Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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

Essential hypertension is a major Public Health issue. Although the number of treated hypertensive patients has increased, only 25% of treated patients have their blood pressure levels under control. The benefit of treating hypertension has been proven, but cardiovascular morbidity and mortality rates remain high. The ideal antihypertensive drug should not only normalize blood pressure levels, but also reduce the associated cardiovascular morbidity and mortality rates. The role of angiotensin II in systemic hypertension and its complications has been recently redefined. The potent trophic effects of angiotensin II on blood vessels and on cardiac cells have been well demonstrated, especially the role of angiotensin II in left ventricular hypertrophy, vascular hypertrophy, endothelial dysfunction, and congestive heart failure. Of all ongoing mortality and morbidity trials in systemic hypertension, VALUE (Valsartan Antihypertensive Long-term Use Evaluation) is the only one comparing an angiotensin II antagonist (valsartan) with a third-generation calcium channel blocker (amlodipine). The main hypothesis of the VALUE trial is that, for an equivalent decrease in blood pressure, valsartan will be more effective than amlodipine in decreasing cardiac mortality and morbidity. VALUE is a prospective, multinational, multicentre, double-blind, randomized, active-controlled, 2-arm parallel group comparison with a response-dependent dose titration scheme. VALUE involves 14,400 patients in over 30 countries, who will be followed for 4 years or until 1450 patients experience a primary endpoint. The population to be included in VALUE consists of hypertensive men and women, aged 50 years or older, and at a relatively high risk of sustaining a cardiovascular event. The high risk profile is defined taking into account age, gender, and a list of cardiovascular risk factors and disease factors. Risk factors are cigarette smoking, hypercholesterolaemia, diabetes mellitus, uncomplicated left ventricular hypertrophy, proteinuria, and high serum creatinine. Disease factors include documented history of myocardial infarction, peripheral vascular disease, stroke or transient ischaemic attack, or the presence of left ventricular hypertrophy with strain on the ECG. A unique feature of VALUE is the assessment of the predictive power of this cardiovascular risk factor scale in a large population of treated hypertensive patients. The trial started on 10 September 1997.
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PMID:The Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial of cardiovascular events in hypertension. Rationale and design. 975 88

Obesity and non-insulin-dependent diabetes mellitus (NIDDM) are closely linked. They frequently occur together in patients, and body mass index (BMI) is the strongest risk factor for the development of NIDDM. Both obesity and NIDDM are also major causes of morbidity and mortality from atherogenic macrovascular disease, and they are independent risk factors for coronary heart disease. The risk of developing NIDDM and cardiovascular disease is affected by the regional distribution of body fat. Visceral obesity is associated with a higher degree of risk than peripheral obesity. The metabolic and circulatory changes associated with visceral obesity lead to the development of insulin resistance and increased lipoprotein synthesis. For example, the change in the population profile of lipoproteins in the blood, and alterations in the levels of oxidative stress lead to an increased cardiovascular and macrovascular risk. The changes in lipid metabolism also affect haemorrheological function. They have been linked to decreased fibrinolysis (a serious cardiovascular risk factor) through elevated levels of plasminogen activator inhibitor factor, high blood viscosity, and increased erythrocyte aggregability. Increased BMI also appears to be associated with endothelial dysfunction, which is a major factor in atheroma plaque formation and development of thrombosis. Visceral obesity therefore adds a significant burden to the already increased cardiovascular risk inherent in NIDDM. However, even moderate weight loss may successfully reverse the majority of changes seen with visceral obesity.
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PMID:Relationship between obesity and the increased risk of major complications in non-insulin-dependent diabetes mellitus. 977 22

