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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A slightly elevated urinary albumin excretion rate (UAER), above 5-10 microgram/min, is a predictor of atherosclerotic cardiovascular disease. Endothelial dysfunction is an important early feature of atherosclerosis. The plasma concentration of von Willebrand factor (vWF), a potential marker of endothelial dysfunction, predicts a subsequent increase of UAER in patients with diabetes. The aim of this study is to test the hypothesis that high concentrations of vWF as well as other haemostatic factors predict progression of UAER in clinically healthy subjects. UAER was measured together with selected markers of haemostatic function-vWF, tissue plasminogen activator (tPA), plasminogen activator inhibitor, factor VII and fibrinogen-in healthy volunteers aged 40-65 years. After a mean follow-up of 4.1 years, 64 of 74 agreed to a re-examination including re-measurement of UAER. Baseline vWF and tPA were both positively correlated to the change in UAER during follow-up (r=0.26, P=0.04 and r=0.40, P=0.001 respectively). The mean UAER increased significantly by 7.6 microgram/min and 7.5 microgram/min respectively in subjects with vWF and tPA above the medians at baseline (P=0.01 and P=0.003 respectively), whereas no changes in UAER were seen in subjects with vWF and tPA below the medians. Subjects with high tPA were also characterized by an excess of other cardiovascular risk factors at baseline. No significant differences in these risk factors were present between subjects with high or low vWF. High plasma concentrations of vWF and tPA are associated with progression of UAER in clinically healthy subjects. Both vWF and tPA are secreted by endothelial cells and the results suggest that endothelial dysfunction leads to progression of UAER.
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PMID:Endothelial haemostatic factors are associated with progression of urinary albumin excretion in clinically healthy subjects: a 4-year prospective study. 1036 4

Atherosclerotic cardiovascular disease is a major health problem in the United States. In particular, coronary heart disease (CHD) is the leading cause of death in men and women in the United States, as well as in other industrialized countries. Extensive observational epidemiologic data within and between populations have strongly linked such various factors as untreated hypertension, diabetes, cigarette smoking, and lipid abnormalities to the development of CHD. With respect to lipoprotein parameters, elevated total and low-density lipoprotein cholesterol (LDL-C) and low levels of high-density lipoprotein cholesterol (HDL-C) have been strongly associated with CHD risk. Emerging evidence suggests that other lipoprotein abnormalities also are associated with premature CHD, including elevated levels of lipoprotein(a), triglyceride-rich lipoproteins such as small very-low-density lipoproteins and intermediate-density lipoproteins, small and dense LDL particles, and the magnitude of postprandial lipemia. Extensive primary and secondary clinical trial evidence has established that favorably altering dyslipidemias through diet and a variety of pharmacologic agents produces clear improvements in CHD end points. The extent of this benefit depends on the presence or absence of clinical atherosclerotic disease, as well as other CHD risk factors, and the severity of one or more lipoprotein abnormalities. CHD patients and individuals with multiple risk factors, but free of clinical CHD, derive the greatest absolute benefit from lipid treatment directed at reducing LDL-C. The dyslipidemias that impart high risk are severely elevated LDL-C (> 200 mg/dL), combined high LDL-C and low HDL-C (< 35 mg/dL), and combined hyperlipidemias (non-HDL-C > 200 mg/dL with low HDL). The purpose of this review is to aid the primary care physician in identifying these important dyslipidemias and to critically analyze the relative importance of various lipoproteins on atherosclerotic risk.
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PMID:Clinical diagnosis of lipid disorders. 1068 61

