Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242339 (dyslipidemia)
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The aim of this study was to investigate the modulating effect of atorvastatin on serum paraoxonase 1 enzyme (PON1) activity in type 2 diabetic Egyptian patients with or without nephropathy. The present study was carried out on the following groups: control group, which consisted of 30 healthy persons; Group I, which consisted of 20 type 2 diabetic patients without nephropathy; and Group II, which consisted of 20 type 2 diabetic patients with nephropathy. All the patients selected were under an antidiabetic regimen of insulin, and patients receiving antihypertensive agents were excluded from the follow-up study to avoid drug interaction fallacies. Twenty-two patients (15 without nephropathy and seven with nephropathy) received atorvastatin in individually adjusted oral dosage (range 10-20 mg) once per day for 12 weeks. All cases were subjected to thorough clinical examination and history taking and measurement of serum levels of PON1 activity, malondialdehyde (MDA), glutathione reductase activity, fasting glucose, total cholesterol, triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL), urea, and creatinine. Urine samples were collected for determination of proteinuria. The obtained results showed that PON1 activity and HDL significantly decreased and fasting glucose significantly increased in Group I and Group II when compared to the control group, with significant difference in their levels between Group II and Group I. MDA, total cholesterol, and LDL levels significantly increased and glutathione reductase activity significantly decreased in Group I and Group II when compared to the control group. Urea, creatinine, and proteinuria levels showed significant increase in Group II when compared to the control group and Group I, with nonsignificant difference between control group and Group I. Atorvastatin therapy caused a significant increase in PON1 activity, and serum levels of MDA and glutathione reductase activity were significantly decreased and increased, respectively. Also, total cholesterol, triglyceride and LDL-cholesterol levels were significantly reduced with a significant increase in HDL-cholesterol levels. There was a significant modest reduction in serum urea and creatinine levels as well as in proteinuria level. Fasting glucose level was significantly reduced under the antidiabetic regimen of insulin through the follow-up period. PON1 activity showed a significant negative correlation with glucose and LDL, and a significant positive correlation with HDL in all the studied groups. It could be concluded that atorvastatin with its pleiotropic effects could provide optimal therapeutic intervention to control not only dyslipidemia, but also oxidative stress status with consequent improvement in the course of type 2 diabetes and diabetic nephropathy. More specifically, restoration of PON1 activity by atorvastatin opens a window to investigate other drugs that could provide a new adjuvant therapeutic line for better control of diabetes and diabetic nephropathy. Further research is also recommended to study the distribution of PON1 genetic polymorphism among the Egyptian population to explain the variability in its activity and its relationship with other factors that associate diabetes and its complications.
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PMID:Modulating effect of atorvastatin on paraoxonase 1 activity in type 2 diabetic Egyptian patients with or without nephropathy. 1955 42

Vascular complications represent the most frequent and the most serious complication of diabetes type 1 and type 2. High attention is paid to all manifestations of microangiopathy and macroangiopathy not only in studies of their pathogenesis, but also in numerous clinical reports revealing significant effect of conservative treatment in vascular diseases. It concerns namely microalbuminuria and proteinuria and also to the manifestations of diabetic nephropathy which are largely affected by antihypertensive and fibrate treatment as well as to diabetic retinopathy treatable by fibrates. In the treatment of diabetic microangiopathy a consistent attention must be paid to the treatment of hypertension and dyslipidemia, preferably using combinations of hypolipidemics. Already during selection of antidiabetics, possible vascular effects should be considered. Vascular wall and manifestations of vascular diseases can be positively influenced by so called insulin sensitizers, derivatives of sulphonylurea and metformin. In preparation there exist some other substances for the treatment of diabetic complications. Already now, every medical doctor should be able to select adequate treatment with antihypertensives, hypolipidemics and antidiabetics for the prevention or therapy of vascular diabetic complications.
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PMID:[Conservative treatment of diabetic microangiopathy and macroangiopathy]. 1963 41

