Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hypertensive patient with type 2 diabetes is especially at risk of adverse cardiovascular events. The United Kingdom Prospective Diabetes Study (UKPDS) and Hypertension Optimal Treatment (HOT) studies suggested that treatment to a lower target blood pressure resulted in better prevention of clinical disease in these patients. Most trials comparing antihypertensive drugs have shown only minimal differences between the various agents. The evidence from the trials suggests that diuretics, beta-blockers, calcium channel blockers (CCBs), angiotensin-converting enzyme (ACE) inhibitors, and the angiotensin-receptor antagonists (ARBs) will all successfully reduce adverse clinical events. The largest of the comparative hypertensive drug trials, the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), demonstrated that a diuretic has a better hypotensive effect, and was more successful in preventing many aspects of cardiovascular disease compared with CCBs and ACE inhibitors. The importance of good blood pressure control and the general equivalence of antihypertensive drugs were again shown in the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial, which compared an ARB with a CCB. Choice of antihypertensive agent should be individualized and guided by the presence of concomitant clinical disease and the need to protect any specific target organ system in the diabetic hypertensive. Diuretics, being potent hypotensive drugs with clearly demonstrated clinical benefit, should form part of the antihypertensive regimen of most diabetic hypertensives. ACE inhibitors and ARBs are especially useful in preventing nephropathy. Most patients will require a combination of antihypertensive drugs to achieve tight blood pressure control of under 130/80 mm Hg in the diabetic hypertensive. The clinician should concentrate on seeking this lower target blood pressure rather than be excessively concerned about which is the best antihypertensive agent.
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PMID:Choice of antihypertensive drug in the diabetic patient. 1636 52

The ABCD (Appropriate Blood Pressure Control in Diabetes) and ABCD-2V (Part 2 with Valsartan) are prospective, randomised clinical trials which will provide important data on the impact of intensive vs. moderate blood pressure (BP) control on microvascular and macrovascular complications in normotensive and hypertensive patients with type 2 diabetes mellitus (DM). The ABCD trial was a five-year study that compared the effects of intensive vs. moderate BP control on the endpoints of nephropathy, retinopathy, neuropathy, and cardiovascular disease events using a calcium channel blocker (CCB) and an angiotensin-converting enzyme (ACE) inhibitor as the primary antihypertensive agents. The recently published results of the hypertensive cohort of ABCD are reviewed herein. The follow-up study, ABCD-2V, is ongoing and was designed to compare intensive vs. moderate BP control on the same endpoints as the ABCD study, using the highly selective angiotensin II receptor blocker (ARB) valsartan as the primary antihypertensive agent. First results of ABCD-2V are expected in 2004. The baseline characteristics for the patients enrolled thus far in the hypertensive cohort of ABCD-2V are reviewed. These studies will provide insight into the role of intensive vs. moderate BP control in the management of normotensive and hypertensive patients with type 2 DM.
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PMID:Improving the prognosis of diabetic patients: evaluating the role of intensive versus moderate blood pressure control with selective angiotensin II receptor blocker (ARB) therapy. 1719 16

We conducted 3 open-label, multiple-dose, 3-period, randomized, crossover studies in healthy subjects to assess the potential pharmacokinetic interaction between vildagliptin, a novel dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes, and representatives of 3 commonly prescribed antihypertensive drug classes: (1) the calcium channel blocker, amlodipine; (2) the angiotensin receptor blocker, valsartan; and (3) the angiotensin-converting enzyme inhibitor, ramipril. Coadministration of vildagliptin 100 mg with amlodipine 5 mg, valsartan 320 mg, or ramipril 5 mg had no clinically significant effect on the pharmacokinetics of these drugs. The 90% confidence intervals of the geometric mean ratios for area under the plasma concentration-time curve from time zero to 24 hours (AUC0-24h) and maximum plasma concentration (Cmax) for vildagliptin, amlodipine, and ramipril (and its active metabolite, ramiprilat) were contained within the acceptance range for bioequivalence (0.80-1.25). Valsartan AUC0-24h and Cmax increased by 24% and 14%, respectively, following coadministration of vildagliptin, but this was not considered clinically significant. Vildagliptin was generally well tolerated when given alone or in combination with amlodipine, valsartan, or ramipril in healthy subjects at steady state. No adjustment in dosage based on pharmacokinetic considerations is required should vildagliptin be coadministered with amlodipine, valsartan, or ramipril in patients with type 2 diabetes and hypertension.
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PMID:Vildagliptin, a novel dipeptidyl peptidase IV inhibitor, has no pharmacokinetic interactions with the antihypertensive agents amlodipine, valsartan, and ramipril in healthy subjects. 1798 25

