Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to determine the impact of the metabolic syndrome on vascular disease risk in patients with type-2 diabetes. A prospective cohort study was carried out. The main dependent variable was the combination of coronary disease, stroke and lower leg amputation. Cox regression modeling was used. In total, 317 patients were followed for a mean of 7.7 years. The prevalence of metabolic syndrome was 87%. Multivariate analysis identified the following as predictors of incident vascular disease: age (relative risk [RR] =1.06, 95% confidence interval [CI], 1.02-1.1; P=.0003), baseline cardiovascular disease (RR=1.8; 95% CI, 1.1-3.0; P=.017), and the simultaneous presence of four metabolic risk factors (RR=5.8; 95% CI, 1.8-18; P=.003). The most predictive factor was microalbuminuria (chi2=5.9; P=.015). Microalbuminuria accounts for the increased risk of vascular disease in patients with metabolic syndrome. In evaluating vascular disease risk in patients with type-2 diabetes, it is more important to consider the total number of metabolic risk factors than the presence of metabolic syndrome alone.
 ...
PMID:[Microalbuminuria accounts for the increased vascular disease risk in diabetic patients with metabolic syndrome]. 1799 82

Diabetes mellitus is associated with an increased risk of cardiovascular disease, even in the presence of intensive glycemic control. Substantial clinical and experimental evidence suggest that both diabetes and insulin resistance cause a combination of endothelial dysfunctions, which may diminish the anti-atherogenic role of the vascular endothelium. Both insulin resistance and endothelial dysfunction appear to precede the development of overt hyperglycemia in patients with type 2 diabetes. Therefore, in patients with diabetes or insulin resistance, endothelial dysfunction may be a critical early target for preventing atherosclerosis and cardiovascular disease. Microalbuminuria is now considered to be an atherosclerotic risk factor and predicts future cardiovascular disease risk in diabetic patients, in elderly patients, as well as in the general population. It has been implicated as an independent risk factor for cardiovascular disease and premature cardiovascular mortality for patients with type 1 and type 2 diabetes mellitus, as well as for patients with essential hypertension. A complete biochemical understanding of the mechanisms by which hyperglycemia causes vascular functional and structural changes associated with the diabetic milieu still eludes us. In recent years, the numerous biochemical and metabolic pathways postulated to have a causal role in the pathogenesis of diabetic vascular disease have been distilled into several unifying hypotheses. The role of chronic hyperglycemia in the development of diabetic microvascular complications and in neuropathy has been clearly established. However, the biochemical or cellular links between elevated blood glucose levels, and the vascular lesions remain incompletely understood. A number of trials have demonstrated that statins therapy as well as angiotensin converting enzyme inhibitors is associated with improvements in endothelial function in diabetes. Although antioxidants provide short-term improvement of endothelial function in humans, all studies of the effectiveness of preventive antioxidant therapy have been disappointing. Control of hyperglycemia thus remains the best way to improve endothelial function and to prevent atherosclerosis and other cardiovascular complications of diabetes. In the present review we provide the up to date details on this subject.
 ...
PMID:Endothelial dysfunction in diabetes mellitus. 1820 Aug 6

Microalbuminuria is an important risk factor for cardiovascular disease and progressive renal impairment. This holds true in the general population and particularly in those with diabetes, in whom it is common and marks out those likely to develop macrovascular disease and progressive renal impairment. Understanding the pathophysiological mechanisms through which microalbuminuria occurs holds the key to designing therapies to arrest its development and prevent these later manifestations. Microalbuminuria arises from the increased passage of albumin through the glomerular filtration barrier. This requires ultrastructural changes rather than alterations in glomerular pressure or filtration rate alone. Compromise of selective glomerular permeability can be confirmed in early diabetic nephropathy but does not correlate well with reported glomerular structural changes. The loss of systemic endothelial glycocalyx--a protein-rich surface layer on the endothelium--in diabetes suggests that damage to this layer represents this missing link. The epidemiology of microalbuminuria reveals a close association with systemic endothelial dysfunction and with vascular disease, also implicating glomerular endothelial dysfunction in microalbuminuria. Our understanding of the metabolic and hormonal sequelae of hyperglycaemia is increasing, and we consider these in the context of damage to the glomerular filtration barrier. Reactive oxygen species, inflammatory cytokines and growth factors are key players in this respect. Taken together with the above observations and the presence of generalised endothelial dysfunction, these considerations lead to the conclusion that glomerular endothelial dysfunction, and in particular damage to its glycocalyx, represents the most likely initiating step in diabetic microalbuminuria.
 ...
PMID:What is the mechanism of microalbuminuria in diabetes: a role for the glomerular endothelium? 1834 77