Microalbuminuria, i.e., slightly elevated albumin excretion in the urine, is considered a novel atheroslerotic risk factor. This supposition is based partly on two preliminary minor studies, partly on the current knowledge within the fields of diabetes mellitus and arterial hypertension. The aims of the present series of studies were 1) to examine whether a relationship exists between microalbuminuria and atherosclerotic cardiovascular disease in the general population, and 2) to illuminate possible pathophysiological mechanisms underlying this association. The studies were performed as sub-studies of the Copenhagen City Heart Study and the Monica Population Study. In the 3rd Copenhagen City Heart Study a cross-sectional analysis comprising 2,613 individuals without diabetes mellitus or renal- or urinary tract disease revealed a positive association between overnight urinary albumin excretion rate and a history of acute myocardial infarction. This association was independent of age, sex, conventional atherosclerotic risk factors, and glomerular filtration rate. Participants with a urinary albumin excretion rate exceeding the upper decile (7 micrograms/min) in the entire study population had a higher frequency of previous acute myocardial infarction than the others. In order to assess the time sequence of the observed association, this population will be followed prospectively. In the 1st Monica Population Study in Copenhagen County, 2,085 individuals without diabetes, mellitus, cardiovascular disease, or renal or urinary tract disease were followed for 10 years. Participants with a urinary albumin/creatinine concentration ratio exceeding the upper decile (0.65, mg/mmol) in the entire study population had a relative risk of 2.3 for developing ischaemic heart disease as compared to participants with a lower urinary albumin/creatinine concentration ratio. This predictive effect was independent of age, sex, and conventional atherosclerotic risk, factors, but it was not known whether participants with a urinary albumin/creatinine concentration ratio above the upper decile had severe subclinical atherosclerosis already at entrance to the study. A group of individuals with persistent microalbuminuria, and an age- and sex-matched control group with persistent normoalbuminuria underwent a clinical physiological and biochemical investigation program. None had developed clinically present atherosclerotic cardiovascular disease. Microalbuminuria was defined as a urinary albumin excretion rate exceeding the upper decile in the entire study population, normoalbuminuria as a lower urinary albumin excretion rate. Measurements of glomerular filtration rate and tubular function made it unlikely that the difference in urinary albumin excretion between the two study groups was due to local renal conditions exclusively, although reductions in both glomerular charge selectivity and size selectivity were observed in the microalbuminuric individuals. Individuals with persistent microalbuminuria had increased systemic transvascular albumin leakage to a level similar to that seen among individuals with severe clinical atherosclerosis. This could be explained neither by differences in blood pressure or concentration of plasma lipoproteins, both of which were more atherogenic in the microalbuminuric individuals, nor by differences in plasma volume or albumin concentration, antropometric factors, insulin sensitivity, or smoking habits. It is hypothesized that the systemic transvascular leakiness may also include lipoproteins, thus allowing for an increased lipid insudation into the vessel walls. The leakiness might be due to haemodynamic factors or structural or functional perturbations of the endothelium or the intracellular matrix beneath. Although endothelial dysfunction could not be demonstrated in the present studies, future research will focus on these possibilities.
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PMID:Microalbuminaria and the risk of atherosclerosis. Clinical epidemiological and physiological investigations. 1082 99

The Framingham Study was initiated in 1948 to investigate an epidemic of coronary disease in the USA, using a prospective epidemiological approach. Insights were provided into the prevalence, incidence, full clinical spectrum and predisposing factors. The major "risk factors" (a term coined by the Framingham Study) for coronary disease, stroke, peripheral artery disease and heart failure were identified and clinical misconceptions dispelled about isolated systolic hypertension, left ventricular hypertrophy, dyslipidemia, atrial fibrillation and glucose intolerance. Average values for blood lipids, blood pressure, body weight, glucose and fibrinogen were shown to be dangerously suboptimal and to have a continuous graded relationship to cardiovascular disease without critical values. Dyslipidemia, glucose intolerance and elevated fibrinogen were shown to have smaller hazard ratios in the elderly, but this was offset by a higher absolute risk. Diabetes was shown to operate more strongly in women, eliminating their advantage over men. Serum total cholesterol was shown to derive its atherogenic potential from its LDL component and also to reflect cholesterol being removed in the HDL fraction. The total/HDL-cholesterol ratio was demonstrated to be the most efficient lipid profile for predicting coronary disease. LDL was shown to be correlated with hemostatic factors, suggesting that there would be additional benefits to lowering LDL. High triglyceride associated with reduced HDL, indicating insulin resistance and small dense LDL, was shown to be associated with excess coronary disease. All the risk factors tended to cluster, and this was shown to be promoted by insulin resistance induced by weight gain. Multivariate risk profiles were produced to facilitate risk stratification of candidates for coronary disease, stroke, peripheral artery disease and heart failure. The Framingham Study is now engaged in quantifying the independent contributions of homocysteine Lp(a), insulin resistance, small dense LDL, C reactive protein, clotting factors and genetic determinants of cardiovascular disease. We are now able to estimate the lifetime risk of all the atherosclerotic cardiovascular disease outcomes.
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PMID:The Framingham Study: ITS 50-year legacy and future promise. 1087 16

