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

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Query: EC:3.4.15.1 (ACE)
18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During long-term treatment of arterial hypertension with calcium antagonists of the dihydropyridine type activation of the sympathetic nervous system and subsequently also of the renin-angiotensin-aldosterone system persists, while the haemodynamic reaction to vasodilatation, manifested by an elevated pulse rate and minute volume from the initial stage of therapy, recedes. In type II diabetics the basal and stimulated response of the renin-angiotensin-aldosterone system is reduced. The administration of calcium antagonists of the dihydropyridine type does not stimulate significantly the renin-angiotensin-aldosterone system as the starting function of the sympathetic nervous system is impaired within the framework of vegetative neuropathy. In almost 20% NIDDM plasma renin activity and aldosterone do not respond to furosemide administration and the vertical posture. In others the response is found but takes place at reduced levels. Hyporeninaemic hypoaldosteronism is thus manifested not so much by a drop of plasma renin and aldosterone beneath the lower range of reference values as by a reduced response to stimulation. Functional hyporeninaemic hypoaldosteronism is another, frequent late complication of diabetes. In advanced forms a further block of the renin-angiotensin-aldosterone system by ACE inhibitors can then produce, even in the absence of diabetic nephropathy, in the stage of chronic renal failure dangerous hyperkaliaemia which may threaten the patient. Dynamic examination of the sympathetic nerve and the renin-angiotensin-aldosterone system makes it possible to predict this condition. In practice it is necessary in diabetics with arterial hypertension after starting with ACE inhibitors during the first days to monitor repeatedly plasma potassium and creatinine. ACE inhibitors and calcium antagonists are otherwise for diabetics drugs of first choice which can arrest the progression of nephropathy, effectively reduced the blood pressure without causing deterioration of insulin resistance and hyperlipoproteinaemia and lead even to regression of hypertrophy of the vascular wall and left ventricle.
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PMID:[The effect of long-term treatment of arterial hypertension with Ca antagonists on the renin-angiotensin-aldosterone system in diabetics. Hyporeninemic hypoaldosteronism]. 857 95

Angiotensin 1 converting enzyme (ACE) catalyses the step which generates angiotensin II, and also inactivates bradykinin, peptides which play a key role in modulating vascular tone. Plasma ACE levels are under genetic control and up to 50% of the variation is due to an insertion/deletion (I/D) polymorphism of ACE gene with highest levels found in DD homozygotes. Studies have shown an association of diabetic nephropathy and ischaemic heart disease with angiotensin converting enzyme gene polymorphism in subjects with diabetes. We examined the association between diabetic retinopathy and ACE gene insertion/deletion polymorphism in 363 subjects with NIDDM (aged 68.3 +/- 10.7 years; 201 male, 162 female), 186 subjects with IDDM (aged 42.4 +/- 15.0 years; 100 male, 86 female) and 98 controls. These subjects were characterized for ACE I/D polymorphism employing standard primers. Diabetic retinopathy was diagnosed by ophthalmoscopy through dilated pupils by an ophthalmologist and classified as non-proliferative or proliferative retinopathy. As expected, diabetic retinopathy was strongly associated with duration of diabetes (p < 0.001) in both IDDM and NIDDM. Any retinopathy was present in 51% subjects with IDDM and 49% of subjects with NIDDM, while 22% of IDDM subjects and 5% of subjects with NIDDM had proliferative retinopathy. The frequency of I allele was 0.477 vs 0.482 vs 0.510 and D allele was 0.523 vs 0.518 vs 0.490, among subjects with IDDM, NIDDM and controls, respectively. The frequency of ACE I/D genotype was similar in subjects with IDDM, NIDDM, and controls (chi 2 = 0.46, df = 4, p = ns). Presence or absence of retinopathy was not significantly associated with ACE genotype in subjects with IDDM (chi 2 = 3.42, df = 2, p = ns) or NIDDM (chi 2 = 0.51, df = 2, p = ns). Among subjects with retinopathy, there was no significant association between ACE genotype and type of retinopathy. Controlled for duration of diabetes, the frequency of I/D genotype was not significantly different in 271 subjects with retinopathy (IDDM and NIDDM combined) when compared with 86 subjects without retinopathy at 15 years or more after diagnosis of diabetes (chi 2 = 1.29, df = 2, p = ns). These findings indicate that I/D polymorphism of ACE gene is not a useful marker and is unlikely to play a major role in determining genetic susceptibility to diabetic retinopathy or the severity of diabetic retinopathy.
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PMID:Angiotensin converting enzyme (ACE) insertion/deletion (I/D) polymorphism, and diabetic retinopathy in subjects with IDDM and NIDDM. 858 33

