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

Diabetic nephropathy is associated with an altered lipid profile characterized by elevated triglyceride rich lipoproteins, present even in the earlier stages of the renal disease. Although many experimental studies have demonstrated a significant deleterious role for hyperlipidemia in both the initiation and progression of renal injury, data remain more conflicting in humans. A few prospective studies, mostly in type 2 diabetes, have suggested an independent role for serum cholesterol level in the subsequent development of incipient or overt diabetic nephropathy. Furthermore, studies have reported in both types of diabetes an independent deleterious influence of serum total cholesterol on the decline in renal function and/or progression of albuminuria. However, the majority of these studies were post hoc analyses of previously controlled therapeutic trials with several observational studies not confirming these findings. It remains controversial whether apolipoprotein E gene polymorphism is an important factor in the development of diabetic nephropathy. Most of the interventional studies with lipid-lowering therapy in diabetic nephropathy have used HMG CoA reductase inhibitors and have been inconclusive. This may be due to a too short follow-up or insufficient number of patients. Further larger prospective studies are therefore required to better ascertain the role of lipids in the progression of diabetic nephropathy.
Diabetes Metab 2000 Sep
PMID:Potential influence of lipids in diabetic nephropathy: insights from experimental data and clinical studies. 1101 Dec 17

Use of lipid-lowering drugs in both primary and secondary prevention of cardiovascular disease (CVD) decreases significantly risk of myocardial infarction, stroke, incidence of cardiovascular events, reduces the cardiovascular mortality and morbidity as well as total mortality. HMG-CoA reductase inhibitors (statins) are most potent cholesterol-lowering drugs. Statins act by inhibition of HMG-CoA reductase activity, a rate--limiting step in synthesis of cholesterol and important metabolites of mevalonate--isoprenoids. The mechanisms by which favourable antiatherogenic actions of statins occur are complex. Statins inhibit proliferation and migration of vascular smooth muscle cells, reduce free-radicals generation and LDL modification, lower Lp(a) concentration, inhibit macrophage-derived foam cells accumulation and inhibit activation of platelets, thromboxane and PAI-1 synthesis. Use of statins in the therapy of hypercholesterolemia is presently recommended by NCEP, especially in high-risk groups (diabetes, post-CABG and PTCA, kidney and heart transplantation). Nevertheless, patients with CAD and moderately elevated LDL-C levels also benefit from the treatment with statins. Because of high costs of the therapy, statins of most favourable pharmacoeconomic profile should be used.
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PMID:[HMG-CoA reductase inhibitors in prevention of cardiovascular diseases: new mechanisms, aspects and trials]. 1105 20

Patients with type 2 diabetes are at high risk for coronary heart disease (CHD); frequently, these patients have abnormal lipid profiles, placing them at even greater risk. A syndrome of insulin resistance, hyperinsulinaemia, hypertension, and high levels of fibrinogen and plasminogen activator inhibitor contributes to cardiovascular risk, which is not sufficiently decreased by glycaemic control alone. In several large interventional trials, CHD risk in patients with diabetes was substantially reduced by aggressive lipid-lowering therapy. In patients with diabetes, CHD, low high-density lipoprotein levels, and normal low-density lipoprotein levels, gemfibrozil reduced fatal and non-fatal CHD events. For lipid-lowering in patients with diabetes and CHD, pravastatin and simvastatin are the only HMG-CoA reductase inhibitors shown to reduce fatal and non-fatal CHD events. Of these, pravastatin has less potential for drug-drug interactions and may be safer to use, particularly for combination therapy with fibric acid derivatives, as may now be important for CHD prevention in mixed dyslipidaemias.
Diabetes Obes Metab 2000 Oct
PMID:Implications of cardiovascular risk in patients with type 2 diabetes who have abnormal lipid profiles: is lower enough? 1122 41

