UMLS:C0011849 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

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

The Heart Outcomes Prevention Evaluation (HOPE) study was designed to test the hypotheses that two preventive intervention strategies, namely angiotensin-converting enzyme (ACE) inhibition or vitamin E, would improve morbidity and mortality in patients at high risk of cardiovascular events compared with placebo. This review addresses the ACE inhibitor (ACE-I) (ramipril) arm of the study, both on the trial population as a whole, and on the large diabetic subgroup. Patients were included in the study who were considered to be at high risk of future fatal or non-fatal cardiovascular events, by virtue of their age (>55 years), existing or previous cardiovascular disease, or diabetes. Diabetics had at least one other risk factor, either known vascular disease or other factors such as cigarette smoking, high cholesterol or hypertension. Ramipril or placebo was added to concomitant medication, which included, in a substantial proportion of patients, antihypertensive drugs (excluding ACE-I), lipid-lowering agents or aspirin. As a result, despite a history of hypertension in nearly 50% of patients, blood pressure (BP) at baseline was normal and the reduction in BP attributable to ramipril modest (a fall of 3-4 mmHg systolic BP and 1-2 mmHg diastolic). The trial was stopped early on the advice of the Data Monitoring Committee because of convincing evidence of the benefit of ramipril treatment on the combined primary endpoint of cardiovascular death, non-fatal myocardial infarct (MI) and non-fatal stroke (14% vs. 17.8% on ramipril and placebo, respectively; relative risk reduction 22%, p<0.001). This comprised a risk reduction of 32% for stroke, 20% for MI, 26% for cardiovascular death and 16% for all-cause mortality, as well as a reduction in the risk of several other endpoints including heart failure and revascularisation procedures. The results among the 3577 diabetic subjects were even more striking, with a reduction of 25% in the combined primary endpoint. This reduction in the combined endpoint and in particular the reduction in MI far exceeded that which would be expected from the modest fall in BP. Furthermore, a multiple regression analysis of the diabetic subgroup showed similar relative risk reductions even after allowing for the effects of the fall in BP. Possible explanations for the non BP-mediated benefits of ramipril include reduction of angiotensin II-induced intimal and vascular smooth muscle proliferation and possible plaque stabilisation. The HOPE study results show that it is both safe and beneficial to lower BP that is already within the 'normal' range, particularly in patients with known vascular risk factors. This should greatly extend the use of ACE-I to a wider group of patients - not only those with left ventricular dysfunction, hypertension or diabetic microalbuminuria, but to the sort of high-risk patients who are currently given prophylactic treatment with aspirin.
...
PMID:The HOPE Study (Heart Outcomes Prevention Evaluation). 1196 89

In people with diabetes, renal disease tends to progress from microalbuminuria to clinical proteinuria to renal insufficiency. Little evidence has been published for the nondiabetic population. This study retrospectively analyzed changes of proteinuria over 4.5 yr in the HOPE (Heart Outcomes and Prevention Evaluation) study, which compared ramipril's effects to placebo in 9297 participants, including 3577 with diabetes and 1956 with microalbuminuria. This report is restricted to 7674 participants with albuminuria data at baseline and at follow-up. Inclusion criteria were known vascular disease or diabetes plus one other cardiovascular risk factor, exclusion criteria included heart failure or known impaired left ventricular function, dipstick-positive proteinuria (>1+), and serum creatinine >2.3 mg/dl (200 microM). Baseline microalbuminuria predicted subsequent clinical proteinuria for the study participants overall (adjusted odds ratio [OR], 17.5; 95% confidence interval [CI], 12.6 to 24.4), in participants without diabetes (OR, 16.7; 95% CI, 8.6 to 32.4), and in participants with diabetes (OR, 18.2; 95% CI, 12.4 to 26.7). Any progression of albuminuria (defined as new microalbuminuria or new clinical proteinuria) occurred in 1859 participants; 1542 developed new microalbuminuria, and 317 participants developed clinical proteinuria. Ramipril reduced the risk for any progression (OR, 0.87; 95% CI, 0.78 to 0.97; P = 0.0146). People without and with diabetes who are at high risk for cardiovascular disease are also at risk for a progressive rise in albuminuria. Microalbuminuria itself predicts clinical proteinuria in nondiabetic and in diabetic people. Ramipril prevents or delays the progression of albuminuria.
...
PMID:Development of renal disease in people at high cardiovascular risk: results of the HOPE randomized study. 1259 99

