Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242339 (dyslipidemia)
 13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of ligand--activated transcription factors. Three PPAR isoforms , designated PPARalpha, -beta/delta, and -gamma, have been identified and attracted enormous attention due to the key role these receptors play in regulating adipogenesis, lipid metabolism, insulin sensitivity, inflammation and blood pressure. Growing evidence points to a causative relationship between PPAR activity and the metabolic syndrome, including insulin resistance, glucose intolerance or type II diabetes, obesity, dyslipidemia, hypertension, atherosclerosis, and albuminuria. Importantly, both PPARalpha activators such as fibric acid class of hypolipidemic drugs and PPARgamma agonists including antidiabetic thiazolidinediones (TZDs) have been proved to be effective for improving metabolic syndrome. All three PPAR isoforms appear to play important roles in the development of type II diabetes and diabetic nephropathy. Accumulating data has begun to emerge suggesting PPARs may serve as potential therapeutic targets for treating the metabolic syndrome and its related complications. Here we review the literature pertaining to the action, ligand selectivity and physiological role of PPARs. Particular emphasis is placed on their pathogenic roles in the metabolic syndrome and the therapeutic utility of PPAR modulators in the treatment of type II diabetes.
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PMID:[PPAR family and its relationship to metabolic syndrome]. 1588 36

Type 2 diabetes is reaching epidemic proportions throughout the world, representing the most common cause of ESRD. Early identification of renal impairment associated with diabetes and initiation of renoprotective therapy are imperative. High BP, dyslipidemia, long duration of diabetes, and poor glycemic control are important risk factors; their modification, renal function monitoring, and combined therapies are the current integrated approaches to treat patients with diabetic kidney disease. Strong evidence suggests that achieving target BP goals via inhibition of the renin-angiotensin-aldosterone system confers significant renal protection for diabetic patients. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers lower BP and reduce both the progression of renal damage and adverse cardiovascular events; some important renoprotective actions seem to be independent of the antihypertensive effect. Stringent quality of glycemic control is another key point to prevent onset of nephropathy or slow its progression. Evidence from basic research and clinical trials indicates that hypolipidemic drugs, mainly statins, contribute to modulate the progression of renal damage in diabetes; their use should be considered in any patient with diabetes. Smoking cessation may slow nephropathy progression; given the additional health benefits of stopping smoking, this advice is an important part of the strategy of diabetic nephropathy treatment and prevention. In conclusion, a target-driven, long-term, intensified intervention aimed at multiple risk factors should be recommended in patients with diabetes to preserve their kidney function.
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PMID:Antihypertensive treatment and multifactorial approach for renal protection in diabetes. 1593 27

Hyperlipidemia and its treatment are currently recognized as important modulators of cardio-vascular mortality in the presence of disordered glucose control. On the other hand, the effects of hyperglycemia and its treatment on hyperlipidemia are not widely appreciated. Hyperglycemia is commonly associated with an increase in intestinal lipoproteins and a reduction in high-density lipoprotein (HDL). This could be a consequence of hyperglycemia-induced glycation of lipoproteins, which reduces the uptake and catabolism of the lipoproteins via the classical low-density lipoprotein (LDL) receptor. A high dietary carbohydrate load increases the glycation of intestinal lipoproteins, prolongs their circulation, and increases their plasma concentration. Hyperglycemia also leads to inhibition of lipoprotein lipase, further aggravating hyperlipidemia. Circulating advanced glycation end-products (AGEs) also bind lipoproteins and delay their clearance, a mechanism that has particularly been implicated in the dyslipidemia of diabetic nephropathy. As uptake via scavenger receptors is not inhibited, glycation increases the proportion of lipoproteins that are taken up via inflammatory cells and decreases the proportion taken up by hepatocytes via classical LDL receptors. This promotes the formation of atheromatous plaques and stimulates inflammation. Hyperglycemia increases the formation of oxidized LDL and glycated LDL, which are important modulators of atherosclerosis and cardiovascular death. The risk of cardiovascular death is increased by even short-term derangement of blood sugar control, owing perhaps to the glycation of lipoproteins and other critical proteins. Glycated LDL could prove very useful in measuring the effect of hyperglycemia on cardiovascular disease, its risk factors, and its complications. Comparing different glucose-lowering and lipid-lowering drugs in respect to their influence on glycated LDL could increase knowledge of the mechanism by which they alter cardiovascular risk.
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PMID:Hyperglycemia, lipoprotein glycation, and vascular disease. 1607 28

