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

Diabetes mellitus type 2 (DM type 2) is a common disease that is associated with high mortality and morbidity due to macrovascular and microvascular complications. CHD mortality and morbidity is 2--3 times higher in diabetic than in non-diabetic patients/. There are many potentially atherogenic factors in diabetes these may underlie this problems. Except major risk factors (high serum cholesterol concentration, hypertension, cigarette smoking), insulin resistance is common in DM type 2 patients. The dyslipidemic component of insulin resistance is "atherogenic lipoprotein phenotype", its components include small LDL particles (pattern B) with higher atherogenic risk. Several recent studies have demonstrated the preponderance of small, dense LDL in patients with DM type 2 and IR. The question of whether small, dense LDL can be explained by triglyceride levels alone or whether it is directly related to DM type 2 and insulin resistance is still the subject of debate. If serum triglycerides exceed 1,3 mmol/l, small, dense LDL increases. The practical implication is that serum triglyceride levels should be maintained as low as possible to prevent the deleterious effects of triglycerides on LDL subclass distribution and size. There are several potential mechanisms to explain the increased atherogenicity of dense LDL (small dense LDL is more susceptible to lipid peroxidation and oxidation leading to its increased uptake by macrophages and subsequent removal by scavenger pathway, also has a lower binding affinity to LDL receptors). Theoretical grounds postulate that the treating of diabetic dyslipoproteinemias would reduce atherosclerosis disease. However, to date, there have been no intervention studies specifically designed to test this postulate in the diabetic population Such studies the Diabetes Atherosclerosis Intervention Study (DAIS), Fenofibrate Intervention and Event Lowering in Diabetes (FIELD), Collaborative Atorvastatin in Diabetes Study and lipid in Diabetes Study are currently in progress (Tab. 4, Fig. 2, Ref. 81.).
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PMID:[In Process Citation] 966 34

Diabetes mellitus type 2 (DM type 2) is a common disease that is associated with high mortality and morbidity due to macrovascular and microvascular complications. CHD mortality and morbidity is 2-3 times higher in diabetic than in non-diabetic patients. There are many potentially atherogenic factors in diabetes these may underlie this problems. Except major risk factors (high serum cholesterol concentration, hypertension, cigarette smoking), insulin resistance is common in DM type 2 patients. The dyslipidemic component of insulin resistance is "atherogenic lipoprotein phenotype", its components include small LDL particles (pattern B) with higher atherogenic risk. Several recent studies have demonstrated the preponderance of small, dense LDL in patients with DM type 2 and IR. The question of whether small, dense LDL can be explained by triglyceride levels alone or whether it is directly related to DM type 2 and insulin resistance is still the subject of debate. If serum triglycerides exceed 1.3 mmol/l, small, dense LDL increases. The practical implication is that serum triglyceride levels should be maintained as low as possible to prevent the deleterious effects of triglycerides on LDL subclass distribution and size. There are several potential mechanisms to explain the increased atherogenicity of dense LDL (small dense LDL is more susceptible to lipid peroxidation and oxidation leading to its increased uptake by macrophages and subsequent removal by scavenger pathway, also has a lower binding affinity to LDL receptors). Theoretical grounds postulate that the treating of diabetic dyslipoproteinemias would reduce atherosclerosis disease. However, to date, there have been no intervention studies specifically designed to test this postulate in the diabetic population. Such studies the Diabetes Atherosclerosis Intervention Study (DAIS), Fenofibrate Intervention and Event Lowering in Diabetes (FIELD), Collaborative Atorvastatin in Diabetes Study and Lipid in Diabetes Study are currently in progress. (Tab. 4, Fig. 2, Ref. 81.)
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PMID:[Relation between insulin resistance and small, dense lipoproteins with low density and the development of atherosclerosis in type 2 diabetes mellitus]. 991 42

