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)

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

The aim of our study was to evaluate whether inhibition of ACE (lisinopril 10-20 mg/day) can reduce the rate of decline in kidney function more than reducing blood pressure with conventional antihypertensive treatment (atenolol 50-100 mg/day), usually in combination with a diuretic. We performed a prospective, randomized, parallel study for 42 months, double blind for the first 12 months and single blind thereafter. Forty-three (21 lisinopril and 22 atenolol) hypertensive NIDDM patients with diabetic nephropathy were enrolled. Data from 36 patients (17 lisinopril and 19 atenolol, 60 +/- 7 years of age, 27 men) who completed at least 12 months of the study period are presented. At baseline, the two groups were comparable: glomerular filtration rate (51Cr-EDTA plasma clearance) was 75 +/- 6 and 74 +/- 8 ml x min(-1) x 1.73 m(-2), mean 24-h ambulatory blood pressure (A&D TM2420) was 110 +/- 3 and 114 +/- 2 mmHg, and 24-h urinary albumin excretion rate was 961 (range 331-5,727) and 1,578 (476-5,806) mg/24 h in the lisinopril and atenolol groups, respectively. The mean follow-up time was similar, 37 and 35 months in the lisinopril and atenolol groups, respectively. Mean ambulatory blood pressure was equally reduced in the two groups, 12 +/- 2 and 10 +/- 2 mmHg in the lisinopril and atenolol groups, respectively. Glomerular filtration rate declined in a biphasic manner with a faster initial (0 to 6 months) change of 1.25 +/- 0.49 and 0.81 +/- 0.29 ml x min(-1) x month(-1) followed by a slower sustained decline (6 to 42 months) of 0.59 +/- 0.10 and 0.54 +/- 0.13 ml x min(-1) x month(-1) in the lisinopril and atenolol groups, respectively. No significant differences were observed in either initial or sustained decline in glomerular filtration rate between the two groups. Urinary albumin excretion was reduced (% reduction of baseline) more in the lisinopril than in the atenolol group, at 55 (95% CI 29-72) and 15% (-13 to 34), respectively (P = 0.01). In conclusion, the relentless decline in kidney function characteristically found in hypertensive NIDDM patients with diabetic nephropathy can be reduced equally effectively by two antihypertensive treatments, the beta-blocker atenolol and the ACE inhibitor lisinopril.
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PMID:Long-term effect of lisinopril and atenolol on kidney function in hypertensive NIDDM subjects with diabetic nephropathy. 920 Jun 54

Base on their own experience with isradipine and results of a multicentric study with amplodipine in the Slovak Republic, as well as based on data in the literature the authors conclude that: 1. In the treatment of arterial hypertension associated in the syndrome of insulin resistance (syndrome X and 5H resp.) with type 2 diabetes, hyperlipiproteinaemia and hyperinsulinism drugs of first choice include ACE-inhibitors and Ca antagonist of the second generation, dihydropiridine type, such as amplodipine, isradipine, fellodipine, nirtendipine etc. ACE inhibitors and Ca antagonist of the dihydropyridine type with prolonged effect have a good tolerance, few undesirable effect, a favourable effect on the decline of BP, regression of hypertrophy of the left ventricle and vascular wall; they do not cause deterioration of insulin resistance and thus do not interfere with compensation of diabetes and associated hyperlipoproteinaemia. 2. ACE inhibitors moreover reduce glomerular filtration and albuminuria and thus retard along with the effect on BP the progression of diabetic nephropathy. 3. In pre-existing hyporeninemic hypoaldosteronism (cca in 18% diabetic subjects) they can however cause dangerous hyperkalinaemia by further inhibition of the damaged renin-angiotensin-aldosterone system. In instances Ca inhibitors are indicated. The latter activate RAAS and do not have an impact on albuminuria. By their effect on the vas deferens they can increase glomerular filtration. 4. Diuretics are not suitable for the treatment of hypertension in X syndrome and the use of beta-blocking agents even with ISA and beta-1-selective preparations in restricted in particular when insulin is administered or other numerous contraindications are present (cardiac failure, bradyarrythmias, bronchitis etc.). Perhaps a combination of ACE-inhibitors and Ca antagonists of the 2nd generation with an alpha-blocking agent or hybrid alpha-beta-blocking agent is a suitable solution.
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PMID:[The role of calcium inhibitors in the treatment of arterial hypertension]. 924 72

