDM should avoid agents that further worsen insulin resistance (nicotinic acid, beta blockers, and thiazides), as subjects with hypertension and dyslipidemia are already at increased risk of NIDDM.
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PMID:The prediabetic problem: development of non-insulin-dependent diabetes mellitus and related abnormalities. 910 90

Marked lowering of plasma total and low-density lipoprotein cholesterol levels that occur during treatment of dyslipidemia with pharmacologic doses of nicotinic acid result from hepatotoxicity. Therefore, a marked reduction in low-density lipoprotein may suggest generalized liver toxicity and drug treatment should be discontinued.
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PMID:Effects of crystalline nicotinic acid-induced hepatic dysfunction on serum low-density lipoprotein cholesterol and lecithin cholesteryl acyl transferase. 952 2

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


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