Rhein (4,5-dihydroxyanthraquinone-2-carboxylic acid) is purified from rhubarb (Rheum officinale), a widely used traditional Chinese herb. In our previous studies, rhein was shown to be effective in ameliorating diabetic renal pathological changes and attenuating hyperlipidemia. Statins have also been proven to ameliorate renal pathological changes associated with diabetic nephropathy (DN) through lipid-dependent and -independent mechanisms. We here study the protective and regulatory effects of rhein on renal injury and dyslipidemia in db/db mice with DN, using simvastatin as the control, and provide information on the mechanisms by which rhein protects against renal damage from DN. The results indicated that urinary albumin excretion (UAE) was reduced after 8 weeks of treatment in the rhein group, and 12 weeks in the simvastatin group. The morphometric analysis revealed that levels of extracellular matrix (ECM) significantly decreased in the rhein group after the full treatment course, but not in the simvastatin group. The more powerful effects of rhein on decreasing transforming growth factor-beta1 (TGF-beta1) and fibronectin immunohistochemistry expression in renal tissue were also observed. And the plasma levels of cholesterol (Chol), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and ApoE all decreased in both the rhein and the simvastatin groups. Together, our data suggested that both rhein and simvastatin regulate dyslipidemia. The powerful effect of rhein in renal protection is due to its widespread effects. Rhein is a new drug that can decrease lipid levels and protect against DN progression in a different fashion with simvastatin.
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PMID:Rhein improves renal lesion and ameliorates dyslipidemia in db/db mice with diabetic nephropathy. 1963 39

Dyslipidemia, often present in patients with metabolic syndrome and chronic kidney disease, contributes to increased cardiovascular risk and progression of renal impairment. In these patients, the probability of death from cardiovascular complications is higher than death consequent to terminal renal failure. Positive neuroprotective effects ofstatins and fibrates are being attributed to hypolipidemic as well as other, lipid-unrelated, properties. Statins are able to slow down the decline in glomerular filtration rate and may decrease proteinuria. Nevertheless, conclusive evidence that statins decrease the incidence of cardiovascular complications in patients with advanced chronic kidney disease is still lacking. Through their effect on albuminuria, fibrates contribute to slowing down ofthe progression of diabetic nephropathy. Controlled trials and clinical practice have shown that monotherapy with statins as well as fibrates is safe. Management of combined dyslipidemia requires, apart from the selection of a suitable statin-fibrate combination, careful monitoring of potential adverse effects and treatment tolerability and compliance. The results of the Czecho-Slovakian pivot study KOLCHRI have demonstrated the efficacy and safety of fenofibrate combined with low dose statin in patients with metabolic syndrome and stage 2-4 chronic kidney disease.
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PMID:[Treatment of dyslipidemia in patients with metabolic syndrome and chronic kidney disease]. 1973 74

There is an ongoing trend of a rapid increment in the frequency of diabetes mellitus, expecially the non-insulin dependent form. By the end of the 2nd millenium 150 million cases were recorded worldwide, while the estimations predicted doubling the number by the year 2030. Numerous chronic complications accompany the disease, among them micro-, as well as macrovascular prevail, affecting small and large blood vessels. This paper provides a literature review on the topic of diabetic nephropathy, the main microvascular complication of diabetic disease. Microalbuminuria is the earliest sign of the diabetic renal involvement, with more than 30 mg and less than 300 mg of albumins in 24 h urine sample. The reduction of renal function begins with albuminuria leaving microalbuminuria level and entering the pathologic proteinuria range. Renal failure advances through the 5 stages, the final fifth occurring fortunately only in a minor proportion of the patients. The final stage ensues in 232 of 100 000 diabetic patients, according to the US data. However, in many developed countries there are 30-40% of new patients entering chronic dialysis treatment for diabetic nephropathy. Pathogenesis of diabetic nephropathy is based on hyperglycemia and distinct hemodynamic changes, glomerular hyperfiltration and high intraglomerular pressure. The important role have oxidative stress, advanced glycation end products, some cytokines, growth factors and sorbitol pathway. Nevertheless, genetic influence is considered by far the most important risk factor for diabetic nephropathy. Heritage determines the susceptibility in one and the protection in another diabetic patient. At the moment of pathologic proteinuria occurrence, glomerular filtration rate begins to decline for 1.2 ml/min/monthly in some patients, making the annual reduction of 7-14 ml/min/1.73 m2 of body surface area. Improving glycemia, blood pressure control, renal anemia correction with rHu-Epo, dyslipidemia control, reduction in protein intake, i.e. management of the nongenetic factors, could slower the renal function loss in some of the patients. Hence, these measures could reduce the proportion of the patients reaching end-stage renal disease, having in mind that morphological and functional changes are reversible only within certain limits. Therefore, the success of kidney protection is better if commenced earlier.
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PMID:[Diabetic nephropathy and prevention of diabetic nephropathy caused chronic renal insufficiency]. 1976 85

