UMLS:C0011849 - FACTA Search

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Query: UMLS:C0011849 (diabetes)
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The Captopril Prevention Project (CAPPP) was a prospective, randomized, open trial which aimed at comparing the prevention by captopril (n = 5492) or by a conventional treatment (n = 5493; diuretics or beta-blockers) of cardiovascular morbidity and mortality in patients with hypertension (diastolic blood pressure > 100 mmHg). After a mean follow-up of 6.1 years, the results regarding the primary endpoint and most secondary endpoints were not significantly different between the two therapeutic modalities. The only differences (perhaps due to a randomisation bias) were a slightly higher incidence of stroke, but a lower risk of diabetes mellitus, in the captopril group than in the group receiving conventional treatment. In conclusion, the CAPPP study demonstrates, for the first time, that captopril, an angiotensin-converting-enzyme inhibitor, is as effective as conventional treatment with diuretics or beta-blockers, two drugs whose efficacy has already been demonstrated when compared to placebo, in the prevention of cardiovascular morbidity and mortality in hypertensive patients.
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PMID:[Clinical study of the month. The CAPPP study: "The Captopril Prevention Project"]. 1032 Nov 12

Diabetes is emerging as a new epidemic world-wide because of the ageing of the population but changes in lifestyle are also contributing. All means to prevent this development should be undertaken. In this context, treatment of hypertension is of importance due to the large number of people treated with antihypertensive drugs, many of which interfere with glucose metabolism. In three prospective cohort studies, treatment with beta-blockers and diuretics has been associated with an increased risk of development of diabetes. Prospective, randomized studies with antihypertensive drugs have demonstrated differences between different classes of drugs regarding effects on insulin sensitivity. Thus, treatment with beta-blockers or high-dose diuretics is associated with impairment in insulin sensitivity, whereas most modern calcium-channel blockers and angiotensin converting enzyme (ACE) inhibitors are neutral. However, there are exceptions within the different classes. Captopril differs from the other ACE inhibitors and results in improvement of insulin sensitivity. The most pronounced improvements have been obtained with alpha1-blockers. In a recent study, the data indicate that also moxonidine, an imidazoline1 receptor agonist, is effective in lowering blood pressure and improving insulin sensitivity in insulin-resistant patients. In populations at high risk for diabetes, it may be justified to select drugs that improve insulin sensitivity when treating hypertension in insulin-resistant individuals.
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PMID:Insulin resistance and diabetes in the context of treatment of hypertension. 1032 52

Early signs of renal dysfunction in glycogen storage disease type Ia (GSD Ia) are glomerular hyperfiltration and proteinuria. In a non-randomized study, the effect of captopril on the improvement of proteinuria in GSD Ia patients with microalbuminuria was investigated. A positive effect has been shown for the insulin-dependent diabetes mellitus patients. Microalbuminuria was defined as albumin/creatinine ratio (mg/mmol) more than 2.5 in spot urine. Nineteen (52.7%) out of 36 patients had microalbuminuria, and 8 patients received captopril at a dose of 1 mg/kg per day. Microalbuminuria was evaluated periodically during the follow-up period. Of the captopril-treated patients, one was lost to follow-up. In the remaining 7 patients, urinary albumin excretion normalized in 3 patients (42.9%) and decreased at least by 50% in another 3 patients (42.8%) after 6 months of treatment. One patient, who was the oldest, did not have any benefit. In untreated patients, only two patients had a decrease in microalbuminuria of more than 50%. Patients with microalbuminuria had significantly higher blood lactate (p < 0.05) and plasma triglyceride (p < 0.01) concentrations and significantly lower blood bicarbonate concentration (p < 0.05) than those patients without it. Additionally, the patients with microalbuminuria had been diagnosed earlier than those without microalbuminuria (p < 0.05). Patients with microalbuminuria have more severe clinical and laboratory findings than those without microalbuminuria. Captopril at a dose of 1 mg/kg per day seems to be effective in at least 50% of GSD Ia patients with microalbuminuria.
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PMID:Short-term effect of captopril on microalbuminuria in children with glycogen storage disease type Ia. 1094

