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

Lipid-lowering agents have been shown to reduce morbidity and mortality associated with coronary artery disease (CAD) in all patients. However, these agents are more cost-effective in high-risk patients whose absolute risk of CAD is greater than that of low-risk patients. Furthermore, from preliminary data, it appears that there is greater risk reduction in those subjects achieving lower low-density lipoprotein cholesterol (LDL-C) levels (ie, lower is better). The identification and aggressive treatment of these patients should therefore be a high priority for clinicians. Guidelines from medical organizations, such as the Adult Treatment Panel (ATP) III of the US National Cholesterol Education Program (NCEP), emphasize that patients with CAD, diabetes, or global risk of CAD >20% over 10 years and LDL-C levels >130 mg/dL should receive drug therapy with a goal of reducing LDL-C levels to <100 mg/dL. The recent results of the United Kingdom's Heart Protection Study (HPS) strongly suggest that even those with CAD or who are at high risk and LDL-C levels >100 mg/dL would benefit from drug therapy. Although optimal LDL-C levels have been set at <100 mg/dL for high-risk patients, recent studies show only about 20% of such patients meet these goals. Thus, a large treatment gap remains that needs to be overcome if we are to continue to make significant inroads into preventing further morbidity and mortality in these high-risk subjects. Of therapeutic options available currently and for the near future, statins remain the most effective and well-tolerated form of lipid-lowering therapy. Other therapies include bile acid sequestrants, niacin, and plant stanols. However, none of these is, in general, sufficiently effective as an initial agent to achieve these more aggressive LDL-C goals in the high-risk patient. However, combination therapy with a statin and 1 of these other lipid-lowering agents is useful in patients who are unable to achieve lipid goals on monotherapy. A number of agents for reducing LDL-C levels currently in development may be available in the near future, including 2 new statins: pitavastatin and rosuvastatin. Rosuvastatin, which is in the later stages of the US Food and Drug Administration (FDA) approval process, has been shown to produce significantly greater reductions in LDL-C levels compared with atorvastatin, simvastatin, and pravastatin, and allows more patients to meet lipid goals. Ezetimibe, the first of an entirely new class of LDL-C-lowering agents that inhibit intestinal cholesterol absorption, also appears to offer significant therapeutic value. It is anticipated that these new options will allow clinicians to optimize the management of dyslipidemia in high-risk patients, thereby further reducing the morbidity and mortality of CAD.
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PMID:Managing dyslipidemia in the high-risk patient. 1190 Jul 20

Vascular defects contribute substantially to neuropathic changes associated with metabolic abnormalities in diabetes. Statins appear to exert beneficial effects on vascular function independent of cholesterol lowering. In studies of the streptozotocin-induced diabetes rat model, rosuvastatin treatment was shown to correct sciatic motor and saphenous sensory nerve conduction velocity deficits (large fiber defects), thermal hyperalgesia (small fiber defects) and deficits in sciatic nerve and superior cervical ganglion blood flow. Rosuvastatin reversed deficits in nitrergic nerve-mediated vasodilation in the corpus cavernosum and corrected deficits in endothelium-derived hyperpolarising factor-mediated vasodilation in mesenteric vessels. Rosuvastatin did not alter plasma cholesterol in diabetic animals (a characteristic effect in this model), but significantly lowered triglycerides at high doses. Treatment with mevalonate reversed the beneficial effects of rosuvastatin on nerve function and blood flow, suggesting that the effects are mediated by inhibition of the cholesterol biosynthesis pathway in the absence of cholesterol reduction. Thus, rosuvastatin has wide-ranging neurovascular actions in diabetic rats that may be independent of lipid-lowering activity.
Diabetes Res Clin Pract 2003 Jul
PMID:Looking to the future: diabetic neuropathy and effects of rosuvastatin on neurovascular function in diabetes models. 1288 Jun 93