Several clinical and metabolic abnormalities, i.e. central obesity, hypertension, impaired glucose tolerance or diabetes and dyslipidemia often cluster together and are commonly found in patients with atherosclerotic cardiovascular disease. Hyperinsulinemia and insulin resistance are often evident in subjects with these metabolic abnormalities, so called insulin resistance or metabolic syndrome. In the present study, we looked into the correlations between serum insulin or index of insulin sensitivity and various clinical and metabolic abnormalities. Subjects consisted of 103 males and 118 females. Oral glucose tolerance test was performed on all subjects. Homeostasis model assessment of insulin sensitivity (HOMA-S) was used to determine insulin sensitivity. In males, HOMA-S was found to be significantly correlated with BMI, plasma glucose, insulin, triglycerides and waist circumference. Male subjects in the highest quartile of HOMA-S also had significantly higher systolic blood pressure compared to those in the lowest quartile. In females, HOMA-S was significantly correlated with BMI, blood pressure, plasma glucose, insulin, triglycerides, HDL-cholesterol, waist circumferences and waist-hip ratio. However, after adjustment for BMI, correlation between HOMA-S and blood pressure in women was no longer statistically significant. We, therefore, concluded that correlations between serum insulin or index of insulin sensitivity with certain metabolic abnormalities also existed in Thai subjects. Some of these correlations seem to be at least in part dependent on obesity.
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PMID:Correlation between serum insulin and features of metabolic syndrome in Thais. 1093 14

Despite the improvements in dialysis technology, the cardiovascular mortality rate is still unacceptably high among dialysis patients. It is obvious that traditional risk factors, such as hypertension, chronic heart failure (CHF), dyslipidemia and diabetes mellitus, may account for a large part of the increased cardiovascular mortality rate in these patients. However, based on recent research it could be speculated that other, non-traditional risk factors might also contribute to the high cardiovascular mortality rate in dialysis patients. Chronic inflammation, as evidenced by increased levels of pro-inflammatory cytokines and C-reactive protein (CRP), is a common feature in dialysis patients and is associated with an increased cardiovascular morbidity and mortality. Indeed, elevated levels of pro-inflammatory cytokines (such as TNF-alpha, IL-1 and IL-6) may cause malnutrition and progressive atherosclerotic cardiovascular disease by several pathogenetic mechanisms, which will be discussed in this review. Based on the strong associations observed between malnutrition, inflammation and atherosclerosis in patients with chronic renal failure (CRF) we have proposed that these features constitute a specific syndrome (MIA), which carries a high mortality rate. As elevated levels of pro-inflammatory cytokines may play a central part in the vicious circle of malnutrition, inflammation and atherosclerosis, further research is needed to investigate whether or not different anti-cytokine treatment strategies may improve survival in dialysis patients.
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PMID:Inflammatory and atherosclerotic interactions in the depleted uremic patient. 1111 78

This paper reviews the clinical trial data that offer insight into the question of whether, and in what groups of people, triglycerides might be an appropriate therapeutic target for the primary or secondary prevention of atherosclerotic cardiovascular disease. Two angiographic trials (the Lopid Coronary Angiography Trial and the Bezafibrate Coronary Atherosclerosis Intervention Trial) and three clinical endpoint trials (the Helsinki Heart Study, the Bezafibrate Infarction Prevention Study, and the VA HDL Intervention Trial) are reviewed. Hypertriglyceridemia per se is probably not an appropriate therapeutic target for the prevention of atherosclerotic cardiovascular disease because it is a poor marker of atherogenic risk and because there have been no clinical trials that have directly addressed the question of whether lowering the triglyceride level reduces the number of clinical events. The studies reviewed here, however, suggest that patients with established coronary heart disease and a high triglyceride level, in association with either a low high-density lipoprotein-cholesterol level or perhaps other features of the metabolic syndrome, such as obesity, diabetes, or hypertension, may benefit from fibrate therapy. For patients without established coronary heart disease, it is reasonable to consider hypertriglyceridemia as a risk marker prompting the aggressive treatment of other risk factors such as hypertension, diabetes, high low-density lipoprotein-cholesterol, and obesity.
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PMID:Triglycerides and coronary heart disease: implications of recent clinical trials. 1114 64