Diabetic nephropathy is the leading cause of chronic renal disease and a major cause of cardiovascular mortality. Diabetic nephropathy has been categorized into stages: microalbuminuria and macroalbuminuria. The cut-off values of micro- and macroalbuminuria are arbitrary and their values have been questioned. Subjects in the upper-normal range of albuminuria seem to be at high risk of progression to micro- or macroalbuminuria and they also had a higher blood pressure than normoalbuminuric subjects in the lower normoalbuminuria range. Diabetic nephropathy screening is made by measuring albumin in spot urine. If abnormal, it should be confirmed in two out three samples collected in a three to six-months interval. Additionally, it is recommended that glomerular filtration rate be routinely estimated for appropriate screening of nephropathy, because some patients present a decreased glomerular filtration rate when urine albumin values are in the normal range. The two main risk factors for diabetic nephropathy are hyperglycemia and arterial hypertension, but the genetic susceptibility in both type 1 and type 2 diabetes is of great importance. Other risk factors are smoking, dyslipidemia, proteinuria, glomerular hyperfiltration and dietary factors. Nephropathy is pathologically characterized in individuals with type 1 diabetes by thickening of glomerular and tubular basal membranes, with progressive mesangial expansion (diffuse or nodular) leading to progressive reduction of glomerular filtration surface. Concurrent interstitial morphological alterations and hyalinization of afferent and efferent glomerular arterioles also occur. Podocytes abnormalities also appear to be involved in the glomerulosclerosis process. In patients with type 2 diabetes, renal lesions are heterogeneous and more complex than in individuals with type 1 diabetes. Treatment of diabetic nephropathy is based on a multiple risk factor approach, and the goal is retarding the development or progression of the disease and to decrease the subject's increased risk of cardiovascular disease. Achieving the best metabolic control, treating hypertension (<130/80 mmHg) and dyslipidemia (LDL cholesterol <100 mg/dl), using drugs that block the renin-angiotensin-aldosterone system, are effective strategies for preventing the development of microalbuminuria, delaying the progression to more advanced stages of nephropathy and reducing cardiovascular mortality in patients with diabetes.
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PMID:Diabetic nephropathy. 1982 47

The burden of microvascular disease in patients with type 2 diabetes mellitus continues to escalate worldwide. Current standards of care reduce but do not eliminate the risk of diabetic retinopathy, nephropathy or neuropathy in these patients. Correction of atherogenic dyslipidemia, which is characterized by elevated triglyceride levels and low levels of HDL cholesterol, might provide additional benefit. Whereas promising data have been published with respect to fibrate therapy for maculopathy, fenofibrate for diabetic retinopathy, and statin or fibrate therapy for diabetic nephropathy, further studies are warranted to define optimal management strategies for reducing the residual microvascular risk. Such strategies are especially relevant in cases of diabetic peripheral neuropathy, where even optimal care fails to affect disease progression. Identification of those factors that are most relevant to residual diabetes-related microvascular risk is a priority of an ongoing multinational epidemiological study. In this Review, we highlight an urgent need to address the issue of microvascular residual risk in patients with or at risk of type 2 diabetes mellitus.
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PMID:Residual microvascular risk in diabetes: unmet needs and future directions. 1985 73