The therapeutic advantage of the long acting ACE-inhibitor benazepril in a 12 weeks intervention period on 23 diabetic (3 IDDM, 20 NIDDM) patients with essential hypertension was studied. Participants-giving informed consent before beginning the study-on the base of repeated casual blood pressure measurements were divided into "slightly" (n = 8) and "moderately" (n = 15) hypertonic groups. Type of diabetes, time elapsed since its manifestation, actual antidiabetic therapy, period of existence of the hypertension (newly discovered vs known and treated for a time) were independent from the point of view of entering the study. Initial dose of benazepril was 5-10 mg/day depending on the blood pressure level, followed by a stepwise dose elevation according to the control investigations (at weeks 2, 4, 8 and 12 casual blood pressure control, at weeks 4 and 12 ambulantory blood pressure monitoring, ABPM as well) to a maximal daily dose of 20 mg. In the majority of patients benazepril was given in a morning single dose, in some cases because of a better tolerability divided into two parts. 20 patients received benazepril in monotherapy, 3 patients combined with other antihypertensive preparations. Parameters indicating severity of hypertension-hypertonic time index, hyperbaric impact-showed significant improvement already at week 4 when analysed in the total of patients and the moderately hypertonic group respectively. As a tendence the same was observed also in the slightly hypertonic group. No remarkable side effects, or alterations of the metabolic state and in the investigated laboratory parameters appeared. Based on these results benazepril is an effective choice in the treatment of diabetic hypertensive patients.
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PMID:[Experience with benazepril, a long-acting ACE inhibitor, in the management of diabetic hypertension]. 927 85

In 826 hypertensive patients including 396 with non-insulin dependent diabetes mellitus safety and efficacy of captopril 50 mg per day was evaluated throughout three months. In all patients blood pressure was significantly reduced. Moreover, in part of the patients with microalbuminuria, these tests turned negative with treatment. In addition, in patients with diabetes fasting and postprandial plasma glucose levels as well as HBA1C levels decreased. Only in 6.8% side effects occurred. In all patients quality of life as evaluated by a 10 item rating scale questionnaire improved. Taken together the results of this observational study confirm improvement of blood pressure levels, kidney function and metabolic derangements in diabetic patients treated with the ACE-inhibitor captopril. Effectiveness of these actions of captopril in respect to longterm prognosis in diabetics, however, remains to be established.
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PMID:[The hypertensive type II diabetic patient treated with captopril in free general practice (Austrian Safety Study). An indications study]. 933 64

Initiation of antihypertensive treatment in hypertensive non-insulin-dependent diabetic (NIDDM) patients with diabetic nephropathy induces a faster initial (0 to 6 months) and slower subsequent (6 months-end) decline in GFR [delta GFR (ml.min-1.1.73 m-2.month-1) approximately 1.5 vs. 0.4]. Whether this initial phenomenon is reversible (hemodynamic) or irreversible (structural damage) after prolonged antihypertensive treatment is not known. To elucidate these mechanisms we investigated 40 hypertensive NIDDM patients (age 61 +/- 7 years, mean +/- SD), known duration of diabetes 14 years (2 to 33 years) [median (range)] with diabetic nephropathy receiving antihypertensive treatment (angiotensin converting enzyme inhibition, N = 30) for 5 years (1 to 20 years). The following variables were measured the last day on antihypertensive treatment and one month after withdrawal of treatment; GFR (51Cr-EDTA), 24-hour arterial blood pressure (24 hr MABP, Takeda TM2420) and albuminuria (ELISA); the mean 24-hour MABP rose from 102 +/- 11 to 111 +/- 10 (P < 0.0001) and albuminuria [geometric mean (antilog SEM)] increased from 634 (1.3) to 1159 (1.2) (P < 0.0001), while GFR (mean +/- SD) remained unchanged (69 +/- 25 to 70 +/- 26 ml.min-1.1.73 m-2, P = 0.21), after withdrawal of antihypertensive treatment. A significant correlation between the relative change in the 24 hour MABP measurement and the relative change in GFR (r = 0.44, P < 0.01) was found. In conclusion, our results suggest that the faster initial decline in GFR after initiating antihypertensive treatment in hypertensive NIDDM patients with diabetic nephropathy is due to a irreversible effect, and should be accounted for when evaluating the beneficial effect of antihypertensive treatment on the progression of diabetic nephropathy in these patients.
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PMID:Kidney function after withdrawal of long-term antihypertensive treatment in diabetic nephropathy. 940 21

Insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene has been shown to be associated with various cardiovascular disorders in diabetic and non-diabetic patients. Its association with the development of non-insulin dependent diabetes mellitus (NIDDM) has been raised. This study was aimed to examine I/D polymorphism of ACE gene in healthy Thai subjects and patients with NIDDM. The I/D ACE genotypes were determined by polymerase chain reaction technique. Healthy unrelated subjects were 151 males and 147 females, 17-70 year old (mean +/- SD = 37.5 +/- 10.4). The unrelated diabetic patients were 42 males and 66 females, 20-79 years of age (mean +/- SD = 54.7 +/- 12.0). In healthy subjects, the ACE genotypes were DD 10.1 per cent, ID 39.2 per cent and II 50.7 per cent. Diabetic patients had similar distribution of ACE genotypes. The frequency of I and D alleles in diabetic patients was 0.69 and 0.31, similar to 0.70 and 0.30, respectively, in healthy subjects (p = 0.69). The frequency of I and D alleles in healthy Thai subjects was similar to the Japanese (I = 0.66 & D = 0.34) but different from Caucasians (I = 0.44-0.46 & D = 0.54-0.56). We conclude that I/D ACE gene polymorphisms may possess a racial difference. The similar frequency of both alleles in diabetic patients and healthy subjects suggests that there is no association between I/D polymorphism of ACE gene and diabetes mellitus in Thai individuals.
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PMID:Angiotensin converting enzyme gene polymorphism in healthy Thais and patients with non-insulin dependent diabetes mellitus. 947 Mar 26

The presence of persistent microalbuminuria in IDDM is strongly predictive of the future development of end stage renal failure and of cardiovascular disease to a lesser extent. Screening for microalbuminuria is an essential component of modern diabetes practice, as effective antihypertensive therapy, and particularly, the use of angiotensin converting enzyme inhibitors is of proven benefit in retarding progression of renal disease. Cost benefit analysis justifies the expense of microalbuminuria screening programmes and early intervention. It has been estimated that the use of angiotensin converting enzyme inhibitors in microalbuminuric IDDM will save 5200 Pounds-11,000 Pounds per year of life saved. Angiotensin converting enzyme inhibitors are not free of side-effects, and it is therefore essential, given the intrinsic variability of the albumin excretion rate, and the regression to normoalbuminuria of a significant proportion of patients, to confirm the diagnosis of microalbuminuria by repeated measurements prior to the commencement of treatment. The value of intensive glycaemic control is unproven, and further prospective studies are required. There are no proven therapies for the prevention of macrovascular disease in IDDM, although the value of cessation of smoking and aggressive blood pressure control are undoubted in the non-diabetic population. Controversy persists about the value of lipid lowering therapy, especially in young patients, although even in this group there is an increased risk of cardiovascular disease. Microalbuminuria is the strongest known predictor of cardiovascular disease in NIDDM; in contrast to the situation in the non-diabetic population, active lipid lowering therapy is not of proven cardiac benefit, but intervention seems justifiable when taken in the context of the very high prevalence of cardiovascular disease. Microalbuminuria is also predictive of end stage renal disease in NIDDM. Although intervention with angiotensin converting enzyme inhibitors has not been proven to prevent end stage renal disease, stabilisation of albumin excretion rate and creatinine clearance have been demonstrated in normotensive NIDDM, and it seems likely that longer term follow-up studies will confirm the benefit of angiotensin converting enzyme inhibitors in the prevention of end-stage renal disease. The observed predictive power of microalbuminuria as regards both cardiac and renal risk in NIDDM when considered in conjunction with the preliminary results of the benefits of angiotensin converting enzyme inhibition lend further support to the employment of microalbuminuria screening in NIDDM.
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PMID:Microalbuminuria: a marker to increased renal and cardiovascular risk in diabetes mellitus. 950 84