During recent decades the importance of perceiving isolated systolic hypertension (ISH) in cardiovascular pathophysiology has been changed from a benign condition to the major cardiovascular risk factor. Aging is per se associated with the deterioration in arterial compliance through both structural and functional changes in large arteries which mainly involves the intima and media. The observed changes result in a decrease of the lumen-to-wall ratio, the overall lumen cross-sectional area and an increase of arterial stiffness which especially involve the aorta and other elastic arteries. In addition to the structural changes in vessel walls, aging is associated with certain functional changes such as an increase in sympathetic system activity probably due to the age-related decreased sensitivity of beta-receptors. While the function of arterial wall alpha-receptors remains intact, in elderly subjects a shift towards arterial vasoconstriction can be observed. In many of the published studies the definition of ISH was based on the criterion 160/95 mm Hg or 160/90 mm Hg while in recognition of the high risk associated with systolic blood pressure (SBP) the WHO/ISH guidelines and Report of the Sixth Joint National Committee on Hypertension indicated that ISH should be diagnosed with SBP as > or =140 mm Hg and diastolic BP (DBP) as <90 mm Hg. Thus the setting down of normal values of SBP will lead to an earlier diagnosis and treatment of ISH. Several prospective studies, such as the US Hypertension Detection and Follow-up Programme, confirmed this and the Multiple Risk Factor Intervention Trial demonstrated that for any given level of DBP, higher SBP was associated with an increase in cardiovascular risk. Moreover, data from the Framingham Study show that ISH was associated not only with increased mortality but also cardiovascular morbidity. Risk of non-fatal stroke and myocardial infarction was increased three and two-times respectively in the presence of ISH. Three major up-to-date studies that included patients with ISH have been published. In concordance to the previously published SHEP and MCR trials, the most recent, the Systolic Hypertension in the Elderly Trial (SYST-EUR), demonstrated that active treatment significantly reduces the risk of stroke and all fatal and non-fatal cardiac end-points, including sudden death. Of note, these benefits were demonstrated with new anti-hypertensive classes such as dihydropiridyne calcium channel blocker (nitrendipine) and the angiotensin-converting enzyme inhibitor (enalapril). The necessity to carefully balance the benefits and risks of anti-hypertensive therapy in the elderly indicates that patients with suspected ISH should undergo careful BP measurements on at least three different occasions before the diagnosis is established and an orthostatic reaction should be evaluated. If non-pharmacological procedures fail, drug therapy should be considered, especially in elderly patients with a SBP over 160 mm Hg, since their risk of complications is markedly higher. Pharmacological treatment should also be strongly considered in patients with a SBP between 140 and 160 mm Hg with such concomitant cardiovascular risk factors as diabetes, angina pectoris, and left ventricular hypertrophy. The drug regimen should be simple, starting with a low dose of a single drug that is titrated slowly. The selection of the first-line anti-hypertensive agent should be based on a careful assessment of pathophysiological and clinical parameters in each individual geriatric patient.
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PMID:Isolated systolic hypertension: pathophysiology, consequences and therapeutic benefits. 978 91

Previous clinical studies reported elevated semicarbazide-sensitive amine oxidase (SSAO) activity in insulin-dependent diabetes mellitus (IDDM), but there are not sufficient data about SSAO in non-insulin-dependent diabetes mellitus (NIDDM). The present study was conducted to investigate serum SSAO activity in NIDDM patients compared with nondiabetic and IDDM patients. Serum SSAO activity in 61 patients with diabetes (n = 34 NIDDM and n = 27 IDDM) and 36 controls was determined using 14C-benzylamine as a substrate. NIDDM and IDDM patients exhibited higher SSAO activity compared with controls ([mean +/- SD] NIDDM, 164.60+/-69.43 pmol/mg protein/h, P<.0001; IDDM, 143.91+/-72.45 pmol/mg protein/h, P<.002; control, 91.46+/-28.11 pmol/mg protein/h). There was a significant positive correlation between serum SSAO activity and the body mass index (BMI), body weight, hemoglobin A1c (HbA1c), fasting plasma glucose, and triglycerides. Within the control group, SSAO correlated with total cholesterol levels. The progression and severity of diabetic complications such as angiopathy may be exacerbated by cytotoxic metabolites (e.g., formaldehyde and hydrogen peroxide) formed by SSAO. These results reveal the possibility that elevated serum SSAO activity in association with obesity and hyperlipidemia may be a cardiovascular risk factor in diabetes mellitus.
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PMID:Elevated serum semicarbazide-sensitive amine oxidase activity in non-insulin-dependent diabetes mellitus: correlation with body mass index and serum triglyceride. 992 Jan 54

Mediacalcinosis (MC) represents a disease of the muscular type arteries characterized by progredient calcification of the media. MC involves most frequently the arteries of the lower extremities. However, a more extensive disease involving the arteries of the pelvis and the abdominal aorta is common. A systemic extension of MC with the involvement of the coronary arteries has been reported, but is however, according to the present opinion, rather rare. MC occurs isolated (primary MC) as well as associated with other diseases (secondary MC). The secondary forms are most frequently due to diabetes mellitus type II and to chronic renal insufficiency and accompanying secondary hyperparathyroidism. The etiopathogenesis of MC has not yet been clarified. The recent evidence based on molecular-biologic investigations suggests an active pathomechanism of an ectopic arterial wall ossification. Genetic predisposition appears possible. The diagnosis of MC is traditionally established by conventional x-ray radiography of the pelvis-lower extremity-region. Among the newer imaging modalities, the computed tomography and the high resolution B-mode ultrasonography are of special importance. The diagnostics of coronary calcification are in descending order of importance relevant the intracoronary ultrasonography (IVUS), the electron beam computed tomography (EBT), the thorax-fluoroscopy and the thorax-radiography. For the diagnosis of coronary MC necessary arterial wall layer specific calcium detection is currently possible only with the IVUS methodology. The prognosis of the primary MC is quoad vitam good. However, the mechanic and biological effects of MC on cardiacal and vascular function have not yet been determined. The secondary MC in type II diabetics represents an independent cardiovascular risk factor. A causal therapy of MC is not known. For the clinical cardiologists, MC is of primary interest as a differential diagnosis to atherosclerosis. For the scientists, MC offers an excellent in vivo model to study processes associated with arterial wall ossifications and ageing.
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PMID:[Media calcinosis from the viewpoint of the cardiologist]. 1002 65