Diabetes mellitus without previous myocardial infarction carries the same risk of a future myocardial infarction as someone who has had one. Intense glucose, lipid, and blood pressure control in diabetic patients is advocated to reduce cardiovascular events and decrease the incidence of end-stage renal disease, retinal damage, and peripheral vascular disease. Recent studies, including the Systolic Hypertension in the Elderly Program, indicate that low-dose diuretics, compared with placebo, reduce fatal and nonfatal myocardial infarctions but not fatal and nonfatal strokes in diabetic patients. Similarly, captopril (and diuretics) compared with diuretics and beta-blockers decreased fatal and nonfatal myocardial infarctions but not fatal and nonfatal strokes in the Captopril Prevention Project. Intense blood pressure therapy with captopril and intense blood pressure therapy with atenolol equally lowered macrovascular and microvascular events compared with less intense blood pressure treatment in the United Kingdom Prospective Diabetes Study. Fewer myocardial infarctions were seen with enalapril than with nisoldipine in the Appropriate Blood Pressure Control in Diabetes trial. Intense blood pressure control with felodipine, enalapril, and hydrochlorothiazide reduced overall cardiovascular events and mortality but not myocardial infarction and strokes in the Hypertension Optimal Treatment trial. Nitrendipine alone or together with enalapril and hydrochlorothiazide decreased fatal and nonfatal strokes and cardiovascular mortality but not myocardial infarctions in the Systolic Hypertension in Europe trial. These trials, in aggregate, reinforce the importance of intense blood pressure control, which can be achieved only with combination drug therapy rather than a specific monotherapy drug class recommendation.
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PMID:Controversies surrounding the treatment of the hypertensive patient with diabetes. 1098 Nov 15

We measured the activities of total Na+, K+-ATPase (Na, K-ATPase), its alpha1 and alpha2/alpha3 isoforms and the angiotensin-converting enzyme (ACE) in the microvascular and neural compartments of the retina, and/or retinal pigment epithelium (RPE) of streptozotocin (STZ)-diabetic rats. The effect of captopril, an ACE inhibitor on Na, K-ATPase activities was also determined and correlated to morphological changes. Insulin-dependent diabetes mellitus was induced by a single intraperitoneal injection of STZ (60 mg/kg) in male Long-Evans rats. ACE activity was inhibited by captopril (10 mg/kg given in the drinking water) for 1 month. Na, K-ATPase activity was measured spectrophotometrically or by a radioassay (32P-labeled ATP). The activity of ACE was determined by a radioassay using tritiated benzoyl-gly-gly-gly as substrate. Both the alpha1 and alpha2/alpha3 isoforms of Na, K-ATPase were present in the microvascular and neural compartments of retinas, whereas only one isoform, the alpha2/alpha3, was found in the RPE. In 2-month diabetic rats, the activity of the alpha2/alpha3 isoform was reduced in both the microvascular and neural compartments of retinas, while the activity of the alpha1 isoform was reduced only in the neural isolates. ACE activity was significantly decreased in the retinal neural compartment and unaltered in the microvascular compartment from 2-month diabetic rats. In 5-month diabetic rats, Na, K-ATPase activity was moderately but not significantly reduced in RPE preparations. Ultrastructural studies revealed a significant deepening of basal infoldings in the RPE and a noticeable increase in the size of the extracellular space between the basal infoldings of 5-month diabetic animals. Captopril stimulated Na, K-ATPase activity in the neural retina, but not in the RPE. Diabetes-induced morphological changes in the RPE were not improved by captopril. An enlargement of intercellular space between the RPE cells was a frequent finding in the treated group. In conclusion, captopril stimulated Na, K-ATPase activity in the neural retina of diabetic rats. This stimulation seems to be beneficial to the neural retina. ACE inhibition, however, did not improve RPE morphological changes. Although the clinical significance of increased intercellular spacing between RPE cells in treated animals is not clearly established, we speculate that it might contribute to an increased alteration of their barrier function. Additional studies are necessary to assess both the desirable and adverse effects of captopril and other ACE inhibitors in the retinas of diabetic patients.
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PMID:Biochemical and ultrastructural studies in the neural retina and retinal pigment epithelium of STZ-diabetic rats: effect of captopril. 1177 81

A non-invasive cine magnetic resonance imaging (MRI) technique was developed to allow, for the first time, detection and characterization of chronic changes in myocardial tissue volume and the effects upon these of treatment by the angiotensin-converting enzyme (ACE) inhibitor captopril in streptozotocin (STZ)-diabetic male Wistar rats. Animals that had been made diabetic at the ages of 7, 10 and 13 weeks and a captopril-treated group of animals made diabetic at the age of 7 weeks were scanned. The findings were compared with the results from age-matched controls. All animal groups (n = 4 animals in each) were consistently scanned at 16 weeks. Left and right ventricular myocardial volumes were reconstructed from complete data sets of left and right ventricular transverse sections which covered systole and most of diastole using twelve equally incremented time points through the cardiac cycle. The calculated volumes remained consistent through all twelve time points of the cardiac cycle in all five experimental groups and agreed with the corresponding post-mortem determinations. These gave consistent myocardial densities whose values could additionally be corroborated by previous reports, confirming the validity of the quantitative MRI results and analysis. The myocardial volumes were conserved in animals whose diabetes was induced at 13 weeks but were significantly increased relative to body weight in animals made diabetic at 7 and 10 weeks. Captopril treatment, which was started immediately after induction of diabetes, prevented the development of this relative hypertrophy in both the left and right ventricles. We have thus introduced and validated quantitative MRI methods in a demonstration, for the first time, of chronic myocardial changes in both the right and left ventricles of STZ-diabetic rats and their prevention by the ACE inhibitor captopril.
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PMID:Non-invasive magnetic resonance imaging assessment of myocardial changes and the effects of angiotensin-converting enzyme inhibition in diabetic rats. 1179 Aug 18