Microalbuminuria is considered as a sign of high risk of renal disease in type 1 diabetes mellitus, and of cardiovascular disease in types 1 and 2 diabetes. In recent years numerous studies have suggested that microalbuminuria may be associated with atherosclerotic vascular disease, independently from diabetes mellitus. The presence of microalbuminuria was investigated in 30 patients suffering from atherosclerotic vascular disease: ischemic heart disease, cerebrovascular disease or arterial disease of the lower extremities. They were divided into two groups similar in age: 13 with type 2 diabetes mellitus, and 17 without diabetes. The aim of the research was to reveal eventually different prevalence of microalbuminuria in patients with vascular disease associated with diabetes or without diabetes. Microalbuminuria was present in 52.9% of the non diabetic patients and in 76.9% of the diabetics, but the difference did not reach statistical significance (in Mann-Whitney test p = 0.18; Chi-square test = 0.83; p = 0.3). No significant correlation was found between microalbuminuria and fibrinogen, total cholesterol, HDL-cholesterol and triglycerides. The hypertensive patients presented higher mean values of microalbuminuria than the normotensive ones (3.2 +/- 3.8 and 2.8 +/- 4.4 mg %, respectively), but the difference was again not significant (t = 0.25; p = 0.8). In the light of this research microalbuminuria seems to be a condition associated with atherosclerotic vascular disease, independently from the presence of diabetes mellitus and arterial hypertension.
 ...
PMID:Significance of microalbuminuria in atherosclerotic vascular disease. 1865 26

Folate status has been associated with endothelial dysfunction in adolescents with type 1 diabetes, and elevated total plasma homoocyst(e)ine (tHcy) is a risk for vascular disease in the non-diabetic population. Polymorphisms in genes involved in folate and homocysteine metabolism are implicated in vascular disease. We aimed to determine whether polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) genes are risk factors for early microvascular disease in a large group of adolescents with type 1 diabetes. Four hundred and eighty adolescents were screened annually for retinopathy and microalbuminuria for a median of 4 yr. Molecular analysis for the polymorphisms 677C-->T, 1298A-->C in MTHFR, and 66A-->G in MTRR was performed. The MTRR 66GG genotype reduced the risk for elevated albumin excretion rate (AER) (OR 0.47, CI 0.25, 0.88, p = 0.018) and showed a trend to reduced risk for microalbuminuria (OR 0.27, CI 0.06-1.21, p = 0.09). Survival without elevated AER was increased with the MTRR 66GG genotype (12.4 vs. 9.7 yr, p = 0.04) and with the MTHFR 1298CC genotype (15.2 vs. 10.2 yr, p = 0.007). Conversely, survival without retinopathy was reduced with the MTHFR 677TT and MTRR 66GG combined genotype (6.2 vs. 10.2 yr, p = 0.015). The MTRR 66GG and MTHFR 1298 CC genotypes may confer protection against early nephropathy, possibly because they are associated with lower tHcy. The MTHFR 677 TT was only related to earlier onset retinopathy in combination with MTRR 66GG.
 ...
PMID:Methylenetetrahydrofolate reductase and methionine synthase reductase gene polymorphisms and protection from microvascular complications in adolescents with type 1 diabetes. 1877 93

Low circulating VVH7-like immunoreactivity (VVH7 i.r) level was amazingly observed in human diabetic sera. Here, we examined the impact of diabetes type, clinico-biological features and metabolic control on circulating VVH7 i.r level in this disease. ELISA test was used to measure VVH7 i.r in sera of 120 diabetic patients (type 1 diabetes in 64, type 2 diabetes in 56). Three enzymatic tests were also applied to determine serum cathepsin D (CD), dipeptidyl peptidase IV (DPP-IV) and angiotensin-converting enzyme (ACE) activities. A subgroup of 24 type 1 diabetic patients negative for microalbuminuria and hypertension were submitted to an ambulatory blood pressure monitoring to evaluate the relationship between VVH7 i.r level and blood pressure parameters. The mean serum concentration of VVH7 i.r was drastically reduced in diabetic patients (0.91+/-0.93 micromol/l versus 5.63+/-1.11 micromol/l in controls) (p<0.001). A negative correlation between VVH7 i.r level and daytime diastolic blood pressure existed in type 1 diabetic patients. There was no association of low VVH7 i.r with either type of diabetes or HbA1c level. An increase of cathepsin D activity was found in serum of diabetic patients compared to controls (0.47 U/ml versus 0.15 U/ml, respectively) whereas DPPIV activity was significantly decreased in diabetic sera (50.81 U/ml versus 282.10 U/l respectively). Diminution of VVH7 i.r in sera of diabetic patients was confirmed but still remained unexplained. Relationships between higher systolic blood pressure and decrease of VVH7 i.r reinforce the need to investigate this pathway in this disease to elucidate its role in macro- and micro-angiopathy.
 ...
PMID:Significant lower VVH7-like immunoreactivity serum level in diabetic patients: evidence for independence from metabolic control and three key enzymes in hemorphin metabolism, cathepsin D, ACE and DPP-IV. 1906 27

