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24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Epidemiological studies have led to the hypothesis that a major component of the risk of diseases such as hypertension, coronary heart disease and non-insulin-dependent diabetes (the 'metabolic syndrome') is established before birth. Although the underlying mechanisms of this 'programming' of disease have not yet been conclusively determined, a reduced fetal nutrient supply as a consequence of poor placental function or unbalanced maternal nutrition is strongly implicated. It has been proposed that one outcome of suboptimal nutrition is exposure of the fetus to excess glucocorticoids, which restrict fetal growth and programme permanent alterations in its cardiovascular, endocrine and metabolic systems. This review focuses on the effects of endogenous and exogenous glucocorticoid exposure in utero on postnatal hypothalamo-pituitary-adrenal (HPA) axis activity, both in humans and experimental animals. The physiological consequences and proposed underlying molecular and cellular mechanisms are discussed. Current data indicate that key targets for programming may include not only the HPA axis but also glucocorticoid receptor gene and 11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2) gene expression in a range of tissues.
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PMID:Prenatal programming of postnatal endocrine responses by glucocorticoids. 1236 63

Hyperglycemia and hyperinsulinemia are central features of the metabolic syndrome and type 2 diabetes mellitus, which contribute to the pathogenesis of coronary heart disease (CHD). Recent data indicate that increased dietary glycemic load (GL) due to replacing fats with carbohydrates or increasing intake of rapidly absorbed carbohydrates (ie, high glycemic index) can create a self-perpetuating insulin resistance state and predicts greater CHD risk. In this paper, we discuss the historic development of the GI and GL concepts and summarize metabolic experiments and epidemiologic observations relating to clinical utilities of these measures. On balance, increased consumption of low-GI foods leads to improvements in glycemia and dyslipidemia in metabolic studies, and a low-GL diet has been associated with lower risk of type 2 diabetes and CHD in prospective cohort studies. We conclude that decreasing dietary GL by reducing the intake of high-glycemic beverages and replacing refined grain products and potatoes with minimally processed plant-based foods such as whole grains, fruits, and vegetables may reduce CHD incidence in sedentary individuals and populations with a high prevalence of overweight. Because of advances in food-processing technologies and changes in ingredients in our food supply, the composition and physiologic effects of foods are likely to change over time. Future efforts should continue to quantify and monitor the metabolic impacts of different foods, and such information should be routinely incorporated into long-term prospective studies to allow for the assessment of the interactive effects of diets and other metabolic determinants on chronic disease risk.
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PMID:Dietary glycemic load and atherothrombotic risk. 1236 93

Dyslipidemia including hypercholesterolemia and hypertriglyceridemia often associated with low levels of HDL-cholesterol is a common and important cluster of risk factors for coronary heart disease. Dyslipidemia is also commonly associated with hypertension, hyperinsulinemia and central obesity in the metabolic syndrome. Lifestyle adjustments including increased physical activity and dietary modifications leading to weight reduction are important first steps in the prevention of coronary heart disease in patients with such abnormalities in lipid metabolism. When these adjustments are insufficient to achieve desirable results, the combined treatment with statins and omega-3 fatty acids is an efficient treatment alternative. Both statins and omega-3 fatty acids have documented their effects against coronary heart disease (CHD) both in primary and secondary prevention trials. The mechanisms involved are only partly explained, however, the synergistic effects of statins and omega-3 fatty acids significantly reduce the risk for CHD in patients with dyslipidemia.
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PMID:Statins and omega-3 fatty acids in the treatment of dyslipidemia and coronary heart disease. 1241 Jan 68

