Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011881 (diabetic nephropathy)
 10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Heart Outcomes Prevention Evaluation (HOPE) study found that the ACE inhibitor ramipril can lower the risk of atherosclerotic disease events and death in patients without heart failure but with known atherosclerosis or with diabetes plus at least one cardiovascular risk factor. This benefit was independent of ramipril's effect on blood pressure. Additional benefits were a reduced risk of diabetic nephropathy in diabetic patients, and a lower likelihood of newly diagnosed diabetes. On the other hand, vitamin E in the doses and duration studied (400 IU/day for 4.5 years) did not lower risk significantly.
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PMID:The HOPE study. Ramipril lowered cardiovascular risk, but vitamin E did not. 1078 Jan 1

Clinical studies evaluating the benefits of angiotensin-converting-enzyme (ACE) inhibitor therapy in patients likely to develop renal disease are reviewed. Patients with diabetes or hypertension are at increased risk for development of renal disease. In patients with diabetic nephropathy, captopril therapy was associated with a 50% reduction in the risk of death, dialysis, and transplantation and a significantly smaller increase in serum creatinine compared with placebo. Therapy with enalapril or lisinopril has been shown to limit the progression of renal disease in normoalbuminuric patients with diabetes. Long-term therapy with enalapril (up to seven years) has demonstrated the ability to preserve renal function in patients with diabetes and microalbuminuria. Over 4.5 years, patients with diabetes and at least one other cardiovascular risk factor had significant reductions in the risk of overt nephropathy with ramipril therapy compared with placebo. In addition, ramipril is associated with preservation of renal function in patients with nondiabetic nephropathy. Evidence suggesting a dissociation of the renal hemodynamic and antiproteinuric effects of ACE inhibition is presented. These positive effects of ACE inhibition cannot be explained by reductions in blood pressure alone. ACE inhibitors have renoprotective properties beyond systemic blood pressure reduction.
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PMID:Role of angiotensin-converting-enzyme inhibition in patients with renal disease. 1103 18

The Reduction in End Points in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study and the Irbesartan Diabetic Nephropathy Trial (IDNT) are two recently reported trials with hard end points, conducted in patients in advanced stages of diabetic nephropathy. Two other studies--the Irbesartan Microalbuminuria Study (IRMA)-2 and the Microalbuminuria Reduction with Valsartan study (MARVAL)--were trials conducted in patients with type 2 diabetes with microalbuminuria, a cardiovascular risk factor associated with early-stage diabetic nephropathy. These trials all had a common theme--that is, does an angiotensin receptor blocker (ARB) interfere with the natural history of diabetic nephropathy in a blood pressure-independent fashion? Without question, the results of these trials legitimatize the use of the ARB class in forestalling the deterioration in renal function, which is almost inevitable in the patient with untreated diabetic nephropathy. These data can now be added to the vast array of evidence supporting angiotensin-converting enzyme (ACE) inhibitor use in patients with nephropathy associated with type 1 diabetes. It now appears a safe conclusion that the patient with diabetic nephropathy should receive therapy with an agent that interrupts the renin-angiotensin system. These studies have not resolved the question as to whether an ACE inhibitor or an ARB is the preferred agent in people with nephropathy from type 1 diabetes, though the optimal doses of these drugs remain to be determined. Head-to-head studies comparing ACE inhibitors to ARBs in diabetic nephropathy are not likely to occur, so it is unlikely that comparable information will be forthcoming with ACE inhibitors. An evidence-based therapeutic approach derived from these trials would argue for ARBs to be the foundation of therapy in the patient with type 2 diabetes and nephropathy.
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PMID:Type 2 diabetes: RENAAL and IDNT--the emergence of new treatment options. 1182 41