Increased arterial stiffness, as estimated from aortic pulse wave velocity (Ao-PWV), and albuminuria are independent predictors for cardiovascular disease in type 2 diabetes mellitus (T2DM). Whether angiotensin receptor blockers (ARBs), drugs with cardio-renal protective effects, improve Ao-PWV to a greater extent than other equipotent antihypertensive medications remains unclear. After a 4-week washout phase, we compared the effects of valsartan (n=66), an ARB, with that of amlodipine (n=65), a calcium channel blocker on Ao-PWV in 131 T2DM patients with pulse pressure (PP) >or=60 mm Hg and raised albumin excretion rate (AER) in a 24-week randomized, double-blind, parallel group study. Hydrochlorothiazide (HCTZ) 25 mg/d was added to valsartan 160 mg and amlodipine 5 mg/od uptitrated to 10 mg/od after 4 weeks to ensure equivalent BP control. After 24 weeks brachial and central aortic PP had fallen to a similar extent with attained mean (SD) brachial and central PP of 61.6 (13.6) and 47.3 (14.1) mm Hg in the valsartan/HCTZ group and 61.5 (12.2) and 47.3 (9.9) mm Hg in the amlodipine group, respectively. Ao-PWV showed a significantly greater reduction, mean (95% CI), -0.9 m/s (-1.4 to -0.3) for valsartan/HCTZ compared to amlodipine (P=0.002). AER fell significantly only with Val/HCTZ from 30.8(20.4, 46.5) to 18.2(12.5, 26.3) mcg/min, (P=0.01) with between treatment difference in favor of Val/HCTZ of -15.3mcg/min (P<0.001). Changes in AER and Ao-PWV were not correlated. Valsartan/HCTZ improves arterial stiffness and AER to a significantly greater extent than amlodipine despite similar central and brachial BP control. These 2 effects, which appear independent of each other, may explain the specific cardio-renal protective properties of ARBs.
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PMID:Valsartan improves arterial stiffness in type 2 diabetes independently of blood pressure lowering. 1842 91

LAF237 [(S)-1-[(3-hydroxy-1-adamantyl)ammo]acetyl-2-cyanopyrrolidine] is an inhibitor of dipeptidyl peptidase IV that delays the degradation of glucagon-like peptide-1 (GLP-1). Valsartan [N-(1-oxopentyl)-N-[[2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-l-valine] is an antagonist of the angiotensin II type 1 receptor (AT1R) that reduces the incidence of type 2 diabetes mellitus. LAF237 and valsartan act on a common target through separate pathways to improve pancreatic islet cell function. We hypothesize that the combination of these two drugs acts in a synergistic or additive manner on islet function and structure. To test this hypothesis, we performed in vitro and in vivo studies. To measure the acute effect of the treatment, pancreatic islets of db/db mice were isolated and stimulated in vitro with glucose in the presence of valsartan (1 microM) and exendin-4 (100 nM), a GLP-1 receptor agonist. Combination treatment with valsartan and exendin-4 significantly enhanced glucose-stimulated insulin secretion from isolated islets. For studies of chronic effect, db/db mice received LAF237 (1 mg/kg/day) and/or valsartan (10 mg/kg/day). Islet cell reactive oxygen species (ROS), proliferation, apoptosis, fibrosis, beta-cell area, and glucose homeostasis were evaluated after 8 weeks of treatment, which showed that combination treatment resulted in a significant increase in pancreatic islet beta-cell area compared with monotherapy. This beneficial effect correlated with an increase in beta-cell proliferation and a decrease in ROS-induced islet apoptosis and fibrosis. These in vitro and in vivo data indicate that combination treatment with LAF237 and valsartan has significant beneficial additive effects on pancreatic beta-cell structure and function compared with their respective monotherapeutic effects.
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PMID:Combination of the dipeptidyl peptidase IV inhibitor LAF237 [(S)-1-[(3-hydroxy-1-adamantyl)ammo]acetyl-2-cyanopyrrolidine] with the angiotensin II type 1 receptor antagonist valsartan [N-(1-oxopentyl)-N-[[2'-(1H-tetrazol-5-yl)-[1,1'-biphenyl]-4-yl]methyl]-L-valine] enhances pancreatic islet morphology and function in a mouse model of type 2 diabetes. 1878 7

