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Diabetic ketoacidosis remains a significant cause of death in cases of insulin-dependent diabetes mellitus (IDDM). Among patients hospitalised for diabetic ketoacidosis, the death rate is 5-10 per cent, cardiovascular disease, infection, and ARDS (adult respiratory distress syndrome) being major contributory factors, whereas the degree of acidosis does not differ from that among survivors. Ketoacidosis is a major determinant of the two-fold higher mortality among the youngest age-groups of IDDM patients. The age-specific incidence of ketoacidosis among patients under 20 years of age is several time higher than that among patients over 50. Intensified insulin treatment, using multiple injections or insulin pumps, probably results in an increased risk of insulin deficiency owing to the smaller insulin depots. Thus, there is a need of intensified testing for ketonuria and improved education of patients, physicians and other health care personnel, in order to promote the prevention or rapid, effective treatment of diabetic ketoacidosis.
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PMID:[Diabetic coma--an unnecessary death]. 140 26

The role of waist-to-hip ratio (WHR) in the metabolic disturbance of IDDM has not been widely explored. Cross-sectional data from the Epidemiology of Diabetes Complications Study were used to examine the associations between WHR and risk factors for IDDM complications such as lipid or lipoprotein levels, blood pressure and fibrinogen. A total of 586 adults (greater than or equal to 18 years of age) were examined. WHR was calculated as the mean of duplicate waist circumference measurements made at mid-point between the iliac crest and the lower costal margin in mid-axillary line divided by the mean of duplicate maximum hip measures. WHR was positively correlated with total cholesterol, LDL-cholesterol, triglycerides, systolic and diastolic blood pressure and fibrinogen univariately for both sexes. WHR was negatively correlated with HDL-cholesterol. These correlations remained significant after adjustment for age among females and became less strong, although still significant, for males. The independent effects of WHR to these IDDM risk factors, assessed by multiple linear regression, indicated WHR was related to adverse lipid and lipoprotein levels, but not to fibrinogen or blood pressure. These findings underscore the importance of targeting intervention to IDDM individuals who have a high WHR to reduce known risk factors for IDDM complications especially those for cardiovascular disease, and is consistent with the hypothesis that insulin resistance may have a role to play in IDDM complications.
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PMID:The association of waist-hip ratio and risk factors for development of IDDM complications in an IDDM adult population. 142 53

Even though oral contraceptives (OCs) with the new 3 progestins are the most widely prescribed OCs in the world, especially in Europe, they still are not available to US women. Gestodene's, desogestrel's, and norgestimate's effective daily dose are only 75 mcg, 150 mcg, and 250 mcg, respectively, while the daily dose of norethindrone in OCs used in the US ranges from 350-1000 mcg. The older progestins alter lipid metabolism, thus increasing cardiovascular disease risks. Some studies indicate that the new progestins induce fewer lipid metabolic changes than the older progestins. A 1988 study in West Germany suggests, however, that women who use gestodene may be at increased risk of thromboembolism. Yet, similar research in the UK and also in West Germany did not find this association. There has been concern for many years about OCs' ability to change glucose metabolism and insulin resistance. 5 studies show that OCs with desogestrel cause fewer such disturbances than those with levonorgestrel. 1 study also finds that OCs with gestodene do not alter glucose and insulin levels. On the other hand, 1 study suggests, that OCs with gestodene increase glucose and insulin levels over 6 months. European studies of the new progestins demonstrate their low 1-year method failure rates (gestodene, 0.07/100 users; desogestrel, 0.04/100 users; and norgestimate, [pregnancy rate] 0.25/100 users). Further, the 3 progestins result in a smaller proportion of women who have side effects (breakthrough bleeding or spotting, 3-9%, breast discomfort or headaches, 10-13%). Yet, researchers have not directly compared the effectiveness and acceptability of the 3 new progestins. A legal dispute between 2 pharmaceutical companies prevented the marketing of norgestimate in 1990. 1 company claims patent infringement. The US Food and Drug Administration is now evaluating gestodene and desogestrel. It probably will not approve gestodene until the question of apparent excess of thromboembolism is resolved.
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PMID:The new pills: awaiting the next generation of oral contraceptives. 142 86