In 2001 the National Cholesterol Education Program (NCEP) released its Adult Treatment Panel (ATP) III report. This was an evidence-based report that upgraded cholesterol management guidelines. The update was made possible by a series of large, cholesterol-lowering clinical trials. These trials demonstrated strongly the efficacy and safety of cholesterol reduction in both primary and secondary prevention of coronary heart disease (CHD). The major recommendations of the report were several. Low-density lipoprotein (LDL) cholesterol continued to be identified as the major target of cholesterol-lowering therapy. However, more emphasis was given to HDL cholesterol and triglycerides as important targets for management. The concept of CHD risk equivalents was introduced. A CHD risk equivalent represents an absolute risk for future CHD events equal to that in persons with established CHD. Diabetes was identified as a CHD risk equivalent, requiring more intensive LDL-lowering therapy. Finally, the report placed more emphasis on the metabolic syndrome as a major, multiplex risk factor requiring increased clinical attention.
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PMID:Approach to lipoprotein management in 2001 National Cholesterol Guidelines. 1241 77

This invesgation examined the impact of hostility and the metabolic syndrome on coronary heart disease (CHD) using prospective data from the Normative Aging Study. Seven hundred seventy-four older, unmedicated men free of cardiovascular disease were included in the study. The total Cook-Medley Hostility (Ho) Scale score, anthropometric data, serum lipids, fasting insulin concentrations, blood pressure, cigarette smoking, alcohol consumption, and total dietary calories were used to predict incident CHD during a 3-year follow-up interval. Multivariate analysis indicated that only Ho positively predicted and high-density lipoprotein cholesterol level negatively predicted incident CHD. Ho's effects on CHD may be mediated though mechanisms other than factors that constitute the metabolic syndrome.
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PMID:Hostility, the metabolic syndrome, and incident coronary heart disease. 1243 11

The seminal studies of Brown and Goldstein (Science 1986;232:34-47) coupled with the findings of the Framingham study revolutionized our understanding of the metabolic basis for vascular disease. These studies led to the widespread use of the coronary risk lipid profile, which uses the total cholesterol/high-density lipoprotein (HDL) ratio (or low-density lipoprotein [LDL]/HDL ratio) in predicting risk for vascular disease and as a tool for therapeutic management of patients at risk for vascular disease. However, although these methods are predictive of coronary artery disease (CAD) in general, it is also well known that the extent of occlusive disease and CAD varies greatly between individuals with similar cholesterol and HDL lipid profiles. For this reason, the National Cholesterol Education Program Expert Panel revised these guidelines and now recommends monitoring LDL and HDL cholesterol in the context of coronary heart disease risk factors and "risk equivalents." In addition, more recent findings indicate that specific alterations in individual lipoprotein subclasses may account for the variations in CAD in subjects with similar lipid profiles. For example, a preponderance of small, dense LDL particles correlates with a marked increase in risk for myocardial infarction independent of LDL levels. In particular, the association of small, dense LDL with elevated triglycerides (large, less dense VLDL) and reduced HDL has been defined as the atherogenic lipoprotein profile, and the key metabolic defect driving this profile may be elevated levels of triglycerides, specifically large, less dense VLDL. In an attempt to explain the physiologic basis for lipoprotein variations, this review describes the basic metabolic scheme underlying the traditional view of lipoprotein metabolism and physiology. It then examines the identity and role of the various lipoprotein subfractions in an attempt to distill a working model of how lipoprotein abnormalities might account for vascular disease in general and the metabolic syndrome in particular.
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PMID:The physiology of lipoproteins. 1246 89

Evolutionary pressures have probably amplified the mechanisms for minimizing the impact of environmental factors through compensatory maternal mechanisms. Nevertheless, experimentally there are clear long-term programming effects of manipulations to the maternal diet on the likelihood of neural-tube defects associated with folate deficiency The fat/lean ratios of the newborn, and subsequent development, seem to be linked to amino acid or folate supply. An altered balance in the hypothalamic-pituitary-adrenal axis, which experimentally has profound effects on brain development, is induced by low-protein maternal diets. Such diets are linked to a reduced pancreatic capacity for insulin production and to an altered hepatic architecture, with a change in the control of glucose metabolism. Human studies suggest that what happens in pregnancy is modified by the child's diet in the first months of life. Low birthweight is linked to early stunting, and predisposes to abdominal obesity and metabolic syndrome in later life. Metabolic syndrome amplifies the risks of diabetes, hypertension, coronary heart disease and probably some cancers. Mothers with gestational diabetes are themselves prone to early type 2 diabetes and produce heavier babies prone to childhood obesity and adolescent type 2 diabetes. There is increasing evidence of an intergenerational effect, with big babies being prone to excess weight gain, which then, in girls, predisposes them to diabetes in pregnancy, which, in turn, promotes an accelerating cycle of early diabetes in subsequent generations. Essential fatty acids and fat soluble vitamins are important, but we need early interventions and monitoring systems to justify coherent policies.
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PMID:Will feeding mothers prevent the Asian metabolic syndrome epidemic? 1249 42

