Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015695 (fatty liver)
 13,941 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ability of insulin to stimulate glucose disposal varies more than six-fold in apparently healthy individuals. The one third of the population that is most insulin resistant is at greatly increased risk to develop cardiovascular disease (CVD), type 2 diabetes, hypertension, stroke, nonalcoholic fatty liver disease, polycystic ovary disease, and certain forms of cancer. Between 25-35% of the variability in insulin action is related to being overweight. The importance of the adverse effects of excess adiposity is apparent in light of the evidence that more than half of the adult population in the United States is classified as being overweight/obese, as defined by a body mass index greater than 25.0 kg/m(2). The current epidemic of overweight/obesity is most-likely related to a combination of increased caloric intake and decreased energy expenditure. In either instance, the fact that CVD risk is increased as individuals gain weight emphasizes the gravity of the health care dilemma posed by the explosive increase in the prevalence of overweight/obesity in the population at large. Given the enormity of the problem, it is necessary to differentiate between the CVD risk related to obesity per se, as distinct from the fact that the prevalence of insulin resistance and compensatory hyperinsulinemia are increased in overweight/obese individuals. Although the majority of individuals in the general population that can be considered insulin resistant are also overweight/obese, not all overweight/obese persons are insulin resistant. Furthermore, the cluster of abnormalities associated with insulin resistance - namely, glucose intolerance, hyperinsulinemia, dyslipidemia, and elevated plasma C-reactive protein concentrations -- is limited to the subset of overweight/obese individuals that are also insulin resistant. Of greater clinical relevance is the fact that significant improvement in these metabolic abnormalities following weight loss is seen only in the subset of overweight/obese individuals that are also insulin resistant. In view of the large number of overweight/obese subjects at potential risk to be insulin resistant/hyperinsulinemic (and at increased CVD risk), and the difficulty in achieving weight loss, it seems essential to identify those overweight/obese individuals who are also insulin resistant and will benefit the most from weight loss, then target this population for the most-intensive efforts to bring about weight loss.
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PMID:Obesity, insulin resistance, and cardiovascular disease. 1474 3

The metabolic syndrome is intended to identify patients who have increased risk of diabetes and/or a cardiac event due to the deleterious effects of weight gain, sedentary lifestyle, and/or an atherogenic diet. The National Cholesterol Education Program's Adult Treatment Panel III definition uses easily measured clinical findings of increased abdominal circumference, elevated triglycerides, low high-density lipoprotein-cholesterol, elevated fasting blood glucose and/or elevated blood pressure. Three of these five are required for diagnosis. The authors also note that other definitions of metabolic syndrome focus more on insulin resistance and its key role in this syndrome. This review focuses on how treatment might affect each of the five components. Abdominal obesity can be treated with a variety of lower calorie diets along with regular exercise. Indeed, all of the five components of the metabolic syndrome are improved by even modest amounts of weight loss achieved with diet and exercise. For those with impaired fasting glucose tolerance, there is good evidence that a high fiber, low saturated fat diet with increased daily exercise can reduce the incidence of diabetes by almost 60%. Of note, subjects who exercise the most, gain the most benefit. Metformin has also been shown to be helpful in these subjects. Thiazolidinedione drugs may prove useful, but further studies are needed. Although intensified therapeutic lifestyle change will help the abnormal lipid profile, some patients may require drug therapy. This review also discusses the use of statins, fibrates, and niacin. Likewise, while hypertension in the metabolic syndrome benefits from therapeutic lifestyle change, physicians should also consider angiotensin converting enzyme inhibitor drugs or angiotensin receptor blockers, due to their effects on preventing complications of diabetes, such as progression of diabetic nephropathy and due to their effects on regression of left ventricular hypertrophy. Aspirin should be considered in those with at least a 10% risk of a coronary event over 10 years. Finally, three related conditions, nonalcoholic fatty liver disease, polycystic ovary syndrome and protease inhibitor associated lipodystrophy improve with therapeutic lifestyle change. Although metformin is shown to be useful with polycystic ovary syndrome, the data supporting drug therapy for the other syndromes is less convincing. More robust studies are needed before any firm recommendations can be made.
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PMID:Treatment of metabolic syndrome. 1515 70

