Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

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

A major factor contributing to cardiovascular mortality in type 2 diabetes is dyslipidemia, characterized by low HDL cholesterol and high triglycerides, rather than elevated LDL cholesterol. Lipoprotein lipase (LPL) is the rate-limiting enzyme of triglyceride removal from plasma and has been implicated in atherosclerosis. Since treatment with statins significantly reduces cardiovascular morbidity in diabetes, we analyzed the lipid profile and LPL activities in 61 patients with type 2 diabetes before and 8 weeks after initiation of atorvastatin (40 mg) or placebo treatment. Lipid parameters and LPL activity were unchanged under treatment with placebo. Atorvastatin treatment resulted in a 30% reduction of total and a 45% reduction of LDL cholesterol (6.06 +/- 1.39 mmol/L versus 4.14 +/- 1.27 mmol/L and 4.11 +/- 1.13 mmol/L versus 2.27 +/- 0.89 mmol/L, both P < 0.0001). Triglycerides and VLDL cholesterol were also significantly reduced by statin therapy (2.24 +/- 2.11 mmol/L versus 1.82 +/- 1.46 mmol/L and 1.08 +/- 1.56 mmol/L versus 0.67 +/- 0.66 mmol/L, both P < 0.05). HDL cholesterol was not different between the atorvastatin and the placebo group. Compared to baseline, LPL activity was increased by 25% after atorvastatin treatment (213.0 +/- 28.1 nmol/mL/min versus 171.9 +/- 17.7 nmol/mL/min, P < 0.01). Our data demonstrate that atorvastatin induces a significant improvement of diabetic dyslipidemia and a significant increase of LPL activity. Since low LPL activity indicates an increased cardiovascular risk, the statin-mediated increase in LPL activity may help to explain the reduction of CAD in diabetic patients treated with statins.
...
PMID:Atorvastatin improves diabetic dyslipidemia and increases lipoprotein lipase activity in vivo. 1526 89

Atorvastatin (Lipitor) is an HMG-CoA reductase inhibitor with well documented lipid-lowering effects. It has recently been evaluated for the primary prevention of major cardiovascular events in patients with type 2 diabetes mellitus without elevated serum low-density lipoprotein (LDL)-cholesterol levels. Atorvastatin 10mg daily for 4 years was effective at reducing the risk of a first major cardiovascular event, including stroke, in a large, placebo-controlled, multicentre trial in patients with type 2 diabetes and at least one other coronary heart disease (CHD) risk factor, but without markedly elevated LDL-cholesterol levels. In this trial, known as CARDS (the Collaborative AtoRvastatin Diabetes Study), atorvastatin had a similar tolerability profile to that of placebo. Thus, atorvastatin has a potential role in the primary prevention of cardiovascular events in diabetic patients at risk of CHD, irrespective of pre-treatment LDL-cholesterol levels.
...
PMID:Atorvastatin: a review of its use in the primary prevention of cardiovascular events in patients with type 2 diabetes mellitus. 1561 62

The Collaborative AtoRvastatin Diabetes Study (CARDS) is the first large primary prevention study to focus specifically on the role of a statin in patients aged 40-75 years with type 2 diabetes, but no signs or symptoms of pre-existing vascular disease and who had only average or below average cholesterol levels. The trial was a prospective double-blind randomised trial with 2383 type 2 diabetic subjects randomised to either 10-mg atorvastatin daily or placebo. Originally designed to run for 5 years, the trial was terminated over a year early in June 2003 on account of a clear benefit demonstrated for the intervention group. Over half of patients had a low-density lipoprotein cholesterol (LDL-C) below 3.3 mmol/l at entry and a quarter had an LDL-C <2.6 mmol/l. Atorvastatin 10 mg reduced LDL-C by 40% (1.2 mmol/l) on average. Results at 4 years showed a 37% relative risk reduction (p <0.001) for atorvastatin 10 mg in the primary endpoint (acute coronary heart disease death, fatal or non-fatal myocardial infarction, unstable angina requiring hospital admission, resuscitated cardiac arrest, coronary revascularisation procedures and stroke). Among the secondary endpoints, total mortality was reduced by 27% (p=0.05), acute coronary events by 36%, coronary revascularisation by 31% and stroke by 48%. The same magnitude of benefit was observed among patients with LDL-C above or below 3 mmol/l. Results observed were against a background where 9% of placebo patients had been permitted to start statin therapy after enrolment and 15% of patients on active treatment had discontinued atorvastatin. The true benefit of the intervention is therefore probably around 25% greater than the intention to treat analysis reports.
...
PMID:The collaborative atorvastatin diabetes study: preliminary results. 1570 77

