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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Halting the reduction in glomerular filtration rate (GFR) is the primary aim of any treatment of patients presenting with progressive chronic renal failure, a very common corollary to diabetes. To improve GFR, the high blood pressure (BP) and proteinuria often seen in these patients must both be controlled. These symptoms lead not only to progressive loss of renal function, but also to an increase in cardiovascular risk. Use of angiotensin-converting enzyme (ACE) inhibitors in these patients has been reported to control BP and reduce protein excretion and cardiovascular risk. Complete blockade of angiotensin II (Ang II) action with the highly selective Ang II receptor blocker (ARB) valsartan, both as monotherapy and in combination with ACE inhibitors, is well-tolerated and efficacious in patients with renal failure. Unlike ACE inhibition, ARB treatment leads to no initial reduction in GFR, thus valsartan may be a better agent for the control of BP, with greater renal protection.
J Renin Angiotensin Aldosterone Syst 2000 Jun
PMID:New clinical investigations with selective angiotensin II receptor blocker therapy in diabetes and renal disease. 1719 17

Angiotensin-converting enzyme (ACE) inhibitors have a well-established role in the management of patients with hypertension, diabetes, heart failure and myocardial infarction (MI). ACE inhibitors have been particularly well studied in acute and chronic MI with consistent and substantial survival benefits demonstrated, particularly in the higher risk groups. The recent development of angiotensin II (Ang II) receptor blockers (ARBs) as a well tolerated pharmacological therapy to more completely inhibit the actions of Ang II at the AT1-receptor level raises questions concerning comparative efficacy with the proven ACE inhibitor experience. Two major trials will provide a direct comparison of ARBs with an ACE inhibitor. The Valsartan in Acute Myocardial Infarction (VALIANT) trial is specifically designed to compare and contrast the ARB, valsartan, used both alone as well as in combination with a proven ACE inhibitor regimen, in a high risk MI population. VALIANT, with its three arms targetting 14,500 patients, is uniquely poised to determine whether the pharmacological advance in the development of ARBs confers additional clinical (survival) value in high risk MI patients.
J Renin Angiotensin Aldosterone Syst 2000 Jun
PMID:Will more complete inhibition of the RAAS with angiotensin receptor blockade improve survival following myocardial infarction? 1719 21

Experimental and clinical evidence is now available that antagonism of angiotensin II (Ang II) with both angiotensin-converting enzyme inhibitors and Ang II receptor antagonists (AIIAs) is effective in slowing the rate of renal functional loss in patients affected by proteinuric kidney diseases. Among AIIAs, telmisartan has been shown to be characterised by a potent and long lasting antihypertensive effect that may be associated with another specific effect of this molecule, the partial agonism of the peroxisome-activated receptor-gamma. Although this action has also been observed with other AIIAs, telmisartan seems to exert a more effective and specific action as in such a way to influence beneficially adipocyte metabolism, diabetes onset and insulin resistance. Recently, we have demonstrated, at the experimental and clinical level, that sustained blockade of Ang II biological activity with this class of compounds can potentially reduce the progression of renal dysfunction and in some circumstances induce the regression of renal functional and structural changes. In this review we analyse available experimental and clinical data that suggest that blocking Ang II with telmisartan may effectively ameliorate renal dysfunction in patients affected by the now frequently observed condition termed metabolic syndrome.
J Renin Angiotensin Aldosterone Syst 2006 Dec
PMID:Potential protective effects of telmisartan on renal function deterioration. 1731 86

The VIPE study was a prospective, non-comparative, open-label clinical evaluation of 97 hypertensive patients (69.1% female; 68.9 +/- 9.5 years; mean blood pressure (BP) 160 +/- 12/90 +/- 9 mmHg) with echocardiographic evidence of left ventricular hypertrophy (LVH). Patients were treated for six months with a candesartan-based regimen (8 mg/16 mg + HCTZ 12.5 mg + additional drugs to lower BP < 140/90 mmHg). After six months, systolic/diastolic BP was decreased by 19.3 +/- 8/9.4 +/- 5 mmHg (p<0.001 for both), and left ventricular mass index (LVMI) decreased 17.01 g/m2 (95%CI: -13.2 to -20.99; p<0.001). During treatment with the candesartan-based regimen all echocardiographic parameters related to LVMI were significantly reduced and 28% achieved a target LVMI [< 134 g/m(2) (men) and < 110 g/m(2) (women)]. No significant changes were observed in ejection fraction, shortening fraction or LV diastolic function. Univariate analysis showed that both age (p=0.03) and diabetes (p=0.029) were predictive of LVH regression. Thus, a candesartan-based regimen for six months significantly reduced echocardiographic LVH in hypertensive patients in general practice. The drug was very well tolerated and no serious adverse events were reported.
J Renin Angiotensin Aldosterone Syst 2006 Dec
PMID:Regression of left ventricular hypertrophy by a candesartan-based regimen in clinical practice. The VIPE study. 1731 94