Alanine aminotransferase (ALT) activity was abnormal in 30% of 70 female infertility patients with polycystic ovary syndrome in whom causes other than nonalcoholic fatty liver disease were excluded by history and serum testing. Women with elevated ALT had significantly higher body mass index, waist circumference, serum triglycerides, total cholesterol-to-HDL-cholesterol ratio, and degree of insulin resistance.
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PMID:Abnormal aminotransferase activity in women with polycystic ovary syndrome. 1570 3

The insulin resistance syndrome (IRS) is considered to be a new target of risk-reduction therapy. The IRS is a cluster of closely associated and interdependent abnormalities and clinical outcomes that occur more commonly in insulin-resistant/hyperinsulinemic individuals. This syndrome predisposes individuals to type 2 diabetes, cardiovascular diseases, essential hypertension, certain forms of cancer, polycystic ovary syndrome, nonalcoholic fatty liver disease, and sleep apnea. In patients at high risk for cardiovascular diseases, endothelial dysfunction is observed in morphologically intact vessels even before the onset of clinically manifest vascular disease. Indeed, there are several lines of evidence that indicate that endothelial function is compromised in situations where there is reduced sensitivity to endogenous insulin. It is well established that a decreased bioavailability of nitric oxide (NO) contributes to endothelial dysfunction. Furthermore, NO may modulate insulin sensitivity. Activation of NO synthase (NOS) augments blood flow to insulin-sensitive tissues (i.e. skeletal muscle, liver, adipose tissue), and its activity is impaired in insulin resistance. Inhibition of NOS reduces the microvascular delivery of nutrients and blunts insulin-stimulated glucose uptake in skeletal muscle. Furthermore, induction of hypertension by administration of the NOS inhibitor NG-monomethyl-L-arginine is also associated with insulin resistance in rats. Increased levels of asymmetric dimethylarginine (ADMA) are associated with endothelial vasodilator dysfunction and increased risk of cardiovascular diseases. An intriguing relationship exists between insulin resistance and ADMA. Plasma levels of ADMA are positively correlated with insulin resistance in nondiabetic, normotensive people. New basic research insights that provide possible mechanisms underlying the development of insulin resistance in the setting of impaired NO bioavailability will be discussed.
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PMID:Insulin resistance: potential role of the endogenous nitric oxide synthase inhibitor ADMA. 1644 67