The most common and clinically important complication in adults with diabetes is cardiovascular disease (CVD), which includes coronary heart disease, peripheral vascular disease, and stroke. Both type 2 diabetes and the insulin resistance syndrome are associated with a marked increase in the risk for CVD. The metabolic syndrome and the closely related insulin resistance syndrome have recently been recognized as important disorders, each being associated with an increase in CVD risk even in the absence of glucose intolerance. Given the significant public health burden of CVD, risk reduction has emerged as a significant clinical challenge for most practitioners. Diabetes and the insulin resistance syndrome are closely related disorders, with insulin resistance being more than a key pathogenic defect in type 2 diabetes. Even in the absence of glucose intolerance, these 2 disorders are both associated with a number of distinct pathologic findings, including hypertension, atherogenic dyslipidemia, a prothrombotic environment, and significant vascular and hemodynamic abnormalities that result from endothelial cell dysfunction. Insulin resistance is now recognized to be closely associated with the development of each of these risk factors. This article uses a case-based approach to discuss the unique features of insulin resistance and type 2 diabetes considered to be key contributors to CVD risk. A systematic approach to both evaluation and management is proposed, with priority given to therapies of demonstrated clinical benefit. Because of its critical and central role in the development of many CVD risk factors, targeted treatment of insulin resistance will also be discussed as such therapy may prove to be a critical component of care in years to come.
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PMID:The metabolic syndrome, type 2 diabetes, and cardiovascular disease: understanding the role of insulin resistance. 1251 Jul 88

The role of low-density lipoprotein in the development of coronary heart disease (CHD) is well recognised. There is also growing evidence that high-density lipoprotein cholesterol (HDL-C) is a powerful inverse predictor for premature CHD and that maintaining a high HDL-C level may guard against atherosclerosis. Patients with low HDL-C levels often also have central obesity, insulin resistance and other features of the metabolic syndrome. This syndrome is both increasingly common and strongly implicated in the growing worldwide epidemic of type 2 diabetes. HDL-C may be increased by lifestyle changes, e.g. weight loss, physical activity and smoking cessation. Pharmacological agents such as fibrates, niacin and statins have also been shown significantly to elevate HDL-C. Although current guidelines are beginning to recognise the protective role of HDL-C level in preventing coronary events, HDL-C should be adopted soon as a target for intervention in its own right.
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PMID:High density lipoprotein: guardian of the vascular system? 1251 Sep 50

Metabolic syndrome, the clustering of hyperglycemia, hypertension and dyslipidemia, increases the risk of coronary heart disease. Abdominal obesity is an important cue for the clinician to consider metabolic syndrome. Measurement of waist circumference is a simple means of identifying abdominal obesity. The development and distribution of pocket tape measures to medical students, residents and attending physicians were initiated to enhance identification and treatment of metabolic syndrome. Distribution of the tape measures was added to a cardiovascular nutrition component in a 4th-y medical school curriculum. The nutrition component continued to include computer-based cases and pocket reference cards. Limited data suggest that the addition of pocket tape measures to the nutrition component of an ambulatory care clerkship may increase the percentage of medical students who use waist circumference to identify patients at risk for metabolic syndrome. It is anticipated that student use will increase with role modeling by residents and attending physicians.
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PMID:Pocket tape measure for waist circumference: training medical students and residents on a simple assessment of body composition. 1256


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