Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 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.
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PMID:Potential influence of lipids in diabetic nephropathy: insights from experimental data and clinical studies. 1101 Dec 17

Patients with diabetic nephropathy frequently show increased levels of circulating low-density lipoprotein (LDL) and oxidized LDL, which have been reported to be related to the generation of oxygen-free radicals. In the present study, we evaluated the effects of insulin and heparin on the superoxide production of glomeruli, which were isolated from rats with streptozotocin-induced diabetes for one week, one month, and three months, respectively, and the glomeruli were stimulated with native and oxidized LDL. LDL was isolated from normal subjects with normolipidemia, and the superoxide was measured by using a spectrophotometer. The results demonstrated that the poorly controlled diabetic rat glomeruli showed a significantly higher production of superoxide than normal glomeruli under basal status and after stimulation, and this production increased further with the progression of diabetes. Insulin suppressed both the basal and stimulated production of superoxide in diabetic glomeruli, but not in normal glomeruli. Heparin suppressed superoxide production of diabetic glomeruli stimulated by either native or oxidized LDL, and it also partly suppressed superoxide production of normal glomeruli stimulated by oxidized LDL. Our results suggest that glomerular injury in diabetics with hyperlipidemia may be mediated through enhanced generation of oxygen-free radicals, which can be partially attenuated by insulin and heparin.
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PMID:Insulin and heparin suppress superoxide production in diabetic rat glomeruli stimulated with low-density lipoprotein. 1116 97

Wistar fatty (WF) rats have a genetic predisposition to hyperglycemia, polyuria, hyperinsulinemia, hyperlipidemia, obesity and nephropathy. These phenotypic characteristics are similar to those observed in obese patients with non-insulin-dependent diabetes mellitus (NIDDM) nephropathy. In this study, the effects of two types of renin-angiotensin system inhibitors, an angiotensin II type 1-receptor antagonist (AT1A) and an angiotensin I-converting enzyme inhibitor (ACEI), on renal injury in WF rats were studied during the progressive phase of diabetic nephropathy. An AT1A, candesartan cilexetil (1 mg/kg), and an ACEI, enalapril (10 mg/kg), were administered orally once a day for 12 weeks, beginning when the rats were 27-week-old and already showed diabetic nephropathy and obesity. Both drugs prevented an increase in proteinuria during the experimental period. Furthermore, after 4-week intervention, the levels of proteinuria were markedly lower in drug-treated rats. At the end of the experiment, both drugs prevented the development of glomerular lesions without affecting glucose metabolism and obesity. In conclusion, the inhibition of angiotensin II activity ameliorated both existing proteinuria and the progression of proteinuria, resulting in preservation of glomerular structure. Thus angiotensin II plays important roles in the development and the progression of nephropathy in genetically obese diabetic WF rats.
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PMID:Involvement of angiotensin II in progression of renal injury in rats with genetic non-insulin-dependent diabetes mellitus (Wistar fatty rats). 1138 46

Diabetic Nephropathy is one of the microvascular complications associated with type 1 diabetes mellitus with a major portion of the excess morbidity and mortality. In order to avoid or at least delay its onset we should detect a very small amount of proteins in the urine (between 15-20 and 200 micrograms/min.) that is a strong predictor of those likely to progress to overt nephropathy. This detection can be obtained evaluating an overnight sample of urine and suggest preventives interventions. such as intensive diabetes management and angiotensin converting enzyme inhibition (ACEi). Furthermore, associated risk factors should be prevented or treated (hypertension, retinopathy, hyperlipidemia and smoking).
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PMID:[Practical considerations on screening for microalbuminuria in children and adolescents with type 1 diabetes]. 1142 22

Renal involvement is one of the major microvascular complications of both type 1 and type 2 diabetes mellitus. Diabetic nephropathy is the major cause of end-stage renal failure in most Western nations and is associated with increased morbidity and mortality as compared to other causes of renal disease. The pathogenesis of renal involvement in diabetes is presumed to be the result of the interplay of metabolic and hemodynamic factors. Significant advances in the prevention and treatment of progression of diabetic nephropathy have been achieved with intensive glycemic control and the treatment of elevated blood pressure. Patients with diabetes should thus be screened regularly for the appearance of any of the risk factors for renal or other complications and treated intensively according to established guidelines for control of hyperglycemia and hypertension. Ancillary therapeutic measures include treatment of hyperlipidemia, low-protein diet, and the cessation of smoking.
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PMID:Diabetic nephropathy. 1147 36

In recent years several multicentric prospective studies have demonstrated the efficacy of some therapeutic measures to slow the progression of renal diseases. Inhibition of renin-angiotensin system (RAS) both by ACE inhibitors (ACEI) and angiotensin II receptor antagonists (ARA) is probably the strongest therapeutic alternative: The antiproteinuric effect of these drugs is an excellent surrogate marker and a predictor of the beneficial influences on the progression of renal failure. The type of renal disease, an inadequate control of blood pressure, and the presence of obesity may counteract the beneficial influences of RAS inhibition, whereas early treatment of all patients with significant proteinuria before the appearance of renal insufficiency and combined therapy with an ACEI and an ARA may augment it. Dietary protein restriction is a classic treatment of chronic renal insufficiency whose effectiveness has been validated by multicentric studies. However, a poor compliance of the patient and the risk of malnutrition with very strict protein restriction could limit the benefits of this treatment. Treatment of hyperlipidemia, prevention of obesity, avoidance of smoking, and regular physical exercise are interventions whose therapeutic potential is progressively recognized, particularly in type 2 diabetic nephropathy. Early correction of anemia may contribute to the slowing of renal disease progression. Although further studies are required, the accumulated evidence and the likelihood of additive beneficial effect of these therapeutic measures advise their combined implementation in patients with chronic renal diseases.
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PMID:Slowing the progression of renal failure. 1198 7

