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Gh Secretion In Abdominal Obesity

With increased adiposity, GH secretion is blunted with a decrease in the mass of GH secreted per burst but without any major impact on GH secretory burst frequency (46). Moreover, the metabolic clearance rate of GH is accelerated (32). The serum insulin-like growth factor (IGF)-1 concentration is primarily GH dependent and influences GH secretion though a negative feed-back system (47). The serum levels of IGF-1 are inversely related to the percentage of body fat (46). In addition, the low serum IGF-1 concentration in obesity is predominantly related to the amount of visceral adipose tissue and not to the amount of subcutaneous fat mass (48). The relationship between regional fat distribution and GH secretion has only recently been considered. No significant correlation was found between the waist-to-hip ratio and 24-h GH secretion rates in a study of 21 healthy men (49). However, measured by computed tomography, the amount of visceral adiposity was a major determinant of stimulated...

NCEPDefined Metabolic Syndrome Diabetes and Prevalence of Coronary Heart Disease Among Nhanes Iii Participants Age 50

Summary Although the individual components of the metabolic syndrome are clearly associated with increased risk for coronary heart disease (CHD), the authors of this study wanted to quantify the increased prevalence of CHD among people with metabolic syndrome. The authors used the Third National Health and Nutrition Examination Survey (NHANES III) to categorize adults over 50 years of age by presence of metabolic syndrome, with or without diabetes. Metabolic syndrome is very common, with approximately 44 percent of the united States population over 50 years of age meeting the criteria. in contrast, diabetes without metabolic syndrome is uncommon (13 percent of those with diabetes). Older Americans over 50 years of age without metabolic syndrome, regardless of diabetes status, had the lowest CHD prevalence. The prevalence of CHD markedly increased with the presence of metabolic syndrome. Among people with diabetes, the prevalence of metabolic syndrome was very high, and those with...

Metabolic Syndrome and Cardiovascular Risk

The disease most studied in relation to obesity is diabetes. The precursor to type 2 diabetes and to cardiovascular disease in many patients is the metabolic syndrome. By definition, this is said to be present if three or more of the following five conditions are met Abdominal obesity waist circumference > 102 cm in men and > 88 cm in women This was the accepted definition of the metabolic syndrome until recently, and, using these criteria, a variety of studies in North America demonstrated that the syndrome was present in 21 to 33 of the population, with even higher prevalence in certain ethnic groups. A recent study (Ford et al., 2004) using the NHANES cohorts compared the prevalence of metabolic syndrome in the 1988-1994 (NHANES III) cohort with the 1999-2000 cohort. The prevalence increased overall, but particularly in women who experienced a 23.5 increase. In fact, the definition of metabolic syndrome is changing with lower cut-off points for waist circumference and for...

Gh Treatment Of Patients With Abdominal Obesity

We have learned that GH can improve several of the aberrations that occur both in GH deficiency and Syndrome X. Thus, in GH-deficient adults the lipolytic effects of GH results in a preferential reduction in visceral adipose tissue (66). Furthermore, GH reduces the diastolic blood pressure (103), reduces total cholesterol, LDL-cholesterol (57,104-106), and increases HDL-cholesterol concentrations (78,105,107). Furthermore, long-term GH treatment does not impair insulin sensitivity (82). With this background we have studied the effects of GH on the metabolic, circulatory, and anthropodometric aberrations associated with abdominal visceral obesity and Syndrome X (108). The men who were studied were moderately obese with a preponderance of abdominal and or visceral localization of body fat. As a group, they had slight to moderate metabolic changes known to be associated with abdominal visceral obesity with serum IGF-1 concentrations in the low normal range and moderate insulin resistance...

Nonneoplastic Conditions

Acute pancreatitis with an overall mortality of 10-15 it is rarely biopsied or resected. The commonest causes are gall stones, sphincter spasm or incompetence with reflux of duodenal fluid and bile, alcohol, trauma and hypothermia. It is due to release of pancreatic enzymes comprising pancreatic haemorrhage, necrosis and inflammation with saponification and chalky calcification of abdominal fat. It is usually a self-limiting process but critical complications include sepsis, shock, bowel paralysis or perforation. Treatment is resuscitative and supportive - operative intervention can include removal of obstructing gall stones (by ERCP) or infected necrotic tissue (necrosectomy).

The Realities Of Overweight

Overweight, central or abdominal fat, weight gain after age 20, and a sedentary lifestyle all increase health risks and increase economic costs of obesity. Intentional weight loss by overweight individuals, on the other hand, reduces these risks. Although data are not yet available, researchers widely believe that long-term intentional weight loss lowers overall mortality, particularly from diabetes, gallbladder disease, hypertension, heart disease, and some types of cancer.

Officebased Obesity Care

Examination rooms should have large gowns available to wear as well as a step stool to mount the examination tables. Each room should be equipped with large adult and thigh blood pressure cuffs for measurement of blood pressure. A bladder cuff that is not the appropriate width for the patient's arm circumference will cause a systematic error in blood pressure measurement if the bladder is too narrow, the pressure will be overestimated and lead to a false diagnosis of hypertension. To avoid errors, the bladder width should be 40-50 of upper-arm circumference. Therefore, a large adult cuff (15 cm wide) should be chosen for patients with mild to moderate obesity, while a thigh cuff (18 cm wide) will need to be used for patients whose arm circumferences are > 16 inches. Lastly, a cloth or metal tape should be available for measurement of waist circumference as per the NHLBI Practical Guide for obesity classification (8). The optimal team composition and management structure will vary...