This editorial considers the use of the first selective oral renin inhibitor, aliskiren, in reducing angiotensin (Ang) II reactivation or aldosterone (ALDO) escape during renin-angiotensin-aldosterone system (RAAS) inhibition. RAAS blockade with angiotensin converting enzyme inhibitors (ACEIs) and/or angiotensin receptor AT(1) blockers (ARBs) is very useful for the treatment of arterial hypertension, chronic heart failure (CHF), atherosclerosis and diabetes. 'Ang II reactivation' and 'ALDO escape' or 'breakthrough' have been observed during either ACEI or ARB treatment, and may attenuate the clinical benefit of RAAS blockade. Renin and Ang I accumulate during ACE inhibition, and might overcome the ability of an ACEI to effectively suppress ACE activity. There is also data suggesting that 30 - 40% of Ang II formation in the healthy human during RAAS activation is formed via renin-dependent, but ACE-independent, pathways. Moreover, ACE gene polymorphisms contribute to the modulation and adequacy of the neurohormonal response to long-term ACE inhibition, at least in patients with CHF (up to 45% of CHF patients have elevated Ang II levels despite the long-term use of an ACEI) or diabetes. The reactivated Ang II promotes ALDO secretion and sodium reabsorption. ALDO breakthrough also occurs during long-term ARB therapy, mainly by an AT(2)-dependent mechanism. This was related to target-organ damage in animal models. Oral renin inhibition with aliskiren has showed excellent efficacy and safety in the treatment of hypertension. Aliskiren can be co-administered with ACEIs, ARBs or hydrochlorothiazide. Furthermore, there is evidence suggesting that aliskiren reduces Ang II reactivation in ACE inhibition and ALDO escape during treatment with an ACEI or an ARB, at least to the degree that this is associated with the RAAS. For RAAS-independent ALDO production, the combination of aliskiren with eplerenone might prove useful.
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PMID:Angiotensin II reactivation and aldosterone escape phenomena in renin-angiotensin-aldosterone system blockade: is oral renin inhibition the solution? 1737 10

The increasing prevalence and costs of type 2 diabetes mellitus (DM) make strategies to prevent its development vitally important. This analysis was conducted to determine if angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) prevent the development of DM. Medline and the Cochrane Central Register of Controlled Trials (1966 to May 2006) were queried for prospective, randomized, placebo-controlled or active-controlled trials of ACE inhibitor or ARB therapy in adults that reported rates of new-onset diabetes during follow-up. Meta-analyses of summary statistics from individual trials were performed using a random-effects model. Thirteen trials with a total of 93,451 patients were identified. Renin-angiotensin system antagonists reduced the incidence of DM from 9% in nontreated patients to 7.1% in those treated, a 26% reduction in odds (odds ratio [OR] 0.74, 95% confidence interval [CI] 0.66 to 0.81, p<0.001). The effect sizes were similar in trials that randomized only hypertensive subjects (OR 0.73, 95% CI 0.66 to 0.82, p<0.001) and trials that studied the impact of renin-angiotensin system inhibition on outcomes of patients with vascular disease or heart failure (OR 0.67, 95% CI 0.50 to 0.90, p=0.008). ACE inhibitors and ARBs had comparable effects on the development of DM. In ACE inhibitor trials, the odds of developing DM were reduced by 28% (OR 0.72, 95% CI 0.63 to 0.84, p<0.001), and in the 5 ARB studies, there was a 27% reduction (OR 0.73, 95% CI 0.64 to 0.84, p<0.001) in the odds. In conclusion, evidence accumulated to date indicates that inhibition of the renin-angiotensin system may contribute to the prevention of DM.
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PMID:Effect of inhibition of the renin-angiotensin system on development of type 2 diabetes mellitus (meta-analysis of randomized trials). 1739 2

Diabetes mellitus (DM) is characterised by alterations in the intrarenal renin-angiotensin system (RAS). Insulin treatment may reverse these changes by an unknown mechanism. We aimed to verify the association between somatic ACE with 136 kDa (sACE) and N-domain ACE with 69 kDa (nACE) from Wistar (W) rat tissue with DM. Three groups were studied: control (CT), insulin treated diabetic (DT) and untreated (D). ACE activity was determined using Hippuryl-His-Leu and Z-Phe-His-Leu as substrates. In D group, urine ACE activity increased for both substrates when compared with CT and DT, despite the decreased activity of renal tissues. Immunostaining of renal tissue demonstrated that ACE is more strongly expressed in the proximal-tubule of D than in the same nephron portion in the other groups. Angiotensin (Ang) 1-7 and Ang II are less expressed in DT group when compared with CT and D. Ang II levels decreased in the D and DT groups showed when compared to the control. Ang 1-7 was detected in all studied groups with low levels in DT. The modulation of angiotensin peptides suggests that sACE, nACE, ACE 2 and NEP could have important functions in renal RAS regulation through a counter-regulatory mechanism to protect the kidney in diabetes mellitus.
J Renin Angiotensin Aldosterone Syst 2007 Mar
PMID:Association of somatic and N-domain angiotensin-converting enzymes from Wistar rat tissue with renal dysfunction in diabetes mellitus. 1748 24