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease and requires renal replacement therapy. Regular screening for microalbuminuria is indispensable for early diagnosis. To prevent or at least delay the onset of DN and progressive renal failure in type 1 and type 2 diabetics, glucose control, blood pressure control and, in particular, the blocking of the renin-angiotensin system are the most effective renoprotective measures. Other factors influencing the course of DN are cigarette smoking and hyperlipidaemia. The latest trials have been reviewed and a treatment involving the cooperation of general practitioners, nephrologists and diabetologists has been suggested.
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PMID:[Diabetes and the kidneys]. 1201 61

To evaluate the efficacy of angiotensin II receptor blockers (ARBs) for use in the treatment of diabetic nephropathy, we examined the effects of olmesartan medoxomil (olmesartan), an angiotensin II type 1 (AT1) specific ARB, on the progression of nephropathy in Zucker diabetic fatty (ZDF) rats, an animal model of type 2 diabetes. We used 2 doses of olmesartan, a sub-antihypertensive dose and an antihypertensive dose, to specifically examine whether the drug exerts beneficial effects on the kidney without lowering blood pressure. Olmesartan mixed in the diet at a concentration of 0.001% (approximately 0.6 mg/kg/day) or 0.01% (approximately 6 mg/kg/day) was administered for 19 weeks starting from 12 weeks of age, when the animals developed microalbuminuria. Lean non-diabetic rats served as controls. ZDF rats had hyperglycemia, hyperinsulinemia, and moderate hypertension as compared to lean control rats. Plasma glucose and insulin concentrations were not affected by olmesartan, and blood pressure was lowered only by the high dose of olmesartan. Progressive proteinuria in ZDF rats was greatly (about 70%) suppressed by the high dose of olmesartan and moderately (about 30%) suppressed by the low dose that did not significantly lower blood pressure. ZDF rats exhibited hyperlipidemia and hypoalbuminemia, both of which were substantially corrected by treatment with olmesartan. The histological evidence of glomerular and tubular damage in the ZDF rats was also reduced by the drug. These results indicate that AT1 receptor blockade with olmesartan retards the progression of nephropathy associated with type 2 diabetes without affecting glucose metabolism, and that this renal protective effect is at least partly independent of the antihypertensive effect of the drug.
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PMID:Renoprotective effects of blockade of angiotensin II AT1 receptors in an animal model of type 2 diabetes. 1204 43

Diabetic nephropathy is the leading cause of end-stage renal disease (ESRD). There are currently no therapeutic Hyperlipidaemiants which directly intervene in the pathogenesis of diabetic nephropathy. The mechanisms behind development of diabetic nephropathy are complex and not completely understood. The hyperglycaemia, hyperlipidaemia and hyperinsulinaemia found in diabetics might all act on the kidney endothelium to induce expression of genes important in kidney dysfunction. We propose that targeting kidney endothelial gene expression may provide a new approach for control of kidney dysfunction.
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PMID:New approaches for treatment of diabetic nephropathy: the endothelium as a target for drug discovery. 1254 Feb 81

The red cell membrane Li+/Na+exchange is a heteroexchange that operates in either direction across the cell membrane. It binds either Li+ or Na+ on one side of the membrane and it exchanges the transported species for either Li+ or Na+ on the opposite side in a stoichiometric ratio of 1:1. In the population, Li+/Na+exchange is unimodally distributed but skewed to the right. Such distribution results from superimposition of two normal distributions. Many laboratories have shown that red-cell Li+/Na+ exchange is increased in patients with essential hypertension, compared with normotensive controls. Among the various alterations of cell membrane cation transport reported in hypertension, the increase of red-cell Li+/Na+ exchange has been most widely investigated and confirmed. Moreover, increased Li+/Na+ exchange has been found in some clinical conditions related to hypertension, such as overweight and diabetes. Among diabetic patients, Li+/Na+ exchange is particularly high in patients with nephropathy, hypertension, and microalbuminuria, leading to the hypothesis that it can be considered a cellular marker of the risk of developing diabetic nephropathy. Furthermore, it is associated with severe and drug-resistant hypertension, insulin resistance, vascular and cardiac hypertrophy, hyperlipidemia, obesity, family history of hypertension, and of major cardiovascular accidents suggesting that high Li+/Na+ exchange could be a biochemical marker for increased cardiovascular risk. Regardless of its the pathophysiological significance, its measurement could be of clinical use as an intermediate phenotype of increased cardiovascular risk.
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PMID:The Li+/Na+ exchange in hypertension. 1270 53


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