Most clinical trials of lipid intervention and coronary artery disease prevention have been conducted in study populations that exclude diabetic individuals. Three trials have conducted post hoc analyses of their diabetic subgroups. One of these was a primary intervention trial with gemfibrozil (Helsinki Heart Study). Although this trial found a reduction in coronary events, the numbers were too small to reach significance. The two other trials (the Scandinavian Simvastatin Survival Study [4S] and Cholesterol and Recurrent Events Trial [CARE]) were secondary intervention trials conducted with hydroxymethylglutaryl-CoA reductase inhibitors, simvastatin, and pravastatin. Both of these trials found a reduction in coronary events. Although these two trials present the strongest evidence in support of the clinical benefits of lipid reduction in diabetes, they must be interpreted with caution. They are post hoc subgroup analyses, they looked at mainly hypercholesterolemic populations, and they are secondary intervention studies. Four studies aimed at testing the "lipid hypothesis" specifically in diabetes are currently under way. Three of these studies (Fenofibrate Intervention and Event Lowering in Diabetes [FIELD], Collaborative Atorvastatin Diabetes Study [CARDS], and Lipids in Diabetes Study [LDS]) are primary prevention trials, with clinical events as the primary end point. FIELD uses micronized fenofibrate, CARDS uses atorvastatin, and LDS uses both micronized fenofibrate and cerivastatin alone or in combination. These trials are in the early stages of starting or recruiting. One study (Diabetes Atherosclerosis Intervention Study [DAIS]) using micronized fenofibrate is nearing completion. It is an angiographic study that combines those with and without preexisting clinical coronary disease.
Diabetes Care 2000 Apr
PMID:Lipid intervention trials in diabetes. 1086 Jan 91

The hypertriglyceridemia attends the physiopathology of the atherosclerosis by various mechanisms: association of low levels of high density lipoprotein-cholesterol (HDL-c), modification of quality of low density lipoprotein-cholesterol (LDL-c), influence on hemostatic processes, association with other hazard's factors (obesity, hypertension, etc.). The hypertriglyceridemia distinguishes in primary and secondary. In primary forms the origin is essentially genetic, while the secondary ones are metabolic consequence of various pathologies (renal, thyroid, diabetes mellitus etc.). The hypertriglyceridemia's treatment is founded on a correct feeding and/or on eventual use of drugs. Apart from the secondary forms, in which is obligatory to treat at first the basal disease, the pharmacological therapy of the hypertriglyceridemia is suggested only in resistant cases to alone dietetic therapy and overall in presence of other factors of atherothrombotic hazard. The most utilized drugs are: omega-3 fatty acids, the nicotinic acid and its derivatives, the fibrates and the statins. The stronghold of alpha-glucosidases inhibitors is the acarbose. It reduces the biosynthesis of very low density lipoproteins (VLDL) by the reduction of substrata with an improvement of glucidic metabolism. Atorvastatin and cerivastatin develop a greater action to reduce serum levels of triglycerides as to the foregoing ones because of the better selectivity of receptor binding, the greater halflife and inhibition of the apolipoprotein's B100 synthesis.
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PMID:[Treatment of hypertriglyceridemia. Current aspects]. 1093 25

Two recently published clinical endpoint trials, Veterans Affairs Cooperative Studies Program High-density Lipoprotein Intervention Trial (VA-HIT) and Atorvastatin Versus Revascularization Treatment (AVERT), studied lipid populations and clinical subgroups not previously evaluated in prior trials. VA-HIT, which used gemfibrozil, resurrected the potential benefits of fibrates in atherosclerotic subjects after previous trials either showed nonsignificant reductions in coronary artery disease (CAD) events or raised questions regarding non-CAD events. This study also raised intriguing questions about mechanisms and reinvigorated the triglyceride-atherothrombotic debate. The latest statin trial, AVERT, helped move the potential use of statins in two directions, addressing whether more LDL-cholesterol reduction is better, and whether lipid lowering offers an alternative to revascularization in certain subgroups. Finally, the design or initiation of a number of innovative and potentially landmark statin, fibrate, or combination studies has been published, or their results made public. The focus is on current gaps in our knowledge as we move toward evidence-based medicine. These include primary and secondary prevention of CAD in the elderly, primary prevention of CAD in persons with diabetes, and primary prevention of stroke.
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PMID:Lipid modulation and atherosclerotic events: extending the clinical spectrum with fibrates and statins. 1112 19

