Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0730345 (microalbuminuria)
 4,018 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

THREE DEFINITIONS: The metabolic or X syndrome is defined by an association of metabolic anomalies leading to an increased risk of cardiovascular complications. Today, there are at least 3 definitions of X syndrome: those of WHO, EGIR and NCEP. To varying degrees they associate increased abdominal fat, hypertension, glucose tolerance abnormality (ranging from hyperinsulinism to diabetes), and hypertriglyceridemia with low HDL cholesterol. FROM AN EPIDEMIOLOGICAL POINT OF VIEW: The prevalence of metabolic syndrome depends on the definition used and varies with the country or ethnic group considered. About 25% of the US and 10% of the French adult populations are concerned. THE RISK OF COMPLICATIONS: According to clinical trials, people with metabolic syndrome have a 2 to 4-fold increase in risk for coronary heart disease. Some of them have a particularly high risk (association of most features of the syndrome, association of an increased waist circumference and hypertriglyceridemia, presence of biological markers such as elevated C-reactive protein or microalbuminuria). Metabolic syndrome is also associated with a 4-fold increase in risk for developing diabetes.
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PMID:[Epidemiological data and screening criteria of the metabolic syndrome]. 1525 40

Microalbuminuria is a novel atherosclerotic risk factor in patients with type 2 diabetes mellitus (DM) and predicts future cardiovascular events. Endothelial dysfunction and systemic inflammation have been proposed as common links between microalbuminuria and cardiovascular disease. However, no study has assessed the relation between microalbuminuria and vascular dysfunction as measured by brachial artery reactivity (BAR) in DM. We evaluated 143 patients (85 men; mean age 60.0 +/- 6.7 years) with DM (mean duration 8.2 +/- 7.4 years) enrolled in the Detection of Ischemia in Asymptomatic Diabetics study. Subjects were categorized as those with microalbuminuria (ratio of urinary albumin to creatinine 30 to 299 microg/mg creatinine, n = 28) and those with normoalbuminuria (ratio of urinary albumin to creatinine 0 to 29.9 microg/mg creatinine, n = 115). High-resolution ultrasound BAR testing was used to measure endothelium-dependent and endothelium-independent vasodilations. C-reactive protein was measured as a marker of systemic inflammation. Patients with microalbuminuria and normoalbuminuria had similar baseline characteristics, with the exception that those with microalbuminuria had a longer duration of DM (p = 0.03). Endothelium-dependent vasodilation at 1 minute (p = 0.01) and endothelium-independent vasodilation at 3 minutes (p = 0.007) were significantly less in patients with microalbuminuria. In addition, 96% of patients with microalbuminuria and 76% of those with normoalbuminuria had impaired endothelium-dependent vasodilation (<8%, p = 0.01). Microalbuminuria was an independent predictor of endothelium-dependent vasodilation in the entire cohort (p = 0.045) and after excluding patients on hormone replacement therapy (p = 0.01). Levels of C-reactive protein were significantly higher in patients with microalbuminuria than in those with normoalbuminuria (p = 0.02). We conclude that in DM the presence of microalbuminuria is associated with impaired endothelium-dependent and endothelium-independent vasodilations of the brachial artery and a higher degree of systemic inflammation. In addition, microalbuminuria is an independent predictor of endothelial dysfunction in asymptomatic patients with DM, especially in the absence of hormone replacement therapy.
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PMID:Brachial artery reactivity in asymptomatic patients with type 2 diabetes mellitus and microalbuminuria (from the Detection of Ischemia in Asymptomatic Diabetics-brachial artery reactivity study). 1527 91

Numerous studies document an almost linear association between the level of albuminuria and risk for a cardiovascular event. Recent data also demonstrate a strong association between the presence of microalbuminuria and elevations in C-reactive protein. Therefore, the increased membrane permeability that generates microalbuminuria might be secondary to an inflammatory process. Progression from microalbuminuria to macroalbuminuria indicates worsening of vascular disease and presence of kidney disease. Recent pharmacologic interventions have resulted in significant delay and even arrest of progression of microalbuminuria to macroalbuminuria as well as kidney disease progression. Therefore, focus should be placed on use of antihypertensive agents that not only lower blood pressure but also lower or normalize albuminuria levels. All recent guideline statements support the use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs). Further lowering of albuminuria may be achieved by adding verapamil, diltiazem, or an ARB to an ACE inhibitor.
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PMID:Clinical importance of microalbuminuria in diabetes and hypertension. 1534 86