The aim of the study was to assess specific cardiovascular lesions in patients with type 2 diabetes mellitus and diabetic nephropathy (DN) and search for the methods of their correction. It included 182 overweight or obese (abdominal type) women above 55 yr with arterial hypertension (AH) divided into groups with normal or low (less than 30 ml/day) albuminuria (n = 87), albuminuria (30-300 mg/day, n = 59), proteinuria (above 30 mg/day, n = 21), and stage I-IIa chronic renal insufficiency (CRI, n = 15). It was shown that structural geometric changes in the left ventricle (LV) with the prevalence of myocardial concentric hypertrophy and diastolic dysfunction (DD), enhanced myocardial hardness, and preserved systolic function undergo progression with increasing severity of DN and decreasing glomerular filtration rate combined with poorly controlled DM2, abnormal lipid profile, long history of AH in the absence of adequate AP control, signs of vascular atherosclerosis (thickening of intima and media in carotid arteries), and large number of macrovascular complications. DN-related insulin resistance (IR) was a factor influencing LV remodeling and DD. Long-term combined therapy affecting IR and markers of cardiovascular disorders (AH, chronic hyperglycemia, dyslipidemia) promoted improvement of LV diastolic function, reverse remodeling of LV myocardium, decrease of atherosclerotic lesions and albuminurea in patients presenting with both low albuminuria and DN; in addition, it improved prognosis of the disease.
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PMID:[Cardiovascular disorders and possibilities of their therapy in patients with type 2 diabetes mellitus and diabetic nephropathy]. 2036 9

The present study was designed to investigate the effects of angiotensin(1-7) (Ang(1-7)) a Mas receptor agonist, and A-779, a Mas receptor antagonist, in streptozotocin-induced diabetic nephropathy (DN). A single administration of streptozotocin (STZ) (50 mg/kg i.p.) to rats produced diabetes, and diabetic nephropathy developed after 8 weeks of STZ administration. The extent of DN was assessed biochemically and morphologically by measuring serum creatinine, creatinine clearance, blood urea nitrogen (BUN), proteinuria, urinary N-acetyl-beta-D glucosaminadase activity, renal collagen contents, lipid profile, serum nitrite/nitrate concentration and kidney weight/body weight (%). Treatments with Ang(1-7) (576 microg/kg/day i.p. for 4 weeks) and Ang(1-7) plus A-779 (744 microg/kg/day i.p. for 4 weeks) were started after 4 weeks of STZ administration. The treatment with Ang(1-7) attenuated STZ-induced nephropathy in rats by decreasing proteinuria, renal collagen content and by improving endothelial functions without preventing tubular damage. It has been shown for the first time that treatment with Ang(1-7) decreases dyslipidemia and BUN in diabetic rats, implying a renoprotective effect of the peptide. However, serum creatinine, creatinine clearance and kidney weight/body weight (%) remained unaffected with Ang(1-7) treatment. It may be concluded that activation by specific agonists of the Mas receptor may be useful in combating glomerular damage in DN.
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PMID:Ameliorative potential of angiotensin1-7/Mas receptor axis in streptozotocin-induced diabetic nephropathy in rats. 2038 42

Diabetic nephropathy is an increasingly important cause of morbidity and mortality worldwide. A large body of evidence suggests that dyslipidemia has an important role in the progression of kidney disease in patients with diabetes. Lipids may induce renal injury by stimulating TGF-beta, thereby inducing the production of reactive oxygen species and causing damage to the glomeruli and glomerular glycocalyx. Findings from basic and clinical studies strongly suggest that excess amounts of a variety of lipoproteins and lipids worsens diabetes-associated microvascular and macrovascular disease, increases glomerular injury, increases tubulointerstitial fibrosis, and accelerates the progression of diabetic nephropathy. The increasing prevalence of obesity, type 2 diabetes mellitus, and diabetic nephropathy means that interventions that can interrupt the pathophysiological cascade of events induced by lipoproteins and lipids could enable major life and cost savings. This Review discusses the structural, cellular, and microscopic findings associated with diabetic nephropathy and the influence of lipoproteins, specifically triglyceride-rich lipoproteins (TGRLs), on the development and perpetuation of diabetic nephropathy. Some of the accepted and hypothesized mechanisms of renal injury relating to TGRLs are also described.
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PMID:Role of triglyceride-rich lipoproteins in diabetic nephropathy. 2044 Feb 76


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