Although there is little information from primary or secondary prevention trials on cholesterol-lowering medication in diabetic patients, the reduction of elevated cholesterol is widely recommended for this group. The American Diabetes Association (ADA) recommends drug therapy in diabetic patients if low density lipoprotein (LDL)-cholesterol remains at > 130 mg/dl, or > 100 mg/dl in patients with macroangiopathy, after dietary intervention. When cholesterollowering medication is indicated, the choice of the drug must take into account the other lipid abnormalities that are often present and the need to maintain optimal glycaemic control. In the present study we compared the efficacy and safety of the novel HMG-CoA reductase inhibitor atorvastatin at the dose of 10 mg/day with simvastatin , lovastatin and pravastatin at doses of 10, 20 and 20 mg/day, respectively, and placebo, in type 2 diabetic patients with moderate elevation of LDL-cholesterol with or without elevation of triglycerides. All the quoted agents are enzyme inhibitors effective in lowering LDL-cholesterol in humans. The efficacy endpoints were the mean per cent changes in plasma LDL-cholesterol (primary), total cholesterol, triglycerides, and high-density lipoprotein (HDL)-cholesterol concentrations from baseline to the end of treatment (24 weeks). Atorvastatin at a dose of 10 mg/day produced: (1) a significant reduction in LDL-cholesterol (-37%) in comparison with equivalent doses of simvastatin (-26%), pravastatin (-23%), lovastatin (-21%), and placebo (-1%); (2) HDL-cholesterol increases (7.4%) comparable to or greater than those obtained with simvastatin (7.1%), pravastatin (3.2%), lovastatin (7.21%), and placebo (-0.5%); (3) a significantly greater reduction in total cholesterol (- 29%) than that obtained with simvastatin (-21%), pravastain (-16%), lovastatin (-18%), and placebo (1%); and (4) a significantly greater reduction in triglycerides than that obtained with all the other drugs and placebo. In all treatment groups no significant variation in fibrinogen concentration was observed. All reductase inhibitors studied had similar levels of tolerance. There were no incidents of persistent elevations of serum aminotransferases or myositis.
Diabetes Obes Metab 2000 Dec
PMID:Comparative efficacy study of atorvastatin vs simvastatin, pravastatin, lovastatin and placebo in type 2 diabetic patients with hypercholesterolaemia. 1122 65

The 6-week efficacy and safety of atorvastatin versus simvastatin was determined during a 54-week, open-label, multicenter, parallel-arm, treat-to-target study. In all, 1,424 patients with mixed dyslipidemia (triglyceride 200 to 600 mg/dl [2.26 to 6.77 mmol/L]) were stratified to 1 of 2 groups (diabetes or no diabetes). Patients were then randomized to receive either atorvastatin 10 mg/ day (n = 730) or simvastatin 10 mg/day (n = 694). Efficacy was determined by measuring changes from baseline in lipid parameters including low-density lipoprotein (LDL) cholesterol, total cholesterol, triglycerides, and apolipoprotein B. Compared with simvastatin, atorvastatin produced significantly greater (p < 0.0001) reductions from baseline in LDL cholesterol (37.2% vs 29.6%), total cholesterol (27.6% vs 21.5%), triglycerides (22.1% vs 16.0%), the ratio of LDL cholesterol to high-density lipoprotein (HDL) cholesterol (41.1% vs 33.7%), and apolipoprotein B (28.3% vs 21.2%), and a comparable increase from baseline in HDL cholesterol (7.4% vs 6.9%). Atorvastatin was also significantly (p < 0.0001) more effective than simvastatin at treating the overall patient population to LDL cholesterol goals (55.6% vs 38.4%). Fewer than 6% of patients in either treatment group experienced drug-attributable adverse events, which were mostly mild to moderate in nature. Diabetic patients treated with either statin had safety characteristics similar to nondiabetics, with atorvastatin exhibiting superior efficacy to simvastatin. In conclusion, atorvastatin, at a dose of 10 mg/day, is more effective than simvastatin 10 mg/day at lowering lipids and reaching LDL cholesterol goals in patients with mixed dyslipidemia. Both statins are well tolerated with safety profiles similar to other members of the statin class.
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PMID:Comparison of efficacy and safety of atorvastatin (10mg) with simvastatin (10mg) at six weeks. ASSET Investigators. 1123 Aug 38

