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)

The aim of this cross-sectional study was to investigate the relationship between low-grade albuminuria (microalbuminuria) and factors of the coagulation- and fibrinolysis systems in 104 clinically healthy 58-year-old men recruited from the general population. Urinary albumin excretion was significantly associated with body mass index, systolic and diastolic blood pressure, plasminogen activator inhibitor (PAI)-1 activity, tissue plasminogen activator (tPA) antigen, tPA activity (negatively) and protein S (P<0.05). There were no associations between urinary albumin excretion and antithrombin III, fibrinogen, protein C, thrombin/antithrombin factor or von Willebrand factor. In multiple regression analysis urinary albumin excretion was independently and significantly associated with PAI-1 activity and systolic blood pressure (P<0.05). In conclusion we report that urinary albumin excretion was independently and significantly associated with PAI-1 activity in clinically healthy 58-year-old men. This relationship may contribute to the previously reported increased cardiovascular morbidity in subjects with microalbuminuria.
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PMID:Independent relationship between microalbuminuria and plasminogen activator inhibitor-1 activity (PAI-1) activity in clinically healthy 58-year-old men. 1142 21

Even small increases in the frequency of thrombotic disease in users of OCs have general health impact because of their widespread use, which is currently expanding to potential risk groups. The present investigations were launched to study the effects of OCs containing 20-40 micrograms of EE combined with the latest developed gonane progestogens on biochemical risk markers within metabolic systems involved in the development of arterial thrombotic disease. The studies included evaluation of carbohydrate and lipid metabolism as well as the haemostatic system and were performed in non-diabetic women and in women with IDDM, who are prone to the development of arterial thrombosis. In the evaluation of the carbohydrate metabolism in non-diabetic women, we found no effect on fasting glucose or insulin and no effect on the insulin response to oral glucose in women using monophasic OCs containing EE combined with DSG or GST. This contrasts the evaluation of triphasic OCs containing EE combined with GST or NGT, which increased fasting insulin and reduced insulin sensitivity without affecting the glucose-effectiveness or the beta-cell function. Impaired glucose tolerance developed in 10% of the women after 6 months. These finding suggest that OCs are able to induce a state of insulin resistance, which should be considered in the prescription for women with potential disturbed insulin sensitivity or reduced beta-cell secretory capacity e.g. women with ovarian hyperandrogenism, obesity, previous GDM or perimenopausal women. We found no change in glycaemic control in 22 women with well-regulated IDDM treated with a monophasic combination of EE and GST for one year and none of the women developed microalbuminuria during treatment. In the women with diabetes we observed an increase in fasting levels of triglycerides, a decrease in LDL-cholesterol, and unchanged concentrations of total cholesterol and HDL-cholesterol during treatment. In non-diabetic women treated with the same compound or an OC containing EE and DSG we found similar changes in triglycerides and total cholesterol, but increased levels of HDL-cholesterol and unchanged LDL-cholesterol concentrations. In the women with IDDM there was a negative correlation between daily insulin requirement and HDL-cholesterol before and during treatment, but no other statistically significant correlation between estimates of glycaemic control and lipids and lipoproteins were observed. In the non-diabetic women, changes in the haemostatic system included an increase in the procoagulant factors fibrinogen and Factor VIIc; the concentration of active t-PA increased, mainly because of decreased inhibition by PAI-1. The ratio between molecular markers of the activity of the coagulation system and the efficacy of fibrinolysis was unchanged. This was also found in the women with IDDM, who showed evidence of increased fibrin formation and an attenuated fibrinolytic response during treatment. The regulation of the t-PA/PAI system was studied in non-diabetic women in order to elucidate if the effects of OCs are caused by a direct effect on synthesis or clearance of these variables or if they are secondary to changed insulin sensitivity, as described in individuals with atherosclerosis. We found no indications that insulin resistance is involved in the regulation of t-PA and PAI-1 antigen levels, neither before nor during intake of OCs. We showed, however, that the decreased t-PA antigen concentration observed in OC users is caused by reduced synthesis outside the splanchnic circulation. The studies indicate that low-dose OCs containing newer gonane progestogens are able to induce insulin resistance and to impair glucose tolerance. Lipoproteins were not adversely influenced by the OCs neither in the diabetic nor the non-diabetic women; on the contrary, there was a tendency towards increased plasma levels of HDL-cholesterol and decreased LDL-cholesterol which are associated with a decreased risk of atherosclerosis. The changes observed within the haemostatic system were in accordance with a maintained balance between coagulation and fibrinolysis although the rate of fibrin formation may be increased in the women with IDDM. Irrespective of OC use, the interrelationships between metabolic systems in young non-diabetic women are different from those reported in individuals with atherosclerosis or insulin resistance. The effects of OCs on the t-PA/PAI system seem to be mediated by a direct effect on the vessel wall and not by changes in the hepatic clearance. The present findings were obtained in diabetic women without vascular complications, so the conclusion that women with IDDM can use OCs without metabolic alterations of known clinical significance is therefore restricted to those without evidence of diseased vessels. When evaluating the results obtained in the non-diabetic women, it should be remembered that women with recognised risk factors were excluded. The results may therefore be of limited value when evaluating the risk of arterial thrombosis in predisposed populations. In healthy individuals, the present integrated evaluation of biochemical markers does not indicate an increased risk of arterial thrombosis during use of low-dose OCs containing newer gonane progestogens; thus, the findings are in accordance with the recent epidemiological studies on these compounds. The application of relevant biochemical markers facilitate the understanding of the non-reproductive effects of sex steroids which have increasing importance because of their expanding use, not only as contraceptives, but also in the treatment of benign gynaecological disorders, as hormone replacement therapy and as prophylactic agents against specific degenerative conditions. Moreover, they may prove to be helpful in the future identification of women, who have increased susceptibility to the metabolic effects of sex steroids due to genetic predisposition.
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PMID:Pharmacodynamic effects of oral contraceptive steroids on biochemical markers for arterial thrombosis. Studies in non-diabetic women and in women with insulin-dependent diabetes mellitus. 1189 23