Relationship to Classical Indexes

It is important to analyze whether the previous analysis methodology for parameterizing the vessel behavior during the flow-mediated dilation test is linked to other clinical parameters and CVD risk factors traditionally used in the medical literature. Serum lipids, particularly cholesterol and the cholesterol fraction carried by low-density lipoproteins (LDL cholesterol) are recognized as a main causal factor of atherosclerosis 34 . In this disease lipids accumulate in the vessel wall, disturbing the vascular function of delivering sufficient blood flow to the affected territories, which ends with the manifestation of a vascular clinical event like heart attack or stroke. Moreover, knowing patients' lipid levels and modifying them with drugs and diet is the main preventive tool against cardiovascular diseases. From this point of view, cholesterol and LDL cholesterol are considered as risk factors, as higher levels identify individuals with higher risk whereas the cholesterol fraction...

Individuals or Populations

A range of higher-risk groups can be defined for special attention based on their increased propensity to obesity or enhanced health hazards from obesity. Five key high-risk groups include those with abdominal obesity Asians and other susceptible ethnic groups families with a history of obesity and or type 2 diabetes overweight adolescents and obese pregnant women. 1 Abdominal Obesity Abdominal obesity has now been clearly linked to an enhanced risk of comorbidities and is a key feature of Syndrome X, or the metabolic syndrome (20,21). Although no clear-cut definition has yet been agreed upon internationally, the syndrome includes a relative excess of abdominal fat, hypertension, insulin resistance, with glucose intolerance or diabetes, dyslipidemia, and microproteinuria. The additional health risk posed by abdominal obesity was highlighted by the WHO specification of two categories of increased risk based on sex-specific waist circumference measurements in its technical report on...

Clinical manifestation

Gressive decline over the ensuing years (Mallon 2003). Peripheral fat loss can be accompanied by an accumulation of visceral fat which can cause mild gastrointestinal symptoms. Truncal fat increases initially after therapy and then remains stable (Mallon 2003). Visceral obesity, as a singular feature of abnormal fat redistribution, appears to occur in only a minority of patients. Fat accumulation may also be found as dorsocervical fat pads (buffalo hump) within the muscle and the liver. Female HIV patients sometimes complain about painful breast enlargement which has been attributed to the lipodystrophy syndrome. Whether gynecomastia in male patients is a component of the syndrome remains unclear. There is now accumulating evidence that the major clinical components - lipoatrophy, central adiposity and the combination of both - result from different pathogenetic developmental processes. The prevalence of lipodystrophy syndrome has been estimated to be between 30 and 50 based on...

HAART lipodystrophy syndrome and cardiovascular risk

The fat redistribution and disturbances in glucose and fat metabolism resemble a clinical situation that is known as the metabolic syndrome in HIV-negative patients. This condition includes symptoms such as central adipositas, insulin resistance and hyperinsulinemia, hyperlipidemia (high LDL, Lp(a) hypertriglyceridemia and low HDL) and hypercoagulopathy. Given the well-established cardiovascular risk resulting from this metabolic syndrome, there is growing concern about a potential therapy-related increased risk of myocardial infarction in HIV patients. These fears are further sustained by reports of arterial hypertension on HAART (Seaberg 2005), a high rate of smoking among HIV patients and increased levels of tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) in patients with lipodystrophy. Although many of the, mainly retrospective, studies dealing with this issue are inconclusive, data from a large international study (D A D study) provide evidence of...

NRTI and lipodystrophy

The patterns of fat redistribution in patients who are exclusively receiving NRTIs are unlike those observed in patients during PI therapy. Peripheral fat loss is the major symptom observed in NRTI therapy (particularly using stavudine and di-danosine combinations), although a few clinical studies have described a minimal intra-abdominal fat increase in these patients, which is clearly less than under PIs. Given that, commonly, only a mild increase in triglycerides has been observed, exclusive NRTI therapy seems to be of minor impact on lipid metabolism. Postpran-dially elevated FFA in patients with lipodystrophy, together with in vitro experiments, have led to the hypothesis that NRTIs could impair fatty acid binding proteins (FABP) which are responsible for cellular fat uptake and intracellular fat transport. In contrast, addition of stavudine (Zerit ) to a dual PI regimen does not result in a further increase in the total cholesterol or triglyceride levels. It is well established...