The current recommendations by all United States guideline committees, including the American Diabetes Association and the JNC 7, include screening for microalbuminuria in those with diabetes or evidence of kidney disease, but not the general population. Internationally, both the Canadian and European Guidelines have concurred with this approach. This recommendation is due in part to the findings from long-term outcome studies that measurement of microalbuminuria, while a strong predictor of cardiovascular risk, fails to shows change in CV events if reduced. Unfortunately, this conclusion may be wrong because no randomized trial has examined the question of whether a reduction in microalbuminuria does correlate with a reduction in CV events. Thus, we don't know the answer to this question. Additionally, a recent cost-effective analysis was just published, suggesting it is not worth measuring urinary albumin because it is too expensive for the information obtained. Unfortunately, these conclusions were based on the same faulty logic that relates changes in microalbuminuria to cardiovascular events. It is clear that microalbuminuria is a cardiovascular risk factor, acknowledged by both the JNC 7 and the European Guidelines. Moreover, presence of microalbuminuria correlates strongly with elevated levels of C-reactive protein and abnormal vascular responsiveness to vasodilating stimuli. Thus, its presence indicates abnormal responses by vascular tissue, perhaps due to underlying inflammatory responses. Every clinical trial that has assessed changes in albuminuria as a secondary end point with clinical outcomes has shown a strongly positive correlation between reduction in albuminuria and greater protection of a given end organ; this effect is, in part, independent of blood pressure reduction. Thus, what is needed is a clinical trial in people at high cardiovascular risk, such as those in the INVEST or ALLHAT trials where the primary end point is change in albuminuria and its relationship to cardiovascular outcomes. Likewise, a cardiovascular primary end point could relate to the secondary end point of changes in microalbuminuria, and the latter powered appropriately to make stronger statements about albuminuria and cardiovascular outcomes. With this data, guidelines can then make much strong statements about intervention on this marker of risk.
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PMID:Inclusion of albuminuria in hypertension and heart guidelines. 1548 6

Albuminuria is recognized in all hypertension guideline statements as a cardiovascular risk factor and indicator of kidney disease. Recent data also demonstrate a strong association between the presence of microalbuminuria and elevations in C-reactive protein. Thus, the increased membrane permeability that generates microalbuminuria may be secondary to an inflammatory process. Progression from microalbuminuria (>30 and < or =300 mg albumin/g creatinine) to macroalbuminuria (>300 mg albumin/g creatinine) indicates a worsening of vascular disease and the presence of kidney disease. Recent outcome trials of kidney disease progression have demonstrated the best results among those with reductions in albuminuria in concert with blood pressure (BP) reduction. Thus, use antihypertensive agents that not only lower BP but also lower or normalize albuminuria levels. All recent guideline statements support the use of agents that block the renin-angiotensin-aldosterone system as part of a regimen to achieve the BP goal. Further lowering of albuminuria may be achieved by adding either a nondihydropyridine calcium antagonist such as verapamil or diltiazem, or aldosterone receptor blockers. Use of an angiotensin receptor blocker added to an angiotensin-converting enzyme inhibitor or vice versa can further lower albuminuria by an additional 30%-40%, which is not true of the additional lowering of BP.
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PMID:Implications of albuminuria on kidney disease progression. 1553 7

To evaluate markers of inflammation, we studied 48 patients with type 1 diabetes [DM1, 23F:25M, 19.9+/-9.8 years and duration of DM of 5 (1-21) years& and 66 non-DM subjects, matched for sex, age, and stages of puberty according to Tanner. C-reactive protein (CRP), alpha1-acid glycoprotein (AGP) and fibrinogen were measured by turbidimetric immunoassay and urinary albumin excretion rate (AER) was determined in timed overnight urine samples by RIA. Microalbuminuria was defined when two out of three urine samples had AER ranging 20-200 microg/min. Retinopathy was evaluated by indirect ophthalmoscopic in DM patients. The CRP and AGP levels were higher in DM1 patients as compared to controls, respectively [0.23 (0.01-2.90) vs. 0.14 (0.01-2.41) mg/dl, p= 0.0172& and [53.5 (37-115) vs. 40 (19-78) mg/dl, p< 0.0001]. Fibrinogen levels were not different between both groups. Stepwise multiple regression analysis showed that HbA1c and plasma glucose were the independents predictive variables of AGP, respectively (r2= 0.26; p< 0.05 and r2= 0,29; p< 0,05); CRP and fibrinogen did not correlate significantly with the independents variables. PCR correlate with HbA1c (r= 0.18; p= 0.05) by Pearson's correlation. In conclusion, CRP and AGP were higher in DM1 patients, without microalbuminuria, retinopathy and clinical macrovascular disease. Prospective studies must be addressed to determine the influence of AGP and CRP in the development of chronic complications.
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PMID:[Markers of inflammation in type 1 diabetic patients]. 1564 Aug 80