Guidelines for medical treatment are becoming increasingly popular and many guidelines have been produced by various societies in diabetes, hypertension, and renal disease as well as general medicine. By their nature, they are outdated considering the rapid and efficient publication of many papers related to the treatment of hypertension in diabetes. Increased blood glucose causes vascular damage and abnormal vascular structure all over the body, an abnormal structure that is especially vulnerable to high blood pressure, even within the so-called normal range. There is now more and more evidence, especially in diabetics, that blood pressure should be as low as possible. In this context, it is important to stress that the so-called J-shaped relationship between blood pressure and mortality may not be so relevant. Major epidemiological studies came from the Framingham and the Multiple Risk Factor Intervention Trial (MRFIT) Diabetic Cohort. The MRFIT Cohort showed that cardiovascular mortality was increased by a factor of 2-4 in diabetic patients, and there was a clear association between systolic blood pressure and complications without any threshold value. It could be suggested that since diabetes is an important cardiovascular risk factor, a lower value (130/85 mmHg) than for non-diabetics (140/90 mmHg) should be proposed. The tight blood pressure control arm of the United Kingdom Prospective Diabetes Study was <150/85 mmHg (achieved 144/82 mmHg) and the aim in the less tight control arm was <180/105 mmHg (achieved 154/87 mmHg). In the tight control group, 29% needed three or more antihypertensive drugs. In the Hypertension Optimal Treatment study, the frequency of major cardiovascular disease events in the group with target <80 mmHg (achieved 144/81 mmHg) was 11.9/1000 patients/year, which was significantly lower than the event rate (24.4/1000 patients/year) in the group with target <90 mmHg (achieved 148/85 mmHg). A reduction in the frequency of diabetic nephropathy by angiotensin-converting enzyme (ACE) inhibitor treatment in normotensive lean microalbuminuric type 2 diabetic patients has been shown. However, it is impossible from the present data to draw any conclusions with respect to effect on the main composite endpoint of ACE inhibition in microalbuminuric type 2 diabetic patients without previous cardiovascular events or without hypertension. Recent published studies have also demonstrated beneficial effects with angiotensin receptor blockers (ARBs) in hypertensive patients with type 2 diabetes and nephropathy. Diuretics form a very important basis for antihypertensive treatment, also often in combination with agents that inhibit the renin-angiotensin system. Several studies show that treatment with the diuretic indapamide reduces the level of microalbuminuria in patients with type 2 diabetes. Diuretics were used as an adjunctive to reduce blood pressure in all studies; it is therefore understandable that many guidelines suggest that diuretics form part of the treatment of hypertension in diabetics. Many studies of an epidemiological nature and follow-up studies in diabetic patients show that blood pressure control is of vital concern in the prevention of diabetic complications, and indeed the usual criteria for good blood pressure control may not be stringent enough in diabetic patients. Many classes of antihypertensives may be used, but it appears that diuretics, such as indapamide sustained release (SR), constitute an important proposal in all treatment strategies.
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PMID:New treatment guidelines for a patient with diabetes and hypertension. 1276 64

Hypertension, the most significant cardiovascular risk factor, appears twice more often in persons with diabetes compared to nondiabetic population. A high percentage of complications (40-70%) in diabetic population is caused just by hypertension. That is why timely diagnosis and consistent treatment of hypertension is stressed in patients with diabetes. Blood pressure of young people with type I diabetes is proved to be higher compared to their healthy peers. Both in people with type I and type II diabetes are, compared to other populations, more frequent incidence of a phenomenon called "white coat", increased variability in blood pressure, and higher percentage of non-dippers with high blood pressure. They are on a higher risk for diabetic nephropathy and its quicker progression. Therefore it is desirable to start medication and alter its combination after confirming blood pressure values by ambulatory monitoring so that the blood pressure is well controlled not only by day but also during sleep and early in the morning.
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PMID:[Ambulatory monitoring of blood pressure in the treatment of hypertension in diabetics]. 1504 Jan 59

Hypertension is a major cardiovascular risk factor, but most patients remain asymptomatic for many years. Successful therapy not only needs to be effective, it also needs to be well tolerated. Angiotensin receptor blockers have emerged as a major therapeutic class because they meet both of these requirements. Numerous studies indicate that all approved angiotensin receptor blockers are highly selective for angiotensin-1 receptors, lower blood pressure as monotherapies, and work well in combination with other drugs - particularly diuretics. The side-effect profile of angiotensin receptor blockers is similar to that of placebo and they have not been associated with known side effects of angiotensin-converting enzyme inhibitors such as cough and angioneurotic edema. Candesartan cilexetil is an angiotensin receptor blocker with insurmountable binding properties to the angiotensin-1 receptor, long duration of action and improved efficacy. In patients with hypertension, candesartan monotherapy has been shown to be safe and effective. Comparative data have shown similar or better results to other monotherapies in blood-pressure control, and in combination with hydrochlorothiazide it has been shown to have additive or synergistic effects. More recent data demonstrate that candesartan cilexetil is useful in the treatment of patients with heart failure and may protect against diabetic nephropathy. Studies have also shown protection from stroke, particularly in patients with isolated systolic hypertension.
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PMID:Candesartan cilexetil in cardiovascular disease. 1550 Apr 28

Total serum homocysteine (tHcy) has been shown to predict de novo and recurrent cardiovascular events in many studies. However, results in diabetic populations with minimal nephropathy are mixed. The independent relationship between tHcy and arteriosclerotic outcomes and congestive heart failure (CHF) events in a population with high cardiovascular risk and diabetic nephropathy was examined. A total of 1575 individuals were enrolled in the international Irbesartan Diabetic Nephropathy Trial (IDNT) and followed for 2.6 yr. All participants had baseline diabetic nephropathy, overt proteinuria, and hypertension and were recruited between 1996 and 1999. A total of 492 total arteriosclerotic outcomes (primary outcome) and 317 CHF events (secondary outcome) were tallied. Established cardiovascular risk factors were highly prevalent, as were high tHcy levels (quintiles [microM]: first 4.5 to 11; second >11 to 13; third >13 to 15; fourth >15 to 19; fifth >19). No association between tHcy and arteriosclerotic outcomes was observed in a univariate model or after adjustment for study randomization and established cardiovascular risk factors. The strongest outcome predictor was the presence of baseline cardiovascular disease, followed by an inverse relationship to diastolic BP. The significant univariate association between tHcy and CHF events disappeared when serum creatinine alone was added to the model. These findings question the utility of tHcy in predicting de novo or recurrent cardiovascular events in individuals with diabetic nephropathy. Further studies are needed to confirm whether these negative results apply to other populations with heavy cardiovascular risk burdens. Previous positive findings can potentially be explained through tHcy's role as a sensitive surrogate marker for kidney disease, itself a recognized cardiovascular risk factor.
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PMID:Total plasma homocysteine and arteriosclerotic outcomes in type 2 diabetes with nephropathy. 1616 14