Genes predisposing to exceptional longevity

Dr Nir Barzilai and his colleagues studying Ashkenazi Jewish centenarians and their families recently found another cardiovascular pathway and gene that is differentiated between centenarians and controls (Barzilai et al., 2003). In Dr Barzilai's study, controls are the spouses of the centenarians' children. It was noted that high-density lipoprotein (HDL) and low-density lipoprotein (LDL) particle sizes were significantly larger among the centenarians and their offspring and the particle size also differentiated between subjects with and without cardiovascular disease, hypertension and metabolic syndrome. In a candidate gene approach the researchers then searched the literature for genes that impact upon HDL and LDL particle size and the came up with hepatic lipase and cholesteryl ester transfer protein (CETP). Comparing centenarians and their offspring against controls, one variation of CETP was noted to be significantly increased among

Terminology and Definitions

The term andropause indicates a particular type of hypogonadism that is related to aging in men and is said to consist of the following diminished sexual desire and erectile function, decrease in intellectual activity, fatigue, depression, decrease in lean body mass, skin alterations, decrease in body hair, decrease in bone mineral density resulting in osteoporosis, and increase in visceral fat and obesity (24). The word andropause is an attempt to draw a parallel in men to

EGCG Modulation of Food Intake and Endocrine Systems

In male rats treated with EGCG for one week, the serum level of protein, fatty acids, and glycerol were not altered, but significant reductions in serum glucose (-32 ), lipids (-15 ), triglycerides (-46 ) and cholesterol (-20 ) were observed. Based on proximate composition analysis, there was no change in water and protein content, a moderate decrease in carbohydrate content, but a very large reduction in fat content, decreasing from 4.1 in control to 1.4 in EGCG-treated group. EGCG treatment also decreases subcutaneous fat by 40 to 70 , and abdominal fat by 20 to 35 in male rats (1, 26). Reduction of body fat may also influence the hormonal levels in animals and influence tumor growth.

Body Fat Distribution

Various anthropometric techniques have been used to predict body fat distribution, for example trunk to total skinfold thickness ratio, sagittal diameter, waist-thigh circumference ratio, waist-hip circumference ratio (WHR), or waist circumference (WC) alone (56). Many epidemiological studies have shown that there is a clearly increased risk for metabolic disorders such as hypertension, glucose intolerance, and hyperlipidemia with increased WHR or WC, and the WHO (30) defines cutoff points for abdominal obesity at a waist circumference level of 80 cm and 95 cm for females and males, respectively, and a WHR of 0.85 and 1.00 for females and males, respectively. Like BMI, these cutoff values are based on observational studies mainly among Caucasians (30). Although all studies in various ethnic groups show a positive relationship between parameters of body fat distribution and morbidity, recent studies suggest that the relationship between anthro-pometric parameters and the actual amount...

Prevention of Obesity in Adults

Sity assume a new dimension in the later stages of life. Even when absolute weight does not increase, changes in body composition begin to accelerate. Foremost is a decline in muscle mass (16,17). As a result, the ratio of adipose tissue to muscle mass usually is higher in older people than in middle age. This change shifts the metabolic balance in ways that favor the development of insulin resistance and the metabolic syndrome 1820 . Loss of muscle mass is brought about in part by an increasingly sedentary lifestyle. In addition, metabolic changes accompanying aging, which are not well understood, probably play a role. In any case, loss of muscle mass makes older people more susceptible to health consequences of obesity.

Assessment of Risk Factors

Overall, the greatest danger of overweight obesity is the development of cardiovascular disease. Moreover, in the long term obesity predisposes to type 2 diabetes, which is itself a risk factor for cardiovascular disease. ATP III provides useful classifications for lipid and nonlipid risk factors. These classifications are shown in Tables 1 and 2, respectively. In ATP III, estimates are made of a person's absolute risk using Framingham risk scoring, which is available through the NHLBI (http htm). This scoring estimates the 10-year risk for developing myocardial infarction or coronary death. It is based on absolute levels of the following risk factors total cholesterol, HDL cholesterol, blood pressure, smoking history, and age. Framingham scoring can be carried out either by manual scoring or with a simple computer program, both of which are available on the NHLBI website. In addition, ATP III defines the metabolic syndrome for clinical practice according to five clinical features...

Assessment for Underlying Risk Factors

Waist Circumference Excess fat in the abdomen independently predicts risk factors and morbidity. Research has shown that the waist circumference correlates with the amount of fat in the abdomen, and thus is an indicator of the severity of abdominal obesity (Table 4). In ATP III (8), increased waist circumference was identified as a strong obesity-associated clinical correlate of the metabolic syndrome. ''Waist'' circumference (1,2) is used instead of''abdomi-nal'' circumference because it more accurately describes the anatomical site of measurement. Abdominal fat has three compartments visceal, retroperitoneal, and subcutaneous. Some studies suggest that visceral fat is the most strongly correlated with risk factors, whereas others indicate that the subcutaneous component is the most highly correlated with insulin resistance. Regardless, the presence of increased total abdominal fat is to be an independent risk predictor even when the BMI is not markedly increased. Therefore, waist...

Management Of Risk Factors In Overweightobese Persons

In patients who are overweight obese, clinical focus should be directed first to the risk factors associated with obesity. Most of these risk factors relate to cardiovascular disease, but some may indicate an increased susceptibility to type 2 diabetes. Management of the metabolic risk factors that are characteristic of the metabolic syndrome will be discussed. However, consideration will be given first to management of elevated low-density lipoprotein (LDL) cholesterol, which is the prime risk factor for development of atherosclerotic coronary heart disease.

Metabolic and Genetic Profiling

Scott and collaborators at Imperial College London have also been concerned with gene discovery using both animal and human models of the metabolic syndrome, which is the constellation of disorders related to insulin resistance and includes obesity, dyslipidaemia, diabetes mellitus, hypertension, and increased risk of atherosclerosis. A biological atlas of insulin resistance (BAIR) is currently under development using genetically engineered and environmental models of insulin resistance along with multimodality phenotyping 53 . This approach aims to integrate tran-scriptomics, phospho- and glycoproteomics, metabonomics, and structural biology to advance new hypothesis-driven research toward better understanding and treatment of metabolic syndrome.