Insulin-mediated glucose disposal varies widely in apparently healthy human beings, and the more insulin resistant an individual, the more insulin they must secrete in order to prevent the development of type 2 diabetes. However, the combination of insulin resistance and compensatory hyperinsulinemia increases the likelihood that an individual will be hypertensive, and have a dyslipidemia characterized by a high plasma triglyceride (TG) and low high-density lipoprotein cholesterol (HDL-C) concentration. These changes increase risk of cardiovascular disease (CVD), and in 1988, this cluster of related abnormalities was designated as comprising a syndrome (X). Several other clinical syndromes are now known to be associated with insulin resistance and compensatory hyperinsulinemia. For example, polycystic ovary syndrome appears to be secondary to insulin resistance and compensatory hyperinsulinemia. More recently, studies have shown that the prevalence of insulin resistance/hyperinsulinemia is increased in patients with nonalcoholic fatty liver disease, and there are reports that certain forms of cancer are more likely to occur in insulin resistant/hyperinsulinemic persons. Finally, there is substantial evidence of an association between insulin resistance/hyperinsulinemia, and sleep disordered breathing. Given the rapid increase in the number of clinical syndromes and abnormalities associated with insulin resistance/hyperinsulinemia, it seems reasonable to suggest that the cluster of these changes related to the defect in insulin action be subsumed under the term of the insulin resistance syndrome. In addition to the identification of additional clinical syndromes related to insulin resistance/hyperinsulinemia, a number of new risk factors have been recognized that would increase CVD risk in these individuals. Thus, in addition to a high TG and a low HDL-C, the atherogenic lipoprotein profile in insulin resistant/hyperinsulinemic individuals also includes the appearance of smaller and denser low density lipoprotein particles, and the enhanced postprandial accumulation of remnant lipoproteins; changes identified as increasing risk of CVD. Elevated plasma concentrations of plasminogen activator inhibitor-1 (PAI-1) have been shown to be associated with increased CVD, and there is evidence of a significant relationship between PAI-1 and fibrinogen levels and both insulin resistance and hyperinsulinemia. Evidence is also accumulating that sympathetic nervous system (SNS) activity is increased in insulin resistant, hyperinsulinemic individuals, and, along with the salt sensitivity associated with insulin resistance/hyperinsulinemia, increases the likelihood that these individuals will develop essential hypertension. The first step in the process of atherogenesis is the binding of mononuclear cells to the endothelium, and mononuclear cells isolated from insulin resistant/hyperinsulinemic individuals adhere with greater avidity. This process is modulated by adhesion molecules produced by endothelial cells, and there is a significant relationship between degree of insulin resistance and the plasma concentration of the several of these adhesion molecules. Further evidence of the relationship between insulin resistance and endothelial dysfunction is the finding that asymmetric dimethylarginine, an endogenous inhibitor of the enzyme nitric oxide synthase, is increased in insulin resistant/hyperinsulinemic individuals. Finally, plasma concentrations of several inflammatory markers are elevated in insulin resistant subjects. It is obvious that the cluster of abnormalities associated with insulin resistance and compensatory hyperinsulinemia contains many well-recognized CVD risk factors, choosing which one, or ones, that are primarily responsible for the accelerated atherogenesis that characterizes this syndrome is not a simple task. Indeed, efforts to try to do so by the use of multiple regression analysis of epidemiological data may be more misleading than helpful.
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PMID:Insulin resistance, the insulin resistance syndrome, and cardiovascular disease. 1648 19

Researchers are only gradually becoming aware of the gravity of the risk that overweight and obesity pose for children's health. In this article Stephen Daniels documents the heavy toll that the obesity epidemic is taking on the health of the nation's children. He discusses both the immediate risks associated with childhood obesity and the longer-term risk that obese children and adolescents will become obese adults and suffer other health problems as a result. Daniels notes that many obesity-related health conditions once thought applicable only to adults are now being seen in children and with increasing frequency. Examples include high blood pressure, early symptoms of hardening of the arteries, type 2 diabetes, nonalcoholic fatty liver disease, polycystic ovary disorder, and disordered breathing during sleep. He systematically surveys the body's systems, showing how obesity in adulthood can damage each and how childhood obesity exacerbates the damage. He explains that obesity can harm the cardiovascular system and that being overweight during childhood can accelerate the development of heart disease. The processes that lead to a heart attack or stroke start in childhood and often take decades to progress to the point of overt disease. Obesity in childhood, adolescence, and young adulthood may accelerate these processes. Daniels shows how much the same generalization applies to other obesity-related disorders-metabolic, digestive, respiratory, skeletal, and psychosocial-that are appearing in children either for the first time or with greater severity or prevalence. Daniels notes that the possibility has even been raised that the increasing prevalence and severity of childhood obesity may reverse the modern era's steady increase in life expectancy, with today's youth on average living less healthy and ultimately shorter lives than their parents-the first such reversal in lifespan in modern history. Such a possibility, he concludes, makes obesity in children an issue of utmost public health concern.
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PMID:The consequences of childhood overweight and obesity. 1653 58

Polycystic ovary syndrome affects 6%-7% of reproductive-aged women, making it the most common endocrine disorder in this population. It is characterized by chronic anovulation and hyperandrogenism. Affected women may present with reproductive manifestations such as irregular menses or infertility, or cutaneous manifestations, including hirsutism, acne, or male-pattern hair loss. Over the past decade, several serious metabolic complications also have been associated with polycystic ovary syndrome including type 2 diabetes mellitus, metabolic syndrome, sleep apnea, and possibly cardiovascular disease and nonalcoholic fatty liver disease. In addition to treating symptoms by regulating menstrual cycles and improving hyperandrogenism, it is imperative that clinicians recognize and treat metabolic complications. Lifestyle therapies are first-line treatment in women with polycystic ovary syndrome, particularly if they are overweight. Pharmacological therapies are also available and should be tailored on an individual basis. This article reviews the diagnosis, clinical manifestations, metabolic complications, and treatment of the syndrome. A table summarizing treatment recommendations is provided.
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PMID:Polycystic ovary syndrome: diagnosis and treatment. 1727 49