Rosiglitazone, a potent member of the thiazolidinedione class of oral antidiabetic agents, reduces hyperglycaemia by improving insulin sensitivity--an important underlying factor in the development of both type 2 diabetes and its related cardiovascular complications. Rosiglitazone has now been available in clinical practice for more than three years, so there is a large body of evidence supporting its efficacy and safety as an antihyperglycaemic agent in patients with type 2 diabetes. Given the significant burden imposed on patients and healthcare resources by diabetes-related cardiovascular disease (CVD), there is growing interest in the thiazolidinediones in terms of their potential to ameliorate CVD risk factors as a result of their insulin-sensitising action and thus improve cardiovascular outcomes in individuals with type 2 diabetes. As reviewed below, rosiglitazone has a beneficial impact on a number of factors associated with insulin resistance and CVD, including microalbuminuria, hypertension, dyslipidaemia, visceral fat, elevated plasminogen activator inhibitor-1 levels and increased concentrations of C-reactive protein. These thiazolidinedione compounds are not problem-free and the long-term implications of some of rosiglitazone side-effects such as weight gain, changes in LDL-cholesterol concentration and fluid retention remain to be resolved. Large-scale clinical outcome studies should give a clearer picture for rosiglitazone and related thiazolidinediones in relation to the extent of their impact on diabetes disease progression and incident cardiovascular events.
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PMID:Rosiglitazone: potential beneficial impact on cardiovascular disease. 1266 97

The simultaneous presence of various cardiovascular risk factors in the same individual is not rare, even in the pediatric age group. The clustering of risk factors can be termed insulin resistance syndrome (IRS) because of the putative central role of tissue insulin insensitivity in the background of the inter-related metabolic disturbances. Fasting hyperinsulinemia, impaired glucose tolerance, dyslipidemia, and hypertension are considered to represent the basic abnormalities of IRS. The most prevalent related disturbances are increased plasma levels of plasminogen activator inhibitor-1, fibrinogen, uric acid, homocysteine, and C-reactive protein, as well as visceral adiposity, microalbuminuria, disturbed essential fatty acid metabolism, low availability of lipid-soluble antioxidant vitamins, and enhanced expression of tumor necrosis factor-alpha in adipose tissues. Certain genetic abnormalities have been associated with IRS, but explain only a small part of the variability in insulin resistance. The exact prevalence of IRS in children remains to be defined; it was found to be 9% in one survey among children with obesity seeking medical attention. Modification of lifestyle, i.e. reduction of energy intake and enhancement of physical activity, are unquestionable prerequisites for long-term success in the management of IRS. In at least two randomized controlled studies, metformin proved to be clinically effective in increasing insulin sensitivity in hyperinsulinemic, nondiabetic adolescents. Thiazolidinediones have been successfully tested for the treatment of insulin resistance in adults, but not in children as yet. Prevention of the development of IRS in children is obviously of great significance for the health status of the community. However, the efficacy of various preventive approaches should be investigated further in carefully designed controlled trials.
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PMID:Insulin resistance syndrome in children : pathophysiology and potential management strategies. 1271 16

