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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetes mellitus type 2 (DM type 2) is a common disease that is associated with high mortality and morbidity due to macrovascular and microvascular complications. CHD mortality and morbidity is 2--3 times higher in diabetic than in non-diabetic patients/. There are many potentially atherogenic factors in diabetes these may underlie this problems. Except major risk factors (high serum cholesterol concentration, hypertension, cigarette smoking), insulin resistance is common in DM type 2 patients. The dyslipidemic component of insulin resistance is "atherogenic lipoprotein phenotype", its components include small LDL particles (pattern B) with higher atherogenic risk. Several recent studies have demonstrated the preponderance of small, dense LDL in patients with DM type 2 and IR. The question of whether small, dense LDL can be explained by triglyceride levels alone or whether it is directly related to DM type 2 and insulin resistance is still the subject of debate. If serum triglycerides exceed 1,3 mmol/l, small, dense LDL increases. The practical implication is that serum triglyceride levels should be maintained as low as possible to prevent the deleterious effects of triglycerides on LDL subclass distribution and size. There are several potential mechanisms to explain the increased atherogenicity of dense LDL (small dense LDL is more susceptible to lipid peroxidation and oxidation leading to its increased uptake by macrophages and subsequent removal by scavenger pathway, also has a lower binding affinity to LDL receptors). Theoretical grounds postulate that the treating of diabetic dyslipoproteinemias would reduce atherosclerosis disease. However, to date, there have been no intervention studies specifically designed to test this postulate in the diabetic population Such studies the Diabetes Atherosclerosis Intervention Study (DAIS), Fenofibrate Intervention and Event Lowering in Diabetes (FIELD), Collaborative Atorvastatin in Diabetes Study and lipid in Diabetes Study are currently in progress (Tab. 4, Fig. 2, Ref. 81.).
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PMID:[In Process Citation] 966 34

Diabetes mellitus type 2 (DM type 2) is a common disease that is associated with high mortality and morbidity due to macrovascular and microvascular complications. CHD mortality and morbidity is 2-3 times higher in diabetic than in non-diabetic patients. There are many potentially atherogenic factors in diabetes these may underlie this problems. Except major risk factors (high serum cholesterol concentration, hypertension, cigarette smoking), insulin resistance is common in DM type 2 patients. The dyslipidemic component of insulin resistance is "atherogenic lipoprotein phenotype", its components include small LDL particles (pattern B) with higher atherogenic risk. Several recent studies have demonstrated the preponderance of small, dense LDL in patients with DM type 2 and IR. The question of whether small, dense LDL can be explained by triglyceride levels alone or whether it is directly related to DM type 2 and insulin resistance is still the subject of debate. If serum triglycerides exceed 1.3 mmol/l, small, dense LDL increases. The practical implication is that serum triglyceride levels should be maintained as low as possible to prevent the deleterious effects of triglycerides on LDL subclass distribution and size. There are several potential mechanisms to explain the increased atherogenicity of dense LDL (small dense LDL is more susceptible to lipid peroxidation and oxidation leading to its increased uptake by macrophages and subsequent removal by scavenger pathway, also has a lower binding affinity to LDL receptors). Theoretical grounds postulate that the treating of diabetic dyslipoproteinemias would reduce atherosclerosis disease. However, to date, there have been no intervention studies specifically designed to test this postulate in the diabetic population. Such studies the Diabetes Atherosclerosis Intervention Study (DAIS), Fenofibrate Intervention and Event Lowering in Diabetes (FIELD), Collaborative Atorvastatin in Diabetes Study and Lipid in Diabetes Study are currently in progress. (Tab. 4, Fig. 2, Ref. 81.)
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PMID:[Relation between insulin resistance and small, dense lipoproteins with low density and the development of atherosclerosis in type 2 diabetes mellitus]. 991 42

