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

Stable compensation of diabetes mellitus, including normolipidemia, underlies the therapy of diabetic angiopathies. Mevacor represents a nonactive lactone form of a certain hydroxy acid, a potent inhibitor of endogenous synthesis of cholesterol, conducive to blood cholesterol reduction. The aim of the present study was the assessment of the efficacy of this drug in therapy of patients with diabetes mellitus. Ten patients were administered mevacor in a dose of 20 mg for a month. Such therapy was conducive to a significant reduction of the levels of cholesterol, LNP cholesterol, triglycerides, and cholesterol/LVP ratio. It also promoted a reduction of the content of lipid peroxidation products in the blood, these products being an active factor of vessel destruction. The levels of hydroperoxides, blood serum and red cell malonic dialdehyde, and superoxide dismutase were also reduced. These results necessitate addition of mevacor to a complex of therapy for diabetes to normalize lipid metabolism.
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PMID:[Use of the lipolytic drug mevacor in the treatment of patients with diabetes mellitus]. 130 47

Hyperlipidemia is a well-recognized complication of renal transplantation. In long-term survivors of renal transplantation, cardiovascular disease accounts for the majority of patient deaths. In the cyclosporine era, cardiovascular disease has surpassed infection as the number one cause of death. Risk factors in the transplant population for hyperlipidemia include age, male sex, diabetes, prednisone dose, graft impairment, obesity, and antihypertensive therapy. Recently, cyclosporine has been implicated as an aggravating factor in the development of hyperlipidemia after transplantation, although its role has been controversial. Because renal transplant recipients have other significant risk factors for the development of coronary artery disease, the amelioration of hyperlipidemia may improve long-term patient survival. Because most late deaths occur in patients with a functioning graft, long-term graft survival could also be improved. The role of corticosteroids in the development of hyperlipidemia is well established. Recent studies employing corticosteroid withdrawal after transplantation have shown a marked reduction in cholesterol despite the use of cyclosporine. Data on corticosteroid withdrawal in living related transplants at our center show a significant reduction in total cholesterol after steroid withdrawal. Data from heart transplant recipients under corticosteroid-free protocols show a similar reduction in total cholesterol. Other treatments for hyperlipidemia include diet and cholesterol-lowering agents, such as Mevacor (lovastatin; Merck Sharp & Dohme, West Point, PA). The efficacy of lowering cholesterol in this high-risk population is unknown.
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PMID:Hyperlipidemia and transplantation: etiologic factors and therapy. 149 81

The chemistry, pharmacology, pharmacokinetics, clinical trials, adverse effects, role in lipid-lowering therapy, and dosage and administration of pravastatin are reviewed. Pravastatin sodium is a new 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor for the treatment of hypercholesterolemia. Its structural formula is similar to those of lovastatin and simvastatin, but it is active in the parent form. It competitively inhibits HMG-CoA reductase, reduces hepatic cellular cholesterol synthesis, increases the expression of hepatic low-density lipoprotein (LDL) receptors, and reduces hepatic very low-density lipoprotein (VLDL) synthesis. Pravastatin has been demonstrated to reduce cholesterol in patients with familial and nonfamilial polygenic hypercholesterolemia and patients with diabetes mellitus. In doses of 10-40 mg/day, pravastatin has been shown to reduce total cholesterol by 15-30% and LDL cholesterol by 15-40%. It also increases high-density lipoprotein cholesterol by 2-20% and reduces triglycerides. It is generally well tolerated, with few adverse effects reported in clinical trials. Pravastatin reduces LDL cholesterol and increases HDL cholesterol comparably to lovastatin but possibly with fewer adverse effects. Further studies and clinical use will be needed to confirm potential differences in adverse effect profiles between the two drugs.
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PMID:Pravastatin: a new drug for the treatment of hypercholesterolemia. 845 77