We have come a long way in our understanding of the epidemiology, pathophysiology, and clinical significance of albuminuria in patients with NIDDM. However, substantial gaps remain to be defined. NIDDM nephropathy is a serious and increasingly burdensome disease for both the diabetic individual and the society at large. Onset of microalbuminuria, an early but common manifestation of NIDDM nephropathy, marks an ominous turn for the NIDDM patient, in whom its development forecasts a grave cardiovascular outcome. Interception of albuminuria with antihypertensive agents such as ACE inhibitors in otherwise healthy NIDDM subjects holds a significant promise but must first await further investigation.
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PMID:Microalbuminuria in patients with NIDDM: an overview. 872 May 42

Hypertension is both an exacerbating factor for, and a consequence of, diabetic renal disease. In diabetic patients, hypertension is associated with increased total body sodium secondary to impaired renal excretion, and increased vascular reactivity, notably to catecholamines and angiotensin II. The mechanisms causing these changes are discussed. Control of hypertension will slow the progression of diabetic renal disease and the inexorable decline in GFR. A number of studies now suggest that in proteinuric IDDM and NIDDM patients angiotensin converting enzyme inhibitors (ACE-I) may have additional reno-protective effects in addition to their hypotensive action. In addition ACE-I will reduce proteinuria and delay the onset of diabetic nephropathy in normotensive microalbuminuric IDDM and NIDDM patients. Use of ambulatory blood pressure monitoring indicates that such patients may not be truly 'normotensive'. On-going studies seem to suggest that the most reno-protective blood pressure is the lowest one achievable, as long as the patient remains asymptomatic. Further studies are required to assess the impact of blood pressure control, and especially ACE-I, on the incidence of end-stage renal failure. In addition, more direct comparisons between different pharmacological agents in early diabetic renal disease would be useful.
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PMID:The management of hypertension in diabetes: with special reference to diabetic kidney disease. 873 20

A total of 168 patients with non-insulin dependent diabetes (NIDDM) followed over 10 years were recruited in this study. The patients were divided into two groups: Group 1 patients had a stable renal function (N = 96) and Group 2 had a declining renal function (N = 72). Group 1 included those whose serum creatinine was normal five years ago but had increased to > or = 2 mg/dl or those who has reached end-stage renal failure (requiring dialysis) by the time of study. All patients were genotyped for the insertion/deletion (I/D) polymorphism of the ACE gene, the M235T polymorphism of the angiotensinogen (Atg) gene and the A1166C polymorphism of the angiotensin II type 1 receptor (AT1) gene. The genotype frequency distributions of M235T Atg and the A116C AT1 gene polymorphisms were not different between Group 1 versus Group 2. While the frequency of the ACE DD genotype in Group 1 (7.3%) was comparable to that of the general population, the DD frequency was significantly higher in Group 2 (26.4%) than in Group 1 (odds ratio, 4.56; 95% confidence interval, 1.80 approximately 11.56, P < 0.001). Among all 168 patients studied, the renal survival rate was significantly lower among DD than ID (P < 0.005) or II patients (P < 0.001). In patients with a declining renal function (Group 2), those with the DD genotype had a significantly shorter time interval from onset of diabetes to the initiation of dialysis (13.4 +/- 1.4 years) than those with ID (20.7 +/- 1.2 years, P < 0.01) or II genotypes (17.5 +/- 1.1 year, P < 0.01). Analysis of the clinical course of the three ACE genotypes revealed that the majority (95%) of patients with the DD genotype who had albuminuria progressed to end-stage renal disease within 10 years of diagnosis of diabetes. Our analysis also revealed that initiation and continuation of dialysis are associated with a progressive decrease in the frequency of the DD genotype. These results indicate that, in NIDDM, the ACE DD genotype has a high prognostic value for progressive deterioration of renal function. Moreover, the DD genotype appears to increase the mortality once dialysis is initiated.
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PMID:Angiotensin I converting enzyme gene polymorphism in non-insulin dependent diabetes mellitus. 884 Feb 99