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

Coronary heart disease (CHD) is a major cause of morbidity and mortality worldwide. Elevated low density lipoprotein-cholesterol (LDL-C) and reduced high density lipoprotein-cholesterol (HDL-C) levels are well recognised CHD risk factors, with recent evidence supporting the benefits of intensive LDL-C reduction on CHD risk. Such observations suggest that the most recent National Cholesterol Education Program Adult Treatment Panel III guidelines, with LDL-C targets of 2.6 mmol/L, may result in under-treatment of a significant number of patients and form the basis for the proposed new joint European Societies treatment targets of 2 and 4 mmol/L, respectively, for LDL and total cholesterol. HMG-CoA reductase inhibitors (statins) reduce LDL-C by inhibiting the rate-limiting step in cholesterol biosynthesis and reduced CHD event rates in primary and secondary prevention trials. The magnitude of this effect is not fully accounted for by LDL-C reduction alone and may relate to effects on other lipid parameters such as HDL-C and apolipoproteins B and A-I, as well as additional anti-inflammatory effects. With increasing focus on the benefits of intensive cholesterol reduction new, more efficacious statins are being developed. Rosuvastatin is a potent, hydrophilic enantiomeric statin producing reductions in LDL-C of up to 55%, with about 80% of patients reaching European LDL-C treatment targets at the 10 mg/day dosage. The Heart Protection Study (HPS) demonstrated that LDL-C reduction to levels as low as 1.7 mmol/L was associated with significant clinical benefit in a wide range of high-risk individuals, including patients with type 2 diabetes mellitus, or peripheral and cerebrovascular disease, irrespective of baseline cholesterol levels, with no apparent lower threshold for LDL-C with respect to risk. Various large endpoint trials, including Treating to New Targets (TNT) and Study of Effectiveness of Additional reductions in Cholesterol and Homocysteine (SEARCH) will attempt to further address the issue of optimal LDL-C reduction. At low LDL-C levels, HDL-C becomes an increasingly important risk factor and is the primary lipid abnormality in over half of CHD patients, with the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study set to assess the effect of raising HDL-C on cardiovascular events in patients with low HDL-C and LDL-C levels below 3 mmol/L. A variety of agents are being developed, which affect both LDL-C and HDL-C metabolism, including inhibitors of acyl-coenzyme A-cholesterol acyl transferase, microsomal transfer protein and cholesterol ester transfer protein, as well as specific receptor agonists. Ezetimibe is a selective cholesterol absorption inhibitor, which produces reductions in LDL-C of up to 25 and 60% reduction in chylomicron cholesterol content with a 10 mg/day dosage. A 1 mmol/L reduction in LDL-C results in a 25% reduction in cardiovascular risk, independent of baseline LDL-C levels. Growing evidence supports the concept that lower is better for LDL-C and that increasing HDL-C represents an important therapeutic target. Furthermore, there is growing appreciation of the role of inflammation in atherogenesis. Consequently, increasing numbers of people should receive lipid-regulating therapy with the development of newer agents offering potential mechanisms of optimising lipid profiles and thus risk reduction. In addition, the pleiotropic anti-inflammatory effects of lipid lowering therapy may provide further risk reduction.
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PMID:Medical lipid-regulating therapy: current evidence, ongoing trials and future developments. 1516 26

Although large-scale statin trials have demonstrated significant reductions in cardiovascular risk, there are many patients who have a cardiovascular event despite receiving statin therapy. There is increasing evidence that larger reductions in low-density lipoprotein cholesterol (LDL-C) are associated with greater improvements in cardiovascular morbidity and mortality, which highlights the need for more efficacious statins. This article will review the lipid-altering effects of two new statins, rosuvastatin and pitavastatin. Rosuvastatin represents an advance in the pharmacological and clinical properties of other available agents. The large LDL-C reductions observed with rosuvastatin, even at the start dose of 10 mg and in patients switched from other statins to rosuvastatin 10 mg, should help to improve goal attainment, while reducing the need for dose titration. The ability of rosuvastatin to improve other elements of the lipid profile, such as high-density lipoprotein cholesterol (HDL-C), triglycerides and non-HDL-C, may be of utility in patients with diabetes and the metabolic syndrome. Increases in HDL-C, along with the greater efficacy of rosuvastatin for reducing LDL-C and non-HDL-C, may obviate the need for combination therapy. Results of a number of outcome studies with rosuvastatin are expected over the next 5 years, which will contribute to the evidence base for statin therapy and cardiovascular disease prevention.
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PMID:Statins: can the new generation make an impression? 1557 84