Captopril, the classic inhibitor of the angiotensin converting enzyme, was employed in several large clinical studies in recent years. The effect of captopril was compared either with placebo, or captopril was selected as the reference ACE inhibitor for comparison with another therapy. In the classic study SAVE, captopril administered to patients after myocardial infarction with a dysfunction of the left chamber reduced mortality by 19%. Though in the study ELITE the AT1 blocker losartan was more effective to reduce mortality in patients with chronic heart failure than captopril, the larger and mortality-oriented study ELITE II did not demonstrate a difference in mortality reduction between captopril and losartan. ACE inhibitors thus remain drugs of choice in chronic heart failure. AT1 blockers are to be used in the cases when ACE inhibitors are not tolerated. The study CAPPP has demonstrated that captopril in hypertonic patients not only effectively decreases blood pressure but exerts a similar effect on mortality reduction as the classic treatment with a diuretic and a betablocker, the most effective being captopril in diabetic patients. Administration of captopril in hypertonic patients with diabetes mellitus in the study UKPDS had an effect on mortality reduction as well as micro- and macrovascular complications of diabetes similar to that of atenolol. The ongoing study VALIANT compares the AT1 blocker valsartan or a combination of valsartan and captopril with captopril alone on patients at risk after myocardial infarction. Also at the beginning of the 21st century captopril maintains a stable position in the treatment of the cardiovascular system.
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PMID:[The ACE inhibitor, captopril, in the light of new clinical studies]. 1192 78

The angiotensin converting enzyme (ACE) inhibitors are widely used in the management of essential hypertension, stable chronic heart failure, myocardial infarction (MI) and diabetic nephropathy. There is an increasing number of new agents to add to the nine ACE inhibitors (benazepril, cilazapril, delapril, fosinopril, lisinopril, pentopril, perindopril, quinapril and ramipril) reviewed in this journal in 1990. The pharmacokinetic properties of five newer ACE inhibitors (trandolapril, moexipril, spirapril, temocapril and imidapril) are reviewed in this update. All of these new agents are characterised by having a carboxyl functional groups and requiring hepatic activation to form pharmacologically active metabolites. They achieve peak plasma concentrations at similar times (t(max)) to those of established agents. Three of these agents (trandolapril, moexipril and imidapril) require dosage reductions in patients with renal impairment. Dosage reductions of moexipril and temocapril are recommended for elderly patients, and dosages of moexipril should be lower in patients who are hepatically impaired. Moexipril should be taken 1 hour before meals, whereas other ACE inhibitors can be taken without regard to meals. The pharmacokinetics of warfarin are not altered by concomitant administration with trandolapril or moexipril. Although imidapril and spirapril have no effect on digoxin pharmacokinetics, the area under the concentration-time curve of imidapril and the peak plasma concentration of the active metabolite imidaprilat are decreased when imidapril is given together with digoxin. Although six ACE inhibitors (captopril, enalapril, fosinopril, lisinopril, quinapril and ramipril) have been approved for use in heart failure by the US Food and Drug Administration, an overview of 32 clinical trials of ACE inhibitors in heart failure showed that no significant heterogeneity in mortality was found among enalapril, ramipril, quinapril, captopril, lisinopril, benazepril, perindopril and cilazapril. Initiation of therapy with captopril, ramipril, and trandolapril at least 3 days after an acute MI resulted in all-cause mortality risk reductions of 18 to 27%. Captopril has been shown to have similar morbidity and mortality benefits to those of diuretics and beta-blockers in hypertensive patients. Captopril has been shown to delay the progression of diabetic nephropathy, and enalapril and lisinopril prevent the development of nephropathy in normoalbuminuric patients with diabetes. ACE inhibitors are generally characterised by flat dose-response curves. Lisinopril is the only ACE inhibitor that exhibits a linear dose-response curve. Despite the fact that most ACE inhibitors are recommended for once-daily administration, only fosinopril, ramipril, and trandolapril have trough-to-peak effect ratios in excess of 50%.
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PMID:Clinical pharmacokinetics and selective pharmacodynamics of new angiotensin converting enzyme inhibitors: an update. 1192 21

