UMLS:C0011854 - FACTA Search

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Query: UMLS:C0011854 (type 1 diabetes)
20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

In Hungary the use of angiotensin converting enzyme inhibitor enalapril has emerged as one of the most important drugs in the treatment of hypertension. The aim of our study was to evaluate the antihypertensive effect of enalapril of Hungarian production in combination therapy and alone, according to sexes, to the body mass index, among smokers and non smokers as well as non diabetic and in patients with diabetes (IDDM and NIDDM). The diurnal blood pressure values were registered by a 24 hour ambulatory blood pressure monitor. During the 6 weeks of the enalapril therapy (n = 28) both the daytime (141/84 vs. 135/80 mmHg) and the night-time (130/78 vs. 124/72 mmHg) blood pressure values decreased; the increase of diurnal indices during the therapy (SI/DI 6/8% vs. 8/10) reflect the 24 hour long lasting effect of the drug. The body mass index had no influence on the efficacy of treatment. Our results indicate that enalapril manufactured in Hungary is an effective antihypertensive drug both in monotherapy and in combination, in both sexes (especially in men), irrespective of the body weight, in non-smokers and especially in smokers, in insulin dependent and in non-insulin dependent diabetes mellitus alike.
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PMID:[The place of enalapril in the management of hypertension]. 952 25

Between 5 and 20% of children with type 1 diabetes may develop microalbuminuria as a sign of incipient nephropathy starting in early puberty. Permanent microalbuminuria has to be distinguished from intermittent and transient microalbuminuria with unknown prognostic relevance. A review of clinical risk factors, retinal examination and an ambulatory 24-h blood pressure profile are recommended. Non-pharmacological interventions such as the improvement of glycemic control, the cessation of smoking or the feasibility of a low protein diet should always be considered. Concerning pharmacological intervention, in particular ACE-inhibitors have been shown to be beneficial in adolescents with hypertension but may also be renoprotective in normotensive patients with microalbuminuria. However, long-term studies with ACE-inhibitors in normotensive patients have shown negligible changes in the glomerular filtration rate, which better reflects the renal status during treatment than changes in the albumin excretion rate. Nevertheless, such treatment is currently recommended also for normotensive adolescents if other interventions are not successful.
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PMID:Controversies on the pathogenesis of diabetic angiopathy: which treatment for normotensive adolescents with microalbuminuria and type 1 diabetes? 964 65

Diabetic nephropathy (DN) clusters in families with type 1 diabetes and the degree of clustering suggests that a major gene having a common disease allele may be responsible. To investigate the chromosomal regions containing genes for the renin-angiotensin system, we performed a linkage study using pairs of siblings with type 1 diabetes who were discordant for DN. Theoretical considerations supported by simulation studies indicated that such discordant pairs, rather than the usual concordant pairs, would be more effective in detecting a major susceptibility gene for DN. We applied this novel strategy to test for linkage between DN and chromosomal regions containing genes for the ACE, angiotensinogen (AGT), and angiotensin II type 1 receptor (AT1). Two polymorphic markers were genotyped in the vicinity of each of the three loci in 66 discordant sib pairs and were analyzed with multipoint methods. The regions containing ACE and AGT loci were not linked with DN, while the region containing the AT1 locus showed linkage with DN. As a result of these positive findings, eight additional polymorphic markers spanning a 63-cM region around AT1 locus were genotyped. Linkage was demonstrated between DN and a 20-cM region that includes AT1 (P = 7.7 x 10(-5)), an obvious candidate gene for DN. To investigate whether AT1 could account for the observed linkage, we sequenced all exons, splicing junctions, and the promoter region and examined the identified polymorphisms/mutations for association with DN using the transmission disequilibrium test. Four new polymorphisms in the gene were found, but neither these nor previously described polymorphisms were associated with DN. Thus, while our study does not implicate AT1 itself in the etiology of DN, it provides very strong evidence that a 20-cM region around AT1 contains a major locus for susceptibility to DN.
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PMID:Major susceptibility locus for nephropathy in type 1 diabetes on chromosome 3q: results of novel discordant sib-pair analysis. 964 45