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

Coronary heart disease (CHD), whose primary aetiology is atherosclerosis, is the leading cause of mortality and a major cause of morbidity in the industrialised world [1]. Serum lipoprotein levels are aetiologically related to the risk of atherosclerosis and CHD [2]. The liver and the gastrointestinal system are the major protagonists involved in regulation of lipoprotein biochemical-physiological mechanisms and the development of hypercholesterolaemia. Furthermore, specific lipoprotein receptors are being discovered as targets for pharmacological intervention to correct lipoprotein disorders. Agents that target lipoprotein regulation in the liver, gastrointestinal-biliary and atherosclerotic tissues resulting in improved serum lipoprotein levels and/or control of primary and secondary dyslipidaemic disorders including diabetes, are currently undergoing clinical trials. The most novel promising compounds, after the greatly effective newest HMG-CoA reductase inhibitors, are drugs that affect peroxisome proliferator-activated receptors, PPARalpha and PPARgamma receptors, bile acid transport mechanisms, cholesterol absorption and cholesterol acyltransferase and other biochemical targets of lipoprotein regulation. Current knowledge and ongoing trials with these agents are described here within the boundaries of investigator confidentiality agreements.
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PMID:New pharmacological agents under clinical investigation for treating disorders of lipoprotein regulation leading to atherosclerosis. 1122 51

Cardiovascular disease (CVD) is the leading cause of death and disability in the United States and in most industrialized nations. Major breakthroughs to modern day cardiovascular/lipid research have been attributed to the findings of the Framingham Heart Study and Gofman and colleagues who made associations between lipoprotein levels (LDL, VLDL and HDL) and CVD. Unfortunately, half of all CVD patients have none of the established coronary risk factors (hypertension, hypercholesterolemia, cigarette smoking, diabetes mellitus, obesity) and new strategies for identifying patients need be considered. Although there remains little disagreement regarding the necessity to lower elevated plasma cholesterol levels, there remains much controversy regarding appropriate dietary means of accomplish this goal. The National Cholesterol Education Program (1993) proposed a dietary reduction (Step I and Step II diets) to the percent saturated fat and cholesterol consumed by at-risk patients. Many currently question about the effectiveness of these diets and an alternative diet, replacing saturated fats by monounsaturated fats (olive oil), has attracted recent attention. While diet modification is considered the foundation of primary treatment, other interventions are frequently required. Although early drug trials demonstrated that agents such as nicotinic acid, clofibrate, gemfibrozil, bile acid-binding resins generally slowed progression of atherosclerotic lesions, lowered plasma cholesterol levels and decreased mortality from CVD, the greatest advance to current drug therapy involved the discovery of the "statins" (HMG-CoA reductase inhibitors). In the current work, mechanisms for vascular dysfunction resulting in myocardial ischemia were explored and potential nutritional (dietary) and pharmacologic interventions were reviewed.
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PMID:Cardiovascular disease: a historic perspective. 1123 77

The metabolic syndrome consists of a cluster of metabolic disorders, many of which promote the development of atherosclerosis and increase the risk to develop cardiovascular disease. The metabolic syndrome is characterized by atherogenic dyslipidemia (elevated triglycerides, increased small dense low-density lipoproteins, and decreased high-density lipoproteins), hypertension, insulin resistance and obesity. To decrease the risk of cardiovascular disease events decreasing body weight by ingesting a healthy diet, increasing physical activity, cessation of smoking and managing dyslipidemia are recommended. Pharmacological treatment of dyslipidemia is based on different drug classes. For LDL-cholesterol-lowering mainly statins and for triglyceride-lowering mainly fibrates are used. In primary and secondary prevention trials of heart disease they have shown to reduce the incidence of coronary artery disease or coronary events by 25-60 percent. Statins reduce mainly LDL-cholesterol levels by competitive inhibition of HMG-CoA reductase but have also shown to reduce fasting and postprandial triglyceride levels. Fibrates effectively reduce fasting and postprandial lipemia, shift the distribution of LDL particles towards less dense particles and increase HDL-cholesterol. Thus fibrates particularly address components of the metabolic syndrome and features of diabetic dyslipidemia. However studies still are needed showing definite evidence on differential therapy in lipid lowering based on prospective controlled trials with endpoints of macro- and microangiopathy in diabetic patients.
Exp Clin Endocrinol Diabetes 2001
PMID:Treatment of dyslipoproteinemia in the metabolic syndrome. 1145 42