Patients with impaired glucose tolerance (IGT) have increased risk for developing type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). Lifestyle modification and medication can prevent or delay progression to diabetes (PD), but whether such interventions also reduce the risk of CVD has not been rigorously tested. The Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial is a multinational, randomized, double-blind, 2 x 2 factorial trial in subjects with IGT (on a screening oral glucose tolerance test [OGTT]) aged > or = 50 years with known CVD or aged > or = 55 years with > or = 1 CVD risk factor. Enrollment began in January 2002 and was completed January 2004, with 9,518 patients randomized to receive 1 of 4 possible treatment combinations as follows: nateglinide with valsartan, nateglinide with valsartan-placebo, nateglinide-placebo with valsartan, or nateglinide-placebo with valsartan-placebo. All subjects are participating in a clinic-based and telephone-based lifestyle intervention aimed at reducing weight and dietary fat and increasing physical activity. The 3 coprimary end points are new onset of T2DM, a "core" composite of major cardiovascular events (death, myocardial infarction, stroke, or hospitalization for heart failure), and an "extended" composite including the components of the core composite plus coronary revascularization and hospitalization for unstable angina. The study was designed to evaluate whether reducing postprandial hyperglycemia, blockade of the renin-angiotensin-aldosterone system, or both interventions reduce the risk of T2DM or cardiovascular events in patients with IGT.
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PMID:Prevention of diabetes and cardiovascular disease in patients with impaired glucose tolerance: rationale and design of the Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) Trial. 1894 90

The objective of the study was to examine the effect of a 6-month daily treatment with 160 mg valsartan, an angiotensin II receptor blocker, on the left ventricular systolic function and aortic elasticity of patients with type 2 diabetes mellitus (T2DM) and healthy subjects. This was a prospective, randomized, double-blind, placebo-controlled crossover study. Thirteen healthy control subjects and 11 patients with T2DM were enrolled in the study. Eight control subjects and 4 T2DM patients completed the study. Cardiovascular magnetic resonance was used to evaluate the effect of valsartan on the left ventricular function and aortic elasticity. At baseline, T2DM patients had increased left ventricular mass (P = .006) when compared with the healthy controls. In the T2DM patients, treatment with valsartan, in comparison with receiving placebo, resulted in a reduction of aortic radius (P = .026) and wall thickness (P = .032) of the ascending aorta. In the abdominal aorta, valsartan treatment, when compared with placebo treatment, reduced the arterial compliance (P = .014) in the T2DM patients. Valsartan treatment for 6 months decreased the diameter and wall thickness of the ascending aorta in patients with T2DM, but may decrease AC of the abdominal aorta.
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PMID:Effect of valsartan on left ventricular anatomy and systolic function and aortic elasticity. 1937 92