The Prader Willi Syndrome

An excellent clinical summary of Prader-Willi syndrome (PWS) is provided in the literature (Holm et al., 1993 Cassidy, 1997). PWS is a multisystemic disorder with numerous manifestations of hypothalamic insufficiency. The neonatal and infantile period is marked by hypotonia, poor suck, feeding problems, and poor weight gain with a failure to thrive. In contrast, between 1 and 6 years of age, excessive weight gain with central obesity occurs, resulting from a voracious appetite. There is global developmental delay, mild to moderate mental retardation, and various learning problems. Characteristic cranio-facial features include dolichocephaly, narrow face or narrow forehead, almond-shaped eyes, small mouth with thin upper lip and downturned corners. Hypogonadism is marked, with hypoplasia of the genitals in both sexes and hypomaturity later on.

The Effects of GH Replacement on Body Composition in Adults with GHDeficiency

In these studies the changes in LBM were associated with reductions in fat mass of approximately 4-6 kg (11-16,20-24). Similarly this reduction occurs equally in both CO and AO GH-deficiency (25). Anthropometric measurements indicate that the most important change occurs in the abdominal region (10), corresponding to reduced visceral fat mass (16,20).

Body Size At Birth And Later Body Composition

People who had low birth weight tend to accumulate fat on the trunk and abdomen, a pattern of adiposity found in the insulin resistance syndrome in which central obesity, impaired glucose tolerance, hypertension, and altered blood lipid concentrations occur in the same patient (9). This disorder is associated with an increased risk of coronary heart disease (10). In two studies in the United Kingdom men who had low birth weight had high ratios of waist-to-hip circumference after allowing for adult body mass index (Table 1) (11). This association with low birth weight has been replicated in a study of men in Sweden (12). In the Swedish study birth weight was also associated with truncal fat, as measured by a high ratio of subscapular to triceps skinfold thickness. After allowing for current body mass index truncal fat increased by 0.30 standard deviations with each kilogram decrease in birth weight. High waist-hip ratio and high truncal fat may reflect different aspects of body...

Methodological issues in the hunt for human obesity genes

Obesity is defined as an excess of body fat, which can be measured directly using dual energy X-ray absorptiometry and isotopic dilution techniques. However, these are costly and their limited availability makes it difficult to perform such measurements in large numbers of subjects. In some studies fat mass has been measured indirectly using bioelectrical impedance or skin-fold thickness both of which correlate reasonably well within the normal range but less so in the very lean or the obese. The most commonly used marker of adiposity is BMI (weight in kg height in m2) which is a measure of heaviness that can be performed in large epidemiological studies and correlates reasonably well with body fat content. Body fat distribution provides an additional risk that is not given by simply the amount of body fat. Abdominal fat mass, for example, can vary significantly within a narrow range of total body fat or BMI. Furthermore, within a given BMI, men have on average twice the amount of...

Obesity as a disease state or adiposity as a continuous variable

Obesity as a clinical condition is currently defined as an excess accumulation of adipose tissue resulting in a BMI greater than 30kg m2. While the diagnosis of obesity by this criterion has clinical relevance with regards to intervention, management, and treatment, from an epidemiological perspective, it may hamper the study of the genetics underlying variation in body fat mass and distribution. For example, BMI exhibits a normal distribution with no clear division between the ''clinically obese (BMI > 30) and the non-obese. Such a pattern of continuous distribution is not restricted to merely BMI but is found in all obesity-related phenotypes, including anthropo-metric measures (e.g. skin folds, and waist circumference), measures of body composition (e.g. percentage body fat, fat mass), and associated biochemical markers (e.g. leptin). Therefore the division of individuals into ''obese'' versus ''non-obese'' categories has a certain degree of arbitrariness that does not appear to...

Lowgrade Inflammation

There are now accumulating data that aging is associated with a low-grade inflammation, coined InflammAging by Claudio Franceschi (Franceschi et al., 2000). This status reflects an imbalance between the innate and the adaptive immune response. Whereas the pro-inflammatory cytokines such as IL-6, TNF-a are increasing, originating in particular from monocytes macrophages as those infiltrating the various adipose tissues (Mazurek et al., 2003 Weisberg et al., 2003), those coming from the adaptive immune response are decreasing. In the meantime, as a compensatory mechanism, the anti-inflammatory cytokines originating from Th-2 cells of the adaptive immune response are also increasing. These changes add to the already increased production of pro-inflammatory cytokines by the increased abdominal fat cell mass (Unger, 2003 Eckel et al., 2005 Sharma et al., 2005). Indeed, central fat not only contributes to insulin resistance by direct secretion of pro-inflammatory cytokines, but also by the...

