Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic complications of type 2 diabetes, in particular, macrovascular complications, confer substantial morbidity and mortality and adversely affect a patient's quality of life. Early intensive intervention to control cardiovascular risk factors is essential in clinical management. Atherogenic dyslipidaemia characterized by elevated triglycerides, a low level of high-density lipoprotein cholesterol (HDL-C), and an increase in the preponderance of small, dense low-density lipoprotein (LDL) particles, is a key modifiable risk factor for macrovascular diabetic complications. Lowering low-density lipoprotein cholesterol (LDL-C) with a statin (or the combination of statin and ezetimibe) is the main focus for reducing cardiovascular risk in patients with diabetes. However, statins fail to address the residual cardiovascular risk associated with low HDL-C. Fibrates are effective against all components of the atherogenic dyslipidaemia associated with type 2 diabetes. Secondary analyses of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study suggest a role for early treatment with fenofibrate in improving cardiovascular risk reduction in type 2 diabetes and provide safety data supporting the use of fenofibrate in combination with a statin. Data from the FIELD study suggest that fenofibrate may also have potential to impact on microvascular diabetic complications associated with type 2 diabetes. Data are awaited from the ongoing Action to Control Cardiovascular Risk in Diabetes (ACCORD) study to evaluate the outcome benefits of combining fenofibrate with a statin in patients with type 2 diabetes. Finally, in view of divergent study results and outstanding data, assessment of the risk of the individual with type 2 diabetes is mandatory to assist clinical decision-making when initiating lipid therapy.
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PMID:Lipid-lowering therapy in patients with type 2 diabetes: the case for early intervention. 1827 35

Patients with type 2 diabetes or metabolic syndrome remain at high residual risk of cardiovascular events even after intensive statin therapy. While treatment guidelines recommend the addition of a fibrate to statin therapy in this setting, concerns about the potential for myopathy may limit the use of this combination in clinical practice. These concerns are certainly justified for gemfibrozil, which interferes with statin glucuronidation, leading to elevation in statin plasma concentrations and an increased risk of myotoxicity in combination with a range of commonly prescribed statins. However, the available evidence refutes suggestions that this is a class effect for fibrates. Fenofibrate does not adversely influence the metabolism or pharmacokinetics of any of the commonly prescribed statins. This in turn translates to a reduced potential for myotoxicity in combination with a statin. Data are awaited from the ongoing Action to Control Cardiovascular Risk in Diabetes (ACCORD) study to evaluate the efficacy and safety of fenofibrate plus simvastatin combination therapy in type 2 diabetes patients.
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PMID:Combination statin-fibrate therapy: safety aspects. 1851 91

The microvascular complications of diabetes mellitus confer substantial morbidity and impair patient quality of life. Dyslipidemia and prolonged hyperglycemia promote an increase in oxidative stress, inflammation, and vascular damage, which together promote endothelial dysfunction and are associated with macrovascular and microvascular complications. Microalbuminuria is an early marker of diabetic nephropathy and an independent risk factor for cardiovascular disease. Diabetic nephropathy is the most common cause of end-stage renal disease in developed countries, and its prevalence is increasing. Preventing or limiting the progression of diabetic nephropathy, as demonstrated in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial, may prevent or delay renal complications, as well as convey important cardioprotective benefits in patients with type 2 diabetes.
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PMID:Microvascular complications of diabetes mellitus: renal protection accompanies cardiovascular protection. 1908 84

Clinical guidelines highlight the importance of managing atherogenic mixed dyslipidemia to reduce the risk of premature cardiovascular disease in type 2 diabetes mellitus and metabolic syndrome. The lipid-modifying activity of fenofibrate, as demonstrated in clinical studies, indicates its effectiveness in treating dyslipidemia characteristic of these conditions. Fenofibrate also has a favorable impact on a number of nonlipid residual risk factors associated with type 2 diabetes and metabolic syndrome, mediated by peroxisome proliferator-activated receptor-alpha. In patients with type 2 diabetes, fenofibrate is effective in reducing the progression of coronary artery disease, as demonstrated by the Diabetes Atherosclerosis Intervention Study (DAIS). In the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study, the primary end point (major coronary events) was not significantly reduced by fenofibrate treatment. However, other findings from this study suggest that fenofibrate reduces cardiovascular risk. Both DAIS and the FIELD study also indicate that fenofibrate may offer additional vascular benefits, specifically affecting the progression of diabetes-related microvascular disease.
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PMID:Fenofibrate for cardiovascular disease prevention in metabolic syndrome and type 2 diabetes mellitus. 1908 87