Microalbuminuria, and recently, hypoadiponectinemia, have been associated with progression of atherosclerotic disease and increased cardiovascular risk. We examined the possible associations of urinary albumin excretion, expressed as the ratio of albumin to creatinine (ACR), with plasma adiponectin and high-sensitivity C-reactive protein (hs-CRP) levels in men who had essential hypertension. The study population consisted of 108 men who did not have diabetes and were newly diagnosed with stage I to II essential hypertension (age 44.6 years, office blood pressure 148/95 mm Hg) and 110 men matched according to age and body mass index as controls. According to ACR values, which were determined as the average of 2 nonconsecutive overnight spot urine samples, subjects who had hypertension were categorized into 2 groups: those who had microalbuminuria (n = 28; mean ACR 30 to 300 mg/g) and those who had normal albuminuria (n = 80; mean ACR <30 mg/g). Subjects who had hypertension compared with controls exhibited higher ACR and log hs-CRP levels and a trend toward lower log adiponectin values (p = 0.062), whereas those who had normal albuminuria compared with controls had similar log adiponectin levels but significantly higher levels of ACR and log hs-CRP. Moreover, subjects who had hypertension and microalbuminuria compared with those who had hypertension and normal albuminuria had higher log hs-CRP and lower log adiponectin concentrations independently of confounding factors. Among those who had hypertension, ACR exhibited an independent positive correlation with log hs-CRP and a negative correlation with log adiponectin. Multiple linear regression analysis showed that age, body mass index, systolic blood pressure, log hs-CRP, and log adiponectin were significant independent predictors of the ACR. In conclusion, microalbuminuria is accompanied by decreased adiponectin and increased hs-CRP levels in the setting of essential hypertension, reflecting a rather diffuse atherosclerotic process.
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PMID:Relation of microalbuminuria to adiponectin and augmented C-reactive protein levels in men with essential hypertension. 1618 22

Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a nuclear transcription factor that comprises the primary molecular target for thiazolidinedione (TZD) insulin-sensitizing drugs. Whilst expressed in many tissues in humans, its abundant expression in adipose tissue is believed to be the focal point through which TZDs regulate genes involved in glucose and lipid metabolism and via which these agents ultimately improve the hyperglycemia of type 2 diabetes. However, TZDs exhibit many additional properties, not least an array of effects which suggest a broad attack on the inflammatory process. Thus, TZDs have been shown to reduce plasma levels of the chemokine, monocyte chemotactic protein-1 (MCP-1), the anti-fibrinolytic protein, plasminogen activator inhibitor-1 (PAI-1), the endothelial cell adhesion molecules, e-selectin and inter-cellular adhesion molecule-1 (ICAM-1), the leucocyte-activating molecule, CD40L, and the tissue-remodeling enzyme, matrix metalloproteinase-9 (MMP-9). Further tangible evidence of a reduction by TZDs of systemic inflammation in patients with the classical metabolic syndrome stems from falls in the white blood cell count, P-selectin-positive platelets and in the acute-phase inflammatory proteins, C-reactive protein, serum amyloid A and fibrinogen. At the tissue level, TZDs improve vascular endothelial function, and reduce the rate of progression of intimal-medial thickening of the carotid artery and the microalbuminuria of type 2 diabetes. Further, TZDs have been shown to be efficacious in inflammatory diseases as wide-ranging as psoriasis, ulcerative colitis and non-alcoholic steatohepatitis (NASH). In the case of the latter, a broad spectrum of TZD-related properties is visible. Here, these drugs improve insulin sensitivity for glucose metabolism, reduce hyperinsulinemia, hepatic steatosis, inflammation and fibrosis, and lower the circulating levels of liver transaminases (ALT, AST), alkaline phosphatase and gamma glutamyl transferase. These effects in humans are also well-supported by investigative animal and in vitro studies. The ameliorative effects on liver fibrosis are of particular interest since they suggest that TZDs are able to activate a program of corrective tissue-remodeling. The basis for this action may be partly an ability to inhibit matrix protein secretion by hepatic stellate cells. An analogous action has also been seen in kidney mesangial cells. In conclusion, TZDs are important new drugs, presently indicated for the treatment of type 2 diabetes but with a spectrum of properties which suggests their potential for treating a number of degenerative inflammatory diseases, including NASH. However, full-scale, long-term clinical trials are needed with TZDs to test their potential to treat NASH, not least because of the (hepatotoxic) legacy of the prototype TZD, troglitazone, but also in view of the escalating burden of liver disease which is accompanying the increasing global prevalence of clinical obesity and type 2 diabetes.
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PMID:Thiazolidinediones: Pleiotropic drugs with potent anti-inflammatory properties for tissue protection. 1619 19