A double-blind, placebo-controlled, parallel-group study was performed to determine whether atorvastatin, a new HMG-CoA reductase inhibitor, could effectively and safely reduce plasma LDL-cholesterol concentrations in Japanese patients with type-2 diabetes without influencing glycemic control. The subjects were patients with hypercholesterolemia (serum cholesterol concentration > or =5.7 mmol/l (220 mg/dl)) and stable glycemic control. The fasting concentrations of hemoglobin A(1C) (HbA(1C)), fructosamine, and 1,5-anhydroglucitol (1,5-AG) were measured as indices of glycemic control. Plasma lipid concentrations and the safety of the drug were also examined. Forty eligible patients in two groups of 20 each were administered atorvastatin (10 mg/day) or placebo. Neither atorvastatin nor placebo caused a significant change in HbA(1C), fructosamine, or 1,5-AG concentrations. Atorvastatin significantly reduced total cholesterol and LDL-cholesterol concentrations from baseline by 29.7% (p<0.0001) and 41.6% (p<0.0001), respectively. The incidence of clinical adverse events and that of abnormal changes in laboratory test values did not differ between the two groups. In this trial, atorvastatin effectively and safely reduced LDL-cholesterol concentrations in diabetic patients with hypercholesterolemia without influencing glycemic control. These findings are clinically important because there are many diabetic patients with hypercholesterolemia and such patients have a high risk of developing arteriosclerotic disease.
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PMID:A double-blind trial on the effects of atorvastatin on glycemic control in Japanese diabetic patients with hypercholesterolemia. 1158 Sep 8

Preliminary evidence from trials with the HMG-CoA reductase inhibitors (statins), simvastatin and pravastatin, suggests that aggressive treatment of diabetic dyslipidaemia will reduce coronary events. Questions regarding the prevention of cardiovascular events in diabetic patients are now being addressed in prospectively designed trials. The first question is, can aggressive treatment of dyslipidaemia lead to primary prevention of cardiovascular events in patients with type 2 diabetes? This is being addressed in the ongoing Atorvastatin Study for the Prevention of coronary heart disease Endpoints in NIDDM (ASPEN) and the Collaborative AtoRvastatin Diabetes Study (CARDS). These trials will randomize over 4000 patients with type 2 diabetes and no previous myocardial infarction to either atorvastatin or placebo for 4 years. The second question is, are there benefits for aggressive lipid lowering to levels below those recommended in current treatment guidelines, i.e. is lower better? Results from the recent Atorvastatin VErsus Revascularization Treatment (AVERT) trial suggest this to be the case. AVERT showed that, in stable coronary heart disease patients who had been referred for revascularization, aggressive lowering of low density lipoprotein (LDL) cholesterol with atorvastatin 80 mg/day (to a mean level of 2.0 mmol/L [77 mg/dL]) reduced the incidence of ischaemic events by 36% compared with angioplasty and usual care (which reduced LDL cholesterol to 3.1 mmol/L [119 mg/dL]). The 36% reduction in events with atorvastatin versus angioplasty and usual care trended towards significance (p=0.048). The benefits of aggressive lipid-lowering therapy are also being investigated in the ongoing Treating to New Targets (TNT) and Incremental Decrease in Endpoints through Aggressive Lipid lowering (IDEAL) trials. These studies will more closely examine the benefits of treating diabetic dyslipidaemia, and will determine how aggressively this abnormal lipid profile should be treated.
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PMID:What does the future hold for diabetic dyslipidaemia? 1182 50

The UK Prospective Diabetes Study (UKPDS) is the largest intervention trial to date of patients with type 2 diabetes, involving 5102 newly diagnosed diabetic patients. Results showed that 59% of patient deaths were from cardiovascular disease. While intensive treatment of glucose produced a significant 25% reduction in microvascular endpoints compared with diet only (p=0.0099), patients with type 2 diabetes usually have a lipid profile that is highly atherogenic. In the UKPDS, intensive treatment of hyperglycaemia and hypertension did not improve lipid levels. In patients without diabetes, lipid-lowering therapy has been shown to reduce the risk of cardiovascular events in both primary and secondary prevention trials. Currently, a number of large-scale trials of lipid-lowering therapy in patients with diabetes are ongoing. For example, the Lipids in Diabetes Study will determine whether lipid lowering with a statin or fibrate can substantially reduce cardiovascular morbidity and mortality in 5000 patients with type 2 diabetes. The Atorvastatin Study for the Prevention of coronary heart disease ENdpoints (ASPEN) is comparing double-blind treatment with atorvastatin and placebo in 2250 US diabetic patients without coronary heart disease, while a sister trial in the UK, the Collaborative AtoRvastatin Diabetes Study (CARDS), is enrolling 1820 diabetic patients. The results from these trials may provide information that which will help determine the future management of diabetic dyslipidaemia.
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PMID:The UKPDS: implications for the dyslipidaemic patient. 1182 52


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