Diabetes mellitus is associated with hyperlipidemia and increased risk of atherosclerosis. A diabetic animal model has been developed to study the effect of treatment with pravastatin, a potent HMG CoA reductase inhibitor, on plasma lipoprotein levels. Hypercholesterolemia was induced in alloxan diabetic and control rabbits by feeding a diet containing 25% casein and 10% hydrogenated coconut oil for 8 weeks. Feeding the casein-coconut oil diet to the diabetic group resulted in a 5-fold increase in serum cholesterol levels, which was not statistically different from the nondiabetic group fed this diet. However, in the diabetic group, there was more cholesterol in the VLDL fraction and less in LDL as compared to the nondiabetic group. Serum triacylglycerol levels in the diabetic rabbits were variable and ranged from 58-943 mg/dl. The diabetic and nondiabetic animals were then treated with pravastatin at a dose of 10 mg/kg per day for 21 days. In the nondiabetic group, pravastatin treatment significantly lowered serum and LDL cholesterol concentrations by 28.5% (52.3 mg/dl, P less than 0.05) and 36.2% (40.7 mg/dl, P less than 0.05) respectively, relative to the placebo group. Serum and VLDL triacylglycerol levels in the nondiabetic group were also significantly decreased following pravastatin treatment. In the diabetic group, serum and LDL cholesterol levels were decreased by 37.0% (69.1 mg/dl, P less than 0.05) and 52.7% (32.1 mg/dl, P less than 0.01), respectively, relative to the diabetics given the placebo. Pravastatin treatment did not adversely affect serum glucose levels. Thus, pravastatin treatment was effective in controlling the hypercholesterolemia present in these diabetic animals.
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PMID:The effect of pravastatin on serum cholesterol levels in hypercholesterolemic diabetic rabbits. 190 19

Pravastatin, a novel inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, was administered to nine hypercholesterolemic patients with diabetes mellitus to examine its effects on diabetic nephropathy. Pravastatin treatment resulted in lowering serum total cholesterol by 22.1% on the average (p less than 0.001), and led to a significant reduction in urinary excretion of albumin and beta 2-microglobulin in patients with an elevated urinary protein excretion rate at the baseline period. But glycemic control, blood pressure, urinary excretion of creatinine and that of N-acetyl-beta-D-glucosaminidase showed no significant change during the study. These results suggest that reduction of atherogenic lipids and lipoproteins with pravastatin could alleviate diabetic glomerular injury.
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PMID:Amelioration of proteinuria with pravastatin in hypercholesterolemic patients with diabetes mellitus. 212 49

In the past history of the pharmaceutical industry, secondary metabolites have been screened almost exclusively for antimicrobial activities. This biased and narrow view has severely limited the potential application of microbial metabolites. Fortunately, this situation is changing and we are now entering into a new era in which microbial metabolites are being applied to diseases heretofore only subjected to synthetic compounds. This new approach is the application of microbial secondary metabolites to diseases that are not caused by other bacteria or fungi. For years, major drugs such as hypotensive and anti-inflammatory agents that are used for non-infectious diseases have been strictly synthetic products. Similarly, major therapeutics for parasitic diseases in animals (for example, coccidiostats and anthelminthics) resulted strictly from screens of chemically synthesized compounds followed by molecular modification. However, today fermentation products such as monensin and lasalocid dominate the coccidiostat market. The avermectins, another group of streptomycete products, have high activity against helminths and arthropods. Indeed, their activity appears to be an order of magnitude greater than previously discovered anthelminthic agents, the vast majority of which are synthetic compounds. Umezawa's group in Japan has isolated many microbial products with important pharmacological activities by screening with simple enzymic assays. There is much interest in a natural inhibitor of intestinal glucosidase, which is produced by an actinomycete of the genus Actinoplanes. The aim is to decrease hyperglycaemia and triacylglycerol synthesis in adipose tissue, liver and the intestinal wall of patients with diabetes, obesity and type IV hyperlipidaemia. Another natural compound of interest is mevinolin, a fungal product which acts as a cholesterol-lowering agent in animals. Mevinolin is produced by Aspergillus terreus. In its hydroxyacid form (mevinolinic acid), mevinolin is a potent competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase from liver. It is clear that, although the microbe has contributed greatly to the benefit of mankind, we have merely scratched the surface of the potential of microbial activity.
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PMID:A new era of exploitation of microbial metabolites. 640 Apr 79

