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Acromegaly is a chronic disorder invariably caused by a growth hormone (GH)-secreting pituitary tumour and is characterised by disabling symptoms (sweating, arthralgia, headache, paraesthesiae, fatigue), significant comorbidities (diabetes mellitus, hypertension, sleep apnoea), and premature mortality. Symptomatic control can be achieved by lowering insulin-like growth factor-I (IGF-I) concentrations to within the age-adjusted normal range, and survival can be improved to match that of the general population. However, even with optimal surgery and current medical therapies (dopamine agonists, somatostatin analogues), 30% to 50% of patients do not achieve target concentrations of IGF-I and GH. Pegvisomant is a new GH-receptor antagonist that blocks GH activity by inhibiting functional dimerisation of GH-receptors. Given as subcutaneous injections at dosages of 10 mg, 15 mg, or 20 mg/day for 3 Months, pegvisomant normalised serum IGF-I concentrations in, respectively, 54%, 81%, and 89% of acromegalic patients. Moreover, long-term pegvisomant therapy normalised IGF-I concentrations in 97% of patients treated for 12 Months or longer, with no evidence of tachyphylaxis. Pegvisomant is the most effective medical therapy, reported to date, in terms of normalisation of circulating IGF-I concentrations. In addition, pegvisomant appears to be safe and well tolerated. Although additional long-term studies are required to further assess safety, the introduction of this innovative treatment should allow for optimal disease control in patients with acromegaly.
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PMID:Pegvisomant: an advance in clinical efficacy in acromegaly. 1267 Feb 98

Patients with end-stage renal disease face a particularly high risk of cardiovascular disease and total mortality. Part of their increased risk is due to higher prevalence of established risk factors such as arterial hypertension, diabetes, smoking and anemia. Hypertension and diabetes have a very high prevalence in dialysis patients and play a major role in their high mortality and morbidity. Hyperparathyroidism, hyperhomocis-teinemia and disordered lipid metabolism represent factors which are peculiarly altered by the uremic state. Inflammatory processes, high sympathetic activity and the accumulation of an endogenous inhibitor of NO synthase (ADMA) have recently emerged as cardiovascular risk factors of paramount importance. Sleep apnea has been linked with nocturnal hypertension and could be implicated in the high prevalence of concentric hypertrophy of the left ventricle in these patients. Hypertension control as well as appropriate treatment of anaemia and cessation of smoking constitute fundamental areas of intervention in dialysis patients. It is possible that in the near future control of chronic inflammatory processes, of high sympathetic activity and endothelial dysfunction will further contribute to curb the exceedingly high cardiovascular mortality of patients on chronic dialysis treatment.
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PMID:[Cardiovascular events in chronic advanced renal insufficiency. Current concepts]. 1267 80

Patients with end-stage renal disease face a particularly high risk of cardiovascular disease and total mortality. Part of their increased risk is due to a higher prevalence of established risk factors, such as arterial hypertension, diabetes, smoking, and anemia. Hypertension and diabetes have a very high prevalence in dialysis patients and play a major role in their high mortality and morbidity. Hyperparathyroidism, hyperhomocysteinemia and disordered lipid metabolism represent factors that are peculiarly altered by the uremic state. Inflammatory processes, high sympathetic activity, and the accumulation of an endogenous inhibitor of NO synthase (ADMA), have recently emerged as cardiovascular risk factors of paramount importance. Sleep apnea has been linked with nocturnal hypertension and could be implicated in the high prevalence of concentric hypertrophy of the left ventricle in these patients. Hypertension control, as well as appropriate treatment of anemia and cessation of smoking, constitutes a fundamental area of intervention in dialysis patients. It appears possible that, in the near future, control of chronic inflammatory processes of high sympathetic activity and endothelial dysfunction will further help to curb the exceedingly high cardiovascular mortality of patients on chronic dialysis treatment.
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PMID:Traditional and emerging cardiovascular risk factors in end-stage renal disease. 1275 78

Obesity is approaching epidemic proportions in the western industrialized world, and is also becoming a major problem among young people in eastern and developing countries. Unfortunately, excess fat or adipose tissue is associated with a wide array of health problems, including increased incidence of type II diabetes, cardiovascular disease, hypertension, sleep apnea, and skeletomuscular problems. Obesity is the second leading cause of death from "unnecessary" causes in the U.S. (after smoking), and costs individuals and society billions of dollars worldwide to treat. Despite common wisdom that "one just needs to eat less and exercise more" and a multi-billion-dollar diet industry, epidemiological data indicate that the incidence of obesity will continue to rise. This alarming trend is, in part, due to the unprecedented availability of energy-dense foods and an increasingly sedentary lifestyle. These environmental factors may be complicated in some individuals by an unfavorable genetic predisposition. Pharmaceutical companies lead active research programs to identify drugs that target weight control centers in the body and which may help individuals control their weight; however, no satisfactory magic bullet to fight obesity has yet come through the pipeline.
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PMID:Signaling pathway puts the break on fat cell formation. 1280 64