Valsartan is a nonpeptide angiotensin receptor antagonist that selectively blocks the binding of angiotensin II to the angiotensin II type 1 receptor. The efficacy, tolerability and safety of valsartan have been demonstrated in large-scale studies in hypertension, heart failure (HF) and post-myocardial infarction (MI). This review focuses on what was learned from the valsartan clinical research programme and other comparative trials published from 1997 to the present. Many studies have demonstrated the efficacy of valsartan in lowering blood pressure (BP) in a variety of patient populations (including elderly, women, children, obese patients, patients with diabetes mellitus, patients with chronic kidney disease [CKD], patients at high risk of cardiovascular [CV] disease, African Americans, Hispanic Americans and Asians) and in improving outcomes in CV disease and CKD. In hypertension, valsartan exhibits dose-dependent efficacy in reducing both systolic and diastolic BP over the once-daily dose range of 80-320 mg; doses as high as 640 mg/day have been studied and found to be efficacious and safe. BP control can be enhanced with a more consistent 24-hour BP-lowering profile by using single-pill, fixed-dose combination therapy with valsartan plus hydrochlorothiazide (HCTZ). The cardioprotective benefits of valsartan have been demonstrated in large-scale outcome trials and include significant reductions in CV morbidity and mortality in HF, following MI, and in patients with co-morbid hypertension and coronary artery disease and/or HF; reductions in HF hospitalizations; and reductions in the incidence of stroke. The magnitude of these effects is comparable with that demonstrated with angiotensin-converting enzyme (ACE) inhibitors; however, valsartan has a more favourable tolerability profile, with a significantly lower incidence of cough and only rare reports of angio-oedema, both class effects of ACE inhibitor use. Consistent with its angiotensin receptor-blocking effects, valsartan also reduces circulating levels of biochemical markers that are associated with angiotensin II-mediated endothelial dysfunction and CV risk (e.g. high-sensitivity C-reactive protein or oxidized low-density lipoprotein). Improvements in CKD with valsartan include statistically and clinically meaningful reductions in urinary albumin and protein excretion in patients with type 2 diabetes and in nondiabetic patients with CKD. In short-term studies, valsartan has improved or stabilized various indices of metabolic function in at-risk patients, including those with co-morbid hypertension, obesity and/or metabolic syndrome. Because of this, valsartan is being prospectively investigated for its ability to reduce the incidence of new-onset diabetes and provide cardioprotection in patients with impaired glucose tolerance. Valsartan and valsartan/HCTZ are well tolerated. In clinical trials, adverse events during valsartan treatment were similar to those occurring with placebo. The combination of valsartan/HCTZ was better tolerated than HCTZ alone. Valsartan is administered once daily for hypertension; doses are usually taken upon awakening. In patients with HF or MI, valsartan is administered twice daily.
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PMID:Valsartan: more than a decade of experience. 1991 55

Evaluating increasing circulating adiponectin levels is becoming an important strategy in the prevention of diabetes mellitus and cardiovascular events. This study was designed to investigate the effect of the angiotensin II receptor blocker valsartan on blood adiponectin levels and insulin sensitivity in patients with type 2 diabetes and mild-to-moderate hypertension. A total of 91 Korean patients were treated with 80 mg/day valsartan for 4 weeks followed by 160 mg/day for a further 8 weeks. Blood pressure, adiponectin levels and metabolic parameters were measured before and after treatment. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated as an insulin sensitivity index. Valsartan significantly decreased mean blood pressure and increased circulating adiponectin levels. There were no differences in metabolic parameters, including HOMA-IR, glycosylated haemoglobin and lipid levels before and after treatment. These results indicated that valsartan increases circulating adiponectin levels, but does not change insulin sensitivity in patients with type 2 diabetes and mild-to-moderate hypertension.
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PMID:Valsartan increases circulating adiponectin levels without changing HOMA-IR in patients with type 2 diabetes mellitus and hypertension. 2023 35

NAVIGATOR ("Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research") is a large international placebo-controlled trial that randomised 9,031 individuals at high risk because of impaired glucose tolerance and established cardiovascular disease or cardiovascular risk factors. This trial aimed at investigating whether valsartan (a selective AT1 receptor antagonist) and/or nateglinide (a short-acting insulin-secreting agent) are able to reduce the incidence of type 2 diabetes and cardiovascular events. After a median follow up of 6.5 years, neither valsartan nor nateglinide improved cardiovascular prognosis in the tested population, which already benefited from a protective pharmacotherapy at baseline and a reinforcement of lifestyle modification throughout the trial. Nateglinide did not diminish the risk of new onset diabetes. In contrast, valsartan reduced the incidence of type 2 diabetes by 14%, confirming the potential interest of the blockade of the renin-angiotensin system in this high-risk population.
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PMID:[NAVIGATOR: A trial of prevention of cardiovascular complications and type 2 diabetes with valsartan and/or nateglinide]. 2049 25


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