The prevalence of abnormally elevated albumin excretion rate (> 30 mg/24 h) is approximately 40% in insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetic patients. Diabetes has become the leading cause of end-stage renal failure in the US, Japan and Europe. Approximately 90% of the direct and indirect cost of caring for diabetic patients are spent on the complications of diabetes. Identification of patients at high risk of developing diabetic nephropathy is possible by screening for microalbuminuria (30-300 mg/24 h). Elevated urinary albumin excretion rate indicates a substantially increased mortality risk in diabetic patients. Randomised controlled trials in normotensive IDDM and NIDDM patients with persistent microalbuminuria indicate that ACE inhibitors diminish urinary albumin excretion rate, postpone it and may even prevent progression to clinical overt nephropathy. These findings indicate that screening and intervention programs are likely to have life saving effects and lead to considerable economic savings. Systemic blood pressure elevation to a hypertensive level is an early and frequent phenomenon in diabetic nephropathy. Furthermore, nocturnal blood pressure elevation (non-dippers) occurs more frequently in patients with nephropathy. Systemic blood pressure elevation and to a lesser degree albuminuria accelerate the progression of diabetic nephropathy. Effective blood pressure reduction with non-ACE-inhibitors and/or ACE-inhibitors frequently in combination with diuretics: (a) reduces albuminuria; (b) delays the progression of nephropathy; (c) postpones renal insufficiency; and (d) improves survival in IDDM and NIDDM patients with diabetic nephropathy. A specific renal protective effect of ACE-inhibitors in diabetic nephropathy has been demonstrated in IDDM patients with moderately reduced kidney function (s-creatinine > 133 mumol/l) while the data conflict with NIDDM patients. Antihypertensive treatment for diabetic nephropathy simultaneously extends life and saves money. Finally, reduced risk of fatal and non-fatal cardiovascular events have been demonstrated when diabetic patients with isolated systolic hypertension are treated with blood pressure lowering agents. Absolute risk reduction with active treatment compared to placebo was twice as great for the diabetic versus non-diabetic patients (101/1000 versus 51/1000 randomised participants at the 5-year follow-up), reflecting the higher risk of diabetic patients. In conclusion, early detection and aggressive treatment of arterial hypertension with ACE-inhibitors, long acting calcium antagonist and low dose diuretics as first line drugs are highly warranted in diabetic patients with or without diabetic renal disease.
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PMID:Is antihypertensive treatment the same for NIDDM and IDDM patients? 964 59

We examined whether the ACE gene insertion/deletion (I/D) polymorphism modulates renal disease progression in IDDM and how ACE inhibitors influence this relationship. The EURODIAB Controlled Trial of Lisinopril in IDDM is a multicenter randomized placebo-controlled trial in 530 nonhypertensive, mainly normoalbuminuric IDDM patients aged 20-59 years. Albumin excretion rate (AER) was measured every 6 months for 2 years. Genotype distribution was 15% II, 58% ID, and 27% DD. Between genotypes, there were no differences in baseline characteristics or in changes in blood pressure and glycemic control throughout the trial. There was a significant interaction between the II and DD genotype groups and treatment on change in AER (P = 0.05). Patients with the II genotype showed the fastest rate of AER progression on placebo but had an enhanced response to lisinopril. AER at 2 years (adjusted for baseline AER) was 51.3% lower on lisinopril than placebo in the II genotype patients (95% CI, 15.7 to 71.8; P = 0.01), 14.8% in the ID group (-7.8 to 32.7; P = 0.2), and 7.7% in the DD group (-36.6 to 37.6; P = 0.7). Absolute differences in AER between placebo and lisinopril at 2 years were 8.1, 1.7, and 0.8 microg/min in the II, ID, and DD groups, respectively. The significant beneficial effect of lisinopril on AER in the II group persisted when adjusted for center, blood pressure, and glycemic control, and also for diastolic blood pressure at 1 month into the study. Progression from normoalbuminuria to microalbuminuria (lisinopril versus placebo) was 0.27 (0.03-2.26; P = 0.2) in the II group, and 1.30 (0.33-5.17; P = 0.7) in the DD group (P = 0.6 for interaction). Knowledge of ACE genotype may be of value in determining the likely impact of ACE inhibitor treatment.
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PMID:Effect of angiotensin-converting enzyme (ACE) gene polymorphism on progression of renal disease and the influence of ACE inhibition in IDDM patients: findings from the EUCLID Randomized Controlled Trial. EURODIAB Controlled Trial of Lisinopril in IDDM. 972 42

