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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 the most common cause of end-stage renal failure in the Western world. It accounts for 15-25% of all renal failure in patients requiring chronic dialysis. About 20% of patients with insulin-dependent diabetes and less than 15% of patients with non-insulin-dependent diabetes develop clinically significant nephropathy. The prevalence of diabetic nephropathy in pregnant patients with insulin-dependent diabetes is estimated to be 6%. Angiotensin converting enzyme (ACE) inhibitors are the drug of choice in treating women with diabetic nephropathy. In addition, many of these drugs may be started before conception. Unfortunately, these agents might be fetotoxic when taken during pregnancy. This article reviews the epidemiology and natural history of diabetic nephropathy, discusses the renoprotective effect of ACE inhibitors, reviews the effect of ACE inhibitors on fetomaternal outcome when used prior to and during pregnancy in women with diabetic nephropathy and discusses the new class of drugs, angiotensin II receptor antagonists, in the management of diabetics who have or are prone to developing diabetic nephropathy.
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PMID:Use of angiotensin-converting enzyme inhibitors in patients with diabetic nephropathy. 1268 51

Renal disease in older diabetic patients is costly in terms of morbidity, mortality and expenditure. Therefore, prevention and treatment of diabetic nephropathy has become a prominent goal in the treatment of patients with diabetes mellitus. Preventive treatment should begin no later than at the stage of microalbuminuria, and regular screening for microalbuminuria is recommended for all patients with diabetes, irrespective of age. Improved metabolic control has been demonstrated to lower urinary albumin excretion. Target glycosylated haemoglobin levels should be below 7%, or 1% above the upper limit of normal of non-diabetic subjects. The use of an intensified treatment regimen is recommended. Insulin therapy has no adverse effects on renal indexes. To preserve renal function in older diabetic patients, blood pressure should be kept at or below 130/80 mm Hg. Treatment with ACE inhibitors or angiotensin II receptor antagonists (angiotensin II receptor blockers; ARBs) is superior to other pharmacological therapy, and should be initiated as first-line treatment. Most of the calcium channel antagonists have been found to increase or to have no effect on microalbuminuria despite blood pressure reduction. Moreover, there is substantial controversy as to whether they may be associated with increased cardiovascular morbidity. Non-dihydropyridine derivatives and calcium channel antagonists, such as nitrendipine, may be nephroprotective and have favourable effects on patients outcomes. A renoprotective action of diuretics may be confined to indapamide. Although beta-adrenoreceptor blockers are effective antihypertensive agents, they may not adequately preserve kidney function in older diabetic patients. However, as add-on treatment to ACE inhibitors or ARBs, they are particularly beneficial in nephropathic patients at risk of cardiovascular disease or with arrhythmias, in whom they may prove life-saving.
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PMID:Prevention and treatment of diabetic nephropathy in older patients. 1271 Aug 62

A body of evidence indicates that microalbuminuria is a well-recognized marker of cardiovascular complications and increased cardiovascular risk in hypertension. However, the prognostic significance of microalbuminuria remains controversial because only the results of a few prospective studies performed in small groups of hypertensive subjects without diabetes mellitus are available. Several factors can affect the prevalence of microalbuminuria in hypertension including age, sex, race, severity of the disease, and concomitant risk factors. This accounts for the large differences in the prevalence of microalbuminuria that can be found in the literature, with prevalence rates going from a low of 4.7% to a high of 46%. The main determinant of albumin excretion rate in subjects with mild hypertension and no cardiovascular complications seems to be the hemodynamic load, whereas in subjects with more severe hypertension and associated target organ damage, the augmented urinary albumin leak is probably the consequence of glomerular damage. Inhibition of the renin-angiotensin system with angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists is particularly effective at reducing the albumin excretion rate, but whether these classes of drugs are more beneficial in patients with microalbuminuria remains to be determined. There is general consensus that evaluation of microalbuminuria is useful for the assessment of overall cardiovascular risk in hypertension, since albumin excretion rate appears to be a cost-effective way to identify patients at higher risk for whom additional preventive and therapeutic measures are advisable.
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PMID:Microalbuminuria in hypertension. 1272 52

In recent years, new drug development and late-breaking research data have put treatment guidelines for diabetic nephropathy in a state of flux. In particular, trials of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs), coupled with enhanced understanding of the renin-angiotensin pathway, have influenced recommendations for patient care. Here, Dr Bakris highlights both the steadfast features and the recent refinements of treatment guidelines for diabetic nephropathy. He describes their backing in research findings and outlines practical antihypertensive and renoprotective therapies to curtail risks of nephropathy and cardiovascular disease in patients with diabetes.
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PMID:The evolution of treatment guidelines for diabetic nephropathy. Strategies integrate JNC VI, more recent protocols. 1276 95