Ramipril is safe and effective in the treatment of hypertension and heart failure, but this is not reviewed here. Ramipril is a lipophilic angiotensin-converting enzyme inhibitor suitable for once-daily administration. In addition to decreasing angiotensin II and increasing bradykinin levels, ramipril increases the levels of vasodilatory renal medullary neutral lipids and inhibits platelet-derived growth factor-induced proliferation of glomerulus cells. Ramipril also decreases transforming growth factor-beta in the kidney. Changes in kidney structure and proteinuria are characteristics of the streptozotocin (STZ) rat model of diabetes, and these are prevented by ramipril. In STZ diabetes, doses of ramipril that have no effect on blood pressure reverse vascular hypertrophy. In animal models of kidney failure (subtotal nephrectomy, stroke-prone spontaneously hypertensive rats), ramipril is renoprotective and some of this renoprotective effect is independent of blood pressure lowering. In humans, clinical doses of ramipril probably do not modify glucose metabolism but do reduce the levels of LDL- and HDL-cholesterol. In clinical trials of renal effects, ramipril has been shown to increase cortical nephron flow in hypertension and to reduce proteinuria in patients with and without diabetes and/or hypertension. Some of the smaller clinical trials showed beneficial effects on kidney function with low doses of ramipril that do not lower blood pressure. A large clinical trial in nondiabetic proteinuria, the Ramipril Efficacy in Nephropathy (REIN) trial, has shown that ramipril 1.25 mg/day, which does not lower blood pressure, arrested the decline in glomerular filtration rate and prolonged the time to end-stage renal failure. In diabetic patients who have had a previous cardiovascular event or having one other cardiovascular risk factor, the MICRO-HOPE clinical trial showed that ramipril lowers the combined risk of myocardial infarction, stroke and cardiovascular death by 25%. In conclusion, ramipril has proven beneficial effects in kidney disease alone or in association with diabetes and in diabetes without kidney disease, and is the pril for diabetes and kidney disease. (c) 2001 Prous Science. All rights reserved.
...
PMID:Is Ramipril the pril for diabetes and kidney disease? 1276 20

Hypertension in combination with clinically overt diabetes mellitus is recognized as a particularly powerful combination of risk factors that greatly increases cardiovascular vulnerability. There is also evidence that presumed pre-diabetic conditions such as insulin resistance, hyperinsulinaemia and compensatory hyperglycaemia may amplify overall cardiovascular risk in patients with hypertension, especially when encountered as part of the condition known as metabolic syndrome X (Reaven's syndrome). The long-term benefits of antihypertensive therapy may be compromised if these drugs exert adverse effects on metabolic parameters such as insulin sensitivity, or if they promote a transition from pre-diabetes to overt diabetes. Class differences in the effects of antihypertensives on metabolic indices may therefore be an important consideration when choosing treatment for patients who exhibit these characteristics. Experience from clinical trials suggests that drugs that target the renin-angiotensin system may have metabolic advantages over drugs such as beta-blockers and diuretics, but this conclusion has not been proved definitively. Moxonidine, which selectively targets imidazoline type-1 receptors in the sympathetic vasomotor centres of the rostral-ventrolateral medulla, is an effective antihypertensive and has been reported to exert favourable metabolic effects in preclinical and clinical studies. The MARRIAGE study (Moxonidine And Ramipril Regarding Insulin And Glucose Evaluation) will extend these preliminary observations by comparing the effects of moxonidine and the ACE inhibitor ramipril--and the combination of both drugs--on metabolic and haemodynamic parameters in patients with hypertension and impaired fasting glycaemia. A description is provided of the design and conduct of MARRIAGE.
...
PMID:Selective imidazoline agonist moxonidine plus the ACE inhibitor ramipril in hypertensive patients with impaired insulin sensitivity: partners in a successful MARRIAGE? 1502 45

