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

Epidemiological studies identified several risk factors as cardiovascular disease correlates, including smoking, obesity, hypertension, diabetes, and increased plasma lipids. High blood cholesterol, and in particular LDL cholesterol levels, represents a major determinant of coronary artery disease, in particular when included in the context of a comprehensive risk profile. The more recent guidelines (especially NCEP ATP III in the United States, and the European Joint Task Force) have suggested the opportunity to favor treatment of those subjects with higher global cardiovascular risk, first of all of those individuals with coronary artery disease or another cardiovascular manifestation or diabetes, then of subjects with clustered risk factors or with markedly raised levels of single risk factors, eventually of other subjects. In this perspective the treatment also of slight dyslipidemias has been shown capable of reducing cardiovascular event incidence and mortality. Recent investigations, aiming at evaluating the impact of these "clinical recommendations" in the treatment of dyslipidemias or other cardiovascular risk factors within a framework of high global cardiovascular risk (EURO-ASPIRE II, L-TAP, etc.), showed inadequate attention of community-based medicine, disclosed by the insufficient number of subjects investigated and by the large number of untreated or undertreated patients. Rosuvastatin, a recently marketed inhibitor of the 3-hydroxy-3-methylglutaryl coenzyme A reductase, is an effective drug which may normalize high plasma cholesterol among high-risk subjects more often than other similar molecules, thus permitting to reach stringent guideline lipid targets. It is hoped that coronary risk charts based on Italian data will be implemented, with the purpose of better finding and treating those subjects who may benefit, at a suitable level of cardiovascular risk.
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PMID:[Dyslipidemia and global cardiovascular risk: treatment guidelines]. 1498 42

Patients with type 2 diabetes on dialysis are at a substantially increased risk of cardiovascular and cerebrovascular diseases. Dyslipidemia characterized by moderately elevated low-density lipoprotein cholesterol and high triglycerides and low high-density lipoprotein cholesterol levels is common in this population. We hypothesized that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors would reduce vascular morbidity and mortality in this patient group. The 'Deutsche Diabetes Dialyse Studie' (4D study) is a prospective, randomized, double-blind study involving 178 dialysis centers throughout Germany. Between March 1998 and October 2002, 1,255 patients were randomized to either atorvastatin 20 mg or placebo; 677 men and 578 women, aged 30-83 years, have been enrolled. The study will be terminated as soon as the predefined number of 424 patients with primary combined end points (i.e., cardiovascular death, nonfatal myocardial infarction, or fatal/nonfatal stroke) will have occurred. The total cohort had the following characteristics at baseline: the mean age was 65.7 years, 54% were men, 89% had a history of hypertension, 21% had coronary artery disease, 17.8% had a history of stroke or a transient ischemic attack, and 45% suffered from peripheral arterial disease. The mean time interval between the diagnosis of diabetes and the onset of dialysis was 17.4 years. On average, the patients were on hemodialysis for 8.3 months. Mean lipid and lipoprotein levels were: total cholesterol 219 +/- 43 mg/dl, low-density lipoprotein cholesterol 126 +/- 30 mg/dl, high-density lipoprotein cholesterol 36 +/- 13 mg/dl, and triglycerides 264 +/- 167 mg/dl. The results of the study will provide important information on the efficacy and safety of atorvastatin to support its use in patients with an impaired renal function who are at a high risk of vascular morbidity and mortality.
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PMID:Randomized controlled trial on the efficacy and safety of atorvastatin in patients with type 2 diabetes on hemodialysis (4D study): demographic and baseline characteristics. 1531 28