The Prospective Pravastatin Pooling (PPP) project is a pooled evaluation of 3 large, placebo-controlled, randomized trials of cholesterol-lowering treatment with pravastatin. It is designed to more reliably evaluate the effect of treatment on coronary and all-cause mortality and on total coronary artery disease (CAD) events for specific populations of interest, including women and the elderly. The trials--Long-Term Intervention With Pravastatin in Ischemic Disease trial, the Cholesterol and Recurrent Events trial, and the West of Scotland Coronary Prevention Study--each have common design features, including drug, dose, and duration. The project prospectively defines the objectives, end points, and analytic plans in a protocol developed before results are known of any individual trial. More than 2,000 (or 10%) of the participants in the pooled data set are women, 1,841 are aged > or = 70 years at trial entry, and > 6,000 have a total cholesterol < 5.5 mmol/L (213 mg/dl). The mean low-density lipoprotein cholesterol level is 4.2 mmol/L (162 mg/dl). The mean blood pressure level is 134/81 mm Hg and 20% are current smokers. Half of the PPP participants have had a prior myocardial infarction. More than 7% have a history of diabetes and 26% have a history of hypertension. PPP is projected to have data on about 1,100 CAD deaths, 500 non-CAD deaths, and > 1,000 cancers by study completion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Design, rational, and baseline characteristics of the Prospective Pravastatin Pooling (PPP) project--a combined analysis of three large-scale randomized trials: Long-term Intervention with Pravastatin in Ischemic Disease (LIPID), Cholesterol and Recurrent Events (CARE), and West of Scotland Coronary Prevention Study (WOSCOPS). 748 29

This study reports the result of a 12-month, open-label multicenter study of the efficacy and tolerability of pravastatin in the management of hypercholesterolemia associated with non-insulin-dependent diabetes mellitus. Pravastatin produced a decrease, in 138 diabetic and 51 non-diabetic patients, in total serum cholesterol by 19 and 20%, in low-density lipoprotein (LDL) cholesterol by 25 and 29%, in apolipoprotein B by 15 and 19% and in triglycerides by 8 and 5%, respectively. High-density lipoprotein cholesterol levels were increased by 9% in both groups. All of these changes were significant (P < 0.001) except for triglycerides changes in non-diabetic patients, where the change was not significant and no significant differences were observed between the two groups. These favorable effects on LDL cholesterol and apolipoprotein B were not influenced by gender, the type of diabetic therapy, baseline hemoglobin A1c levels and by the presence of hypertension or gross proteinuria, although a decrease in the two variables were less in those with body mass index > or = 26.4 kg/m2 or in those with age < 60 years. Adverse experiences were similar between treatment groups and the drug was well tolerated. Only one diabetic patient was withdrawn from the study because of pruritus. Pravastatin produced no change in fasting plasma glucose concentrations and hemoglobin A1c levels in diabetic patients throughout the study. Pravastatin was generally effective in improving the serum lipids of hypercholesterolemic diabetic patients.
Diabetes Res Clin Pract 1995 Jan
PMID:Long-term efficacy and tolerability of pravastatin in hypercholesterolemia in patients with non-insulin-dependent diabetes mellitus. Hyogo Pravastatin Study Group. 778 95