BP is an important determinant of kidney disease among patients with diabetes. The recommended thresholds to initiate treatment to lower BP are 130/80 and 125/75 mmHg for people with diabetes and nephropathy, respectively. We sought to determine the effects of lowering BP below these currently recommended thresholds on renal outcomes among 11,140 patients who had type 2 diabetes and participated in the Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation (ADVANCE) study. Patients were randomly assigned to fixed combination perindopril-indapamide or placebo, regardless of their BP at entry. During a mean follow-up of 4.3 yr, active treatment reduced the risk for renal events by 21% (P < 0.0001), which was driven by reduced risks for developing microalbuminuria and macroalbuminuria (both P < 0.003). Effects of active treatment were consistent across subgroups defined by baseline systolic or diastolic BP. Lower systolic BP levels during follow-up, even to <110 mmHg, was associated with progressively lower rates of renal events. In conclusion, BP-lowering treatment with perindopril-indapamide administered routinely to individuals with type 2 diabetes provides important renoprotection, even among those with initial BP <120/70 mmHg. We could not identify a BP threshold below which renal benefit is lost.
 ...
PMID:Lowering blood pressure reduces renal events in type 2 diabetes. 1922 38

Type 2 Diabetes (T2D) is an important cause of renal dysfunction and the most common cause of end-stage renal disease (ESRD). Diabetic nephropathy is also associated with an increased risk of vascular disease and patient mortality. Aggressive management of hypertension to reduce microalbuminuria, together with tight glycaemic control are important therapeutic strategies for renal and vascular disease prevention in T2D. The main pathophysiological mechanisms associated with diabetic nephropathy result from activation of the renin-angiotensin-aldosterone system (RAAS), protein kinase C pathway, pro-inflammatory cytokines and various growth factors. Angiotensin II and transforming growth factor-beta (TGF-beta) are two important molecular mediators. The production of advanced glycation end-products (AGEs) and increased oxidative stress further exacerbates renal injury. These molecular changes within the renal tissue result in mesangial expansion, increased extracellular matrix deposition and an alteration in podocyte structure and function. Therapeutic targeting of these molecular pathways is an important area of translational research in diabetes. The elucidation of new genetic associations and proteomic biomarkers of diabetic kidney disease will also assist in the identification and treatment of high-risk patients. This review article will discuss both the molecular and clinical aspects of diabetic nephropathy, providing a bench-to-bedside research perspective to potential new therapeutic strategies.
 ...
PMID:Therapeutic strategies in the treatment of diabetic nephropathy - a translational medicine approach. 1927 8

Endothelial dysfunction is a fundamental step in the atherosclerotic disease process. Its presence is a risk factor for the development of clinical events, and may represent a marker of atherothrombotic burden. Also, endothelial dysfunction contributes to enhanced plaque vulnerability, may trigger plaque rupture, and favors thrombus formation. The assessment of endothelial vasomotion is a useful marker of atherosclerotic vascular disease. There are different methods to assess endothelial function: endothelium-dependent vasodilatation brachial flow-mediated dilation, cerebrovascular reactivity to L-arginine, and the determination of some biomarkers such as microalbuminuria, platelet function, and C-reactive protein. Endothelial dysfunction has been observed in stroke patients and has been related to stroke physiopathology, stroke subtypes, clinical severity and outcome. Resting ankle-brachial index (ABI) is also considered an indicator of generalized atherosclerosis, and a low ABI is associated with an increase in stroke incidence in the elderly. Despite all these data, there are no studies analyzing the predictive value of ABI for new cardiovascular events in patients after suffering an acute ischemic stroke. ARTICO is an ongoing prospective, observational, multicenter study being performed in 50 Spanish hospitals. The aim of the ARTICO study is to evaluate the prognostic value of a pathological ABI (<or=0.9) in the presence of a major cardiovascular event during a 1-year follow-up after first-ever ischemic stroke. Secondary objectives include the evaluation of the predictive value for major cardiovascular events of the carotid intima-media thickness, carotid duplex findings, and certain biomarkers. Data from the ARTICO study will increase the knowledge of patient outcome after ischemic stroke and may help to improve our ability to detect patients at high risk of stroke recurrence or major cardiovascular events.
 ...
PMID:Endothelial dysfunction, vascular disease and stroke: the ARTICO study. 1934 31

Difficulties in achieving a reduction in morbidity and mortality in patients with diabetes are a result of the complexity of the disease and its intertwined relationship with hypertension and renal impairment. In the recently published Action in Diabetes and Vascular disease: PreterAx and DiamicroN-MR Controlled Evaluation (ADVANCE) trial, treatment of patients with diabetes with the fixed combination perindopril/indapamide on top of background treatments provided clinically and statistically significant reductions in blood pressure (from 145/81 to 136/73 mmHg), all-cause mortality (-14%), cardiovascular mortality (-18%), major cardiovascular events (-9%), renal events (-21%) and new-onset microalbuminuria (-21%) when compared with placebo. As the ADVANCE trial included both hypertensive and normotensive patients, its results suggest that systematically treating all patients with diabetes with perindopril/indapamide, independently of their baseline blood pressure, may have significant long-term value that can be explained partly by the reversal of end-organ damage to the kidney and the heart. Considering that patients with both hypertension and diabetes are characterized by generalized macro- and microvascular disease, the results of the ADVANCE trial, taken together with results of other perindopril/indapamide hypertension studies, support a broad use of perindopril/indapamide treatment for the long-term improvement of prognosis in hypertensive patients as well as in patients with diabetes.
 ...
PMID:Protection of patients with diabetes, with or without hypertension: implications of ADVANCE for clinical practice. 1948 4


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>