In this article, 2 leading physicians debate the strength of outcome data on the efficacy of angiotensin-converting enzyme (ACE) inhibitors versus angiotensin II receptor blockers (ARBs) for reducing the incidence of cardiovascular, cerebrovascular, and renovascular events. Dr. Stephen G. Ball notes that the efficacy of ACE inhibitors for reducing the risk for myocardial infarction independent of their effects on blood pressure is controversial. In the Heart Outcomes Prevention Evaluation (HOPE) study, ramipril treatment in high-risk patients was associated with a 20% reduction in the risk for myocardial infarction; mean reduction in blood pressure was 3 mm Hg for systolic blood pressure and 1 mm Hg for diastolic blood pressure. The HOPE investigators propose that the 20% reduction was much greater than would be expected based on the observed blood pressure reduction. However, a meta-regression analysis of blood pressure reduction in >20 antihypertensive therapy outcome trials found that the reduction in myocardial infarction risk with ramipril observed in HOPE was consistent with the modest blood pressure reduction seen with that agent. Nevertheless, there are convincing data for prevention of myocardial infarction with ACE inhibitors in patients with heart failure, including those with heart failure after myocardial infarction, as well as supportive evidence from studies in patients with diabetes mellitus and concomitant hypertension. On the other hand, Dr. William B. White takes the position that ARBs are well-tolerated antihypertensive agents that specifically antagonize the angiotensin II type 1 (AT(1)) receptor and provide a more complete block of the pathologic effects of angiotensin II-which are mediated via the AT(1) receptor-than ACE inhibitors. The Evaluation of Losartan in the Elderly (ELITE) II study and the Valsartan Heart Failure Trial (ValHeFT) suggest that ARBs reduce the risk for mortality in patients with congestive heart failure. The Losartan Intervention for Endpoint (LIFE) Reduction in Hypertension trial also demonstrated beneficial effects of ARBs in the prevention of stroke events. The Irbesartan in Patients with Diabetes and Microalbuminuria (IRMA) study, the Irbesartan Diabetic Nephropathy Trial (IDNT), and the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study demonstrated significant reductions in the rate of progression of renal disease in patients receiving ARBs, independent of effects on blood pressure. These data support the use of ARBs, in addition to the standard of care, in hypertensive patients with heart failure who are intolerant of ACE inhibitors, and also provide compelling evidence for their use in patients with hypertension and type 2 diabetes.
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PMID:Debate: angiotensin-converting enzyme inhibitors versus angiotensin II receptor blockers--a gap in evidence-based medicine. 1451 6

Blood pressure reduction and intensive antihypertensive treatment are effective in reducing both microvascular and macrovascular complications in type 2 diabetes. Blood pressure target levels < 130/85 or 130/80 mmHg are now recommended. Antagonism of the renin-angiotensin-aldosterone system seems to be an important goal in the treatment of hypertension and diabetes-related complications. The renoprotective role of angiotensin-converting enzyme (ACE)-inhibitors has been well documented in type 1 diabetes; in type 2 diabetes ACE-inhibitors have been deemed more effective than other traditional drugs in reducing the onset of overt nephropathy in microalbuminuric patients (secondary prevention) but not in reducing renal dysfunction in patients with clinical proteinuria (tertiary prevention). Recently, four large trials performed on type 2 diabetes showed that angiotensin II receptor blockers (ARBs) prevent the development of clinical proteinuria in microalbuminuric patients (IRMA and MARVAL studies) and delay the progression of nephropathy towards end-stage renal failure in patients with overt nephropathy (IDNT and RENAAL studies). Moreover, ARBs have been deemed more effective in reducing hospitalizations for heart failure compared to placebo (IDNT and RENAAL studies) and in reducing cardiovascular morbidity and mortality compared to conventional therapy (LIFE study) in type 2 diabetes. In conclusion, ARBs are effective in preventing and delaying renal damage in type 2 diabetes. Thus, the recent guidelines for the prevention and treatment of diabetic nephropathy state that ACE-inhibitors are the first-choice drugs in type 1 diabetes while ARBs are considered as the first-choice drugs in secondary prevention, the same as ACE-inhibitors, and are the unique first-choice drug in tertiary prevention of end-stage renal failure in type 2 diabetes. Finally, ACE-inhibitors and ARBs are both first-choice drugs in cardiovascular prevention in type 2 diabetes.
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PMID:[The role of angiotensin II AT1-receptor antagonists in renal and cardiac protection in type-2 diabetes mellitus]. 1278 55

The ability of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) to lower blood pressure (BP) is well established. ACE inhibitors (ACE-Is) have also been shown to improve the prognosis of a broad range of patients at high cardiovascular risk, including those with heart failure, post-myocardial infarction (MI), and nephropathy. These benefits suggest that interrupting the renin-angiotensin-aldosterone system (RAAS) with ACE-Is has a widespread vasculoprotective effect, provided that BP is also adequately controlled. Evidence that RAAS blockade by ARBs also improves long-term clinical outcomes in patients with cardiovascular disease has started to accumulate, and will be tested further during the coming years as a number of large-scale, prospective trials are completed. These trials are investigating the long-term protective effects of ARBs on morbidity and mortality in patients with hypertension, heart failure, diabetes mellitus, acute MI, or established vascular disease. The results should establish the extent to which ARBs exhibit the vasculoprotective properties demonstrated by ACE-Is in patients at high cardiovascular risk. If ARBs are found to provide benefits that are similar to, or even greater than ACE-Is, it may have important implications for drug selection, given the excellent tolerability of ARBs. Some studies are also investigating whether more extensive RAAS blockade using a combination of an ARB and an ACE-I will offer even greater protection than either agent alone.
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PMID:Angiotensin II receptor blockers and cardiovascular outcomes: what does the future hold? 1280 87