Type 2 diabetes is characterised by insulin resistance in association with clustering of atherothrombotic risk factors (dysglycaemia, hyperinsulinaemia, hypertension, raised triglyceride, low HDL cholesterol and increased levels of plasminogen activator inhibitor-1 (PAI-1) and clotting factor VII). There is a 3-5 fold increase in risk of myocardial infarction rising to 10-20 fold in the presence of microalbuminuria and overall around 70-75% of subjects with type 2 diabetes die of cardiovascular disease. However, classical risk factors which associate with insulin resistance do not account for all the increased burden of vascular disease in diabetic subjects. Metformin is a biguanide compound which is antihyperglycaemic, reduces insulin resistance and has cardioprotective effects on lipids, thrombosis and blood flow. Metformin has a weight neutral/weight lowering effect and reduces hypertriglyceridaemia, elevated levels of PAI-1, factor VII and C-reactive protein. In addition recent studies indicate that metformin has direct effects on fibrin structure/function and stabilises platelets, two important components of arterial thrombus. The United Kingdom Prospective Diabetes Study (UKPDS) reported that metformin was associated with a 32% reduction in any diabetes related endpoint (p<0.002), a 39% reduction in myocardial infarction (p<0.01) and a non-significant 29% fall in microvascular complications. The figures for macrovascular complications compare favourably for those described for other cardioprotective agents such as ACE inhibitors and statins. These findings confirm metformin as first line therapy in the management of obese insulin resistant type 2 diabetes and in the prevention of the vascular complications of this common condition.
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PMID:Beneficial effects of metformin on haemostasis and vascular function in man. 1450

Insulin resistance, both in nondiabetic and diabetic subjects, is frequently associated with obesity, particularly an excess of central fat. Many of the features that have been ascribed to the metabolic or insulin-resistance syndrome are also more commonly found in obese subjects. These phenotypes include diabetic dyslipidaemia, elevation of levels of plasminogen activator inhibitor-1, microalbuminuria and endothelial dysfunction. More recently, features of acute-phase activation and low-grade inflammation, including elevated levels of fibrinogen, C-reactive protein and interleukin-6, have been associated with (central) obesity. Adipose tissue generation of cytokines has been shown in vitro and in vivo, and a number of novel cytokine-like molecules, collectively termed adipocytokines, have been identified as adipocyte products. While several of these, such as tumour necrosis factor-alpha, may act predominantly in autocrine or paracrine fashion, others are released into the systemic circulation, acting as signalling molecules to remote tissues, including liver, skeletal muscle and endothelium. A clearer understanding of adipose tissue signalling, and its contribution to the state of low-grade inflammation of obesity, will require physiological, as well as cellular and molecular, studies.
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PMID:Adipose tissue, insulin action and vascular disease: inflammatory signals. 1470 40

Testicular cancer patients have an increased risk for coronary artery disease more than ten years after cisplatin-based chemotherapy. We investigated whether vascular changes, including endothelial dysfunction, are present earlier. Ninety chemotherapy-treated testicular cancer patients (median follow-up of seven years) were compared with 44 patients after orchidectomy only and 47 healthy men. Microalbuminuria was present in 10 (12%) chemotherapy patients, one stage I patient and none of the controls. Chemotherapy patients had higher levels of fibrinogen, C-reactive protein (hs-CRP), von Willebrand factor (vWF), plasminogen activator inhibitor (PAI-1), and tissue-type plasminogen activator (t-PA). Chemotherapy patients with elevated PAI-1 (25/90) showed clustering of cardiovascular risk factors resembling the metabolic syndrome. In conclusion, cured testicular cancer patients showed a high prevalence of microalbuminuria and increased plasma levels of endothelial and inflammatory marker proteins, which might progress to more severe endothelial dysfunction and overt atherosclerosis.
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PMID:Microalbuminuria, decreased fibrinolysis, and inflammation as early signs of atherosclerosis in long-term survivors of disseminated testicular cancer. 1501 71