The aim of the study was to evaluate the effect of an insertion/deletion polymorphism of the angiotensin converting enzyme (ACE) gene on progression of diabetic nephropathy. We performed an observational follow-up study of 35 patients with insulin-dependent diabetes and diabetic nephropathy. Patients were investigated during captopril treatment for a median of seven (range three to nine) years. Eleven patients were homozygous for the deletion allele (DD) and 24 were hetero- or homozygous for the insertion allele (ID + II). The two groups had comparable glomerular filtration rate, albuminuria and blood pressure at baseline and captopril induced nearly the same mean reduction in blood pressure--to 103 (SD 5) mm Hg in the DD-group and 102 (8) mm Hg in the ID + II-group. The rate of decline in glomerular filtration rate was significantly steeper in the DD group than in the other group (mean 5.7 (SD 3.7) versus 2.6 (2.8) ml/min/year, p = 0.01). In conclusion, the deletion polymorphism in the ACE gene reduces the long term beneficial effect of ACE inhibition on the progression of diabetic nephropathy in patients with insulin dependent diabetes.
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PMID:[The significance of deletion polymorphism in the ACE gene for progression of diabetic nephropathies treated with ACE inhibitors]. 974 Dec 57

The aim of the present study was to examine the relationships between ambulatory blood pressure (ABPM) and urinary albumin excretion (UAE) in diabetic (non-insulin dependent [NIDDM] and insulin-dependent [IDDM]) hypertensives at baseline and after treatment by an angiotensin converting enzyme (ACE) inhibitor. After a 3-week placebo period, patients were treated for 16 weeks with trandolapril, 2 to 4 mg/day. The UAE and blood pressure (mercury sphygmomanometer and 24-h ABPM) were measured at baseline and repeated on trandolapril. Predictive factors of abnormal UAE (24-h UAE > or = 30 mg) were determined using univariate and multivariate analysis (logistic regression). Predictors of UAE decrease were also searched. One hundred seventy-one patients entered the analysis. Baseline office BP was 164+/-14 / 97+/-6 mm Hg and 24-h BP was 142+/-17 / 83+/-10 mm Hg. Seventy-four patients (43%) had UAE > or = 30 mg. Independent risk factors for abnormal UAE were nighttime diastolic BP (odds ratio [OR] = 4.1, confidence interval [CI] = 2.0 to 8.6, P = .0001), diabetes duration (OR = 2.4, CI = 1.1 to 5.0, P = .025), and presence of retinopathy (OR = 3.2, CI = 1.0 to 10.0, P = .047). Conversely, office BP level was not significantly related to UAE. On treatment, office BP levels decreased to 143+/-13 / 82+/-8 mm Hg (P < .0001) and 24-h BP levels to 134+/-17 / 78+/-9 mm Hg (P < .0001). In the abnormal UAE group, UAE significantly decreased from 76 to 50 mg/day (P = .006). After treatment, independent predictive factors of abnormal UAE were: on-drug fasting plasma glucose (OR = 3.5, CI = 1.7 to 7.4, P = .0009) and on-drug nighttime diastolic BP (OR = 3.5, CI = 1.7 to 7.4, P = .001). The only predictor of UAE decrease was a 24-h systolic BP decrease (OR = 2.3, CI = 1.3 to 4.3, P = .007). We conclude that in diabetic hypertensives with abnormal UAE, trandolapril exhibited a sustained 24-h antihypertensive effect and provided a consistent reduction of microalbuminuria. This study confirmed the superiority of ABPM over clinical BP to predict target organ damage.
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PMID:Ambulatory blood pressure and urinary albumin excretion in diabetic (non-insulin-dependent and insulin-dependent) hypertensive patients: relationships at baseline and after treatment by the angiotensin converting enzyme inhibitor trandolapril. 975 91