Patients with diabetes are at significantly increased risk for coronary heart disease (CHD); even those patients without a history of a previous myocardial infarction (MI) have as high a risk of a fatal or nonfatal MI as nondiabetic patients with a history of previous MI. As a result it is now generally recommended that cardiovascular risk factors be treated as aggressively in patients with diabetes as in nondiabetic patients with a history of CHD. Results from the recently published Collaborative Atorvastatin Diabetes Study (CARDS) and meta-analysis of primary and secondary interventions trials confirm that there is a uniform relative risk reduction across a wide range of high-risk patients including diabetes patients without established CHD. A highly significant 22-24% reduction in risk of future vascular events is evident when patients with diabetes are treated with statins in trials. Current guidelines, including the recently updated National Cholesterol Education Program (NCEP) guidelines, endorse aggressive, early intervention in very-high-risk patients, such as those with diabetes plus cardiovascular disease (CVD), regardless of baseline low-density lipoprotein cholesterol (LDL-C) level in order to achieve an LDL-C goal of 70 mg/dL (1.8 mmol/L). However, despite increasing evidence and knowledge of the value of lipid lowering, a recent survey of diabetes specialists indicates that many patients with diabetes remain untreated or undertreated. The availability of more effective statins should help to close this "action gap", in concert with other measures such as initiatives to improve patient compliance.
...
PMID:Diabetic dyslipidaemia: effective management reduces cardiovascular risk. 1582 95

Insulin resistance plays an important role not only in the development and progression of diabetes mellitus but also in the establishment of metabolic syndrome. Improvement of insulin resistance is thus of great importance both in improving glucose metabolism and preventing atherosclerosis. Although HMG-CoA reductase inhibitors appear to favorably affect glucose metabolism, as indicated by the results of a subanalysis in the West of Scotland Coronary Prevention Study (WOSCOPS), their effects on glucose metabolism and insulin resistance have not been thoroughly investigated in animal models. In this study, the effects of atorvastatin on the glucose metabolism and insulin resistance of KK/Ay mice, an animal model of type II diabetes, were investigated. Atorvastatin significantly decreased the non-HDL-cholesterol level in the oral glucose tolerance test, inhibited increase in the 30-min glucose level, decreased plasma insulin levels before and 30 and 60 minutes after glucose loading, and decreased the insulin resistance index, compared with corresponding values in controls, indicating that atorvastatin appeared to improve glucose metabolism by improving insulin resistance. Northern blot analysis revealed decreases in levels of mRNA of sterol regulatory element binding protein-1 (SREBP-1) and glucose-6-phosphatase (G6Pase), and it may play a role in the improvement of glucose metabolism and insulin resistance.
...
PMID:Effects of atorvastatin on glucose metabolism and insulin resistance in KK/Ay mice. 1594 17

The introduction of statins has drastically changed the treatment and prevention of atherosclerotic vascular disease. By lowering lipid levels and reducing the risk of coronary heart disease, these drugs are among the most effective at reducing morbidity and mortality available to clinical practice. In fact, these compounds have demonstrated the reversible nature of the process of atherosclerosis and can be considered the most useful drugs we currently have in our armamentarium in the prevention of atherosclerosis and its clinical sequelae. Atorvastatin provides pronounced lipid lowering in a broad range of individuals with hypercholesterolaemia and, as such, is an appropriate first-line therapy for patients at low to high risk of coronary heart disease. Reductions in total and low-density lipoprotein cholesterol achieved with atorvastatin have been shown to translate into reductions in risk of cardiovascular morbidity and mortality in both primary and secondary prevention settings. Significant clinical benefits have specifically been observed among patients with Type 2 diabetes and in those with acute coronary syndromes. In common with other members of the statin class, atorvastatin is well tolerated, and adverse events are generally mild and transient in nature. Despite the significant clinical benefits provided by atorvastatin, its full potential in the management of atherosclerotic disease has yet to be wholly explored; however, studies currently ongoing will answer many of the outstanding questions.
...
PMID:Atorvastatin. 1595 72