Recent trials have helped to clarify indications for the initial pharmacological therapy of hypertension. Both the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) and World Health Organization-international Society of Hypertension (WHO-ISH) recommendations should be revised. The more recent trials indicate that: (1) diuretics and beta-blockers appear to be as effective in reducing overall morbidity/ mortality as other agents (Swedish Trial in Old Patients with Hypertension [STOP-2], United Kingdom Prospective Diabetes Study [UKPDS], Intervention as a Goal in Hypertension Treatment [INSIGHT], Nordic diltiazem [NORDIL]); (2) the use of an a-blocker results in more cardiovascular events, especially congestive heart failure, when compared with a diuretic (Antihypertensive Therapy and Lipid Lowering Heart Attack Trial [ALLHAT]); (3)the use of an angiotensin-converting enzyme (ACE) inhibitor results in fewer myocardial infarctions and episodes of heart failure than calcium channel blockers in the elderly and in diabetic patients (Fosinopril vs. Amlodipine Cardiovascular Events Randomized Trial [FACET], Appropriate Blood Pressure Control in Diabetes [ABCD], STOP-2) - other data (Captopril Prevention Project [CAPPP]) suggest that the use of an ACE inhibitor is preferred in diabetic patients; (4) overall cardiovascular events are similar with calcium channel blockers compared with a diuretic - however, there are fewer strokes with non-dihydropyridine calcium channel blockers (NORDIL) and a trend towards an increase in heart failure and myocardial infarctions with either a dihydropyridine or non-dihydropyridine calcium channel blockers compared with a diuretic (INSIGHT, NORDIL); (5) angiotensin receptor blockers (ARBs) will decrease proteinuria and slow progression of renal disease in type 2 diabetic patients when compared with regimens that do not include an ARB or an ACE inhibitor (Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan [RENAAL], Irbesartan Type II Diabetic Nephropathy Trial [IDNT], Irbesartan Type II Diabetes with Microalbuminuria [IRMA Il]). The debate over initial therapy may be moot. High-risk hypertensive patients should probably be treated initially with combination therapy, one of which should be a diuretic. The use of diuretics and beta-blockers as well as ACE-inhibitors alone or with a diuretic should be considered as initial therapy (a change from JNCVI). Alpha-blockers should be reserved for special situations, i.e. prostatic hypertrophy (in contrast to WHO-ISH recommendations). An ACE-inhibitor or ARB, usually along with a diuretic, can be considered as preferred therapy in hypertensive diabetic patients. Some data suggest equal or greater reduction in strokes with a calcium channel blocker than other medications.
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PMID:Current recommendations for the treatment of hypertension: are they still valid? 1199 97

Glomerular mesangial cells play a major role in glomerular hemodynamics, considered also as antigen-presenting cells participating in immune response. Mesangial dysfunction and proliferation are typical lesions of diabetic glomerulopathy. Adenosine, a local hormone, produced by mesangial cells is a metabolic regulator of renal blood flow, capable of decreasing glomerular filtration rate (GFR), exerting immunosuppressive, antiproliferative and anti-inflammatory properties. Since it was well established that antioxidants confer protection against increased oxidative stress that occurs in diabetes, the effect of captopril, reduced glutathione and melatonin on adenosine metabolism was investigated. Glomerular mesangial cells obtained from collagenase treated glomeruli, isolated from renal cortex of Sprague-Dowley rats, were grown under high glucose conditions (30 mmol/L) as a model of diabetic microenvironment. The activity of adenosine metabolizing enzymes: 5'-nucleotidease (5'-NU) responsible for its production and adenosine deaminase (ADA) responsible for its degradation were investigated. Hyperglycemic conditions led to decreased adenosine production via 5'-NU and decreased removal via ADA. Captopril, given in therapeutic concentration induced enzyme activities in normoglycemic conditions and restored hyperglycemia-induced decrease. In order to investigate if the presence of SH groups may be responsible for this improvement, the cells were exposed to reduced glutathione, and it exerted almost equal effect, given in physiological and higher concentrations. Melatonin increased 5'-NU activity only in physiological glucose conditions. Presented results confirm potential renoprotective effect of SH-group containing antioxidant supplementation during diabetes in restoring adenosine metabolism.
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PMID:Antioxidants modulate adenosine metabolism in rat mesangial cells cultured under high glucose conditions. 1247 93

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