We examined the association between the polymorphism of the apolipoprotein E (apoE) and the ACE genes and the intima-media thickness (IMT) of the carotid and femoral arteries measured using ultrasonography. The values of IMT of each artery were significantly higher in NIDDM patients (n = 356) than in control subjects (n = 235). The E4 allele or the D allele did not affect clinical characteristics, including age, fasting plasma glucose, total cholesterol, HDL cholesterol, LDL cholesterol, or blood pressure, in NIDDM or control subjects. No difference in the carotid IMT value was noted among the apoE genotypes in control or diabetic subjects. The carotid IMT was significantly higher in diabetic patients with the DD genotype (1.200 +/- 0.586 mm) than in those with the II genotypes (0.990 +/- 0.364 mm). Neither the E4 allele nor the D allele affected the femoral IMT in control or diabetic subjects. Multiple regression analysis demonstrated that the carotid IMT of NIDDM patients was associated with age, the D allele, and LDL cholesterol but not with the E4 allele, whereas that of control subjects was associated with age, sex, systolic blood pressure, LDL cholesterol, and HDL cholesterol, inversely. These results suggested that the E4 allele was not associated with the carotid or femoral IMTs, but that the D allele was statistically associated with carotid IMT in NIDDM patients but not control subjects. However, since the association was weak (2.3% explanatory power), its biological significance remains to be determined.
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PMID:Effect of polymorphism of apolipoprotein E and angiotensin-converting enzyme genes on arterial wall thickness. 907 11

Microalbuminuria and proteinuria are strong independent predictors for increased cardiovascular mortality in non-insulin-dependent diabetic (NIDDM) patients. In such patients, angiotensin converting enzyme (ACE) inhibition improves the evolution of diabetic nephropathy; however, no data are currently available on the effects of such intervention on cardiovascular morbidity and mortality. The aim of the Diab-Hycar study is to test the hypothesis that ACE inhibition with a low daily dose of 1.25 mg ramipril, which has no significant effect on blood pressure, may reduce cardiovascular morbidity and/or mortality in normotensive or hypertensive NIDDM patients with persistent albuminuria. Selected and followed by general practitioners, 4000 patients will receive their usual oral antidiabetic treatment and if necessary antihypertensive treatment (ACE inhibitors excluded). In addition in a randomized, double-blind trial they will be given either a placebo or 1.25 mg ramipril daily. The follow-up is currently scheduled to last 3 years. The efficacy of ACE-inhibition will be assessed by the following major end-points: cardiovascular death, sudden death, myocardial infarction, stroke, renal replacement therapy. The Diab-Hycar study started on 3 February 1995. By 1 September 1995, 11,000 urine samples were tested. The prevalence of persistent albuminuria was 23%, 964 patients were initially included in the study, with 619 eligible patients included soon after. Different strategies have been developed to record cardiovascular events correctly and to minimize the number of patients lost to follow-up.
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PMID:The DIAB-HYCAR Study. 908 52

Diabetes mellitus comprises a heterogeneous group of diseases which have chronic hyperglycaemia in common as well as the resulting microvascular, macrovascular and neurological complications of this condition. Familial studies have provided strong evidence for the existence of genetic determinants in the different types of diabetes. In particular, monozygotic twin studies have indicated a higher rate of concordance in non-insulin-dependent (NIDDM) than in insulin-dependent diabetes mellitus (IDDM). In IDDM, 8 susceptibility loci have been identified, notably the HLA complex and insulin promotor gene. Rigorous family studies have identified monogenic subtypes representing 10-15% of all NIDDM: MODY2 related to glucokinase gene mutations, MODY1 and MODY3 secondary to mutation of hepatic nuclear factors, and diabetes resulting from deletion or mutation of mitochondrial DNA. Most NIDDM result from polygenic heredity, and susceptibility genes conducive to increased receptivity to deleterious environmental influences are now under investigation, such as beta 3 adrenergic receptor, FABP2 and OB. Precise analysis of phenotypes in the remaining families or systematic screening of the genome could allow the genes of each subtype to be identified. Finally, susceptibility genes for the increased severity and frequency of vascular complications have been identified, such as angiotensin converting enzyme, aldose reductase and aldehyde dehydrogenase genes. This progress has been facilitated by developments in molecular biology.
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PMID:Diabetes: from phenotypes to genotypes. 910 79