Recent epidemiological data have reaffirmed that elevated plasma triglyceride and low HDL-cholesterol levels are important risk factors for atherosclerotic vascular disease. The rationale for the clinical use of fibric acid derivatives, which are designed to correct this metabolic nexus, is now on firmer ground. The mechanism of action of fibrates on lipoprotein metabolism has recently been elucidated at the molecular level and involves the activation of peroxisome proliferator-activated receptor-alpha 1 in the liver, with the net effect of improving the plasma transport rates of several lipoproteins. Other potential anti-atherothrombotic effects include the inhibition of coagulation and enhancement of fibrinolysis, as well as the inhibition of inflammatory mediators involved in atherogenesis. These consequences probably underpin the favourable effects of fibrates seen in recent angiographic and clinical trials. Two important clinical trials on the effect of gemfibrozil (Veterans Administration-HDL-Cholesterol Intervention Trial) and bezafibrate (Bezafibrate Infarction Prevention Study) have recently been completed in subjects with elevated triglyceride, low HDL and normal or near-normal LDL-cholesterol levels. The results testify to the efficacy of these agents in decreasing the incidence of cardiovascular events, particularly in patients with multiple risk factors and plasma triglyceride levels of over 2.2 mmol/l. The findings of these trials are compared with the statin-based Air Force/Texas Coronary Atherosclerosis Prevention Study, with a recommendation that future studies in appropriately selected patients should examine the synergistic effect of the fibrate/statin combination. The absolute risk reduction in the incidence of coronary events in the Veterans Administration-HDL-Cholesterol Intervention Trial compares favourably with the statin trials. The therapeutic aspects of the efficacy and safety of fibrates are reviewed. Besides primary mixed hyperlipidaemias, particular indications for the clinical use of fibrates include type 2 diabetes, the metabolic syndrome and renal insufficiency. The St Mary's, Ealing, Northwick Park Diabetes Cardiovascular Disease Prevention Study has suggested that fibrates may decrease the incidence of coronary events in type 2 diabetes, but this hypothesis will be more extensively tested in the Diabetes Atherosclerosis Intervention Study, Fenofibrate in Event Lowering in Diabetes Study and Lipids in Diabetes Study projects. Although significant new knowledge has accrued over the past few years concerning the fundamental and clinical aspects of fibrates, the success of these agents in clinical practice depends on the availability of methods for assessing cardiovascular risk as well as on treatment guidelines, which as presently designed and recommended may be inaccurate and suboptimal.
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PMID:Fibrates, dyslipoproteinaemia and cardiovascular disease. 1068 50

Activators of peroxisome proliferator activated receptors (PPARs) are effective drugs to improve the metabolic abnormalities linking hypertriglyceridemia to diabetes, hyperglycemia, insulin-resistance, and atherosclerosis. We compared the pharmacological profile of a PPARalpha activator, fenofibrate, and a PPARgamma activator, rosiglitazone, on serum parameters, target gene expression, and body weight gain in (fa/fa) fatty Zucker rats and db/db mice as well as their association in db/db mice. Fenofibrate faithfully modified the expression of PPARalpha responsive genes. Rosiglitazone increased adipose tissue aP2 mRNA in both models while increasing liver acyl CoA oxidase mRNA in db/db mice but not in fatty Zucker rats. Both drugs lowered serum triglycerides yet rosiglitazone markedly increased body weight gain while fenofibrate decreased body weight gain in fatty Zucker rats. KRP 297, which has been reported to be a PPARalpha and gamma co-activator, also affected serum triglycerides and insulin in fatty Zucker rats although no change in body weight gain was noted. These results serve to clearly differentiate the metabolic finality of two distinct classes of drugs, as well as their corresponding nuclear receptors, having similar effects on serum triglycerides.
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PMID:Fenofibrate and rosiglitazone lower serum triglycerides with opposing effects on body weight. 1079 17