European and American recommendations for coronary heart disease prevention put patients with clinically manifest coronary heart disease, or other major atherosclerotic disease, as the top priority for prevention. Coronary patients should have professional support to stop smoking, eat a healthier diet (reduce the dietary intake of fat to 30% or less of total energy; saturated fat to no more than one third of total fat intake, cholesterol to less than 300 mg per day; increase monounsaturated and polyunsaturated fat from both vegetables and marine sources; increase fresh fruit and vegetables) achieve optimal weight, and become physically fitter through regular aerobic exercise. The intensity of lifestyle intervention and the level of professional support required to achieve change should be determined by the absolute risk of a further major ischaemic event, based on an assessment of all risk factors, and this should also influence the threshold for drug therapy in relation to blood pressure, lipoproteins and glucose, rather than just the individual levels of these risk factors. In addition to lifestyle changes (reducing weight and restricting salt and alcohol as appropriate) blood pressure in coronary patients should be lowered if necessary with drug therapy. For these patients blood pressure should be consistently less than 140/90 mmHg. Lifestyle changes will reduce total cholesterol (and in particular LDL cholesterol) increase HDL cholesterol and lower triglycerides. Drug therapy may also be required and in coronary patients total cholesterol should be kept consistently below 4.8 mmol.l-1, and this threshold may be further reduced with the publication of new trial results. In insulin-dependent diabetes, rigorous metabolic control reduces the risk of microvascular complications and therefore for coronary patients with insulin-dependent or non-insulin dependent diabetes mellitus this is a desirable objective. As diabetics with coronary disease are at substantially higher risk of coronary morbidity and mortality compared with non-diabetics the threshold for treating blood pressure and lipids with drug therapy should be lower. In coronary patients, selected prophylactic drug therapy is indicated in the form of aspirin, beta-blockers, ACE inhibitors and systemic anticoagulants which, together with lipid lowering drug therapy, have all been shown to reduce coronary mortality and improve life expectancy. When a patient presents with coronary disease, and particularly when there is a family history of premature coronary heart disease, the opportunity of screening first degree relatives should be taken with a view to primary prevention.
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PMID:European and American recommendations for coronary heart disease prevention. 951 37

The prevention of coronary artery disease is based on the control of several factors associated with a disease or clinical condition and suspected to play a pathogenetic role, defined as 'risk factors'. Smoking is a powerful risk factor for coronary artery disease, with risk of events increasing in relation to the number of cigarettes smoked daily. Smoking cessation is associated within 3-4 years, with a significant reduction in cardiovascular risk. Hyperlipidaemia is a powerful predictor of coronary disease with a strong, independent, continuous and graded positive association between cholesterol levels and risk of coronary events. Several large studies have shown the benefit of cholesterol reduction, and there is clear evidence of the efficacy of statins in the reduction of events in primary and secondary prevention. Hypertension is a significant, strong and independent risk factor for coronary artery disease morbidity and mortality and the reduction of events and mortality by antihypertensive treatment is well documented. Obesity is associated with an increase in all-cause mortality and cardiovascular mortality, with a particularly high risk for subjects with central obesity. Central obesity is also part of the so-called 'metabolic X syndrome' including insulin resistance, which appears to be associated with a particularly high risk of coronary artery disease. Type 1 and type 2 diabetes mellitus are associated with an increased risk of cardiovascular disease, especially in women. Several studies have shown that good metabolic control and multifactorial risk factor reduction significantly lower the coronary risk in these patients. Recent evidence is accumulating that some clotting factors (fibrinogen, factor VII, von Willebrand factor) and fibrinolytic factors (t-PA and PAI-1) are associated with an increased risk of coronary artery disease. The European Concerted Action on Thrombosis (ECAT) showed that the levels of fibrinogen, von Willebrand factor antigen, and t-PA antigen are independent predictors of subsequent coronary syndromes in patients with angina pectoris, and that low fibrinogen is associated with a low risk of events despite high cholesterol levels. Post-menopausal status is associated with increased risk of coronary artery disease, particularly when menopause is premature (before the age of 45) or abrupt (surgical). There is strong, thought not yet completely definite evidence that post-menopausal hormone replacement therapy may significantly reduce the risk of events and improve survival. Hyperhomocysteinaemia is an emerging risk factor independently associated with an increased risk of coronary artery disease, cerebral vascular disease, and peripheral vascular disease. The administration of vitamin B6, B12 or folate seems to be useful and is currently under further evaluation. Recently, attention has been focused on the correlation between coronary artery disease and genetic factors, such as ACE gene polymorphism or the gene polymorphism for the IIIa-moiety of the platelet fibrinogen receptor IIb-IIIa. In primary prevention, control of the major risk factors mainly in patients with clustered factors will substantially reduce the risk of ischaemic events. Secondary prevention of CHD is based on: aggressive behavioural advice, blood pressure reduction in hypertensives, good metabolic control of diabetes, and cholesterol reduction. Aspirin, beta-blockers, ACE inhibitors, and oral anticoagulants, may be useful in selected patients.
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PMID:Classical risk factors and emerging elements in the risk profile for coronary artery disease. 951 44


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