Patients with type 1 diabetes mellitus, especially those with nephropathy, are at increased risk for coronary heart disease (CHD). However, information on the predictive value of cardiovascular risk factors and the degree of hyperglycemia with respect to CHD events in patients with type 1 diabetes without nephropathy is still incomplete. Therefore, we performed a prospective study on risk factors for CHD in patients with type 1 diabetes free of clinical nephropathy. At baseline examination, cardiovascular risk factor levels of CHD were determined in 177 patients with type 1 diabetes (87 men and 90 women), age 45 to 64 years at baseline and >/=30 years at the time of diagnosis of diabetes. These patients were followed up to 7 years with respect to CHD events. Altogether, 20 patients with type 1 diabetes (13 men [7.3%] and 7 women [3.9%]) died of CHD and 28 patients with type 1 diabetes (17 men [9.6%] and 11 women [6.2%]) had a serious CHD event (death from CHD or nonfatal myocardial infarction). In multivariate Cox regression analysis, a previous history of myocardial infarction (hazard ratio [HR] and its 95% confidence interval, 8.0 [3.1 to 21.0], P<0.001), high glycohemoglobin A1 (>10.4%, the highest tertile, HR 5.4 [1.4 to 20.4], P=0.013), and the duration of diabetes (>16 years, the highest tertile, HR 4.2 [1.3 to 12.9], P=0.013) were the only variables associated with CHD death even after adjustment for other cardiovascular risk factors. These variables also predicted the incidence of all CHD events. Our results indicate that poor metabolic control is a strong predictor of CHD events in patients with late-onset type 1 diabetes without nephropathy, independently of other cardiovascular risk factors.
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PMID:Poor glycemic control predicts coronary heart disease events in patients with type 1 diabetes without nephropathy. 1019 30

Although obstructive sleep apnea (OSA) appears to be a cardiovascular risk factor, its frequency in patients with transient ischemic attack (TIA) and stroke remains poorly known. We prospectively studied 128 patients (mean +/- SD age = 59 +/- 15 years) with stroke (n = 75) or TIA (n = 53). Assessment included body mass index (BMI); history of snoring and daytime sleepiness; cardiovascular risk factors and diseases; and severity of stroke (Scandinavian Stroke Scale = SSS). Polysomnography (PSG) was obtained in 80 subjects (group 1), a mean of 9 days (range, 1-71 days) after TIA or stroke. In 48 subjects (group 2), PSG was not available, refused, or inadequate. Groups 1 and 2 were similar with the exception of gender distribution. Clinical and PSG data were compared to those of 25 healthy controls matched for age, gender, and BMI. An apnea-hypopnea index (AHI) > 10 was found in 62.5% of subjects and 12.5% of controls. Between patients and controls there was a significant difference in AHI (mean [range]: 28 (0-140) vs 5 (0-24), p < 0.001), maximal apnea duration (mean + SD: 37 +/- 23 vs 23 +/- 13 seconds, p = 0.009), and minimal oxygen saturation (mean + SD: 82 +/- 10% vs 90 +/- 5%, p < 0.001). Conversely, frequency and severity of OSA were similar in stroke and TIA subjects. Multiple regression analysis identified age, BMI, diabetes, and SSS as independent predictors of AHI. Sleep apnea has a high frequency in patients with TIA and stroke, particularly in older patients with high BMI, diabetes, and severe stroke. These results may have implications for prevention, acute treatment, and rehabilitation of patients with acute cerebrovascular diseases.
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PMID:Sleep apnea in acute cerebrovascular diseases: final report on 128 patients. 1020 Oct 66