Microalbuminuria is significant both as the earliest stage of diabetic nephropathy and as an independent cardiovascular risk factor in nondiabetic subjects, in whom it is associated with insulin resistance. The link between disorders of cellular insulin metabolism and albuminuria has been elusive. Here, we report using novel conditionally immortalized human podocytes in vitro and human glomeruli ex vivo that the podocyte, the principal cell responsible for prevention of urinary protein loss, is insulin responsive and able to approximately double its glucose uptake within 15 min of insulin stimulation. Conditionally immortalized human glomerular endothelial cells do not respond to insulin, suggesting that insulin has a specific effect on the podocyte in the glomerular filtration barrier. The insulin response of the podocyte occurs via the facilitative glucose transporters GLUT1 and GLUT4, and this process is dependent on the filamentous actin cytoskeleton. Insulin responsiveness in this key structural component of the glomerular filtration barrier may have central relevance for understanding of diabetic nephropathy and for the association of albuminuria with states of insulin resistance.
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PMID:The human glomerular podocyte is a novel target for insulin action. 1624 31

Abdominal obesity is associated with cardiovascular disease. This study aims to compare two measures of abdominal obesity [waist and wais-to-hip ratio (WHR)] in patients with DM2 to identify cardiovascular risk factors: ischemic cardiopathy, hypertension, dislipidemia, obesity and diabetic nephropathy. A multicentric study was performed in 820 patients with type 2 DM. Waist circumference strongly correlated with body mass index (BMI), for men (r= 0.814; P< 0.05) and women (r= 0.770; P< 0.05). On the other hand, WRH was weakly correlated (r= 0.263, P< 0.05 for men; r= 0.092, P< 0.05 for women). Only waist circumference correlated with systolic pressure (r= 0.211, P< 0.05 for men; r= 0,224, P< 0.05 for women). ROC curve analysis demonstrated the superiority of waist circumference measurement compared to WHR regarding obesity and hypertension for men and women, and dyslipidemia for men. In conclusion, waist circumference is better correlated with cardiovascular risk factor than WRH.
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PMID:[Waist measure and waist-to-hip ratio and identification of clinical conditions of cardiovascular risk: multicentric study in type 2 diabetes mellitus patients]. 1754 44

HSPs (heat-shock proteins) are molecular chaperones synthesized under stress conditions, and are involved in renal cell survival and matrix remodelling in acute and chronic renal diseases. In the present study, we investigated whether the HSP70 gene polymorphisms affect susceptibility to DN (diabetic nephropathy) in patients with T2DM (Type 2 diabetes mellitus). The study group consisted of 452 patients with nephropathy. Two control subgroups involved 340 healthy individuals and 132 patients with T2DM lasting > or =10 years who were free of nephropathy. Subjects were genotyped for the HSP70-1 +190 G/C and -110 A/C, HSP70-2 +1267 A/G and HSP70-hom +2437 T/C polymorphisms by PCR, followed by digestion with restriction endonucleases. There were no statistically significant differences in genotype distribution between patients with T2DM with DN and controls for the HSP70-hom polymorphism. Significant differences were observed for HSP70-1 and HSP70-2 polymorphisms. CC homozygotes of the -110 and +190 HSP70-1 polymorphisms were more frequent in patients with T2DM with DN compared with healthy controls (22 compared with 6% and 15 compared with 6.5% respectively; P<0.01). The OR (odds ratio) for the risk allele was 2.17 [95% CI (confidence interval), 1.73-2.72] for the -110 A/C and 1.74 (95% CI, 1.40-2.15) for +190 G/C polymorphisms. A strong association with DN was found for the +1267 HSP70-2 polymorphism. The GG genotype and the G allele were associated with DN, with the OR for the G allele being 4.77 (95% CI, 3.81-5.96). All GG homozygotes in the patient group had higher LDL (low-density lipoprotein)-cholesterol levels than AA homozygotes (P<0.01), suggesting that the observed effect might be associated with this cardiovascular risk factor. These patients progressed faster to end-stage renal failure than those with other genotypes. In conclusion, our results indicate that the HSP70-1 and HSP70-2 polymorphisms are associated with renal complications in T2DM and may be useful in identifying patients with increased risk of DN.
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PMID:Heat-shock protein gene polymorphisms and the risk of nephropathy in patients with Type 2 diabetes. 1851 60


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