Most clinical trials of lipid intervention and coronary artery disease prevention have been conducted in study populations that exclude diabetic individuals. Three trials have conducted post hoc analyses of their diabetic subgroups. One of these was a primary intervention trial with gemfibrozil (Helsinki Heart Study). Although this trial found a reduction in coronary events, the numbers were too small to reach significance. The two other trials (the Scandinavian Simvastatin Survival Study [4S] and Cholesterol and Recurrent Events Trial [CARE]) were secondary intervention trials conducted with hydroxymethylglutaryl-CoA reductase inhibitors, simvastatin, and pravastatin. Both of these trials found a reduction in coronary events. Although these two trials present the strongest evidence in support of the clinical benefits of lipid reduction in diabetes, they must be interpreted with caution. They are post hoc subgroup analyses, they looked at mainly hypercholesterolemic populations, and they are secondary intervention studies. Four studies aimed at testing the "lipid hypothesis" specifically in diabetes are currently under way. Three of these studies (Fenofibrate Intervention and Event Lowering in Diabetes [FIELD], Collaborative Atorvastatin Diabetes Study [CARDS], and Lipids in Diabetes Study [LDS]) are primary prevention trials, with clinical events as the primary end point. FIELD uses micronized fenofibrate, CARDS uses atorvastatin, and LDS uses both micronized fenofibrate and cerivastatin alone or in combination. These trials are in the early stages of starting or recruiting. One study (Diabetes Atherosclerosis Intervention Study [DAIS]) using micronized fenofibrate is nearing completion. It is an angiographic study that combines those with and without preexisting clinical coronary disease.
Diabetes Care 2000 Apr
PMID:Lipid intervention trials in diabetes. 1086 Jan 91

A clinical outcomes model was developed to estimate the ability of fibrates and statins to reduce the relative and absolute risk of developing coronary heart disease (CHD) in patients with diabetes. A database was constructed, drawing on results from 83 applicable published studies. Risk factor outcomes reported by the model were chosen according to those found to be statistically significant in the data set parameters from the Framingham Heart Study. In the analysis, fenofibrate was compared with gemfibrozil (an earlier fibrate) and six 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase-inhibitor or "statin" agents. Among the agents studied, only fenofibrate was found to significantly affect all six cardiovascular disease risk factors used in this analysis. For men with diabetes, the estimated absolute risk of developing CHD after five years of treatment was lowered equally and most effectively by fenofibrate, simvastatin, and atorvastatin, from 10% to 6%. For women with diabetes, fenofibrate and simvastatin reduced absolute risk from 9% to 6% over five years of treatment, while atorvastatin reduced risk from 9% to 6%. An accompanying cost comparison analysis found that reducing absolute risk of CHD in these patients would result in significant reductions in the medical expense of treating cardiac events, and that significant differences in the amount saved were driven by treatment choice. Fenofibrate, simvastatin, and atorvastatin produced the greatest long-term savings.
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PMID:Predicting risk reduction of coronary disease in patients who are glucose intolerant: a comparison of treatment with fenofibrate and other lipid-modifying agents. 1106 77

A number of studies have shown that hyperuricaemia is associated with an increased incidence of coronary heart disease. It has been proposed that the elevated serum uric acid levels are linked to other risk factors, such as hypertension, dyslipidaemia and diabetes. Hyperuricaemia is commonly encountered in patients with essential hypertension and is considered as a risk factor for morbidity and mortality associated with hypertension. In addition, lipid abnormalities (mainly hypertriglyceridaemia) are also found more frequently in hypertensive patients than in normotensives. There is evidence that the angiotensin II receptor antagonist, losartan, increases urate excretion by reducing reabsorption of urate in the renal proximal tubule. It is also known that fibric acid derivatives (fibrates) have several beneficial actions in addition to their lipid-lowering capacity. Fenofibrate administration is associated with a uric acid lowering effect. In this respect, we present two patients with hypertension and dyslipidaemia together with elevated serum uric acid levels. We also discuss (in the format of questions and answers) the pathophysiological mechanisms underlying the association of serum uric acid with cardiovascular disease, and we review the relevant literature to justify an evidence-based decision to choose an antihypetensive agent (losartan) or a lipid-lowering drug (fenofibrate) with an additional hypouricaemic effect.
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PMID:Management of hypertension and dyslipidaemia in patients presenting with hyperuricaemia: case histories. 1119 Oct 5