The metabolic syndrome is strongly associated with insulin resistance and consists of a constellation of factors such as hypertension and hyperlipidemia that raise the risk for cardiovascular diseases and diabetes mellitus. There is a growing body of evidence to show that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, statins, reduce cardiovascular-related morbidity and mortality in patients with or without coronary artery disease. Recent clinical observations argue for a simple strategy of considering routine statin therapy for patients with type 2 diabetes. Furthermore, statin therapy is also found to be effective in allowing LDL-cholesterol goal achievement in hypercholesterolemic high-risk patients with the metabolic syndrome. However, the effects of statins on the pathogenesis of the metabolic syndrome remain to be elucidated. Several types of statins are commercially available now. Among them, pravastatin is unique because it is the only statin that has been shown to have protective role against the development of diabetes in a large clinical trial. Moreover, a recent clinical study revealed that pravastatin treatment improved insulin sensitivity in 25 women with the metabolic syndrome with impaired glucose intolerance. These observations let us to speculate that pravastatin is a promising strategy for the treatment of hypercholesterolemic patients with the metabolic syndrome. It may improve the insulin sensitivity in these patients and subsequently prevent the development of type 2 diabetes. In this paper, we would like to propose the possible ways of testing our hypothesis as follows. (1) Does pravastatin treatment improve insulin resistance in patients of the metabolic syndrome or in insulin resistant hypertensive or obese patients? If the answers are yes, are these beneficial effects of pravastatin superior to those of other anti-hyperlipidemic statins with equihypolipidemic properties? (2) Does pravastatin treatment actually reduce the development of diabetes in these insulin resistant patients? At that time, does pravastatin treatment increase serum levels of adiponectin, a key adipokine with insulin-sensitizing property? How about the effects of pravastatin treatment on adipokines that could elicit insulin resistance such as tumor necrosis factor-alpha? These clinical studies will provide further information whether pravastatin treatment can improve insulin resistance and subsequently reduce the development of diabetes in insulin resistant patients with the metabolic syndrome.
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PMID:Protective role of pravastatin in the pathogenesis of the metabolic syndrome. 1617 51

Diabetic retinopathy is a common and potentially devastating microvascular complication in diabetes and is a leading cause of acquired blindness among the people of occupational age. However, therapeutic options for the treatment of proliferative diabetic retinopathy, photocoagulation and vitrectomy, are limited by considerable side effects. Therefore, to develop novel therapeutic strategies that specifically target diabetic retinopathy is desired for patients with diabetes. In diabetes mellitus, the formation and accumulation of advanced glycation end products (AGEs) progress. There is a growing body of evidence to show that AGEs-their receptor (RAGE) interactions are involved in the development and progression of diabetic retinopathy. Statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, have been recently shown to reduce the risk for cardiovascular events in diabetic patients with or without coronary artery disease. However, the efficacy of statin therapy for diabetic retinopathy is not fully investigated. We have recently found that protein prenylation is crucial for the AGE-RAGE signaling in microvascular endothelial cells. By blocking the protein prenylation, cerivastatin completely prevented the AGE-RAGE-elicited angiogenesis via suppression of vascular endothelial growth factor (VEGF). These observations let us to speculate that statins might be a promising remedy for treating patients with diabetic retinopathy by acting as a potential inhibitor of the AGE-RAGE signaling pathway in microvascular endothelial cells. In this paper, we would like to propose the possible ways of testing our hypotheses. (1) Does treatment with statins decrease the risk for the development and progression of diabetic retinopathy in patients with normocholesterolemia? (2) If the answer is yes, is this beneficial effect of statins superior to that of other cholesterol-lowering agents with equihypolipidemic properties? (3) Does statin treatment suppress retinal VEGF expression in diabetic patients? (4) Does treatment with pyridoxamine, a post-Amadori inhibitor of AGE formation, attenuate the beneficial effects of statins on diabetic retinopathy? These clinical studies could clarify whether the use of statins is of benefit in patients with AGE-RAGE-related disorders such as diabetic retinopathy, even in the absence of hypercholesterolemia.
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PMID:Potential utility of statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors in diabetic retinopathy. 1618 92