The hypothesis of the atherogenic role of endogenous insulin was based on a series of epidemiological studies. Several large-scale prospective studies have demonstrated that diabetes constitutes an independent risk factor for cardiovascular disease. However, neither the duration of diabetes nor the blood glucose level appear to be predictive of the incidence of a cardiovascular accident. More recent prospective studies (Finland, Australia, Paris) in non-diabetic men have shown that hyperinsulinemia, while fasting or after glucose stimulation, constitutes a risk factor for fatal myocardial infarction, but they failed to show whether diabetes or the blood glucose level constituted a risk factor for the disease. Cross-sectional studies have provided similar results. Insulin resistance affects the majority of non-insulin-dependent diabetics and glucose-intolerant patients. It has also been observed in 25 percent of non-obese subjects with a normal glucose tolerance test. Associated hyperinsulinemia prevents the development of diabetes, but diabetes appears when the beta-cell function is altered and can no longer maintain this hyperinsulinemia. However, hyperinsulinemia is not devoid of cardiovascular consequences. Insulin resistance and hyperinsulinemia are also observed in patients with essential hypertension: a correlation between plasma insulin and blood pressure has been reported. These data, together with other experimental arguments, suggest that excessive endogenous insulin may participate in the rise in blood pressure. Furthermore, hypertensive patients have a high risk of coronary heart disease and this risk is not significantly decreased by anti-hypertensive treatments. This is probably related to the presence of other metabolic risk factors associated with insulin resistance: hyperinsulinemia, glucose intolerance, hypertriglyceridemia, decreased HDL cholesterol. These metabolic disorders have been grouped together under the term "syndrome X". All of these risk factors are probably also involved in the development of coronary heart disease in general population. In conclusion, epidemiological studies now suggest that insulin resistance and hyperinsulinemia increase the risk of hypertension and coronary heart disease. A great many experimental studies support this hypothesis. Lastly, it can be proposed that the increased cardiovascular risk in non-insulin-dependent diabetics is related to the fact that they belong to a larger group of insulin-resistant subjects. The management of diabetes, hypertension, and all of the metabolic abnormalities would appear to be the only way of reducing the incidence of cardiovascular disease.
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PMID:[Pathogenic role of hyperinsulinism in macroangiopathy. Epidemiological data]. 143 99

The relationship between obesity and type II diabetes mellitus is well established and a majority of type II diabetic individuals are classified as obese. The pathogenesis of type II diabetes mellitus is not fully understood; however, multiple organ systems are involved, including abnormalities of insulin secretion, peripheral insulin resistance and hepatic insulin resistance. The goal of the treatment for the obese diabetic is to normalise these alterations and achieve normoglycaemia. Traditionally, the initial therapy, aiming to accomplish weight reduction, is diet and exercise. In obese type II diabetic patients, the whole body insulin-dose response curve is markedly depressed. A single exercise session improves and partially normalises both insulin responsiveness and sensitivity for glucose utilisation. Furthermore, a single bout of physical activity often results in decreased plasma glucose levels, which persists into the postoperative period. Type II diabetes patients participating in regular exercise programmes can potentially improve their metabolic control. An improved glucose control in both lean and obese type II diabetic patients under the age of 55 years has been demonstrated by improved HbA1C levels and glucose tolerance tests following physical training programmes. The effect of regular exercise on the metabolic control in these younger patients does not appear to be correlated with weight reduction. For most type II diabetic men over 55 years of age, physical training is not a feasible form of therapy because of other interfering diseases which may complicate or severely hinder all physical training apart from very low intensity exercise programmes. Lean, older, type II diabetic patients who have been able to exercise for 10 weeks or up to 2 years demonstrate no change in HbA1C levels, glucose tolerance or bodyweight. Thus, there is a clear difference in metabolic response to regular exercise between younger and older type II diabetic patients. The younger patient appears to be more inclined to respond to physical training with improvements in the metabolic control. The reason for this apparent difference is not clear, but possible explanations may include differences in training intensity, the presence or degree of complicating diseases, pretraining level of metabolic control or bodyweight. Type II diabetics are predisposed to cardiovascular disease and are characterised by hyperlipidaemia. In obese type II diabetic individuals, physical training improves the blood lipid profile as measured by decreased levels of triglycerides and total cholesterol. In young, overweight diabetics, improved lipid profiles can be achieved despite no change in bodyweight, while no apparent effects are reported for lean patients.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Exercise training in obese diabetic patients. Special considerations. 143 93