Adipose Tissue Dysfunction

Lipodystrophic syndromes has been associated with intramyocellular and intrahepatic fat accumulation, profound insulin resistance, and type 2 diabetes (Lewis et al., 2002). Recently, a cross-sectional study in a large cohort of elderly has shown an association between higher subcutaneous thigh fat and favorable plasma glucose and triglyceride levels, independent of visceral fat (Snijder et al., 2005). However, there is almost no data to show how central adipose tissue redistribution with aging may contribute to increased pro-inflammatory cytokine production, including TNF- , compared to that of the innate immune cells such as monocyte macrophages. Moreover, the role of adipocytokine secretion is also controversial with aging (Ryan et al., 2003 Kanaya et al., 2004). Leptin is released from adipocytes and acts on the central nervous system to decrease appetite. Lower, higher, and no change in leptin levels have been reported in the elderly. The strong positive correlation between fat...

Pancreatic Beta Cell Dysfunction

The role of impaired insulin secretion due to pancreatic beta cell dysfunction in age-related glucose intolerance and type 2 diabetes has been well known from animal studies. In humans this aspect of type 2 diabetes has remained controversial during a long period (Chang et al., 2003). This was probably due to the earlier failure of taking into account the degree of insulin resistance in the evaluation of beta cell function in vivo with techniques such as the OGTT. The relationship between insulin secretion and insulin sensitivity follows a hyperbolic curve so that a reduction in insulin sensitivity normally is associated with an increase in insulin secretion. Thus, similar absolute insulin secretion observed in older vs. younger individuals suggests inappropriate beta cell response in view of the reduced insulin sensitivity in the former group. This only very recently was recognized in IGT and type 2 diabetes of elderly subjects by methods able to assess insulin sensitivity as well as...

Experimental Models Linking Diabetes Mellitus to Aging and Longevity

Syndrome characterized by other risk factors such as abdominal obesity, hypertension, and specific dyslipide-mia, leading to increased incidence of coronary heart disease. Since atherosclerosis is a disease of later age, it is notable that in euglycemic centenarians insulinemia is low and insulin sensitivity high. This means, as seen in the decreased replicative senescence of cells originated from diabetic subjects, that diabetes type 2 is a model of partial premature aging. Thus, sensitivity, and consequently normal IR signal transduction, are a prerequisite to longevity as shown in caloric restriction studies in rodents and nonhuman primates, as well as in centenarians.

Changes In Adiposity With

The limited studies available suggest that visceral fat deposition also changes substantially through childhood and adolescence. Visceral fat occupies 50 of the cross-sectional abdominal fat area in 11- to 13-year-old children (65-67), but between adolescence and adulthood, this area increases four- to fivefold (68). However, these measurements are probably not as relevant metabolically as the ratio of intraabdominal adipose tissue to total body fat. As Goran et al. have pointed out, the ratio of intra-abdominal adipose tissue to total body fat almost triples from early childhood to adulthood (65). Longitudinal or cross-sectional studies to examine the interrelationships between visceral and total body fat in adolescents, and the relationship of changes in the ratio of intra-abdominal to visceral fat to the timing of puberty, have not yet been done. Although the foregoing studies do not encompass the entire range of childhood and adolescence, they suggest that the most rapid increases...

Pathogenic Mechanisms

The blood flow from visceral fat depot is drained via the portal vein to the liver, in contrast to other fat depots that are drained to the systemic circulation. Visceral adipose tissue has a higher turnover rate of fat, in both men and women, than other adipose tissue depots (11). Both lipid accumulation, by the action of lipoprotein lipase (LPL), and the lipolytic response to catecholamines are elevated (11-13). The increased lipolytic activity of visceral fat combined with its anatomical localization means that the liver is exposed to higher concentrations of free fatty acids (FFA) than any other organ. FFA have important influence on the liver metabolism. Increased levels of FFA attenuates the hepatic clearance of insulin from the pancreas and enhances the gluconeogenesis and the secretion of very low density lipoproteins (VLDL) from the liver (14-17). Therefore, with enlarged visceral adipose tissue depots, as in visceral obesity, these effects of FFA on the liver would be...

Development Of Overweight

The argument that fetal life represents a critical period for adiposity has not been totally resolved, the evidence from the infants of mothers with diabetes notwithstanding. Several large studies have shown an association between high birth weight and child adiposity (75-78) or adult adiposity after controlling for gestational age (77,78), but most did not adjust for confounding variables such as parental fatness, maternal smoking, gestational diabetes, or socioeconomic status (79). Conversely, low birth weight may be associated with an increase in intra-abdominal fat deposition that may in turn account for an increased likelihood of risk factors for cardiovascular disease, including hypertension, diabetes, and hyperlipidemia (80). However, the association between lower birth weight and the development of overweight has not been clearly demonstrated. Although babies with lower birth weight have been shown to have an increased risk of syndrome X and of heart and pulmonary disease in...

Endocrine Aberrations

Recent results from testosterone intervention studies in men with abdominal visceral obesity (33,36) may support this hypothesis. A physiological amount of testosterone in middle-aged men with abdominal visceral adiposity induced improved insulin sensitivity, plasma lipid levels, and diastolic blood pressure, as well as a specific decrease in visceral adipose tissue mass. This might theoretically be explained by direct effects of testosterone on adipose tissue. However, as testosterone treatment in men with Cortisol is of interest as it causes accumulation of abdominal visceral adipose tissue (39) and an increased release of FFA. The latter will, in turn, cause reduced insulin binding in the liver and thereby higher circulating levels of insulin, glucose, and blood lipids by the mechanisms discussed above. The role of cortisol in obesity has been controversial during many years. Several authors have found decreased plasma cortisol levels in obese subjects while other have reported an...