Obstructive sleep apnoea (OSA) is a very prevalent disorder particularly amongst middle-aged, obese men, although its existence in women as well as in lean individuals is increasingly recognized. Despite the early recognition of the strong association between OSA and obesity, and OSA and cardiovascular problems, sleep apnoea has been treated as a 'local abnormality' of the respiratory track rather than as a 'systemic illness'. In 1997, we first reported that the pro-inflammatory cytokines interleukin (IL)-6 and tumour necrosis factor-alpha (TNF alpha) were elevated in patients with disorders of excessive daytime sleepiness (EDS) and proposed that these cytokines were mediators of daytime sleepiness. Also, we reported a positive correlation between IL-6 or TNF alpha plasma levels and the body mass index (BMI). In subsequent studies, we showed that IL-6, TNF alpha, leptin and insulin levels were elevated in sleep apnoea independently of obesity and that visceral fat, was the primary parameter linked with sleep apnoea. The association of OSA with insulin resistance and diabetes type 2 has been confirmed since then in several epidemiological and clinical studies. Furthermore, our findings that women with polycystic ovary syndrome (PCOS, a condition associated with hyperandrogenism and insulin resistance) were much more likely than controls to have sleep disordered breathing (SDB) and daytime sleepiness support the pathogenetic role of insulin resistance in OSA. Other findings that support the view that sleep apnoea and sleepiness may be manifestations of a serious metabolic disorder, namely the Metabolic or Visceral Obesity Syndrome, include: obesity without sleep apnoea is associated with daytime sleepiness; PCOS and diabetes type 2 are independently associated with EDS after controlling for SDB, obesity and age; and increased prevalence of sleep apnoea in postmenopausal women, with hormonal replacement therapy associated with a significantly reduced risk for OSA. In conclusion, accumulating evidence provides support to our model of the bi-directional, feedforward, pernicious association between sleep apnoea, sleepiness, inflammation and insulin resistance, all promoting atherosclerosis and cardiovascular disease.
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PMID:Metabolic disturbances in obesity versus sleep apnoea: the importance of visceral obesity and insulin resistance. 1282 41

Obesity is a progressive disease of unwanted fat accumulation which has multiple, organ-specific pathological consequences. The manifestations of obesity occur within virtually every subspecialty of medicine or surgery and they interact importantly to accelerate the ageing process in many organs. Many of the hazards of obesity have multiple causes (e.g., diabetes, heart disease, stroke, colonic and breast cancer, urinary incontinence, tiredness, back pain, breathlessness). All of these conditions become more prevalent with age and are also more prevalent among overweight persons, particularly those with a central fat distribution marked by a high waist circumference. Hypertension may be caused or aggravated by weight gain. It is mediated by the physical demands of an expanded circulating volume and increased metabolic rate by metabolic mechanisms related to central fat distribution and the "metabolic syndrome", and to increased sodium consumption by overweight people (because they need more food to maintain a higher metabolic rate). Since body mass index (BMI) and waist circumference increase significantly with age there is an escalation of the burden of ill health from obesity with age. The best simple indicator of disease risk with obesity is the waist circumference since this identifies people who have a high body fat content and also those who have an increased intraabdominal accumulation of fat. The quantitative burden of ill health from overweight and obesity varies within different specialties, but up to 80% of type 2 diabetes or polycystic ovarian syndrome can be attributed to obesity. Obesity is the cause of sleep apnea syndrome in around 50% of cases and heart disease in perhaps 10-20% of cases. In Scotland 80% of people with existing cardiovascular disease are overweight compared with 57% of the general population. The financial burden to health services from overweight and obesity has been incompletely assessed, although it is estimated that around 4% of total health care budgets are attributable to people having BMI > 25 kg/m(2). This is similar to the entire cost of diabetes, epilepsy or major cancers. Obesity is therefore an extremely expensive disease based on these conservative estimates from limited evaluations. More general assessments show how obesity increases the amount of time taken off work, the number of drugs prescribed and the expenditure from social services support. Thus, obesity represents a huge burden not only on the individual patient physically, psychologically, socially and financially but also on families and careers and is a huge drain on health care resources. Overweight affects well over half of all adults worldwide, progressing to BMI > 30 kg/m(2) in around 20% outside subsistence rural communities. Its rapidly increasing prevalence now described as an epidemic demands major preventive measures, as well as better medical treatment for individuals affected.
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PMID:Obesity: burdens of illness and strategies for prevention or management. 1284 36

Vascular dementia is the second most common type of dementia. The subcortical ischaemic form (SIVD) frequently causes cognitive impairment and dementia in elderly people. SIVD results from small-vessel disease, which produces either arteriolar occlusion and lacunes or widespread incomplete infarction of white matter due to critical stenosis of medullary arterioles and hypoperfusion (Binswanger's disease). Symptoms include motor and cognitive dysexecutive slowing, forgetfulness, dysarthria, mood changes, urinary symptoms, and short-stepped gait. These manifestations probably result from ischaemic interruption of parallel circuits from the prefrontal cortex to the basal ganglia and corresponding thalamocortical connections. Brain imaging (computed tomography and magnetic resonance imaging) is essential for correct diagnosis. The main risk factors are advanced age, hypertension, diabetes, smoking, hyperhomocysteinaemia, hyperfibrinogenaemia, and other conditions that can cause brain hypoperfusion such as obstructive sleep apnoea, congestive heart failure, cardiac arrhythmias, and orthostatic hypotension. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL)and some forms of cerebral amyloid angiopathy have a genetic basis. Treatment is symptomatic and prevention requires control of treatable risk factors.
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PMID:Subcortical ischaemic vascular dementia. 1284 65