The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study provides an extensive evidence base for the efficacy and tolerability of fenofibrate treatment in patients with type 2 diabetes mellitus, predominantly in a primary prevention setting. The FIELD study did not show a significant effect with fenofibrate on the primary end point, coronary artery disease death or nonfatal myocardial infarction (p = 0.16). Treatment with fenofibrate did reduce all cardiovascular disease (CVD) events, the secondary end point (by 11%, p = 0.035). The primary end point was reduced by the same percentage. The modest percent reduction in the primary and secondary end points is probably a result of a number of study confounders, notably an excess of statin drop-in therapy and disproportionate treatment with other drugs for CVD prevention in the placebo arm. Estimates of relative risk reduction used by the FIELD investigators to equalize the use of statins in the fenofibrate and placebo groups suggest a true benefit of treatment on reduction of CVD events of 17%-21%. There was no excess of elevated serum liver enzymes and no cases of rhabdomyolysis in patients receiving both fenofibrate and a statin. Prevention of microvascular disease, specifically, reduction in the rate of laser treatment for retinopathy (by 30%, p = 0.0003), progression of albuminuria (p = 0.002), and nontraumatic amputations (by 38%, p = 0.011), may well be the most innovative finding of the FIELD study, especially in view of the current lack of effective preventative treatments for diabetic retinopathy and the need for additional treatments that slow the progression of diabetic nephropathy. These findings also give impetus to investigate mechanisms by which fenofibrate and peroxisome proliferator-activated receptor-alpha activation may protect the endothelium of small blood vessels in patients with type 2 diabetes.
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PMID:After the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study: implications for fenofibrate. 1908 88

Even with optimal statin therapy, many patients with type 2 diabetes mellitus or metabolic syndrome fail to achieve all lipid targets and remain at high risk of cardiovascular events. Add-on lipid-modifying therapy that is effective in improving the triglyceride and high-density lipoprotein (HDL) cholesterol abnormalities characteristic of these conditions is a recommended approach to reduce this risk. Fibrates or niacin is a logical option, supported by clinical studies showing improved lipid control in combination with a statin. Of the fibrates, fenofibrate may offer microvascular benefits in type 2 diabetes--as demonstrated by the Diabetes Atherosclerosis Intervention Study (DAIS) and the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study--as well as a low risk of myopathy when combined with statins compared with gemfibrozil. Although there is good evidence that both agents favorably affect clinical outcome, we need to evaluate their impact against a baseline of statin therapy. We await data from ongoing large-scale studies to evaluate the efficacy and safety of these combinations and to determine the most appropriate option for reducing residual cardiovascular risk in this important patient population.
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PMID:Expert perspective: reducing cardiovascular risk in metabolic syndrome and type 2 diabetes mellitus beyond low-density lipoprotein cholesterol lowering. 1908 89

Fibrates are widely prescribed lipid-lowering drug in the treatment of dyslipidemia. Their main clinical effects, mediated by peroxisome proliferative activated receptor (PPAR) alpha activation, are a moderate reduction in total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels, a marked reduction in triglycerides (TG) and an increase in high-density lipoprotein cholesterol (HDL-C), usually dependent of their baseline levels and dyslipidemia type. A beneficial effect on cardiovascular outcomes but also on inflammatory and thrombogenesis pathways as well as antioxidant properties have been evidenced conferring other pleiotropic effects to fibrates. Diabetic retinopathy, nephropathy and neuropathy are the major microvascular complications of Type 2 diabetes mellitus (T2DM) and their presence can accentuate the risk of cardiovascular disease. Hyperglycemia, hypertension, genetic susceptibility among other risk factors play a significant role in the development and progression of these complications. Plasma lipid abnormalities are also involved in the pathogenesis of microvascular diseases suggesting a potential benefit of lipid lowering drugs in their prevention. Clofibrate was the first fibrate in the 60's to show an improvement in the retinal hard exudation in subjects with diabetic retinopathy. Recently, in the Fenofibrate Intervention in Event Lowering in Diabetes (FIELD) study fenofibrate treatment demonstrated a significant 30% reduction in the need for laser therapy in patients with and without known diabetic retinopathy, and more particularly in the first course of laser treatment for both macular edema and proliferative retinopathy. In addition, fenofibrate treatment was associated with less albuminuria progression and reduced risk of non traumatic distal amputations. These results, along with previous evidence of positive effects on microvascular complications, suggest that fibrates, and particularly fenofibrate, offer good opportunity to prevent the most serious complications of diabetes.
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PMID:Fibrates and microvascular complications in diabetes--insight from the FIELD study. 1919 80