Patients with non-insulin-dependent diabetes (NIDDM) have an increased incidence of ischaemic heart disease (IHD) when compared with nondiabetic subjects. In addition, they have a worse prognosis after their first myocardial infarction (MI). According to the recent USA recommendations, the threshold for initiation of dietary intervention in diabetic subjects is an LDL greater than 2.6 mmol/l, with the goal to achieve levels less than 2.6 mmol/l (100 mg/dl). This is also the threshold for initiation and treatment goal for pharmacological intervention in diabetic subjects, unless they are completely free of IHD, peripheral vascular disease or cerebrovascular disease and have no other IHD risk factors. In the latter circumstances, the threshold for treatment is an LDL greater than 3.38 mmol/l (130 mg/dl), with the goal to achieve levels less than 3.38 mmol/l. The HMG-CoA reductase inhibitors (statins) can improve the lipid profile effectively and safely in NIDDM. Results from post hoc analyses of diabetic subgroups in the large intervention trials suggest that some statins significantly reduce the risk for IHD-related mortality/morbidity. However, because these results are derived from secondary prevention trials, we cannot be sure if these benefits apply to all diabetic subjects or only to those who already have IHD. Nevertheless, it seems logical to assume that this benefit also applies to NIDDM patients who do not have IHD because they share a similar vascular risk as nondiabetic subjects who have IHD. Intervention trials using statins and fibrates, alone or in combination, in NIDDM are under way. In a few years these trials will provide definitive end-point-based evidence in this high-risk group of patients.
J Diabetes Complications
PMID:Treating dyslipidaemia in non-insulin-dependent diabetes mellitus -- a special reference to statins. 1145 74

Plasma levels of fibrinogen have been identified as independent risk predictors of cardiovascular disease. This has greatly increased interest in the regulation of plasma fibrinogen levels. Many demographic and environmental factors are known to affect fibrinogen levels, such as diet, use of several drugs, age, smoking, body mass, gender, physical exercise, race, and season. Additionally, it is also known that genetic factors determine the fibrinogen levels, and also that they determine the response of fibrinogen levels to environmental factors. Estimates, based on twin studies, suggest that 30-50% of the plasma fibrinogen level is genetically determined. The effect of dietary components on plasma fibrinogen levels is modest. Several components have been identified as factors that influence fibrinogen levels. Among those are fish oil, other lipids, and fibers. Dietary components that were expected to have an effect on fibrinogen, but for which no association was observed are black and green tea. Several drugs are known to influence fibrinogen levels, the most studied of which are platelet aggregation inhibiting drugs, such as ticlopidine, and the lipid lowering fibric acid derivatives (fibrates). Both types of drugs decreased the plasma fibrinogen level by about 10%, and bezafibrate lowers fibrinogen even more in patients with diabetes. No clear effect was observed for the HMG-CoA reductase inhibitors (statins). In the Bezalip study, fibrinogen levels decreased in patients treated with bezafibrate, but this had no clear effect on the risk of cardiovascular disease. This suggests that several mechanisms influence the fibrinogen level and that these mechanisms may contribute differently to cardiovascular disease. Several variations in the fibrinogen genes have been described and especially variations in the promoter region of the fibrinogen beta-gene are interesting, because the synthesis of the fibrinogen B beta chain is considered to be the rate limiting step in the fibrinogen biosynthesis. In many studies the fibrinogen beta-gene polymorphisms (-455G/A, -148C/T, and BclI) are found to be associated with the plasma levels of fibrinogen. However, they are not associated with the risk of cardiovascular events, although in several studies an association with the severity and progression of atherosclerosis has been reported. It has also been observed frequently that the fibrinogen beta-gene promoter polymorphisms are associated with the response of fibrinogen levels to environmental factors, such as exercise and trauma. In conclusion, plasma fibrinogen levels are regulated by an interesting and complex interplay between environmental and genetic factors.
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PMID:Effects of diet, drugs, and genes on plasma fibrinogen levels. 1146 May 8

The statins, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, act to regulate the biosynthesis of cholesterol. Statins also deplete nonsterol cholesterol precursors, the isoprenoids, which are necessary for prenylation of critical membrane proteins that regulate cellular communication, including the inflammatory response. In a retrospective review of 388 bacteremic infections due to aerobic gram-negative bacilli and Staphylococcus aureus, there was a significant reduction in both overall (6% vs. 28%; P=.002) and attributable (3% vs. 20%; P=.010) mortality among patients taking statins compared with patients not taking statins. This reduction in mortality persisted in a multivariate analysis (odds ratio, 7.6; 95% confidence interval, 1.01-57.5). Among the statin group, diabetes, hypertension, and coronary artery disease were more prevalent (P<.001), and there were more skin and soft tissue infections identified as sources of bacteremia (P=.008). These data suggest a potential clinical role of statins in bacteremic infection; however, the mechanism by which mortality is reduced remains undefined.
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PMID:The effect of statins on mortality in patients with bacteremia. 1191 9


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