A low level of high-density lipoprotein cholesterol (HDL-C) is a key feature of the metabolic syndrome and type 2 diabetes. HDL particles exert an anti-atherogenic effect, and low HDL-C levels are associated with increased cardiovascular disease risk. The profile of lipoprotein sub-classes may also be abnormal in patients with the metabolic syndrome or type 2 diabetes, with an excess of atherogenic small low-density lipoprotein (LDL) particles. Statins are first-line lipid-modifying drugs that, in addition to varying in their effects on LDL-C, differ in their effects on HDL-C. Rosuvastatin has been shown to be at least as effective at increasing HDL-C compared with atorvastatin, pravastatin or simvastatin. Selecting an agent that will increase HDL-C levels, as well as lowering LDL-C levels, may be particularly beneficial in the treatment of patients with the metabolic syndrome and type 2 diabetes.
Diabetes Res Clin Pract 2005 Jun
PMID:HDL-C and the diabetic patient: target for therapeutic intervention? 1595 6

It has been estimated that 92% of individuals with type 2 diabetes, without cardiovascular disease (CVD), have a dyslipidaemic profile. Several guidelines on cardiovascular risk now recommend that patients with diabetes should be considered at high risk of CVD and should thus receive lipid-lowering therapy to reduce low-density lipoprotein cholesterol (LDL-C) to below 2.5 mmol/L. Since their introduction in 1987, statins have revolutionized the management of CVD. The most recent statin to be introduced, rosuvastatin, has been shown to be the most effective at lowering LDL-C, as well as consistently raising HDL-C across the 10-40 mg dose range. This has been confirmed by many studies, including the Measuring Effective Reductions in Cholesterol Using Rosuvastatin Therapy (MERCURY I) study in which rosuvastatin 10 mg was shown to be more effective than commonly used doses of other statins, both for LDL-C reduction and achieving treatment target goals. The effectiveness of rosuvastatin has also been studied in type 2 diabetes patients in three studies: the URANUS (Use of Rosuvastatin vs. Atorvastatin iN type 2 diabetes mellitUS), ANDROMEDA (A raNdomized, Double-blind study to compare Rosuvastatin [10 & 20 mg] and atOrvastatin [10 & 20 Mg] in patiEnts with type II DiAbetes) and CORALL (COmpare Rosuvastatin [10-40 mg] with Atorvastatin [20-80 mg] on apo B/apo A-1 ratio in patients with type 2 diabetes meLLitus and dyslipidaemia) studies. URANUS and ANDROMEDA showed rosuvastatin to be more effective than atorvastatin at reducing LDL-C and achieving treatment target goals. CORALL demonstrated rosuvastatin 10, 20 and 40 mg to be more effective at lowering LDL-C than 20, 40 and 80 mg of atorvastatin, respectively. Ongoing studies will evaluate whether these properties of rosuvastatin translate into beneficial effects on atherosclerosis and significant reductions in cardiovascular events.
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PMID:A review of the efficacy of rosuvastatin in patients with type 2 diabetes. 1603 94