Burgeoning obesity is increasing the prevalence of type II diabetes mellitus. As a consequence, there will be an even greater burden of cardiovascular disease, end-stage renal disease, blindness, and lower extremity amputations. If diagnosed, impaired glucose tolerance presents an opportunity for intervention that potentially could delay or prevent the development of diabetes. Recent prospective studies document the effectiveness of exercise and weight reduction in preventing diabetes. Metformin is less effective than intense lifestyle interventions. Acarbose, losartan, orlistat, pravastatin, ramipril, and hormone replacement therapy are associated with lower rates of the development of diabetes. The Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication (DREAM) trial and the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial were designed to assess not only the prevention of diabetes but also the impact on cardiovascular morbidity and mortality.
...
PMID:Preventing type II diabetes mellitus. 1505 49

Hypertension and diabetes mellitus are closely interrelated and coexist in as many as two-thirds of patients with type 2 diabetes. The consequent risk of such an association is an accelerated development of atherosclerotic cardiovascular disease and nephropathy complications.In choosing an antihypertensive agent, effectiveness needs to be accompanied by favourable metabolic, cardioprotective, and nephroprotective properties. Given the multifactorial nature of hypertension, the approach that has gained widespread agreement is treatment with more than one agent. Agents with different mechanisms of action increase antihypertensive efficacy because of synergistic impacts on the cardiovascular system. Combination therapy allows the use of lower doses of each antihypertensive agent which accounts for the excellent tolerability of combination products.The aim of the present study is to quantify the efficacy of combination therapy of Eprosartan 600 mg respectively Ramipril 5 mg with low-dose Hydrochlorothiazide and Moxonidine on blood pressure levels in patients with essential hypertension and associated diabetes mellitus type 2.The use of monotherapy (Eprosartan or Ramipril) followed by addition of low-dose Hydrochlorothiazide as second agent and of Moxonidine as a third agent will be individualized to the severity of hypertension in the particular patient and to his/her degree of response to current treatment.
...
PMID:A novel approach to treatment of hypertension in diabetic patients - a multicenter, double-blind, randomized study comparing the efficacy of combination therapy of Eprosartan versus Ramipril with low-dose Hydrochlorothiazide and Moxonidine on blood pressure levels in patients with hypertension and associated diabetes mellitus type 2 - rationale and design [ISRCTN55725285]. 1546 84