Diabetic nephropathy is diagnosed either when persistent increase of urinary albumin excretion rate (UAER) above 30 mg/24h in a patient with diabetes was discovered (early or incipient nephropathy) or when UAER values are persistently elevated above 300 mg/24h (overt or clinical nephropathy). In both situations the additional criteria of presence of diabetic retinopathy and the absence of the evidence of other kidney or renal tract disease should be fulfilled. It was found that the excess of cardiovascular events and mortality occurs already in diabetic patients with persistent microalbuminuria, but is particularly evident in macroalbuminuric diabetic patients and results not only from end-stage renal failure (ESRF) but rather from cardiovascular disease (CVD), the latter mainly in type 2 diabetic patients. Several traditional risk factor for atherosclerosis has been identified in diabetic patients with micro- or macroalbuminuria including elevated blood pressure levels, dyslipidemia and procoagulatory state associated with endothelial dysfunction. Microalbuminuria is currently regarded as a marker of generalized endothelial damage, it reflects transvascular albumin leakage, now recognized as an early event in atherogenesis. Recently the association of microalbuminuria with the marker of chronic inflammation (C-reactive protein) and with increased production of vascular endothelial growth factor (VEGE) was described. Thus, multiple mechanisms are involved in the development and progression of cardiovascular complications both in micro- and macroalbuminuric diabetic patients and all these mechanisms should be regarded as the target for therapeutic intervention.
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PMID:Diabetic nephropathy and cardiovascular diseases. 1635 50

In 70 nonobese inpatients with Type 2 diabetes [body mass index (BMI): 24.0+/-4.4 kg/m(2)], we examined circulating monocyte chemoattractant protein (MCP) -1 as a candidate marker of atherosclerosis by comparison with established markers: serum high-sensitivity C-reactive protein (hsCRP), plasma fibrinogen, and combined carotid artery intimal-medial thickness (IMT). In addition, an association was sought between circulating MCP-1 and urinary albumin excretion (UAE), reflecting diabetic renal microangiopathy. Serum MCP-1 was determined by enzyme-linked immunosorbent assay (ELISA). Patients were grouped by UAE: normoalbuminuria, below 30 mg/g of creatinine (Cr); microalbuminuria, 30 to 300 mg/g Cr; or macroalbuminuria, over 300 mg/g Cr. Serum MCP-1 for all participants, men, and women was 280.0+/-78.9, 269.0+/-68.8, and 294.9+/-87.9 pg/ml, respectively, showing no difference between genders. No correlation was noted between MCP-1 and hsCRP, fibrinogen, or carotid artery IMT. No correlation of MCP-1 was observed with age, duration of diabetes, fasting plasma glucose (FPG), hemoglobin (Hb) A(1C), BMI, diastolic blood pressure (DBP), or serum lipid concentrations, but significant correlations were found with systolic blood pressure (SBP; R=.2723, P=.0225) and with log(10)-transformed (log) UAE (R=.3343, P=.0047). Patients with macroalbuminuria had significant higher circulating MCP-1 than did those with normo- or microalbuminuria (P=.0063 and P=.0188, respectively). By stepwise regression analysis, only log UAE independently predicted serum MCP-1 (beta=.3700, P=.0020). Thus, in nonobese Type 2 diabetic patients, MCP-1 might not be a marker of atherosclerosis and might be influenced significantly by diabetic nephropathy.
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PMID:Association between circulating monocyte chemoattractant protein-1 and urinary albumin excretion in nonobese Type 2 diabetic patients. 1650 38


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