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

Hypertriglyceridemia is a commonly encountered lipid abnormality frequently associated with other lipid and metabolic derangements. The National Cholesterol Education Program recommends obtaining a fasting lipid panel in adults over the age of 20. The discovery of hypertriglyceridemia should prompt an investigation for secondary causes such as high fat diet, excessive alcohol intake, certain medications, and medical conditions (eg, diabetes mellitus, hypothyroidism). In addition, patients should be evaluated for other components of the metabolic syndrome. These include abdominal obesity, insulin resistance, low high-density lipoprotein (HDL), high triglyceride, and hypertension. Hypertriglyceridemia is classified as primary hypertriglyceridemia when there are no secondary causes identified. Primary hypertriglyceridemia is the result of various genetic defects leading to disordered triglyceride metabolism. It is important to treat hypertriglyceridemia to prevent pancreatitis by reducing triglyceride levels to <500 mg/dL. Furthermore, lowering triglycerides while treating other dyslipidemias and components of the metabolic syndrome will reduce coronary events. However, it is controversial how much isolated hypertriglyceridemia correlates directly with coronary artery disease and further studies are needed to clarify whether treatment for this condition leads to meaningful clinical outcomes. Therapeutic lifestyle changes (TLC) are the first line of treatment for hypertriglyceridemia. These changes include a low saturated fat, carbohydrate-controlled diet, combined with alcohol reduction, smoking cessation, and regular aerobic exercise. High doses of omega-3 fatty acids from fish and fish oil supplements will lower triglyceride levels significantly. When patients do not reach their goals by TLC, drug therapy should be started. In cases of isolated hypertriglyceridemia, fibrates are initially considered. When elevated low-density lipoprotein levels accompany hypertriglyceridemia, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors are preferred. In patients with low HDL levels and hypertriglyceridemia, extended release niacin can be considered. A combination of the medicines may be necessary in recalcitrant cases.
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PMID:Hypertriglyceridemia. 1667 84

A rice bran oil (RBO) diet can reduce plasma lipids; this was attributed to the specific components, gamma-oryzanol and gamma-tocotrienol, which individually were shown to be hypocholesterolemic; however, the mechanism of their effects on diabetic hyperlipidemia and the development of diabetes is not known. Rats with streptozotocin/nicotinamide-induced type 2 diabetes were divided into control, RO10, and RO15 groups, and fed cholesterol-free diets containing 0, 10, and 15 g RBO with 0, 352, and 528 g gamma-oryzanol and 0, 6.0 and 9.0 mg gamma-tocotrienol/100 g diet for 4 wk. Diabetic rats fed the RBO diet had greater insulin sensitivity (P = 0.02) than rats fed the control diet. Diabetic rats fed the RBO diet also had lower plasma triglyceride (P = 0.003), LDL cholesterol (P = 0.028), and hepatic triglyceride concentrations (P = 0.04), as well as greater fecal neutral sterol and bile acid excretion than those fed the control diet. After 4 wk, there was an approximately 100% (P < 0.001) increase in the abundance of hepatic cholesterol 7alpha-hydroxylase, an 89% (P < 0.001) increase in the hepatic LDL-receptor, and a 50% (P < 0.001) increase in hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase mRNA in rats fed the RBO diet compared with those fed the control diet. These findings support the conclusion that a rice bran oil-containing diet can significantly suppress hyperlipidemic and hyperinsulinemic responses in diabetic rats. The high contents of gamma-oryzanol and gamma-tocotrienol in RBO can lead to increased fecal neutral sterol and bile acid excretion, via upregulation of cholesterol synthesis and catabolism.
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PMID:A rice bran oil diet increases LDL-receptor and HMG-CoA reductase mRNA expressions and insulin sensitivity in rats with streptozotocin/nicotinamide-induced type 2 diabetes. 1670 6

Over 100 million prescriptions were filled for statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) in 2004. Statins were originally developed to lower plasma cholesterol in patients with hypercholesterolemia and are the most effective drugs on the market in doing so. Because of the discovered pleiotropic effects of statins, the use has expanded to the treatment of many other conditions, including ventricular arrythmias, idiopathic dilated cardiomyopathy, cancer, osteoporosis, and diabetes. The elderly population is growing. Therefore, it is estimated that the number of statin users will also increase. Fortunately, the use of statins is relatively safe with few side effects. Myopathy is the most common side effect with symptoms ranging from fatigue, weakness, and pain to symptoms associated with rhabdomyolysis which is a life-threatening condition. The development of statin-induced rhabdomyolysis is rare occurring in approximately 0.1% of patients; however, the occurrence of less severe symptoms is underreported and may be 1-5% or more. Physical exercise appears to increase the likelihood for the development of myopathy in patients taking statins. It is thought that as many as 25% of statin users who exercise may experience muscle fatigue, weakness, aches, and cramping due to statin therapy and potentially dismissed by the patient and physician. The mechanisms causing statin-induced myopathy have not been elucidated; however, research efforts suggest that apoptosis of myofibers may contribute. The mitochondrion is considered a regulatory center of apoptosis, and therefore its role in the induction of apoptosis will be discussed as well as the mechanism of statin-induced apoptosis and myopathy.
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PMID:Statin-induced apoptosis and skeletal myopathy. 1688 96