Type 2 diabetes mellitus is becoming a major health problem associated with excess morbidity and mortality. As the prevalence of type 2 diabetes is rapidly increasing, prevention of the disease should be considered as a key objective in the near future. Besides lifestyle changes, various pharmacological treatments have proven their efficacy in placebo-controlled clinical trials, including antidiabetic drugs such as metformin, acarbose and troglitazone, or antiobesity agents such as orlistat. Arterial hypertension, a clinical entity in which insulin resistance is common, is strongly associated with type 2 diabetes and may precede the disease by several years. While antihypertensive agents such as diuretics or beta-adrenoceptor antagonists may worsen insulin resistance and impair glucose tolerance, newer antihypertensive agents exert neutral or even slightly positive metabolic effects. Numerous clinical trials have investigated the effects of ACE inhibitors or angiotensin II receptor antagonists (ARAs) on insulin sensitivity in hypertensive patients, with or without diabetes, with no consistent results. Almost half of the studies with ACE inhibitors in hypertensive nondiabetic individuals demonstrated a slight but significant increase in insulin sensitivity as assessed by insulin-stimulated glucose disposal during a euglycaemic hyperinsulinaemic clamp, while the other half failed to reveal any significant change. The effects of ARAs on insulin sensitivity are neutral in most studies. Mechanisms of improvement of glucose tolerance and insulin sensitivity through the inhibition of the renin-angiotensin system (RAS) are complex. They may include improvement of blood flow and microcirculation in skeletal muscles and, thereby, enhancement of insulin and glucose delivery to the insulin-sensitive tissues, facilitating insulin signalling at the cellular level and improvement of insulin secretion by the beta cells. Six recent large-scale clinical studies reported a remarkably consistent reduction in the incidence of type 2 diabetes in hypertensive patients treated with either ACE inhibitors or ARAs for 3-6 years, compared with a thiazide diuretic, beta-adrenoceptor antagonist, the calcium channel antagonist amlodipine or even placebo. The relative risk reduction averaged 14% (p = 0.034) in the CAPPP (Captopril Prevention Project) with captopril compared with a thiazide or beta1-adrenoceptor antagonist, 34% (p < 0.001) in the HOPE (Heart Outcomes Prevention Evaluation) study with ramipril compared with placebo, 30% (p < 0.001) in the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) with lisinopril compared with chlortalidone, 25% (p < 0.001) in the LIFE (Losartan Intervention For Endpoint reduction in hypertension study) with losartan compared with atenolol, and 25% (p = 0.09) in the SCOPE (Study on Cognition and Prognosis in the Elderly) with candesartan cilexetil compared with placebo, and 23% (p < 0.0001) in the VALUE (Valsartan Antihypertensive Long-term Use Evaluation) trial with valsartan compared with amlodipine. All these studies considered the development of diabetes as a secondary endpoint, except the HOPE trial where it was a post hoc analysis. These encouraging observations led to the initiation of two large, prospective, placebo-controlled randomised clinical trials whose primary outcome is the prevention of type 2 diabetes: the DREAM (Diabetes REduction Approaches with ramipril and rosiglitazone Medications) trial with the ACE inhibitor ramipril and the NAVIGATOR (Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research) trial with the ARA valsartan. Finally, ONTARGET (ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial) will also investigate as a secondary endpoint whether it is possible to prevent the development of type 2 diabetes by blocking the RAS with either an ACE inhibitor or an ARA or a combination of both. Thus, the recent consistent observations of a 14-34% reduction of the development of diabetes in hypertensive patients receiving ACE inhibitors or ARAs are exciting. From a theoretical point of view, they emphasise that there are many aspects of the pathogenesis, prevention and treatment of type 2 diabetes that still need to be uncovered. From a practical point of view, they may offer a new strategy to reduce the ongoing epidemic and burden of type 2 diabetes.
...
PMID:Prevention of type 2 diabetes mellitus through inhibition of the Renin-Angiotensin system. 1551 53