Arterial hypertension (AH) per se is, together with diabetes mellitus, the most important cause of renal failure and of dialysis in the western world. AH is also a well known consequence of chronic renal disease, and at the same time one of the main factors which causes diabetic and/or non-diabetic chronic renal failure progression. AH is mostly registered in patients with focal segmental glomerulosclerosis and with membranoproliferative glomerulonephritis. The pathophysiology and the mechanism of AH within primary glomerular diseases are complex, including activation of the sympathetic nervous system, the renin-angiotensin system (RAS), sodium retention, volume expansion and decreased synthesis of vasodilatatory substances. As autoregulation of glomerular pressure in chronic glomerular disease is disturbed, the increment in systemic blood pressure leads to the rise in glomerular pressure. Glomerular hypertension results in glomerular capillary wall stretch, endothelial damage and a rise in protein glomerular filtration. These processes, in turn, cause changes of mesangial and proximal tubular cells, ultimately resulting in the replacement of functional by non-functional connective tissue and the development of fibrosis. One of the most important factors in the progression of chronic renal failure is activation of the RAS. Its effect is not only elevated blood pressure, but also the promotion of cell proliferation, inflammation and matrix accumulation. Many studies, first in experimental animals and later in humans, have shown that the lowering of blood pressure (and proteinuria) is associated with a slower progression of kidney disease. It seems that angiotensin-converting enzyme inhibitors (ACEIs) are more renoprotective than other antihypertensives (the protection beyond the antihypertensive effect), although some studies have also confirmed a comparatively beneficial effect of non-dihydropiridine calcium channel blockers (CCBs) and angiotensin II receptor blockers (ARBs). Moreover, it seems that a combination of antihypertensives (e.g. ACEI + CCB, ACEI + ARB) has a more effective action than either of the drugs alone. However, the effects depend first on the degree of blood pressure reduction. According to comprehensive studies, the achievement of adequate blood pressure (not higher than 130/85 mmHg) is the most important factor. An even lower blood pressure (125/75 mmHg) has been suggested as the limit value in patients with proteinuria of >1 g/24 h and in Blacks.
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PMID:The role of arterial hypertension in the progression of non-diabetic glomerular diseases. 1281 64

Obesity is closely associated with the metabolic syndrome, a combination of disorders including insulin resistance, diabetes, dyslipidemia, and hypertension. A role for local glucocorticoid reamplification in obesity and the metabolic syndrome has been suggested. The enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) regenerates active cortisol from inactive 11-keto forms, and aP2-HSD1 mice with relative transgenic overexpression of this enzyme in fat cells develop visceral obesity with insulin resistance and dyslipidemia. Here we report that aP2-HSD1 mice also have high arterial blood pressure (BP). The mice have increased sensitivity to dietary salt and increased plasma levels of angiotensinogen, angiotensin II, and aldosterone. This hypertension is abolished by selective angiotensin II receptor AT-1 antagonist at a low dose that does not affect BP in non-Tg littermates. These findings suggest that activation of the circulating renin-angiotensin system (RAS) develops in aP2-HSD1 mice. The long-term hypertension is further reflected by an appreciable hypertrophy and hyperplasia of the distal tubule epithelium of the nephron, resembling salt-sensitive or angiotensin II-mediated hypertension. Taken together, our findings suggest that overexpression of 11beta-HSD1 in fat is sufficient to cause salt-sensitive hypertension mediated by an activated RAS. The potential role of adipose 11beta-HSD1 in mediating critical features of the metabolic syndrome extends beyond obesity and metabolic complications to include the most central cardiovascular feature of this disorder.
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PMID:Transgenic amplification of glucocorticoid action in adipose tissue causes high blood pressure in mice. 1284 62

Hypertension is often accompanied with type-2 diabetes mellitus. Based on insulin resistance and/or resultant hyperinsulinemia, diabetes mellitus, hypertension, lipid disorders and atherosclerotic vascular diseases are often seen in the same individuals. Lifestyle modification to reduce insulin resistance is very important to manage diabetic patients with hypertension. When the doctors use anti-hypertensive medication, we have to take care not to worsen glucose or lipid profiles. Taking recent guidelines from US, Japan and Europe into considerations, blood pressure of diabetic patients should be controlled below 130-135/80 mmHg. ACE inhibitors, angiotensin II receptor antagonists are commonly recommended as first-line medicine to choose. However, Ca-channel blockers, alpha 1-blockers, beta-blockers and diuretics are often needed to achieve the goal: preventing organ damage which would be the most important issue for diabetic patients.
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PMID:[How to use anti-hypertensive medication in management of diabetic patients]. 1287 86


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