The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors or statins are the most successful cardiovascular drugs of all time. By interrupting cholesterol synthesis in the liver, they activate hepatocyte low-density lipoprotein (LDL) receptors and produce consistent and predictable reductions in circulating LDL cholesterol with resulting reproducible improvements in cardiovascular risk by retarding or even regressing the march of atherosclerosis in all major arterial trees (coronary, cerebral and peripheral). Clinical trials have demonstrated their capacity not only to extend life, but also to improve its quality by retarding the progression of diabetes mellitus and chronic renal disease and by enhancing central and peripheral blood flow. They are amongst the most extensively investigated pharmaceutical agents in current clinical use. In cardiovascular end-point trials they have proven ability to help prevent that first and all important myocardial infarction and to reduce the likelihood of a recurrence in those who do succumb. They are equally effective in men and women of all ages and at all levels of cardiovascular risk, whether caused by hypercholesterolaemia, hypertension, cigarette smoking, diabetes mellitus or the metabolic syndrome. In addition, they improve the outlook of patients with familial hypercholesterolaemia whose LDL receptor function is deficient or defective; and all of this comes at minimal risk to the recipient. Their most important potential side effect is myopathy, which on very rare occasions may lead to rhabdomyolysis. Clinical experience shows that myopathic symptoms with creatine kinase levels raised to more than 10 times the upper limit of normal is seen in <0.01% of recipients and progression to fatal rhabdomyolysis because of renal failure has been recorded in only 0.15 cases per million prescriptions. Liver function abnormalities are also, rarely, seen. Again, the frequency of raised aspartate or alanine aminotransferase to more than three times the normal limit is encountered in no more than 1-2% of all treated patients and is completely reversible upon withdrawal of treatment. Progression to hepatitis or liver failure does not occur. This constellation of benefits with little side effect penalty has resulted in the comparison of statins with antibiotics in the global battle against cardiovascular disease.
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PMID:Who should receive a statin these days? Lessons from recent clinical trials. 1696 68

Lowering of low-density lipoprotein cholesterol with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) is clearly efficacious in the treatment and prevention of coronary artery disease. However, despite increasing use of statins, a significant number of coronary events still occur and many of such events take place in patients presenting with type 2 diabetes and metabolic syndrome. More and more attention is being paid now to combined atherogenic dyslipidemia which typically presents in patients with type 2 diabetes and metabolic syndrome. This mixed dyslipidemia (or "lipid quartet"): hypertriglyceridemia, low high-density lipoprotein cholesterol levels, a preponderance of small, dense low-density lipoprotein particles and an accumulation of cholesterol-rich remnant particles (e.g. high levels of apolipoprotein B)--emerged as the greatest "competitor" of low-density lipoprotein-cholesterol among lipid risk factors for cardiovascular disease. Most recent extensions of the fibrates trials (BIP - Bezafibrate Infarction Prevention study, HHS - Helsinki Heart Study, VAHIT--Veterans Affairs High-density lipoprotein cholesterol Intervention Trial and FIELD--Fenofibrate Intervention and Event Lowering in Diabetes) give further support to the hypothesis that patients with insulin-resistant syndromes such as diabetes and/or metabolic syndrome might be the ones to derive the most benefit from therapy with fibrates. However, different fibrates may have a somewhat different spectrum of effects. Other lipid-modifying strategies included using of niacin, ezetimibe, bile acid sequestrants and cholesteryl ester transfer protein inhibition. In addition, bezafibrate as pan-peroxisome proliferator activated receptor activator has clearly demonstrated beneficial pleiotropic effects related to glucose metabolism and insulin sensitivity. Because fibrates, niacin, ezetimibe and statins each regulate serum lipids by different mechanisms, combination therapy--selected on the basis of their safety and effectiveness - may offer particularly desirable benefits in patients with combined hyperlipidemia as compared with statins monotherapy.
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PMID:Atherogenic dyslipidemia in metabolic syndrome and type 2 diabetes: therapeutic options beyond statins. 1700 98


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