The increase of glomerular filtration can often be observed in patients with insulin dependent diabetes mellitus, even in the early stage of the disease and it does not require the presence of microalbuminuria. This phenomenon can be explained by vasoconstriction occurring in the efferent arterioles. Eighteen normotensive, diabetic patients (aged: 28-42) who developed increased glomerular filtration were recruited in this study. The specific objectives were: 1. to study the beneficial effect of angiotensin converting enzyme inhibitor on the glomerular filtration, 2. to evaluate the effect of this treatment on blood pressure and hemodynamic parameters in normotensive, diabetic subjects. After a placebo period of one week, patients were treated orally a daily dose of 3 x 6.25 mg of captopril for twelve weeks. Glomerular filtration was assessed by the isotopic clearance method and blood pressure recordings were taken every 30 minutes throughout a day using an automatic programmable device. Preload, afterload and linear ejection fraction were estimated by echocardiograph, whereas cardiac index was measured by isotopic first pass technique. At the end of the treatment period a significant decrease of glomerular filtration was observed (from 141.9 +/- 10 ml/min to 98.9 +/- 12 ml/min; p < 0.01. Similarly, the afterload exhibited a significant drop due to drug treatment (45.6 +/- 5.8 x 10(3) dyn/cm2 vs. 55.4 +/- 4.7 x 10(3) dyn/cm2 at the end of the placebo period (p < 0.01). However, preload, linear ejection fraction, and cardiac index did not significantly change during the treatment. According to the results obtained from this study a beneficial effect of captopril on the early development of the glomerular hyperfiltration was demonstrated in normotensive diabetic patients who did not develop microalbuminuria. This issue needs to be investigated further in a large scale clinical trial.
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PMID:[Beneficial effect of the ACE inhibitor captopril in normotensive patients with insulin-dependent diabetes]. 978 84

Diabetic nephropathy has become the single most important cause of endstage renal failure in most countries of the Western world. Against this background, the role of the renin-angiotensin system (RAS) and its blockade command considerable interest. In diabetic patients and in diabetic animals, the circulating components of the RAS are suppressed. Although the evidence is not completely uniform, there are indirect arguments (renal hemodynamic response to RAS blockade, AT1 receptor expression), however, which would be consistent with increased intrarenal action of angiotensin (ANG) II. There is solid evidence that ACE inhibitors effectively interfere with progression of micro-albuminuria both in IDDM and NIDDM. They also prevent progression of advanced renal failure in IDDM, while there is only preliminary evidence in this respect for NIDDM. ACE inhibitors are superior to conventional antihypertensive agents (with the possible exception of some calcium channel blockers), but such superiority is seen only when the levels of blood pressure are relatively high. In diabetic animals, treatment with ANG II receptor blockers interferes with the development of glomerular lesions. In acute and subacute studies on diabetic patients, ANG II receptor blockers reduced albuminuria (or proteinuria) more than beta-blockers. Head-on comparison of equipotent doses ACE inhibitors and ANG II receptor blockers in non-diabetic patients produced equal reductions in proteinuria. The long-term effects of ANG II receptor blockers on progression of advanced diabetic nephropathy is the object of two large international studies. The results will not be available before the year 2000.
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PMID:Diabetes--renal function--what are the special problems? 983 74

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