Rates of type 2 diabetes mellitus are increasing worldwide at an explosive rate. This "epidemic" is largely driven by a concomitant obesity epidemic, which is seen not only in affluent countries, but in industrializing countries as well, concomitant with the rapid change toward Western life-style patterns worldwide. Recent clinical trials such as Heart Outcomes Prevention Evaluation (HOPE), Losartan Intervention for Endpoint reduction (LIFE), and Study of Cognition and Prognosis in the Elderly (SCOPE) have indicated that blocking the renin-angiotensin system (RAS) may reduce the risk of developing type 2 diabetes mellitus. This effect may be explained by a variety of diabetogenic factors, which seem to be moderated by angiotensin II, such as free fatty acids (FFA) and the phenomena of adipocyte differentiation, as well as inflammation and oxidative damage. Insulin resistance, usually present in cases of impaired glucose tolerance, is the major identifiable defect in subjects at risk for type 2 diabetes. Elevated FFA levels result in reduced activation of phosphoinositol-3 kinase, an enzyme that is essential for normal insulin-stimulated glucose uptake. This reduction is potentiated by angiotensin II and consequently insulin-stimulated glucose uptake is improved by RAS inhibition. Furthermore, blockade of the angiotensin II AT(1)-receptor has been shown to stimulate the differentiation of adipocytes that store FFAs, which leads to reduced plasma FFA levels and decreased insulin resistance. There are also data suggesting that AT(1)-receptor blockade reduces inflammatory activation and the production of reactive oxygen species (ROS), a major factor in the pathophysiology of diabetes and a major cardiovascular risk factor. Both proinflammatory molecules and ROS increase the risk of insulin resistance and atherogenesis. It is thought that FFAs and hyperglycemia increase ROS production and oxidative stress, leading to the activation of signaling molecules such as nuclear factor kappa-B and other mediators of stress-sensitive pathways, which increases insulin resistance and will lead to beta-cell dysfunction and diabetic complications during the longer term. Inhibiting the RAS seems to have an effect on several steps in this cascade. There is an obvious need for large-scale clinical trials specifically designed to assess the protective benefits of blocking the RAS in individuals at risk of developing type 2 diabetes. Two such trials on the prevention of type 2 diabetes are ongoing, the Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medications (DREAM) study and the more ambitious Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial, which is also assessing prevention of cardiovascular events.
...
PMID:Of the renin-angiotensin system and reactive oxygen species Type 2 diabetes and angiotensin II inhibition. 1569 26

The role of the RAAS in development and maintenance of blood pressure is well established. In addition, the deleterious effects of angiotensin II on the heart, vasculature, and kidneys have been clearly defined. There seems to be a close relationship between endothelial dysfunction, insulin resistance (a precursor to diabetes and coronary artery disease) and angiotensin II. The signaling pathways for insulin in the vascular wall interacts with the angiotensin signaling, giving rise to potential mechanisms for development of diabetes and resulting harmful effects. A large number of clinical trials using ACE inhibitors or ARBs have shown significant reduction in secondary endpoints in the development of new onset of diabetes. Ongoing prospective studies involving ARBs (eg, the Nateglinide and Valsartan Impaired Glucose Tolerance Outcomes Research trial) and ACE inhibitors (eg, the Diabetes Re-duction Assessment with Ramipril and Rosiglita-zone Medication trial) are testing the ability of certain agents to prevent type 2 diabetes. In the meantime, it is important to recognize insulin resistance and metabolic syndrome as entities that increase the risk for cardiovascular disease. In addition to lifestyle modifications, managing endothelial dysfunction and protecting the vasculature will help prevent diabetes and cardiovascular disease.
...
PMID:The renin angiotensin system as a therapeutic target to prevent diabetes and its complications. 1569 45

Type 2 diabetes is a serious, costly, and increasingly common disease. Several conditions commonly seen in family medicine settings confer increased risk of developing diabetes. Among these conditions are impaired glucose tolerance, impaired fasting glucose, obesity, gestational diabetes, hypertension, hyperlipidemia, and menopause. We here present the results of a systematic review of the literature examining the evidence for different strategies aimed at preventing type 2 diabetes in patients with these conditions. The strongest evidence supports an intensive lifestyle intervention designed to induce modest weight loss. The greatest degree of prevention, based on lesser quality evidence, may be imparted by bariatric surgery. Metformin and troglitazone have appreciable evidence in specific populations, and orlistat and acarbose have slightly less evidence among obese patients, for preventing diabetes. Ramipril, captopril, losartan, pravastatin, and estrogens show some very preliminary promise for preventing diabetes in patients treated for hypertension, hyperlipidemia, and menopause, but each needs a more rigorous evaluation. Although more questions remain to be answered, family physicians now have tools available to help our patients lead lives free of diabetes.
...
PMID:Preventing type 2 diabetes mellitus. 1570 62

<< Previous 1 2 3 4 5 6 7 8 Next >>