Diabetic nephropathy accounts for almost a third of all causes of ESRD. Microalbuminuria screening among diabetics can offer early detection of incipient nephropathy. Aggressive treatment with ACE inhibitors may delay the onset of overt renal failure or delay its progression. Furthermore, intensive control of blood glucose has also been proven to prevent the microvascular complications of diabetes and should be pursued in both IDDM and NIDDM. The high association of diabetes mellitus with hypertension presents another problem to the clinician. It is necessary to control blood pressure to prevent further progression of renal failure. The choice of antihypertensive medications, however, becomes a therapeutic dilemma because of the metabolic and lipid disturbances that some drugs can cause. ACE inhibitors, CCBs, alpha-agonists, and low-dose diuretics, alone or in combination, may be tried to normalize blood pressures. Although beta-blockers are widely used and effective in nondiabetics, these agents should be considered the drugs of last resort because of their adverse effects, which are particularly troublesome for diabetics. Moderate protein restriction should also be advocated as a helpful adjunct to therapy.
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PMID:Diabetic nephropathy. 916 51

Lisinopril, like other ACE inhibitors, lowers blood pressure and preserves renal function in hypertensive patients with non-insulin-dependent or insulin-dependent diabetes mellitus (NIDDM or IDDM) and early or overt nephropathy, without adversely affecting glycaemic control or lipid profiles. On available evidence, renoprotective effects appear to be greater with lisinopril than with comparator calcium channel blockers, diuretics and beta-blockers, despite similar antihypertensive efficacy. As shown by the EUCLID (EUrodiab Controlled trial of Lisinopril in Insulin-Dependent Diabetes) trial, lisinopril is also renoprotective in normotensive patients with IDDM and microalbuminuria. The effect in normotensive patients with normoalbuminuria was smaller than in those with microalbuminuria, and no conclusions can yet be made about its use in patients with normoalbuminuria. In complications other than nephropathy, lisinopril has shown some benefit. Progression to retinopathy was slowed during 2 years' lisinopril therapy in the EUCLID study. Although not yet fully published, these results provide the most convincing evidence to date for an effect of an ACE inhibitor in retinopathy. The drug may also improve neurological function, but this finding is preliminary. Lastly, post hoc analysis of the GISSI-3 trial indicates that lisinopril reduces 6-week mortality rates in diabetic patients when begun as early treatment after an acute myocardial infarction. The tolerability profile of lisinopril is typical of ACE inhibitors and appears to be similar in diabetic and nondiabetic individuals. Hypoglycaemia has occurred at a similar frequency with lisinopril and placebo, as shown in the EUCLID trial. In addition, the GISSI-3 study indicates that the incidence of persistent hypotension and renal dysfunction is increased with lisinopril in general, but the presence of diabetes does not appear to confer additional risk of these events in diabetic patients with acute myocardial infarction receiving lisinopril. In summary, lisinopril lowers blood pressure and produces a renoprotective effect in patients with IDDM and NIDDM without detriment to glycaemic control or lipid profiles. Like other ACE inhibitors, lisinopril should thus be viewed as a first-line agent for reducing blood pressure and preventing or attenuating nephropathy in hypertensive diabetic patients with IDDM or NIDDM and microalbuminuria or overt renal disease. The EUCLID study, using lisinopril, provides new data supporting an additional place in managing normotensive patients with microalbuminuria and IDDM. These findings, together with some evidence for an effect of lisinopril in delaying progression of retinopathy and in reducing mortality, suggest a broader role for the drug in managing diabetic vascular complications.
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PMID:Lisinopril. A review of its pharmacology and use in the management of the complications of diabetes mellitus. 917 32


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