Effectiveness of a simultaneous inhibition of cholesterol absorption and synthesis, caused by sitostanol ester margarine and pravastatin, was studied to control mild hypercholesterolemia in men with non-insulin-dependent diabetes mellitus (NIDDM) (n = 8). Margarine, 24 g daily, was a basal dietary treatment. Four 7-week intervention periods included margarine, sitostanol (3 g/day) ester margarine, pravastatin (40 mg/day), and sitostanol ester margarine plus pravastatin in a random order. Pravastatin lowered serum total (-32%) and LDL cholesterol (-38%) and apolipoprotein B (-39%) because of enhanced removal (+20%) and decreased production (-26%) of LDL apolipoprotein B, and reduced synthesis (-9%) and turnover (-8%) of cholesterol, which resulted in reduced biliary cholesterol seretion (-18%). Even though serum triglycerides were lowered by 28%, VLDL, IDL, and light and dense LDL became triglyceride-enriched. Despite increasing cholesterol synthesis, sitostanol lowered LDL cholesterol (-14%) by inhibiting cholesterol absorption (-68%) and LDL apolipoprotein B production rate (-20%). Combination of pravastatin and sitostanol ester lowered serum total, VLDL, IDL, and LDL cholesterol and LDL apolipoprotein B by the highest rate, 35%, 50%, 35%, 44%, and 45% from the control margarine period, respectively, because of reduced apolipoprotein B transport rate (but unchanged removal), in both the total and dense LDL subfractions. HDL cholesterol and apolipoprotein A-I kinetics were unchanged. In spite of decreased absorption, cholesterol synthesis was not compensatorily increased. In conclusion, simultaneous inhibition of cholesterol absorption and synthesis lowers LDL cholesterol and apolipoprotein B by 44-45% solely through inhibition of LDL apolipoprotein B production rate in hypercholesterolemic NIDDM patients. A combination of statin to sitostanol ester margarine-resistant patients offers a safe and effective measure to normalize abnormally high cholesterol values, probably with a lowered statin dose.
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PMID:Effects of inhibiting cholesterol absorption and synthesis on cholesterol and lipoprotein metabolism in hypercholesterolemic non-insulin-dependent diabetic men. 886 62

Pravastatin is an HMG-CoA reductase inhibitor which lowers plasma cholesterol levels by inhibiting de novo cholesterol synthesis. Pravastatin produces consistent dose-dependent reductions in both total and low density lipoprotein (LDL)-cholesterol levels in patients with primary hypercholesterolaemia. Favourable changes in other parameters such as total triglyceride and high density lipoprotein (HDL)-cholesterol levels are generally modest. Combination therapy with other antihyperlipidaemic agents such as cholestyramine further enhances the efficacy of pravastatin in patients with severe dyslipidaemias. Available data suggest that pravastatin is effective in elderly patients and in patients with hypercholesterolaemia secondary to diabetes mellitus or renal disease. The benefit of cholesterol-lowering in terms of patient outcomes is currently an area of considerable interest. Recently completed regression studies (PLAC I, PLAC II, KAPS and REGRESS) show that pravastatin slows progression of atherosclerosis and lowers the incidence of coronary events in patients with mild to moderately severe hypercholesterolaemia and known coronary heart disease. Large scale primary (WOSCOPS) and secondary (CARE) prevention studies, moreover, demonstrate that pravastatin has beneficial effects on coronary morbidity and mortality. In WOSCOPS, all-cause mortality was reduced by 22%. Pravastatin is generally well tolerated by most patients (including the elderly), as evidenced by data from studies of up to 5 years in duration. As with other HMG-CoA reductase inhibitors, myopathy occurs rarely (< 0.1% of patients treated with pravastatin): approximately 1 to 2% of patients may present with raised serum levels of hepatic transaminases. Thus, with its favourable effects on cardiovascular morbidity/mortality and total mortality, pravastatin should be considered a first-line agent in patients with elevated cholesterol levels, multiple risk factors or coronary heart disease who are at high risk of cardiovascular morbidity.
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PMID:Pravastatin. A reappraisal of its pharmacological properties and clinical effectiveness in the management of coronary heart disease. 902 47


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