Syndrome X And Gh Deficiency In Adults

Striking similarities exist between Syndrome X (3,35) and untreated GH deficiency in adults (55). The most central findings in both these syndromes are abdominal visceral obesity and insulin resistance (35,56-58). Other features common to both conditions are high triglyceride and low high-density lipoprotein (HDL) cholesterol concentrations, an increased prevalence of hypertension, elevated levels of plasma fibrinogen and plasminogen activator inhibitor (PAI)-1 activity, premature atherosclerosis, and increased mortality from cardiovascular diseases (35,56,59-62). Because of these similarities between GH deficiency in adults and Syndrome X, undetectable and low levels of GH, respectively, may be of importance for their metabolic consequences in these conditions.

Genetic and environmental contributions to CHD pathogenesis

In this chapter, we discuss first the evidence from family studies that genetic influences are important in susceptibility to CHD. Secondly, we review the genetics of lipid risk factors, including the genetic basis of monogenic and complex dyslipidaemias, and their impact on CHD susceptibility. Thirdly, we review genetic studies of human CHD and its risk factors, including consideration of the role played by the metabolic syndrome, whose prevalence is increasing rapidly Insulin resistance, metabolic syndrome and type 2 diabetes

Genetics of human coronary heart disease

A meta-analysis was applied to four of the CHD genome-wide studies (Chiodini and Lewis, 2003). The genetic region 3q26-27 showed the strongest evidence for linkage (P 0.0001), which is one of the regions of linkage found in the Mauritian population (Francke et al., 2001). This result is of interest, and the subject of further investigation, given the existence of several candidate genes involved in the homeostasis of glucose and lipid metabolism in this chromosomal region and the important association between CHD and the metabolic syndrome. The Metabolic Syndrome and Cardiovascular Disease coronary heart disease, estimated to be as high as 60 in some populations (McKeigue et al., 1993 Reaven, 1988). Since the original description of the Metabolic Syndrome, its component features have expanded to include microalbuminuria, central obesity, raised levels of plasminogen activator inhibitor-1 (PAI-1) and uric acid. Genetic associations have been shown in case-control studies, although many...

Candidate gene investigations

An interesting source of candidate genes for hypertension is arising through the investigation of genetic models of blood regulation in rodents, particularly the rat (Stoll and Jacob, 2001). As an example, we cite recent work on the type II SH2 domain containing the inositol 5-phosphatase (SH1P2) gene (Clement et al., 2001). SH1P2 maps to a region of linkage to traits related to metabolic syndrome on rat chromosome 1 in several disease models including Goto-Kakizaki (GK) diabetic rat and spontaneously hypertensive rat strains. These two strains harbour an identical SH1P2 mutation that disrupts a potential class II ligand for Src homology (SH)-3 domain and slightly impairs insulin signaling in vitro (Marion et al., 2002). Analysis of SH1P2 SNPs in UK patients with noninsulin dependent diabetes and their siblings showed strong evidence of association with hypertension (p 9.3 x 10 6) and related traits in French diabetics, an association was found only with hypertension (p 0.01) (Kaisaki...

Role Of Lif In Cancer

Results of in vivo animal trials shed light on some of the possible roles of LIF in cancer and cancer metastasis. Cachexia (43,44), subcutaneous and abdominal fat loss, and elevated leukocyte and platelet counts often found in patients with metastatic cancer were induced by LIF in both mice and monkeys (46-48). In addition, at a high dose, LIF induced myelosclerosis whereas a low dose induced megakaryocytosis, reduced marrow cellularity and caused lymphopenia (48) suggesting a possible role for LIF in the pathogenesis of myeloproliferative disorders such as myelofibrosis and in marrow sclerosis. Furthermore, mice engrafted with FDS-P1 cells that produce high levels of LIF developed a fatal syndrome with cachexia, atrophy of liver and kidney, and excess bone formation with increased osteoblastic activity that resulted in metastatic-type calcifications (47) implying a role for LIF in bone tumours and neoplasms metastasizing to bone.

Influence on Mortality

Data from the Rotterdam study (Visscher et al., 2001) illustrate the difficulty in defining obesity in the elderly and the importance of considering visceral adiposity as the major risk factor. In this study of around 6,300 elderly subjects followed for three years, the overall influence of BMI on mortality was modest, but increased waist circumference showed a more marked association with poor prognosis during the follow-up period. In summary, obesity does reduce life expectancy, but there is a survival bias in subjects who are obese and survive into old age, and the effect of obesity acquired later in life on life expectancy is not known. Although obesity is a determinant of life expectancy in the elderly, its effect is much less than in younger cohorts. It is possible, with the rise in obesity in the elderly, that life expectancy may reach a peak and then begin to decrease because of the high prevalence of obesity in this age group.

