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Query: UMLS:C0011860 (type 2 diabetes)
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Hypertension is a powerful risk factor for cardiovascular (CV) morbidity and mortality; therefore, blood pressure (BP) lowering plays a central role in reducing the cardiovascular complications of hypertension, including stroke. Recent outcomes studies--Losartan Intervention For Endpoint reduction in hypertension, Reduction of Endpoints in Non-insulin-dependent Diabetes Mellitus with the Angiotensin II Antagonist Losartan, and the Irbesartan Type 2 Diabetic Nephropathy Trial--suggest that some angiotensin II antagonists are associated with CV and renal effects beyond their ability to lower BP in patients with hypertension or diabetic nephropathy and may play a role in the prevention of new-onset type 2 diabetes. Angiotensin II antagonists are associated with a wide variety of vascular, cardiac, and renal effects, as well as molecule-specific effects independent of those induced by the angiotensin-I receptor. These actions may offer a mechanistic explanation for the outcome benefits observed in patients with hypertension or diabetic nephropathy. Angiotensin-converting enzyme inhibitors and calcium-channel blockers may also have effects that are not completely explained by differences in the antihypertensive response to these agents, but the evidence is less robust. Collectively, these findings suggest that management of patients with hypertension, with or without diabetes or renal disease, should no longer be viewed as simply a matter of correcting elevated BP. Antihypertensive agents that possess CV benefits beyond their BP-reducing effects should be used to prevent the development of end-organ damage.
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PMID:Do angiotensin II antagonists provide benefits beyond blood pressure reduction? 1602 Apr 2

Angiotensin-converting enzyme (ACE) inhibitors have favourable effects on hypertension and diabetic nephropathy, but persistent use may result in incomplete blockade of the renin-angiotensin system. Long-term effects of dual blockade using the ACE inhibitor lisinopril and the long-acting angiotensin II receptor blocker (ARB) telmisartan on blood pressure and albumin excretion rate (AER) were evaluated. Patients with type 2 diabetes mellitus, hypertension (systolic blood pressure [SBP] >or=140 mmHg or diastolic blood pressure [DBP] >or=90 mmHg) and microalbuminuria (AER 30-300 mg/24h) received 20mg of lisinopril or 80 mg of telmisartan once a day for 24 weeks. Patients were then randomised to continuing treatment with the respective monotherapy or with lisinopril plus telmisartan for a further 28 weeks. Significant (P<0.001) declines in SBP (11.1 mmHg versus 10.0 mmHg), DBP (5.6 mmHg versus 5.3 mmHg) and AER (98 mg/24 h versus 80 mg/24 h) were achieved with lisinopril (n=95) or telmisartan (n=97), respectively, after 24 weeks. Subsequent treatment with lisinopril plus telmisartan for 28 weeks resulted in further significant reductions (P<0.001) in SBP, DBP and AER compared with either monotherapy. All treatments were well tolerated. Lisinopril plus telmisartan thus provides superior blood pressure and AER control than either monotherapy. We conclude that use of dual blockade may provide a new approach to prevention of diabetic nephropathy in patients with type 2 diabetes, hypertension and microalbuminuria.
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PMID:Beneficial effect of lisinopril plus telmisartan in patients with type 2 diabetes, microalbuminuria and hypertension. 1611 44

Proteinuria is a graded marker for kidney damage, as well as the risk for future cardiovascular events. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) reduce urinary protein excretion and slow progression of renal impairment, independent of blood pressure lowering. Both the Irbesartan Diabetic Nephropathy Trial (IDNT) and the Reduction in Endpoints in NIDDM with the Angiotensin Antagonist Losartan (RENAAL) study were large, randomized, prospective studies in type 2 diabetic patients with proteinuria. There was no reduction in the incidence of myocardial infarction or stroke with the ARBs compared to placebo in either trial. A broader overview of clinical trials comparing ACEIs and ARBs with other antihypertensive drugs fails to show any substantive blood pressure-independent effects on stroke or myocardial infarction with these classes of drugs. Therefore, for cardiovascular end points (as opposed to renal end points), it may be more important that the blood pressure is reduced, rather than how the process is started.
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PMID:Antihypertensive, antiproteinuric therapy and myocardial infarction and stroke prevention. 1615 81

