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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A prospective, randomized, three-armed, double-blind, placebo-controlled clinical trial has been completed in 210 sites worldwide to determine whether the angiotensin II receptor blocker irbesartan or the calcium channel blocker amlodipine has a renoprotective effect in patients with overt type 2 diabetic nephropathy. A total of 1,715 subjects randomized during a 3-year period were followed a minimum of 2 years. The goal for all treatment groups was to achieve equivalent blood pressure control, with the blinded study drug (irbesartan, amlodipine, or placebo) as primary therapy with additional antihypertensive drugs, excluding angiotensin-converting enzyme inhibitors, calcium antagonists, and angiotensin II receptor antagonists, to achieve seated systolic blood pressure less than 135 mm Hg and diastolic blood pressure less than 85 mm Hg. The primary outcome was the combined endpoint of time to doubling of entry serum creatinine, end-stage renal disease, or death. Secondary outcomes included fatal and nonfatal cardiovascular events. A Clinical Management Committee monitored the conduct of the study. An Outcome Confirmation Committee classified all study outcome events in blinded fashion. An external Data Safety Monitoring Committee monitored unblinded data for interim safety and efficacy analyses of the study. Eligibility criteria included informed consent, age 30 to 70 years, adult-onset diabetes, hypertension, urine protein excretion greater than 900 mg/24 hours, and serum creatinine values of 90 to 265 micromol/L in women and 110 to 265 micromol/L in men. Baseline characteristics were age, 59 +/- 8 years; body mass index, 31 +/- 7 kg/m(2); 67% male; 73% white, 14% black, and 13% other; duration of diabetes, 15 +/- 9 years; retinopathy, 66%; neuropathy, 48%; congestive heart failure, 7.5%; screening seated systolic blood pressure, 156 +/- 18 mm Hg, and diastolic blood pressure, 85 +/- 11 mm Hg; urine protein excretion, 4.0 +/- 3.5 g/24 hours; serum creatinine, 150 +/- 53 micromol/L; serum potassium, 4.6 +/- 0.5 mEq/L; total cholesterol, 229 +/- 58 mg/dL; and hemoglobin A(1c), 8.1 +/- 1.7%. This large-scale international trial should help define the clinical course and standards of care for hypertensive adults with type 2 diabetes mellitus and nephropathy. Results available on May 19, 2001, will help in defining the current controversy of the risks and benefits of blockade of the renin-angiotensin system versus calcium channel blockade versus standard antihypertensive therapy in this large patient population.
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PMID:A clinical trial in type 2 diabetic nephropathy. 1157 53

Nephropathy associated with type 2 diabetes mellitus is a rising cause of end-stage renal disease and is a major public health problem. If blocking of the renin angiotensin system has a well established nephroprotective effect in type 1 diabetic nephropathy, this remained to be shown for type 2 diabetes. Two large outcome trials using angiotensin II receptor antagonists (ARA's) in proteinuric chronic renal impairment and hypertensive type 2 diabetic patients have now closed this gap: the Irbesartan Diabetic Nephropathy Trial (IDNT) and the Reduction of Endpoints in NIDDM with Angiotensin II Antagonist Losartan (RENAAL) trial. Both trials showed a significant reduction in the primary pre-specified end-point of death, or worsening of renal function (doubling of serum creatinine) or the development of end-stage renal disease. This effect goes beyond the reduction in blood pressure and makes of ARA's one of the important tools in the treatment of type 2 diabetic nephropathy.
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PMID:[Clinical study of the month. Nephroprotective role of angiotensin II receptor antagonists in type 2 diabetes: results of the IDNT and RENAAL trials]. 1176 85

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

The incidence of hypertension is increased in individuals with diabetes mellitus. This is especially true in patients with type 2 diabetes. In these patients high blood pressure is common at the time of diagnosis of diabetes, but the development of diabetes is often preceded by a period during which hyperinsulinemia and insulin resistance is already present. Diabetes represents by itself a major risk of cardiovascular morbidity and mortality. This risk is considerably enhanced by the co-existence of hypertension. One of the main complications of type 2 diabetes is nephropathy, which manifests initially by microalbuminuria, then by clinical proteinuria, leading to a progressive chronic renal failure and end-stage renal disease. Microalbuminuria is considered today as an indicator of renal endothelial dysfunction as well as an independent predictor of the cardiovascular risk. During recent years a number of studies have shown that tight blood pressure control is essential in diabetic patients in order to provide maximal protection against cardiovascular events and the deterioration of renal function. Of note, there is recent evidence indicating that blockade of the renin-angiotensin system with angiotensin II antagonists has marked nephroprotective effects in patients with hypertension and type 2 diabetes, both at early and late stages of renal disease.
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PMID:Diabetes and hypertension. 1182 35