Insuun Resistance Vascular Disease

It has now been confirmed in a range of studies that low-grade inflammation, as evidenced by increased circulating levels of C-reactive protein and other acute phase proteins, predicts the development of vascular disease and is of prognostic importance in patients with vascular disease. These changes also precede development of diabetes and are predictive for development of the condition. A variety of molecules has been implicated, and a full review is beyond the scope of this chapter. Tumor necrosis factor-a (TNF-a) is thought to be one of the mediators responsible for the metabolic syndrome. Its actions in the liver and other target tissues oppose that of the protective molecule adiponectin. TNF-a levels in the circulation tend to rise progressively with age, and they correlate with the degree of metabolic control in patients with type 2 diabetes. Increased TNF-a expression has also been documented in other pathological states, including atherosclerotic disease and Alzheimer's...

Possible Mechanisms Responsible For Hypertension

Many, but not all, men and women gain weight with aging. Weight gain has been shown to be associated with increases in blood pressure in human and animal studies. Furthermore, obesity is associated with increased incidence of type II diabetes, which is also a strong mediator of cardiovascular disease and hypertension. In a study in which body mass index was similar for pre-and postmenopausal women, postmenopausal women experienced significantly higher blood pressure, waist circumference, and waist-to-hip ratio, compared with premenopausal women, which suggests that even without a change in BMI with age, body fat distribution changes following menopause. It is well known that abdominal fat accumulation, as opposed to lower body fat accumulation, is a risk factor for cardiovascular disease. Obesity is also accompanied by an increase in sympathetic activity (Esler et al., 2001), particularly in the kidney, which would lead to an increase in renin release and contribute to hypertension.

Age Related Changes in Fat Distribution

Intra-abdominal fat accumulation, known to be independently related to the metabolic concomitants of obesity (39-44), has also been demonstrated to be greater at any given BMI or BF in older individuals (45-47). While the accumulation of intra-abdominal fat with aging may be progressive in men, it appears to greatly accelerate in women following menopause (62,48). demonstrated relatively greater amounts of central and intra-abdominal fat when compared to Caucasians, and a strong relationship exists between intra-abdomi-nal fat and the development of insulin resistance and NIDDM frequently observed in this population (43,44,55).

Genetic Models Of Hypertension

The aging SHR is a good model in which to study the effects of chronic hypertension in aging, and in the case of females, to study a model of postmenopausal hypertension. One disadvantage of the model is that they fail to gain a considerable amount of weight, as other rats do. The females are typically 300 and 350 g at 18 months, whereas the males are typically 400 to 450 g at that age. Therefore, for investigators studying aging, metabolic syndrome, and hypertension, these animals would not be appropriate.

Clinical Classification

Liposarcoma Lump

Measuring fat distribution in subcutaneous versus visceral compartments is important because visceral fat predicts development of health risks better than total body fat. The distribution of body fat can be estimated by a variety of techniques. The ratio of waist circumference divided by hip circumference waist-hip ratio (WHR) was used in the pioneering studies that brought scientific recognition in the 1980s to the relationship of centrally located fat to the risk of developing heart disease, diabetes, and other chronic problems associated with obesity (8-10). This concept was originally suggested by Vague in 1948 (11) and is now widely accepted. The subscapular skinfold has also been valuable in estimating central fat in epidemiologic studies (12). The sagittal diameter, measured as the distance between the surface of the midabdominal skin and the table beneath a recumbent subject, has been used as an index of central fat (13). The only truly reliable estimates of visceral fat,...

Increased Physical Activity

Increased physical activity improves cardiorespira-tory fitness, with or without weight loss. The latter improves the quality of life in overweight patients by improving mood, self-esteem, and physical function in daily activities. Physical activity reduces elevated levels of CVD risk factors, including blood pressure and triglycerides, increases HDL cholesterol, and improves glucose tolerance with or without weight loss. Furthermore, the more active an individual is, the lower the risk for CVD morbidity and mortality, and diabetes. Physical activity apparently has a favorable effect on distribution of body fat. Several studies showed an inverse association between energy expenditure through physical activity and several indicators of body fat distribution. Only a few randomized controlled trials that have tested the effect of physical activity on weight loss measured waist circumference. In some (but not all) studies, physical activity was found to produce only modest weight loss and...

Monogenic disorders causing impaired reverse cholesterol transport

Low HDL cholesterol is a common finding in patients with premature CHD and usually precedes clinically apparent CHD (Goldbourt et al., 1997). Low HDL concentrations are most frequently associated with the components of the metabolic syndrome X and are rarely due to single-gene disorders (Durrington, 2003). The rare Tangier disease, characterized by very low or even

Of Overweight Patients

As part of any clinical encounter, the nurse or physician should measure several so-called vital signs including height, weight (BMI), pulse, blood pressure, waist circumference, and if indicated by the patient's complaints, temperature. This is the first step in assessing risk. Current classifications of obesity are based on BMI and waist circumference. The one recommended by the World Health Organization (105) and the National Heart, Lung and Blood Institute (100) is shown in Table 11.

Metabolic problems

'Metabolic syndrome' is a combination of truncal obesity, abnormal blood lipids, disturbed insulin and glucose metabolism, and high blood pressure it is associated with the development of diabetes mellitus and coronary heart disease. It is more frequent in patients with schizophrenia than in the general population. It may be particularly contributed to by antipsychotic medication, especially some of the newer 'atypical' agents such as olanzepine, which seems to have appetite-stimulating qualities.