In 29 lean, premenopausal, never-treated hypertensive women (142 +/- 2/93 +/- 1 mmHg, mean +/- SEM) plasminogen activator inhibitor (PAI-1) was elevated (11.0 +/- 1.5 U/ml vs 6.3 +/- 1.0 U/ml, p less than 0.05) compared to healthy, normotensive women (113 +/- 2/71 +/- 2 mmHg). Euglobulin clot lysis time tended to be longer in the hypertensive than in the normotensive women (p = 0.06). PAI-1 was positively correlated to triglycerides (r = 0.60, p less than 0.001), haematocrit (r = 0.45, p less than 0.05), insulin (r = 0.38, p less than 0.05) and body mass index (r = 0.38, p less than 0.05), and inversely correlated to HDL cholesterol (r = -0.43, p less than 0.05) in the hypertensive women. Fibrinogen was not significantly different in the hypertensive and normotensive women, while the hypertensive smokers had higher fibrinogen than the hypertensive non-smokers (3.01 +/- 0.17 g/l vs 2.54 +/- 0.10 g/l, p less than 0.05). All participants were investigated in the same phase of the menstrual cycle. Despite that, oestradiol was significantly lower in the hypertensive than in the normotensive women (0.57 +/- 0.06 vs 0.81 +/- 0.09 nmol l-1, p less than 0.05), while progesterone was similar in the two groups. These results suggest that premenopausal, never-treated hypertensive women are characterized by low oestradiol levels as well as decreased fibrinolytic activity. PAI-1 seems to be associated with other risk factors for cardiovascular disease in hypertensive women.
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PMID:Evidence of decreased fibrinolytic activity in hypertensive premenopausal women. 143 14

Cross-sectional associations between leukocyte count and sociodemographic and cardiovascular risk factors were investigated in 14,679 participants aged 45-64 years in the Atherosclerosis Risk in Communities Study carried out in four US communities in 1986-1989. Leukocyte count was strongly associated with present or past history of cigarette smoking and was higher in males than in females and in white subjects than in black subjects. Among never smokers, no sex differences were evident after adjustment for other risk factors. Race-associated differences were substantially reduced after other factors were taken into account in multivariate analyses. In never smokers, leukocyte count was higher in those who reported poor health, and it was inversely associated with high density lipoprotein cholesterol, forced expiratory volume at 1 second, physical activity, and, among whites, height and socioeconomic indicators. It was directly associated with indices of body weight and body fat, heart rate, blood pressure, hemoglobin, platelet count, uric acid, fasting insulin and glycemia, triglycerides, fibrinogen, antithrombin III, protein C, factors VII and VIII, and von Willebrand factor. The associations of leukocyte count with cardiovascular risk factors may either represent manifestation of subclinical disease or suggest that leukocyte count is part of the causal chain leading to atherosclerosis. Alternatively, the relation of leukocyte count to cardiovascular disease may be confounded by risk factors and thus be noncausal.
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PMID:Leukocyte count correlates in middle-aged adults: the Atherosclerosis Risk in Communities (ARIC) Study. 144 16