Polycystic ovary syndrome (PCOS) affects 6-7% of reproductive-aged women. Although the diagnostic criteria for PCOS have been debated, it is frequently characterized by hyperandrogenism (hirsutism, acne, male-pattern hair loss), oligo-anovulation, and polycystic ovaries on ultrasound. The reproductive and metabolic complications associated with the syndrome can be serious, so a comprehensive approach to the evaluation and treatment of affected women is important. Menstrual cycle control is necessary to prevent endometrial hyperplasia, and this can be accomplished with hormonal contraception, progesterone therapy, and weight loss (if overweight). In women desiring pregnancy, commonly used ovulation induction therapies include weight loss, clomiphene citrate, and/or metformin. Cosmetic issues such as hirsutism, acne and male-pattern hair loss can be challenging to cope with. Treatment options include estrogen-containing hormonal contraceptive agents, antiandrogens, and topical agents. More permanent hair reduction can be achieved with electrolysis and laser therapy. Evaluation of metabolic complications includes risk assessment for diabetes, dyslipidemia, hypertension, and nonalcoholic fatty liver disease. Women with PCOS should also be screened for sleep apnea, as this has been reported to occur more commonly in women with PCOS. Finally, mental health issues such as depression and eating disorders may be present. Many of the complications associated with PCOS can be managed with therapeutic lifestyle change, including a healthy diet, exercise, weight loss (if overweight), and psychological support. Pharmacological therapies are also available to effectively regulate menstrual cycles and manage cosmetic complications. This article will review the current diagnostic and therapeutic strategies in PCOS.
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PMID:Comprehensive clinical management of polycystic ovary syndrome. 1759 39

Extreme forms of insulin resistance are a rare cause of type 2 diabetes. However, individuals with severe insulin resistance pose unique diagnostic and therapeutic challenges, and have often acted as 'experiments of nature' providing important novel information regarding endocrine physiology and mechanistic insights relevant to the study of more common disorders. Progress in understanding the molecular pathogenesis of such syndromes is also beginning to yield novel therapeutic options. Severe insulin resistance typically presents in 1 of 3 ways: (1) disordered glucose metabolism including both diabetes and/or paradoxical hypoglycaemia; (2) acanthosis nigricans, a velvety hyperpigmentation of axilliary and flexural skin often associated with skin tags; or (3) hyperandrogenism in girls (hirsutism, oligo-/amenorrhoea and polycystic ovaries). Lipodystrophy is a major cause of severe insulin resistance and needs to be looked for very carefully, particularly in the patients with significant dyslipidaemia and fatty liver. Specific treatments are now available for some forms of severe insulin resistance; for example, leptin replacement in patients with generalized lipodystrophy. In the absence of a specific diagnosis and therapy, metformin is a useful insulin sensitizer and should be used in conjunction with aggressive diet and exercise interventions.
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PMID:A clinical approach to severe insulin resistance. 1798 32

Obesity has emerged as one of the most serious public health concerns in the 21st century. Obese children tend to become obese adults. The dramatic rise in pediatric obesity closely parallels the rapid increase in the prevalence of adult obesity. As overweight children become adults they face the multitude of health problems associated with obesity at younger ages. The morbidity and mortality associated with obesity continue to increase. Obesity is one of the leading causes of preventable death. Complications of obesity include cardiovascular risks, hypertension, dyslipidemia, endothelial dysfunction, type 2 diabetes mellitus and impaired glucose tolerance, acanthosis nigricans, hepatic steatosis, premature puberty, hypogonadism and polycystic ovary syndrome, obstructive sleep disorder, orthopedic complications, cholelithiasis and pseudotumor cerebri. Genetic and molecular and environmental factors play an important role in the assessment and management of obesity.
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PMID:Obesity: genetic, molecular, and environmental aspects. 1800 Sep 69


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