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

Excess body weight may be associated with various functional/structural lesions of the kidney. The spectrum ranges from glomerulomegaly with or without focal or segmental glomerulosclerosis, to diabetic nephropathy, to carcinoma of the kidney and nephrolithiasis. The first sign of renal injury is microalbuminuria or frank proteinuria, in particular in the presence of hypertension. The occurrence of microalbuminuria and/or chronic kidney insufficiency (glomerular filtration rate < 60 mL/min/1.73 m2) is related to the increasing number of components of the metabolic syndrome, ie, central obesity, elevated fasting blood glucose level, hypertriglycerides, low high-density lipoprotein cholesterol, and hypertension. In the long run, end-stage renal failure may develop. An increased body mass index is particularly harmful in patients with reduced renal functional mass (unilateral renal agenesis or nephrectomy) and other renal diseases (immunoglobulin A nephritis and chronic graft dysfunction after kidney transplantation). In the pathogenesis of obesity-associated glomerulopathy, hyperfiltration is of fundamental importance. The factors involved are energy intake (high protein and salt), hyperinsulinemia, and enhanced tubuloglomerular feedback because of increased sodium reabsorption. The adrenergic and renin-angiotensin-aldosterone systems as well as glucocorticoids are stimulated. In addition, several active proteins generated in the central adipose tissue, such as leptin, proinflammatory cytokines, plasminogen activator inhibitor-1, angiotensinogen, and growth factors (transforming growth factor-beta1), as well as low levels of the protective adiponectin, may contribute to renal injury. Of greatest importance is the development of hypertension and of diabetes, which are directly related to the severity of central obesity. Obesity-associated renal disease should be prevented or retarded by weight reduction following lifestyle modification (salt restriction, hypocaloric diet, aerobic exercise), or eventually by antiobesity medication or bariatric surgery. In the presence of glomerulopathy and/or hypertension, angiotensin converting enzyme inhibitors or angiotensin II type I receptor blockers are the drugs of choice to improve glomerular hyperfiltration.
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PMID:Renal disease in obesity: the need for greater attention. 1682 23

Microalbuminuria (MA) is known as a marker for generalized vascular dysfunction. It occurs most commonly in the setting of diabetes and hypertension; however, its association with cerebral small vessel disease (SVD) in community-based elderly remains to be clarified. In this cross-sectional analysis, we evaluated the association between MA and cerebral SVD in total 651 community-based elderly subjects. We assessed cardiovascular risk factors by interviews and physical examinations, including an evaluation of urinary albumin creatinine ratio (UACR). All subjects underwent brain magnetic resonance imaging (MRI) and carotid ultrasonography. As endothelial markers, the serum levels of thrombomodulin (TM) and a tissue-type plasminogen activator/ plasminogen activator inhibitor-1 complex were also studied. The mean TM and UACR were higher in subjects with lacunar infarcts or with moderate white matter hyperintensities (mWMH) on MRI than in those without them. Additionally, the prevalence of lacunar infarcts or mWMH was higher in the highest tertile of UACR level than in the lowest or middle tertile. Furthermore, in logistic regression analysis, the elevation of logarithmically transformed UACR (log UACR) was associated with the higher likelihood for total lacunar infarcts (odds ratio [OR], 1.85 per one log UACR increase), multiple lacunar infarcts (OR, 1.89 per one log UACR increase), and mWMH (OR, 2.15 per one log UACR increase). The present study revealed that levels of urinary albumin are associated with cerebral SVD, independently of traditional cerebrovascular risk factors, in community-based elderly.
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PMID:Microalbuminuria is a risk factor for cerebral small vessel disease in community-based elderly subjects. 1732 Sep 8


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