The aim of this study was to study the effect of adding polyunsaturated fatty acid (PUFA) n-3 or placebo (containing oleic acid) to a combined statin-fibrate treatment on plasma lipoproteins, lipoperoxidation, glucose homeostasis, total homocysteine (tHcy) and microalbuminuria (MA) in patients with diabetic dyslipidemia (DDL). Twenty-four patients, who did not fulfill the recommended target lipid values with combined hypolipidemic therapy (pravastatin 20 mg+micronized fenofibrate 200 mg daily), were supplemented with 3.6 g PUFA n-3 daily for 3 months or placebo (olive oil) for the next 3 months. The concentrations of plasma lipids, fatty acid (FA) profiles of phosphatidylcholine (PC), cholesteryl esters (CE) and triglycerides (TG), tHcy levels, concentrations of conjugated dienes (CD) in low-density lipoprotein (LDL), and MA were determined in baseline state, after the PUFA n-3 and placebo treatment period. Supplementation with PUFA n-3 led to a significant decrease in plasma tHcy (-29%, P < .01) and TG (-28%, P < .05) levels, as well as to a significant decrease in MA (-24%, P < .05). The decrease in MA correlated significantly with the increase in total PUFA n-3 (r = -.509, P < or = .05) and docosahexaenoic acid (r = -.52, P < .01) in TG. The concentrations of CD in LDL increased significantly (+15%, P < .05). The supplementation with PUFA n-3 to the combined statin-fibrate treatment in patients with DDL decreased the TG and tHcy levels as well as MA. It could lead to decreased risk of atherothrombosis and delay of diabetic nephropathy onset and progression.
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PMID:N-3 fatty acid supplementation decreases plasma homocysteine in diabetic dyslipidemia treated with statin-fibrate combination. 1621 29

This paper addresses the consequences of diabetes and obesity, diseases that have become epidemic in our society, particularly in the past 20 years. Specifically, it summarizes current knowledge about some of the risk factors and mechanisms for the vascular complications of diabetes. These complications can be broadly divided into microvascular disease, such as diabetic retinopathy and diabetic nephropathy, and macrovascular disease, such as accelerated atherosclerosis, and they are the main cause for morbidity and premature mortality among diabetic patients. The roles of hyperglycemia, dyslipidemia and dyslipoproteinemia, oxidative stress, and endothelial dysfunction will be considered. Finally, the "treatment gap" will be addressed. This gap refers to our failure to achieve currently accepted goals to reduce established risk factors for complications in the clinical management of diabetic patients.
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PMID:A lethal tetrad in diabetes: hyperglycemia, dyslipidemia, oxidative stress, and endothelial dysfunction. 1628 82

Diabetic nephropathy is commonly associated with dyslipidemia, but the role of lipids in the progression of this disorder remains unresolved. In particular, the role of lipid-lowering drugs, such as 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors and fibrates, as renoprotective agents is not clarified. Experimental studies have demonstrated that dietary lipids promote renal injury and that statins, independent of their lipid-lowering effects, confer renoprotection via effects on intrarenal hemodynamics and renal cytokine and chemokine expression. Clinical studies have in general been underpowered, but a recent meta-analysis and findings from the Heart Protection Study suggest that statins may be renoprotective. Nevertheless, with the convincing antiatherosclerotic effects of these agents, including in the setting of diabetes, they should be widely administered in the diabetic population with or at risk for nephropathy.
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PMID:Lipids and diabetic renal disease. 1631 96

Diabetes (particularly type 2 diabetes) represents a global health problem of epidemic proportions. Individuals with diabetes are not only more likely to develop hypertension, dyslipidemia, and obesity, but are also at a significantly higher risk for coronary heart disease, peripheral vascular disease, and stroke. Angiotensin II plays a key pathophysiological role in the progression of diabetic renal disease, and blockade of the renin-angiotensin system with angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II antagonists has therefore become an important therapeutic strategy to reduce renal and cardiovascular events in patients with diabetes. Several studies have demonstrated the effects of angiotensin II antagonists on the reduction of albuminuria and the progression of renal disease from microalbuminuria to macroalbuminuria. More importantly, several endpoint trials have shown that the antiproteinuric effects of losartan and irbesartan translate into cardiovascular and renoprotective benefits beyond blood pressure lowering, thereby delaying the need for dialysis or kidney transplantation by several years. These and other studies indicate that angiotensin II antagonists not only improve survival and quality of life of patients with diabetic nephropathy, but also have the potential to reduce the substantial healthcare burden associated with managing these patients. ACEi also appear to exert similar beneficial effects in diabetic patients, but whether clinically significant differences in renoprotection or mortality exist between angiotensin II antagonists and ACEi in patients with type 2 diabetes remains to be fully investigated in appropriate head-to-head studies.
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PMID:Blockade of the renin-angiotensin-aldosterone system: a key therapeutic strategy to reduce renal and cardiovascular events in patients with diabetes. 1633 Oct 93