We investigated the influence of major cardiovascular risk factors (smoking, hypercholesterolemia, diabetes mellitus) on the association between angiotensin-converting enzyme (ACE) gene insertion (I)/deletion (D) polymorphism and echocardiographic left ventricular mass in 225 patients with sustained hypertension, assessed by ambulatory blood pressure monitoring. When the study population was analyzed as a whole, the 3 ACE genotypes did not differ in left ventricular mass (II, 47 g/m2.7; ID, 49 g/m2.7; DD, 51 g/m2.7; p = NS). No difference was found in subjects (n = 135) in whom at least 1 major cardiovascular risk factor was present (II, 51 g/m2.7; ID, 51 g/m2.7; DD: 52 g/m2.7; p = NS). In contrast, in the absence of cardiovascular risk factors, DD subjects (n = 32) exhibited left ventricular mass index higher than non-DD (ID/II) subjects (n = 75; p <0.05). After controlling for age and sex, in the absence of cardiovascular risk factors, the risk of left ventricular hypertrophy was 3.8-fold higher in DD than in non-DD patients (odds ratio 3.8; 95% confidence interval 1.2 to 12.1, p <0.02). We conclude that in the present setting of patients with established sustained systemic hypertension, the absence of risk factors potentially affecting cardiovascular adaptation allows for the detection of a positive association between homozygosity for the D allele of the ACE gene and left ventricular hypertrophy.
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PMID:Cardiovascular risk factors, angiotensin-converting enzyme gene I/D polymorphism, and left ventricular mass in systemic hypertension. 1021 83

Apolipoprotein(a) [apo(a)] is the specific apolipoprotein of lipoprotein(a) [Lp(a)], a recognized cardiovascular risk factor. Apo(a) is characterized by a high genetic polymorphism with at least 34 isoforms in plasma. Recent studies have shown that in atherothrombosis apo(a) polymorphism could play a role independent of Lp(a) levels. In particular, apo(a) phenotypes seem to have their highest predictive value for coronary heart disease, when apo(a) isoforms are detected by high resolution phenotyping methods and when an adequate operative cut-off of apo(a) polymorphism is used. A strong association between apo(a) phenotypes and coronary heart disease has been also found in hypertensive, diabetic, and uremic patients. Moreover, apo(a) phenotypes seem to correlate well with the severity of coronary atherosclerosis and the age of clinical onset of coronary heart disease. These studies suggest that apo(a) polymorphism may have a great clinical usefulness in a primary prevention setting, since apo(a) phenotypes could be used together with Lp(a) levels as strong genetic predictors of atherothrombosis. The analysis of apo(a) polymorphism appears to be particularly useful in healthy subjects with a family history of atherothrombotic diseases, in patients with diseases at high cardiovascular risk (diabetes, hypertension, hypercholesterolemia) and in subjects with conditions modifying Lp(a) levels.
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PMID:Genetics and cardiovascular risk: a role for apolipoprotein(a) polymorphism. 1037 86

The discovery that peroxisome proliferator-activated receptor (PPAR)-gamma was the molecular target of the thiazolidinedione class of antidiabetic agents suggested a key role for PPAR-gamma in the regulation of carbohydrate and lipid metabolism. Through the use of high-throughput biochemical assays, GW1929, a novel N-aryl tyrosine activator of human PPAR-gamma, was identified. Chronic oral administration of GW1929 or troglitazone to Zucker diabetic fatty (ZDF) rats resulted in dose-dependent decreases in daily glucose, free fatty acid, and triglyceride exposure compared with pretreatment values, as well as significant decreases in glycosylated hemoglobin. Whole body insulin sensitivity, as determined by the euglycemic-hyperinsulinemic clamp technique, was significantly increased in treated animals. Comparison of the magnitude of glucose lowering as a function of serum drug concentrations showed that GW1929 was 2 orders of magnitude more potent than troglitazone in vivo. These data were consistent with the relative in vitro potencies of GW1929 and troglitazone. Isolated perfused pancreas studies performed at the end of the study confirmed that pancreata from vehicle-treated rats showed no increase in insulin secretion in response to a step change in glucose from 3 to 10 mmol/l. In contrast, pancreata from animals treated with GW1929 showed a first- and second-phase insulin secretion pattern. Consistent with the functional data from the perfusion experiments, animals treated with the PPAR-gamma agonist had more normal islet architecture with preserved insulin staining compared with vehicle-treated ZDF rats. This is the first demonstration of in vivo efficacy of a novel nonthiazolidinedione identified as a high-affinity ligand for human PPAR-gamma. The increased potency of GW1929 compared with troglitazone both in vitro and in vivo may translate into improved clinical efficacy when used as monotherapy in type 2 diabetic patients. In addition, the significant improvement in daily meal tolerance may impact cardiovascular risk factor management in these patients.
Diabetes 1999 Jul
PMID:A novel N-aryl tyrosine activator of peroxisome proliferator-activated receptor-gamma reverses the diabetic phenotype of the Zucker diabetic fatty rat. 1038 47


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