Type 2 diabetes is widely recognized as a major risk factor for atherosclerotic cardiovascular disease, including subclinical atherosclerosis as measured by noninvasive procedures. However, the role of genetic factors that contribute to various measures of subclinical atherosclerosis is largely unknown. We hypothesize that subclinical atherosclerosis, measured as coronary artery calcification (CAC), will be extensive in individuals with type 2 diabetes and that its presence depends on both genetic and environmental factors. The genetic factors should result in the familial aggregation of CAC. To determine the extent of familial aggregation of CAC in the presence of type 2 diabetes, we studied 122 individuals with type 2 diabetes (mean age 60 years) and 13 individuals without diabetes in 56 families. CAC was measured by fast-gated helical computed tomography. Other measured factors included blood pressure, body size, lipids, HbA1c, and self-reported medical history. To test for an association between CAC and these factors while accounting for the potential familial correlation of CAC, generalized estimating equations were used. CAC was detectable in 80% of individuals with diabetes (median score 84, range 0-5,776). Extent of CAC, adjusted for age, was positively associated with male sex (P = 0.0003), reduced HDL (P = 0.02), albumin-to-creatinine ratio (P = 0.008), and cigarette pack-years (P = 0.03). CAC was also positively associated with a history of angina, myocardial infarction, stroke, and vascular procedures (all P < 0.01). HbA1c and fasting glucose were positively, but nonsignificantly, associated with the extent of CAC (P = 0.14 and 0.08, respectively). CAC, adjusted for age, sex, race, and diabetes status, was heritable (h2 = 0.50; P = 0.009). In multivariate analysis with additional adjustment for HDL, BMI, hypertension, and smoking, h2 = 0.40 (P = 0.038). These results suggest that strong (independent) genetic factors as well as environmental factors contribute to the variance of CAC in individuals with type 2 diabetes. In these data, CAC seems heritable and may serve as an important feature in designing studies to map genes contributing to both atherosclerosis and type 2 diabetes.
Diabetes 2001 Apr
PMID:Familial aggregation of coronary artery calcium in families with type 2 diabetes. 1128 53

Dehydroascorbic acid, the oxidized form of vitamin C, is transported into mammalian cells via facilitative glucose transporters and hyperglycemia inhibits this process by competitive inhibition. This inhibited transport may promote oxidative stress and contribute to the increase in atherosclerotic cardiovascular disease observed in patients with diabetes mellitus. This review explores the importance of this proposed mechanism in light of current research. For example, recent reports suggest that administration of antioxidants, such as vitamin C, may slow atherogenesis by improving endothelium-dependent vasodilation in individuals with abnormal glucose and lipid metabolism, perhaps by preventing the oxidation of nitric oxide, an important regulator of vasomotor tone. Endothelial dysfunction plays a key role in the development of atherosclerosis and endothelial cells may be particularly affected by hyperglycemia-induced ascorbic acid deficiency as they line the interior of blood vessels. In addition, we discuss evidence of several other mechanisms by which vitamin C status may affect the development of atherosclerotic cardiovascular disease, particularly its inverse relationship to multiple cardiovascular disease risk factors and indicators. Given these factors, vitamin C administration is recommended during periods of both acute and chronic hyperglycemia to help preserve endothelial function.
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PMID:Hyperglycemia-induced ascorbic acid deficiency promotes endothelial dysfunction and the development of atherosclerosis. 1150 Jan 68

Three different growth factor systems have been described acting via endothelial cell-specific receptor tyrosine kinases (RTKs). These are vascular endothelial growth factors (VEGFs), angiopoietins, and ephrins. Recent studies on gene targeting suggest that they play critical roles in embryonic development and contribute to the integrity and responses to environmental factors in the adult vasculature. Coagulation, inflammation, immune response regulation, vascular tone, stromal component synthesis, and angiogenesis are all dependent on the physiological and pathological events that affect endothelial cells in the heart, arteries, veins, and lymphatic vessels. Angiogenesis, the formation of new blood vessels from preexisting ones, takes place in adults only during hormonal control of female reproduction. All other activation of angiogenesis in adulthood occurs in response to injury or pathological processes such as tumorigenesis, diabetes, or inflammatory conditions. Insufficient growth of collateral vessels is a major problem in atherosclerotic cardiovascular disease. Controlled stimulation of angiogenesis would be of therapeutic value. Lymphangiogenesis, the mechanisms involved in the development of lymphatic vessels, was studied intensively nearly a century ago, although since then it has been neglected, perhaps because, unlike the disorders of blood vessels, those of the lymphatic vessels are seldom life-threatening. Interrupting this one-way system can cause severe disorders, including liver dysfunction, genetic disease (e.g., Milroys disease), and degenerative disease (e.g., primary lymphangiosclerosis). Recently, novel growth factors, receptors, cell surface proteins, and transcription factors have been found which play a role in the lymphatic endothelium. These are VEGF-C, VEGF-D, VEGFR-3, LYVE-1, podoplanin, and Prox-1. Until recently lymphatic vessels have been difficult to study due to a lack of appropriate tools. Monoclonal antibodies raised against VEGFR-3 and against its ligands, VEGF-C and VEGF-D, have offered an insight into expression studies in tissues. In this review, we summarize the recent data on VEGFs in the human vasculature.
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PMID:Lymphatic versus blood vascular endothelial growth factors and receptors in humans. 1159 56


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