Diabetic nephropathy is diagnosed either when persistent increase of urinary albumin excretion rate (UAER) above 30 mg/24h in a patient with diabetes was discovered (early or incipient nephropathy) or when UAER values are persistently elevated above 300 mg/24h (overt or clinical nephropathy). In both situations the additional criteria of presence of diabetic retinopathy and the absence of the evidence of other kidney or renal tract disease should be fulfilled. It was found that the excess of cardiovascular events and mortality occurs already in diabetic patients with persistent microalbuminuria, but is particularly evident in macroalbuminuric diabetic patients and results not only from end-stage renal failure (ESRF) but rather from cardiovascular disease (CVD), the latter mainly in type 2 diabetic patients. Several traditional risk factor for atherosclerosis has been identified in diabetic patients with micro- or macroalbuminuria including elevated blood pressure levels, dyslipidemia and procoagulatory state associated with endothelial dysfunction. Microalbuminuria is currently regarded as a marker of generalized endothelial damage, it reflects transvascular albumin leakage, now recognized as an early event in atherogenesis. Recently the association of microalbuminuria with the marker of chronic inflammation (C-reactive protein) and with increased production of vascular endothelial growth factor (VEGE) was described. Thus, multiple mechanisms are involved in the development and progression of cardiovascular complications both in micro- and macroalbuminuric diabetic patients and all these mechanisms should be regarded as the target for therapeutic intervention.
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PMID:Diabetic nephropathy and cardiovascular diseases. 1635 50

Fibrate peroxisome proliferator-activated receptor (PPAR)-alpha ligands are mainly used as hypolipidemic drugs. But this commentary highlights their potential in treating insulin resistance, dyslipidemia, and hypertension and in preventing diabetic nephropathy, inflammation, and cardiovascular disease. Because diabetes is a major contributor to chronic kidney disease and cardiovascular disease, PPAR-alpha agonists may provide greater opportunities for hitting multiple targets in this complex metabolic disease.
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PMID:The PPARalpha ligand fenofibrate: meeting multiple targets in diabetic nephropathy. 1667 21

Fasudil, a Rho-kinase inhibitor, may improve insulin signaling. However, its long-term effect on metabolic abnormalities and its preventive effect on diabetic nephropathy are still unknown. We assessed these effects of fasudil in insulin-resistant diabetic rats, comparing them with those of an angiotensin II receptor blocker, olmesartan. Male Otsuka Long-Evans Tokushima fatty (OLETF) and Long-Evans Tokushima Otsuka, non-diabetic control, rats at 15 weeks of age were used. OLETF rats were randomized to receive a low or a high dose of fasudil or olmesartan for 25 weeks. To examine the therapeutic effects after the development of diabetes, OLETF rats at 30 weeks of age were given fasudil for 10 weeks. Administration of high-dose fasudil completely suppressed the development of diabetes, obesity, and dyslipidemia and increased serum adiponectin levels in OLETF rats. High-dose olmesartan also decreased hemoglobin A1c and increased serum adiponectin. There was a significant correlation between hemoglobin A1c and serum adiponectin or free fatty acid levels. The treatment with high-dose fasudil ameliorated proteinuria, glomerulosclerosis, renal interstitial fibrosis, and macrophage infiltration in OLETF rats. Olmesartan, even at the low dose, suppressed renal complications. The treatment with fasudil after the development of diabetes improved the metabolic abnormalities in OLETF rats, but could not suppress the progression of nephropathy. We conclude that the long-term treatment with fasudil prevents the development of diabetes, at least in part, by improving adipocyte differentiation in insulin-resistant diabetic rats. Early use of fasudil may prevent diabetic nephropathy.
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PMID:A Rho-kinase inhibitor, fasudil, prevents development of diabetes and nephropathy in insulin-resistant diabetic rats. 1733 27


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