Statins may have favorable effects on endothelial barrier function, possibly through reduction of oxidative stress and modulation of expression of vasoactive proteins. The permeability of human umbilical endothelial cells in culture to a group of fluorescein isothiocyanate dextrans of different molecular weights were studied under various experimental conditions. Superoxide anion production was measured with an ethidium bromide fluorescence method. Cellular endothelin 1 mRNA and endothelin 1 in culture media were measured with Northern blots and enzyme immunoassays, respectively. Rosuvastatin (10 nmol/l) normalized the 500 mg/dl dextrose-induced permeability changes. Superoxide anion production induced by 500 mg/dl dextrose was inhibited by therapeutic concentrations of rosuvastatin or simvastatin (10 nmol/l), whereas the increased levels of cellular endothelin 1 mRNA and endothelin 1 in culture media was inhibited by supratherapeutic concentrations of statins (> or =0.1 micromol/l). In conclusion, 1) endothelial cell barrier dysfunction occurs in cells treated with high concentrations of dextrose, 2) statin treatment of endothelial cells normalizes barrier permeability, and 3) the favorable effects of statins may be attributed to the inhibition of the dextrose-induced increase in superoxide anions, whereas inhibition of endothelin expression was observed only at supratherapeutic concentrations.
Diabetes 2006 Feb
PMID:Statins prevent dextrose-induced endothelial barrier dysfunction, possibly through inhibition of superoxide formation. 1644 83

To define the effect of short-term rosuvastatin treatment on the estimated glomerular filtration rate (eGFR), the database of controlled clinical trials in the Rosuvastatin Clinical Development Program was reviewed. Thirteen studies comprising 3,956 rosuvastatin-treated patients were selected based on a serum creatinine measurement at 6 or 8 weeks after initiation of rosuvastatin treatment, randomization to approved and marketed rosuvastatin doses (5 to 40 mg), and unchanged rosuvastatin dose from treatment initiation (baseline) through 6 to 8 weeks of treatment. eGFR was determined with the Modification of Diet in Renal Disease formula. eGFR significantly increased for each dose of rosuvastatin individually and for all doses combined compared with baseline (range +0.9 to +3.2 ml/min/1.73 m2). Further analysis of 5 blinded, placebo-controlled trials comprising 525 patients showed an increase in eGFR of +0.8 ml/min/1.73 m2 (95% confidence interval +0.1 to +1.5) for all rosuvastatin-treated patients, which was significantly different from baseline (p <0.04) and from a change of -1.5 ml/min/1.73 m2 in the placebo-treated patients (95% confidence interval -2.5 to -0.5, p <0.001). The increase in eGFR for rosuvastatin-treated patients was consistent across all major demographic and clinical subgroups of interest, including patients with baseline proteinuria, baseline eGFR <60 ml/min/1.73 m2, and in patients with hypertension and/or diabetes. In conclusion, these results are consistent with previous rosuvastatin studies that showed an upward trend in eGFR with long-term treatment (> or =96 weeks) and with the hypothesis that statins may have pleiotropic mechanisms of action that include beneficial renal effects.
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PMID:Effect of short-term rosuvastatin treatment on estimated glomerular filtration rate. 1672 22

Guidelines from the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) focus the need for the most intensive efforts to lower low-density lipoprotein cholesterol (LDL-C) in the patients at greatest risk of a major future clinical coronary heart disease event. Major clinical trials, such as Pravastatin or Atorvastatin Evaluation and Infection Therapy and the Heart Protection Study, demonstrated the value of lowering LDL-C levels in high-risk patients to well below the ATP III target of <100 mg/dL. In 2004, the NCEP writing group suggested that a more aggressive LDL-C goal of <70 mg/dL is an option when treating high-risk patients, particularly those with the presence of established cardiovascular disease plus major multiple risk factors (especially diabetes), severe and poorly controlled risk factors (ie, cigarette smoking), multiple criteria of the metabolic syndrome, or an acute coronary syndrome. With stricter targets, high-risk patients are less likely to achieve their cholesterol goals than lower risk patients. Recent large trials comparing rosuvastatin with other statin monotherapies have shown a greater LDL-C reduction and better attainment of goals with rosuvastatin. In addition, the MERCURY [Measuring Effective Reductions in Cholesterol Using Rosuvastatin Therapy] trials demonstrate that switching to rosuvastatin significantly increased the percentage of patients who achieved their ATP III LDL-C targets.
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PMID:Rising to the challenge of treating high-risk patients. 1704 74


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