In Australia the number of patients developing end-stage kidney disease is growing. Almost 70% of new cases of treated end-stage kidney disease are due to diabetes, hypertension or glomerulonephritis. The majority of these patients have a chronic decline of renal function over many years before dialysis is required, even when the initial insult is no longer present. Hypertension and the degree of proteinuria are the most important determinants for this progression and ample evidence suggests that angiotensin II is the key player in sustaining both hypertension and proteinuria. Angiotensin II mediates not only haemodynamic changes but also profibrotic and pro-inflammatory processes. Blockade of the renin-angiotensin system decreases proteinuria and slows the progression of both diabetic and non-diabetic proteinuric renal disease. Angiotensin-converting enzyme (ACE) inhibitors are first-line therapy in patients with type 1 diabetes mellitus and nephropathy, whereas angiotensin receptor blockers (ARB) are first-line therapy in patients with type 2 diabetes mellitus and microalbuminuria or overt nephropathy. Finally, treatment with ACE inhibitors delays the progression of proteinuric nephropathy in non-diabetic patients. Combination therapy with ACE inhibitors and ARB may allow a more complete blockade of the renin-angiotensin system and clinical trials show that ACE inhibitor-ARB combinations have an additive antiproteinuric effect of up to 40% compared with ACE inhibitor or ARB alone, without additional blood pressure-lowering effect. Finally, it is important to emphasize that progressive lowering of blood pressure to 120 mmHg is associated with improved renal outcome and that this effect is independent of baseline renal function.
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PMID:Prescribing angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in chronic kidney disease. 1729 66

Cardiovascular diseases are directly affected by arterial hypertension. When associated with diabetes mellitus, the potential deleterious effects are well amplified. Both conditions play a central role in the pathogenesis of coronary artery disease, heart failure, stroke, and renal insufficiency. Prevalence of hypertension is much higher among diabetic than non-diabetic patients, and the hypertensive patient is more likely to develop type 2 diabetes. Current international guidelines recommend aggressive reductions in blood pressure (BP) in hypertensive patients with additional risk factors, including cardiovascular risk factors, and emphasize the relevance of intensive reduction in patients with diabetes mellitus; a goal of 130/80 mm Hg is required. To achieve BP target a combination of antihypertensives will be needed, and the use of long-acting drugs that are able to provide 24-hour efficacy with a once-daily dosing confers the noteworthy advantages of compliance improvement and BP variation lessening. Lower dosages of the individual treatments of the combination therapy can be administered for the same antihypertensive efficiency as that attained with high dosages of monotherapy. Angiotensin-converting enzyme inhibitors and calcium-channel blockers as a combination have theoretically compelling advantages for vessel homeostasis. Trandolapril/verapamil sustained release combination has showed beneficial effects on cardiac and renal systems as well as its antihypertensive efficacy, with no metabolic disturbances. This combination can be considered as an effective therapy for the diabetic hypertensive population.
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PMID:Trandolapril/verapamil combination in hypertensive diabetic patients. 1758 77

National Diabetes Education Program of NIH, Mayo Clinic and American Diabetes Association recommend eggplant-based diet as a choice for management of type 2 diabetes. The rationale for this suggestion is the high fiber and low soluble carbohydrate content of eggplant. We propose that a more physiologically relevant explanation lies in the phenolic-linked antioxidant activity and alpha-glucosidase inhibitory potential of eggplant which could reduce hyperglycemia-induced pathogenesis. Results from this study indicate that phenolic-enriched extracts of eggplant with moderate free radical scavenging-linked antioxidant activity had high alpha-glucosidase inhibitory activity and in specific cases moderate to high angiotensin I-converting enzyme (ACE) inhibitory activity. Inhibition of these enzymes provide a strong biochemical basis for management of type 2 diabetes by controlling glucose absorption and reducing associated hypertension, respectively. This phenolic antioxidant-enriched dietary strategy also has the potential to reduce hyperglycemia-induced pathogenesis linked to cellular oxidation stress. These results provide strong rationale for further animal and clinical studies.
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PMID:In vitro studies of eggplant (Solanum melongena) phenolics as inhibitors of key enzymes relevant for type 2 diabetes and hypertension. 1770 16

Angiotensin-converting enzyme inhibitors are an important treatment option for hypertension, especially when elevated blood pressure exists in the presence of diabetes mellitus, chronic kidney disease, or congestive heart failure. This article reviews some of the pathophysiologic mechanisms involved in patients with hypertension and these comorbidities and how they relate to the renin-angiotensin system (RAS). Inhibition of the RAS when utilized along with other antihypertensive medications has been particularly effective in hypertensive patients with type 2 diabetes, chronic kidney disease, and vascular disorders; consensus group guidelines have reflected this in their treatment recommendations. Clinical trial data demonstrate that the effectiveness of RAS blockers is enhanced by maximizing the daily dose and combining these medications with thiazide diuretics.
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PMID:Angiotensin-converting enzyme inhibitors in the treatment of hypertension: an update. 1797 95