Diabetic patients are at increased risk of cardiovascular disease, particularly when proteinuria is present. Lipoprotein(a)[Lp(a)] levels were assessed in 37 patients with insulin dependent (IDDM) and in 75 patients with non-insulin dependent (NIDDM) diabetes who showed varying degrees of proteinuria and glycaemic control. Median Lp(a) in 112 diabetic patients was significantly greater than in 116 healthy controls (113 vs 48 mg/L; p less than 0.01). 86 of the patients had first morning urine albumin concentration less than 30 mg/L (normoalbuminuria = NA), 16 patients 30-200 mg/L (microalbuminuria = MA) and ten patients greater than 200 mg/L (albuminuria = ALB). There was no significant difference in median Lp(a) concentration between the three groups (NA = 108, MA = 163, ALB = 98 mg/L; p greater than 0.5). No significant difference in median Lp(a) or NIDDM treated with oral agents and/or diet (120, 98, 115 mg/L respectively; p greater than 0.7). When the 86 NA patients were divided on the basis of median fructosamine concentration (357 mumol/L), no significant difference was found in median Lp(a) levels between those grouped below or above this median (98 mg/L vs 118 mg/L; p greater than 0.5). Across all diabetics studied there was no significant correlation present between Lp(a) and urinary protein or glycaemic control. These cross-sectional results suggest that median Lp(a) concentration is increased in both IDDM and NIDDM patients, but this increase is not related to the degree of proteinuria or short-term glycaemic control.
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PMID:Lipoprotein(a) concentration in diabetes: relationship to proteinuria and diabetes control. 144 18

We examined the association between oral contraceptive use and incidence of Type 2 (non-insulin-dependent) diabetes mellitus among 115117 female nurses free of diabetes, cardiovascular disease and cancer in 1976 and followed-up for 12 years. During 1237440 person years of follow-up, 2276 women who provided information on oral contraceptive use were clinically diagnosed with Type 2 diabetes. Women who used oral contraceptives in the past had only a slight and marginally increased relative risk of 1.10 (95% confidence interval 1.01, 1.21) compared to those women who had never used oral contraceptives after controlling for known risk factors of disease. We found no evidence of increased risk with longer duration of use or with shorter interval since last use. Current users did not have an increased risk of Type 2 diabetes (relative risk = 0.86, 95% confidence interval 0.46, 1.61) when compared to women who had never used the drug. There was no effect modification by obesity, family history of diabetes, or physical activity. These data suggest that past or current oral contraceptive use does not substantially influence subsequent risk of Type 2 diabetes.
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PMID:Oral contraceptive use and the risk of type 2 (non-insulin-dependent) diabetes mellitus in a large prospective study of women. 145 55

Only a subset of insulin-dependent diabetic patients are at risk of developing nephropathy. Prospective studies of uncomplicated insulin-dependent diabetic cohorts have shown that a rise in systemic arterial pressure is a concomitant feature of the progression to early nephropathy. The development of hypertension is an integral feature of established nephropathy in diabetes, and its amelioration retards the progression of disease and may improve overall mortality. Family studies have suggested that nondiabetic parents of insulin-dependent diabetic patients with nephropathy have a greater prevalence of hypertension, and in certain groups of non-insulin dependent patients, it has been found that the blood pressure before the onset of diabetes correlates with the development of nephropathy after the onset of diabetes. These results indicate that a propensity to hypertension may be part of the genetic predisposition to nephropathy. This contention is further supported by the finding that a raised erythrocyte sodium-lithium countertransport, a biochemical marker of hypertension and cardiovascular disease whose activity is largely genetically determined, occurs with greater frequency in proteinuric diabetic patients and their nondiabetic parents than in those diabetic patients without nephropathy and their parents. Recent family studies have also shown that a family history of cardiovascular disease significantly increases the risk of nephropathy by up to three-fold in insulin-dependent diabetes. It is suggested that the cardiorenal complications of diabetes mellitus may be linked to reduced insulin sensitivity, which itself is associated with hypertension, raised sodium-lithium countertransport rates, and cardiovascular disease.
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PMID:Predisposition to essential hypertension and the development of diabetic nephropathy. 145 58


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