This study focused on the regulation and affinity modulation of angiotensin II (Ang II) binding to its receptor subtypes (AT(1)- and AT(2)-receptor) in the coronary endothelium (CE) and cardiomyocytes (CM) of Sprague-Dawley male rats in normal (N), normal treated with losartan (NL), streptozotocin-induced diabetic (D), insulin-treated diabetic (DI), losartan-treated diabetic (DL), and diabetic co-treated with insulin and losartan (DIL). Heart perfusion was used to estimate Ang II binding affinity (tau=1/k-(n)) to its receptor subtypes on CE and CM. Diabetes decreased tau value on CE and increased it on CM as compared to normal. In DL group, the tau value decreased on CE but was normalised on CM. Insulin treatment alone (DI) or with losartan (DIL) restored t to normal on both CE and CM. Western blot results for AT(1)-receptor density showed an increase in diabetics compared to normal with no normalising effect with insulin treatment. The AT(1)-receptor density was normalised in the diabetic groups treated with losartan +/- insulin. Results for AT(2)-receptor regulation revealed a significant difference between untreated (D) and losartan-treated (DL, DIL) diabetic groups. All of these data show the interrelated pathway and cross-talk between insulin and Ang II system indicating potentially negative effects on the diabetic heart.
J Renin Angiotensin Aldosterone Syst 2007 Jun
PMID:Cross-talk related to insulin and angiotensin II binding on myocardial remodelling in diabetic rat hearts. 1770 31

Renin system blockade in diabetes exerts a strong positive influence on complications, especially nephropathy. In hyperglycaemic diabetic subjects, however, blockade of the renin-angiotensin system with angiotensin-converting enzyme inhibitors results in a marked rise in plasma renin. We investigated whether glycaemic fluctuations measured in hours, or those measured in weeks by Haemoglobin A(1C) (HbA(1C)) , influenced the plasma renin response to captopril. Fifty-four type 1 diabetic subjects were studied in high-salt balance. After an all night fast and in the supine position, baseline serum glucose level was drawn. Iv. glucose and insulin were then administered to keep serum glucose between 100 and 150 mg/dL (target). When target was reached, captopril 25 mg pre os was administered and plasma renin activity (PRA) and finger stick glucose were drawn, then serially every 45 minutes for 225 minutes. Baseline glucose and baseline PRA were drawn hours apart. Peak PRA corresponded to the renin level at peak captopril effect, 90' after administration. Renin response (RR) = peak PRA - baseline PRA. Correlation of baseline glucose with baseline PRA was weak (r=0.3, p=0.02), but strong with peak PRA (r=0.65; p=0.002). Drop in glucose had a weak, negative correlation with baseline PRA (r=-0.3, p=0.03) but a much stronger one with peak PRA (r=-0.7, p<0.0001). After adjustment for baseline PRA and baseline glucose, mean RR correlated strongly with mean drop in glucose (r=-0.72; p=0.008). Conversely, HbA1C correlated with none of the measures of renin system activation (r=0.05;p=0.7). In type 1 diabetic subjects, short-term hyperglycaemia, but not long-term glycaemic control, enhanced the RR to captopril.
J Renin Angiotensin Aldosterone Syst 2007 Jun
PMID:Short- and long-term glycaemic control and the state of the renin system in type 1 diabetes mellitus. 1770 35

Hypertension is more prevalent and more difficult to control and is associated with a higher mortality rate in patients with diabetes than in nondiabetic patients. Elevated blood pressure contributes importantly to the development of albuminuria and progression of renal damage in diabetic nephropathy. Strong evidence indicates that the presence of albuminuria and overt nephropathy in patients with type 1 and type 2 diabetes is associated with a marked increase in the rate of fatal and nonfatal cardiovascular events. Blockade of the renin-angiotensin system in patients with type 2 diabetes with or without chronic kidney disease is associated with a significant reduction in risk for cardiovascular events. Renin-angiotensin system-blocking agents should be considered first-step pharmacologic therapy for hypertension in diabetic patients, with addition of other agents, if needed, to meet the recommended blood pressure goal of <130/80 mm Hg. In most instances, a diuretic is also needed to reduce blood pressure.
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PMID:Reducing cardiovascular events in high-risk patients: the challenge of managing hypertension in patients with diabetic renal disease. 1808 Mar 58


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