Fibrates are widely prescribed as hypolipidemic drugs and are considered as safe. We report the case of a 69 year-old woman who probably developed a major allergic reaction following a Fenofibrate prescription (generic form) of 300 mg per day. Clinical features included asthenia, hyperthermia (40.5 degrees C) and slight muscular pain. Biological abnormalities were mildly elevated muscular enzymes and pancytopenia rapidly developed. All bacteriologic, virologic, immune and radiologic investigations were normal. Evolution was spontaneously favorable with Fenofibrate withdrawal. This is the first reported case of major fever and pancytopenia following a Fenofibrate prescription. Adverse effects of Fenofibrate are briefly reviewed and their usual favorable outcomes following drug removal are outlined.
Diabetes Metab 2001 Feb
PMID:Rare side-effects of fenofibrate. 1124 Apr 49

The inverse relation between coronary artery disease and the concentration of high-density lipoprotein cholesterol (HDL-C) is well established. A low HDL-C concentration is frequently accompanied by the features of the metabolic syndrome found in patients with type 2 diabetes and in individuals who are abdominally obese. Results from 3 independent trials are consistent in showing that fenofibrate is able to increase HDL-C levels across a wide range of dyslipidemic states. The HDL-C-increasing effect of fenofibrate is proportionately greater when baseline levels are low. Comparing results from published trials, the absolute increase in HDL-C produced by fenofibrate is greater than that with statins across all baseline HDL-C levels, and a 40-mg/dL treatment target HDL-C level is more likely to be achieved with fenofibrate therapy. Fenofibrate has favorable pleiotropic effects on several features of the metabolic syndrome, which are likely to explain the clinical benefits of fibrate therapy, beyond an impact on HDL-C levels. The additional reciprocal beneficial effect of fenofibrate in lowering low-density lipoprotein cholesterol (LDL-C) benefits those patients with low HDL-C and moderately increased LDL-C; the American Diabetes Association now recommends fibrate therapy in this case. Another trial, the Diabetes Atherosclerosis Intervention Study (DAIS) has also provided angiographic evidence to show that fenofibrate treatment may slow coronary artery disease progression in type 2 diabetes. Treatment effects on apolipoproteins suggest that not all fibrates affect HDL-C to an equal degree. A trial with fenofibrate focusing on coronary artery disease risk and mortality reduction in patients with type 2 diabetes that is currently under way, the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial is expected to report in 2005.
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PMID:Increasing high-density lipoprotein cholesterol: an update on fenofibrate. 1178 28

Hepatic triacylglycerol secretion is elevated in insulin-resistant states. Microsomal diacylglycerol acyltransferase (DGAT) catalyzes the final reaction in the synthesis of triacylglycerol (TAG). We have previously described two DGAT activities in rat liver microsomes, one overt (cytosol-facing) and one latent (endoplasmic reticulum lumen-facing) (Owen MR, Corstorphine CG, Zammit VA: Overt and latent activities of diacylglycerol acytransferase in rat liver microsomes: possible roles in very-low-density lipoprotein triacylglycerol secretion. Biochem J 323:17-21, 1977). It was suggested that they are involved in the synthesis of TAG for the cytosolic droplet and VLDL lipidation, respectively. In the present study, we measured the overt and latent DGAT activities in rats fed diets containing one of two hypolipidemic drugs: fenofibrate (a peroxisome proliferator-activated receptor alpha [PPARalpha] agonist) and simvastatin (a 3-hydroxy-3-methylglutaryl [HMG]-CoA reductase inhibitor). We found that the activities of the two DGATs could be varied independently by these treatments. Fenofibrate raised overt DGAT activity but lowered that of latent DGAT. In contrast, simvastatin markedly lowered overt DGAT activity without affecting that of latent DGAT. The increase in overt DGAT activity induced by fenofibrate could not be mimicked by feeding a diet enriched in n-3 polyunsaturated fatty acids (PUFA), which lowered overt DGAT activity but did not affect latent DGAT, suggesting that n-3 PUFA act through a mechanism independent of PPARalpha activation. The fibrate-induced increase in overt DGAT activity and the inhibition of latent DGAT may provide a mechanism through which acyl moieties are retained within the liver for oxidation through the pathways concomitantly upregulated by PPARalpha activation.
Diabetes 2002 Jun
PMID:Differential effects of fenofibrate or simvastatin treatment of rats on hepatic microsomal overt and latent diacylglycerol acyltransferase activities. 1203 56


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