The aim of this cross-sectional study was to evaluate the frequency of type-2 diabetes and impaired glucose tolerance (IGT) in a large clinic-based male population presenting various degrees of obstructive sleep apnoea syndrome (OSAS) and to analyse the relationship between OSAS and glucose-insulin metabolism. Male patients (n=595) with suspected OSAS underwent both nocturnal polysomnography and a 2-h oral glucose-tolerance test with measurements of fasting and postload blood glucose and plasma insulin. Insulin sensitivity was evaluated by the ratio of fasting glucose to fasting insulin. OSAS was diagnosed in 494 patients, while 101 patients were nonapnoeic snorers. Type-2 diabetes was present in 30.1% of OSAS patients and 13.9% of nonapnoeic snorers. IGT was diagnosed in 20.0% of OSAS patients and 13.9% of nonapnoeic snorers. Fasting and postload blood glucose increased with severity of sleep apnoea. Insulin sensitivity decreased with increasing severity of sleep apnoea. In addition to body mass index and age, the apnoea/hypopnoea index independently influenced postload blood glucose and insulin sensitivity. The authors conclude that in a clinic-based sample of patients, obstructive sleep apnoea syndrome is associated with a high frequency of type-2 diabetes and impaired glucose tolerance. The relationship between sleep-disordered breathing and impaired glucose-insulin metabolism is independent of obesity and age.
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PMID:Impaired glucose-insulin metabolism in males with obstructive sleep apnoea syndrome. 1288 66

This article reviews several aspects of the association between obesity and cancer. Current perspectives of cancers of the breast, endometrium, colon and prostate are described. Obesity is a growing problem in contemporary societies, due to the rapid adoption of a modernized lifestyle that results in increased carbohydrate and fat-rich dietary intake, reduced physical activity and extended life expectancy. More than half of adult Americans are overweight or obese, and so is the population of many other countries. There are several definitions for the state of obesity. The body mass index (BMI), which measures overall adiposity, is universally available, the easiest to determine, and therefore the most commonly studied. Anthropometric measurements of subcutaneous fat distribution, such as measurement of girth, circumference of the arms, hips and thighs, or of skinfolds in various body regions are also often used. They allow to categorize the distribution of subcutaneous fat into android and gynoid types (den Tonkelaar, Seidell et al., 1994; Huang, Willett et al., 1999). The android, or abdominal, fat is determined from the waist to hip ratio, and is of particular relevance to cancer. Increased body weight and fat are associated with high health risks, and therefore body fat distribution and BMI are major predictors of obesity associated risks (Calle, Thun et al., 1999; "Overweight, obesity, and health risk," Yanovski, 2000). These include diabetes mellitus type 2, coronary heart disease, sleep apnea and pulmonary dysfunction, stroke, diseases of the gallbladder, liver and the musculoskeleton, reproductive dysfunction, venous insufficiency, deep vein thrombosis, poor wound healing, and more (Pi Sunyer, 1993; "Overweight, obesity, and health risk", Yanovski, 2000). All these are associated with increased mortality, especially in individuals with other risk factors (Calle, Thun et al., 1999). Cancer is also associated with obesity (Garfinkel, 1985), and the present paper attempts to summarize current perspectives of this association, especially in cancers of the breast, endometrium, colon and prostate.
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PMID:Obesity and cancer. 1293 6

The obstructive sleep apnea syndrome is typically associated with conditions known to increase insulin resistance as hypertension, obesity, and diabetes. We investigated whether obstructive sleep apnea itself is an independent risk factor for increased insulin resistance and whether continuous positive airway pressure (CPAP) treatment improves insulin sensitivity. Forty patients (apnea-hypopnea index > 20) were treated with CPAP. Before, 2 days after, and after 3 months of effective CPAP treatment, hyperinsulinemic euglycemic clamp studies were performed. Insulin sensitivity significantly increased after 2 days (5.75 +/- 4.20 baseline versus 6.79 +/- 4.91 micromol/kg.min; p = 0.003) and remained stable after 3 months of treatment. The improvement in insulin sensitivity after 2 days was much greater in patients with a body mass index less than 30 kg/m2 than in more obese patients. The improved insulin sensitivity after 2 nights of treatment may reflect a decreasing sympathetic activity, indicating that sleep apnea is an independent risk factor for increased insulin resistance. The effect of CPAP on insulin sensitivity is smaller in obese patients than in nonobese patients, suggesting that in obese individuals insulin sensitivity is mainly determined by obesity and, to a smaller extent, by sleep apnea.
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PMID:Continuous positive airway pressure treatment rapidly improves insulin sensitivity in patients with obstructive sleep apnea syndrome. 1471 27


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