The metabolic syndrome (MS), a cluster of risk factors, such as obesity, hyperglycemia, hypertension and dyslipidemia, contributes to the development of cardio-vascular diseases and type 2 diabetes mellitus (DM2). Insulin resistance (IR) plays a key role in MS being strongly linked to abdominal visceral fat. Treatment for obese patients with MS should aim at improving IR, delaying the onset of DM2 and at reducing cardio-vascular risk. Weight loss, first therapeutic target, may be obtained through life-style modifications and anti-obesity drugs or bariatric surgery, at need. In these patients drug therapy is necessary if therapeutic life-style changes are not sufficient. Some drugs have adverse metabolic effects, therefore the therapeutic choices must be specific and rational. Metformin, Thiazolidinediones and Acarbose are anti-hyperglycemic drugs of choice: they reduce the incidence of DM2 and IR (or improve insulin sensitivity) and they decrease or stabilize the visceral adipose tissue mass (Thiazolidinediones increases subcutaneous fat only). Also Angiotensin II receptor blockers and Angiotensin-converting enzyme inhibitors reduce the incidence of DM2 and insulin resistance and they are first-line antihypertensive drugs in MS. Calcium channel blockers, Alpha-1 antagonists and Alpha-2 agonists drugs are metabolically neutral and slight weight gains are related to the hydro-sodium retention. Beta-blockers and Diuretics, except for Indapamide and Anti-aldosterone drugs, can reduce insulin sensitivity, impair lipid profile and increase DM2 incidence; they are not first-line therapy yet they are necessary in selected cases only. Statins, Fibrates and omega-3 Fatty acids are indicated to normalize dyslipidemia. Low doses of acetylsalicylic acid are also recommended.
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PMID:[Therapeutic options for metabolic syndrome in obese patients]. 1806 54

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers can decrease hemoglobin, causing anemia and this may be an independent risk factor for chronic kidney disease progression. We studied the relationship between a decline in hemoglobin and outcome in 1513 patients with type 2 diabetes and kidney disease by a post hoc analysis of the RENAAL Study (Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan) with an average follow-up of 3.4 years. The relationship between baseline and year-1 hemoglobin and treatment on end-stage renal disease (ESRD) and ESRD or death was evaluated using multivariate Cox models (covariates: baseline hemoglobin, proteinuria, serum albumin, serum creatinine, and year-1 hemoglobin). Compared with placebo, losartan treatment was associated with a significant decrease of hemoglobin, with the largest between-group difference at 1 year. After adjustment, there were significant relative risk reductions for losartan compared with placebo for ESRD and for ESRD or death regardless of the baseline hemoglobin even in those patients with a baseline hemoglobin below 120 g l(-1). Hence, the renoprotective properties of losartan were maintained despite a significant lowering of the hemoglobin concentration.
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PMID:The effect of losartan on hemoglobin concentration and renal outcome in diabetic nephropathy of type 2 diabetes. 1809 75

Angiotensin-converting enzyme (ACE) inhibitors can improve cardiovascular outcome in patients with type 2 diabetes mellitus (T2DM). Myocardial diastolic function (Ve) is a known marker of cardiovascular prognosis. It could potentially indicate the effects of preventive therapy if evaluated by tissue Doppler. We tested the hypothesis that treatment with the ACE inhibitor ramipril has beneficial effects on Ve. In this study, 16 subjects on insulin therapy (eight receiving 10 mg ramipril/day compared to eight matched controls who were not treated with an ACE inhibitor) were followed up for a period of nine months. Myocardial and vascular function were assessed by tissue Doppler and ultrasound. In the ramipril group, Ve improved significantly after nine months of treatment (7.8+/-0.9 cm/s to 8.6+/-0.9 cm/s, p<0.04). Systolic blood pressure and intima media thickness (IMT) demonstrated a trend towards improvement. In controls, Ve remained unchanged and there was a trend towards deterioration in stiffness index beta (p<0.07). In conclusion, the observed improvement of myocardial diastolic function with ramipril in patients with T2DM is an encouraging result. It might contribute to the overall improvement that has been observed with hard cardiovascular end points.
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PMID:Beneficial effects of ramipril on myocardial diastolic function in patients with type 2 diabetes mellitus, normal LV systolic function and without coronary artery disease: a prospective study using tissue Doppler. 1815 8


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