We have documented, contrary to expectation, that the renin-angiotensin-aldosterone system (RAAS) is stimulated normally by restriction of sodium intake inpatients with Type 2 diabetes mellitus (DM) and hypertension. Conversely, plasma renin activity (PRA)is suppressed less than in normal subjects by a high-salt diet in these patients. Increasing plasma angiotensin II (Ang II) concentration through intravenous Ang II infusion also suppresses renin release, via the short feedback loop. In this study, we sought to ascertain whether the limited renin suppression in Type 2 diabetes mellitus via high-salt intake is a unique defect or part of a more generalised abnormality of PRA suppression. We studied 38 patients with Type 2 DM and hypertension, 158 hypertensive control patients, and 61 normotensive controls. All patients were studied while in metabolic balance on a 10 mEq sodium (Na) diet. The response to the Ang II infusion at 3 ng/kg/min for 45 minutes was measured. We found that PRA fell significantly in normal subjects, from 4.0 +/- 0.33 to 2.5 +/- 0.23 ngAngI/ml/hr (p=0.0056). In patients with essential hypertension, the Ang II infusion also led to a fall in PRA from 3.51 +/- 0.23 to 2.76 +/- 0.17 ng Angl/ml/hr(p=0.014). In patients with DM, despite a similar basal PRA (3.7 +/- 0.40 ng AngI/ml/hr), the infusion of Ang II did nor influence PRA significantly (3.43 +/- 0.42ng AngI/ml/hr; p > 0.77), though these patients had the most robust mean arterial pressure response. Our data are in complete accord with the concept of high intrarenal Ang II in DM and suggest lower systemic Ang II despite comparable PRA.
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PMID:Blunted suppression of plasma renin activity in diabetes. 1188 Oct 33

Overexpression of the renin-angiotensin system is important in the pathogenesis of macroangiopathy (MA). Patients with diabetes with end-stage renal failure have elevated serum angiotensin-converting enzyme (ACE) activity compared with their nonuremic counterparts. Because their major cause of death is MA, the significance of serum ACE activity on outcome of this group of patients is studied. We performed a prospective cohort study of 49 patients with type 2 diabetes on continuous ambulatory peritoneal dialysis (CAPD) therapy. Baseline serum ACE activity was determined by a modified spectrophotometric method and followed up at a median of 34 months. The prevalence of MA (defined as ischemic heart disease, sudden cardiac arrest, stroke, or peripheral vascular disease) and all-cause mortality rates were studied. Risk for MA is associated with serum ACE activity (median with MA, 69.0 U/L [range, 46.0 to 100.1 U/L] versus without MA, 57.2 U/L [range, 36.3 to 81.0 U/L]; P = 0.02). At the end of follow-up, 48% of patients (24 of 49 patients) died, 70% of MA. The group that died had increased baseline serum ACE activity (nonsurvivors, 65.0 U/L [range, 33.5 to 100.0 U/L] versus survivors, 49.4 U/L [range, 36.4 to 86.5 U/L]; P < 0.05) and MA rates (nonsurvivors, 77% versus survivors, 36%; P < 0.01). Cox regression analysis performed with age, sex, mean blood pressure, body mass index, metabolic control, Kt/V, residual renal function, serum albumin level, and ACE activity showed that baseline serum ACE activity (P = 0.033) is an independent predictor for mortality in patients with type 2 diabetes on CAPD therapy. Among patients with type 2 diabetes on CAPD therapy, serum ACE activity is associated with risk for MA and is an independent predictor for mortality. Whether ACE inhibition will have a beneficial effect on the outcome of these patients needs further investigation.
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PMID:Prognostic role of serum ACE activity on outcome of type 2 diabetic patients on chronic ambulatory peritoneal dialysis. 1197 50

There is a unique relationship between the kidney and blood pressure (BP): on the one hand, renal dysfunction and particularly renal disease cause an increase in BP, while on the other hand, high BP accelerates loss of function of the diseased kidney. Transplantation studies, both in experimental animals and humans, documented that "blood pressure goes with the kidney," a normotensive recipient of a kidney genetically programmed for hypertension (HT) will develop HT, while conversely hypertensive patients with renal failure receiving the kidney of a normotensive donor may develop normotension. Family studies showed higher BP values and more frequent HT in first degree relatives of patients with primary glomerulonephritis or diabetic nephropathy, both type 1 and type 2. The notion that HT accelerates the loss of renal function has been proposed at the turn of the century, but definite evidence by observational and interventional studies has only been provided in the last two decades. The issue has been much confounded by the mistaken believe that damaged kidneys require higher BP values in order to function properly. The mechanisms of BP increase in renal disease comprise: salt retention, inappropriate activity of the renin-angiotensin system (RAS) and of the sympathetic nerve system as well as impaired endothelial cell-mediated vasodilatation. There is ample evidence both in primary renal disease (AIPRI and REIN trials) and in nephropathy of type 1 and type 2 diabetes (IDNT, RENAAL) that pharmacological blockade of the RAS by angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor blockers has BP-independent renoprotective effects. More recently, it has also been shown that blockade of the sympathetic nerve system has BP-independent effects on albuminuria and on glomerulosclerosis.
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PMID:Kidney and hypertension. 1198 15