The effect of atorvastatin (Lipitor) on diabetes-induced changes in plasma lipids, oxidative stress and the ability of aortic tissues to generate prostacyclin was studied in streptozotocin diabetic rats. In diabetic rats, plasma total cholesterol, triglycerides and serum glucose significantly increased compared to nondiabetic rats. Atorvastatin administration to diabetic rats did not affect hyperglycemia but significantly reduced plasma total cholesterol and triglycerides compared to diabetic rats. The oxidative stress markers urinary isoprostane, liver thiobarbituric acid reactive substances (TBARS) and plasma protein carbonyl content significantly increased in diabetic rats compared to nondiabetic rats. Atorvastatin admnistration to diabetic rats significantly reduced oxidative stress levels compared to diabetic rats, but urinary isoprostane and liver TBARS remained significantly higher than nondiabetic rats. Prostacyclin (PGI(2)) generation by aortic tissues significantly decreased in diabetic rats compared to nondiabetic rats. Atorvastatin administration to diabetic rats did not reverse that inhibition. These results were discussed in the light of the possible effects of hyperglycemia and statins on NAD(P)H-oxidase and cyclooxygenase-2 activities and the genetic difference between rats and other mammals regarding the level of vascular superoxide dismutase (SOD) activity.
...
PMID:Atorvastatin reduces the plasma lipids and oxidative stress but did not reverse the inhibition of prostacyclin generation by aortas in streptozotocin diabetic rats. 1596 62

Atorvastatin reduces both plasma cholesterol and triglyceride concentrations in patients with type 2 diabetes, but mechanisms underlying triglyceride decrease and the effect of atorvastatin on high density lipoprotein (HDL) still remain unclear. Apolipoprotein (apo) E plays a crucial role in modulating production and clearance of triglyceride-rich very low density lipoprotein (VLDL). The main effect of apoAI is to modulate HDL metabolism. The aim of this work was to study the influence of atorvastatin on apoAI and apoE kinetics and to determine whether its hypocholesterolemic and hypotriglyceridemic effects could be related to changes in this apolipoprotein metabolism. Plasma VLDL-apoE, HDL-apoE, and HDL-apoAI were studied in seven patients with diabetes with mixed hyperlipidemia using a stable isotope labeling technique ([(2)H3]leucine-primed constant infusion) and monocompartmental model before and after 2 months of treatment with 40 mg/day of atorvastatin. Plasma apoE concentration was significantly reduced (44.1 +/- 19.1 versus 32 +/- 11.6 mg/l, p < 0.05) after treatment. This decrease was associated with a diminution of HDL-apoE concentration (17.46 +/- 6.71 versus 13.37 +/- 6.05 mg/l, p < 0.05) and production rate (0.202 +/- 0.085 versus 0.119 +/- 0.047 mg/kg/day, p < 0.05), whereas an increase in VLDL-apoE concentration (6.44 +/- 2.16 before versus 9.23 +/- 4.02 mg/l after, p < 0.05) and production rate (0.827 +/- 0.367 versus 1.524 +/- 0.664 mg/kg/day, p < 0.05) was observed. No significant difference was observed after treatment for apoAI parameters. We conclude that atorvastatin treatment promotes different apoE distribution between HDL and VLDL, favoring VLDL apoE content. The increased number of apoE per VLDL particle suggests that atorvastatin could enhance the direct catabolism of triglyceride-rich VLDL through apoE receptor pathways.
...
PMID:Influence of atorvastatin on apolipoprotein E and AI kinetics in patients with type 2 diabetes. 1601 56

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.
...
PMID:A review of the efficacy of rosuvastatin in patients with type 2 diabetes. 1603 94

Both the American Diabetes Association (ADA) and the National Cholesterol Education Program (NCEP) consider type 2 diabetes mellitus to be a coronary artery disease (CAD) risk equivalent and thus suggest that patients with either diabetes or CAD should have their plasma levels of low-density lipoprotein (LDL) cholesterol lowered to <2.59 mmol/L (<100 mg/dL). Recently the NCEP issued a white paper suggesting an even lower plasma LDL cholesterol goal of <1.81 mmol/L (<70 mg/dL) for patients at high cardiovascular risk, including patients with diabetes. This rationale was based partly on the higher risk of future cardiovascular disease seen in patients who have diabetes with or without preexisting cardiovascular disease than in nondiabetic subjects with preexisting cardiovascular disease. Additionally, as reported in the Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE-IT) study, high-dose lipid-lowering therapy has been shown to further reduce CAD event rates compared with conventional therapy.
...
PMID:Rationale for new American Diabetes Association Guidelines: are national cholesterol education program goals adequate for the patient with diabetes mellitus? 1609 41


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---