Cardiovascular disease is the leading cause of morbidity and mortality world-wide. The burden of disease is also increasing as a result of the global epidemics of diabetes and obesity. Peroxisome proliferator-activated receptor alpha (PPARalpha), a member of this nuclear receptor family, has emerged as an important player in this scenario, with evidence supporting a central co-ordinated role in the regulation of fatty acid oxidation, lipid and lipoprotein metabolism and inflammatory and vascular responses, all of which would be predicted to reduce atherosclerotic risk. Additionally, the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study has indicated the possibility of preventive effects in diabetes-related microvascular complications, although the mechanisms of these effects warrant further study. The multimodal pharmacological profile of PPARalpha has prompted development of selective PPAR modulators (SPPARMs) to maximise therapeutic potential. It is anticipated that PPARalpha will continue to have important clinical application in addressing the major challenge of cardiometabolic risk associated with type 2 diabetes, obesity and metabolic syndrome.
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PMID:Peroxisome proliferator-activated receptor-alpha (PPARalpha): at the crossroads of obesity, diabetes and cardiovascular disease. 1938 11

Achieving adequate control of cardiovascular risk in type 2 diabetes mellitus (DM) is crucially important; however, the atherogenic dyslipidaemia (including low high-density lipoprotein cholesterol and hypertriglyceridaemia) typically encountered in type 2 DM is often managed inadequately. Evidence from the Fenofibrate Intervention and Event Lowering in Diabetes study suggests that fenofibrate reduces the risk of long-term macrovascular and microvascular type 2 diabetic complications, especially in patients demonstrating features of the metabolic syndrome. Fenofibrate represents a useful treatment option for controlling cardiovascular risk in type 2 diabetes patients in the community setting.
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PMID:Clinical insights from the Fenofibrate Intervention and Event Lowering in Diabetes study: a community practice perspective. 1949 Feb 1

Dyslipidaemia contributes to endothelial dysfunction and CVD (cardiovascular disease) in Type 2 diabetes mellitus. While statin therapy reduces CVD in these patients, residual risk remains high. Fenofibrate corrects atherogenic dyslipidaemia, but it is unclear whether adding fenofibrate to statin therapy lowers CVD risk. We investigated whether fenofibrate improves endothelial dysfunction in statin-treated Type 2 diabetic patients. In a cross-over study, 15 statin-treated Type 2 diabetic patients, with LDL (low-density lipoprotein)-cholesterol <2.6 mmol/l and endothelial dysfunction [brachial artery FMD (flow-mediated dilatation) <6.0%] were randomized, double-blind, to fenofibrate 145 mg/day or matching placebo for 12 weeks, with 4 weeks washout between treatment periods. Brachial artery FMD and endothelium-independent NMD (nitrate-mediated dilatation) were measured by ultrasonography at the start and end of each treatment period. PIFBF (post-ischaemic forearm blood flow), a measure of microcirculatory endothelial function, and serum lipids, lipoproteins and apo (apolipoprotein) concentrations were also measured. Compared with placebo, fenofibrate increased FMD (mean absolute 2.1+/-0.6 compared with -0.3+/-0.6%, P=0.04), but did not alter NMD (P=0.75). Fenofibrate also increased maximal PIFBF {median 3.5 [IQR (interquartile range) 5.8] compared with 0.3 (2.1) ml/100 ml/min, P=0.001} and flow debt repayment [median 1.0 (IQR 3.5) compared with -1.5 (3.0) ml/100 ml, P=0.01]. Fenofibrate lowered serum cholesterol, triacylgycerols (triglycerides), LDL-cholesterol, apoB-100 and apoC-III (P < or = 0.03), but did not alter HDL (high-density lipoprotein)-cholesterol or apoA-I. Improvement in FMD was inversely associated with on-treatment LDL-cholesterol (r=-0.61, P=0.02) and apoB-100 (r=-0.54, P=0.04) concentrations. Fenofibrate improves endothelial dysfunction in statin-treated Type 2 diabetic patients. This may relate partly to enhanced reduction in LDL-cholesterol and apoB-100 concentrations.
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PMID:Fenofibrate improves endothelial function in the brachial artery and forearm resistance arterioles of statin-treated Type 2 diabetic patients. 2004 60


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