Scientific evidence currently available supports the concept that renin-angiotensin blockade with angiotensin converting enzyme inhibitors as a first-line treatment exhibits in arterial hypertension beneficial effects in the prevention of mortality and morbidity comparable to those achieved with diuretics and beta-blockers. In addition, the renin-angiotensin blockade has also proved to be beneficial in the secondary prevention of several complications of hypertensive disease such as after myocardial infarction and congestive heart failure, as well as in the prevention of the incidence of type 2 diabetes, and the progression of diabetic and nondiabetic nephropathy. In this later regard, recent evidence with angiotensin II receptor antagonists in reducing the progression of nephropathy in type 2 diabetes strongly confirms that antagonism of the renin-angiotensin system is an effective approach to cardiovascular and renal disease. Finally, the renin-angiotensin blockade in high-risk patients may reduce cardiovascular mortality independently of the effect on blood pressure (BP). The effect of other antihypertensive drugs on cardiovascular risk in patients with high-normal BP should be investigated to establish whether they exhibit a comparable effect or whether there is a class-related benefit of drugs blocking the renin-angiotensin system. Such a strategy could also be encouraged to design future interventional studies with the newer classes of compounds (angiotensin II AT1-receptor antagonists, vasopeptidase inhibitors, endothelin antagonists), which would have the additional potential advantage of providing information more easily transferable to large-scale clinical practice.
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PMID:ACE inhibition and cardiovascular mortality and morbidity in essential hypertension: the end of the search or a need for further investigations? 1199 Dec 25

In three groups of subjects, those with type 2 diabetes and nephropathy, those with type 1 diabetes without nephropathy, and healthy volunteers subjected to short-term hyperglycemia, we observed a counterintuitive relationship. In all three groups, baseline renal plasma flow (RPF) was positively correlated with the RPF response to blocking the renin-angiotensin system (RAS). This seems paradoxical in that an opposite result would have been expected if angiotensin-dependent renal vasoconstriction was responsible for the renal vasodilator response to RAS blockade. This suggests a link between the renal vasodilator response, mediated by nitric oxide (NO), and the activation of the intrarenal RAS. The complex interrelationships between hyperglycemia, insulin, NO, and the RAS may result in phenotypes that indicate varying risk of diabetic nephropathy and underlying genetic polymorphisms.
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PMID:Renal perfusion and the renal hemodynamic response to blocking the renin system in diabetes: are the forces leading to vasodilation and vasoconstriction linked? 1208 29

In the 1970s and 1980s it became evident that progression of renal disease and blood pressure are correlated. Subsequently, it was shown that antihypertensive treatment, especially with agents that block the renin-angiotensin system (RAS), could slow the progression of diabetic renal disease. Several studies, particularly with RAS blockers, have confirmed beneficial effects on urinary albumin excretion in patients with diabetes and microalbuminuria or proteinuria. There are good reasons to explore dual blockade of the RAS with an AT(1)-receptor blocker and an ACE inhibitor. Receptor blockers may block the effects of angiotensin II more effectively than ACE inhibitors; moreover, ACE inhibitors increase bradykinins which may have positive effects on blood pressure and renal function. Such combination treatment has been found to be well tolerated and more effective in reducing blood pressure than either monotherapy. Positive effects on microalbuminuria or proteinuria have also been noted. Studies have shown that treatment with AT(1)-receptor blockers postpones end-stage renal disease and reduces the rate of decline in glomerular filtration rate (GFR) in patients with type 2 diabetes and nephropathy. Moreover, albuminuria was reduced to a greater extent with AT(1)-receptor blockers than with conventional antihypertensive therapy producing the same blood pressure reductions. In summary, AT(1)-receptor blockers are effective in all stages of diabetic renal disease, and have an excellent tolerability profile. Usually the side-effect profile is comparable with placebo. In certain situations, there may be a slight, readily reversible, increase in serum potassium. There may also be a slight reduction in GFR, reflecting a decrease in glomerular filtration pressure.
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PMID:The reno-protective role of AT(1)-receptor blockers. 1214 Jul 29


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