Both the lack of a formal definition and uncertainty about the pathogenesis and possible long-term consequences, leads to a continuing discussion about appropriate guidelines for the assessment and management of HIV lipodystrophy syndrome and its metabolic abnormalities. Outside clinical studies, the diagnosis relies principally on the occurrence of apparent clinical signs and the patient reporting them. A standardized data collection form may assist in diagnosis (Grinspoon 2005). This appears sufficient for the routine clinical assessment, especially when the body habitus changes develop rather rapidly and severely. For clinical investigations however, especially in epidemiological and interventional studies, more reliable measurements are required. But so far, no technique has demonstrated sufficient sensitivity, specificity or predictive value to definitively diagnose the HIV lipodystrophy syndrome by comparison with results obtained from a normal population. A recent multicentre...


Elevations of triglycerides and low levels of high-density < lipoprotein (HDL) are common in overweight obese patients. They are especially common when patients have other risk factors of the metabolic syndrome (4-6). 5 ATP III classification of serum triglycerides is shown in Table 8. In patients with atherogenic dyslipidemia (triglyceride > 150 mg dL, small LDL particles, and low HDL cholesterol (< 40 mg dL) , a three-part ther- I

Future Directions

The challenges in establishing criteria for frailty are analogous to those faced in establishing the diagnostic criteria for the metabolic syndrome (also known as syndrome X, the dysmetabolic syndrome, the insulin resistance syndrome, and the deadly quartet). This is a cluster of abnormalities (glucose intolerance, obesity, hypertension, dyslipidemia) that are well-documented risk factors for cardiovascular disease in themselves (Eckel et al., 2005). The grouping of certain characteristics known to independently predict adverse outcomes can be justified only if they are synergistic in their effect or have a common etiology (Domanski et al., 2004). This appears to be the case in the metabolic syndrome. Whether a similar synergistic effect on outcomes will be seen with the components of frailty requires confirmation.

Insulin Resistance

Insulin resistance is a common condition and can be seen, for example, in NIDDM, obesity, and hypertension. The inter-relationship between insulin resistance and these conditions, as well as the exact mechanisms for insulin resistance, have not yet been fully clarified. It has recently been clear that GH-deficient adults are also insulin resistant in peripheral tissues (as measured using the hyperinsulinemic euglycemic clamp technique 67,68 ). In our study, glucose disposal rate (GDR) in the GH-deficient group was less than half that of controls, when calculated according to body weight and when corrected for body fat (67). The decreased lean body mass and the increased abdominal obesity in GH deficiency may be of importance for this finding as the association between increased body fat mass and insulin resistance is stronger in the presence of abdominal obesity (69). Low levels of serum IGF-1 may also contribute to insulin resistance (70) as IGF-1 stimulates the glucose transport in...


Plasminogen activator inhibitor (PAI)-1, the fast-acting tissue plasminogen activator (t-PA) inhibitor, is the major regulator of fibrinolytic activity in plasma. Increased PAI-1 activity acts in a thrombogenic direction. Elevated PAI-1 activity has been associated with coronary artery disease (84,85), increased risk of myocardial infarction in young patients (86), recurrent myocardial infarction (87), and deep vein thrombosis (88). High PAI-1 activity has previously been found in patients with hypertension, insulin resistance, and abdominal obesity (89-91). In addition, we have recently shown that elevated PAI-1 activity in GH-deficient adults as compared with healthy controls matched for age, sex, and body mass index (58). Previous population-based studies have shown that fibrinogen is an independent risk factor for stroke as well as myocardial infarction, and is at least as important as blood lipids and blood pressure (92,93). Obesity has been associated with both increased...

General Conclusion

The high and abnormal activity of the HPA axis, low levels of sex steroids, and attenuating GH secretion in abdominal obesity suggests a central neuroendocrine dysregulation in abdominal obesity. Whether this is of primary importance for the evolution of abdominal obesity or merely a secondary phenomenon to the obese condition remains to be elucidated. The finding that replacement with testosterone and GH to men with abdominal obesity are able to diminish the negative metabolic consequences of the visceral obesity suggest that the low levels of these hormones are of primary importance for the metabolic consequences associated with visceral abdominal obesity.

On Mortality

There have been few published reports of dietary weight loss interventions specifically in older subjects. While the study by Williamson (129) supports a benefit to intentional weight loss in middle-aged subjects, it is possible that exacerbation of the usual age-related loss of lean mass could be worsened by a weight loss diet. However, in a recently published study of otherwise healthy obese older men (mean of 60 yr) who underwent a 10-month calorie restriction, only 23 of the 9.3 kg of weight that was lost, was lost as FFM (134). This is similar to studies in our laboratory (135) in which 16 healthy obese older men (mean 66 yr) lost 10 kg on a 1200-kcal dietary restriction (Phase I American Heart Association Diet.). In this study only 20 of weight loss was as FFM. The percentages of weight lost as FFM in these relatively healthy older individuals is similar to that found in younger subjects. In both of the above studies, weight loss produced a small but significant improvement in...

Syndrome X

Syndrome X, also known as metabolic syndrome or insulin resistance syndrome, is a highly prevalent condition that significantly increases the risk of coronary heart disease and is associated with elevated triglycerides, low HDL-cholesterol, and LDL-cholesterol. As niacin raises HDL-cholesterol, lowers triglycerides and increases LDL-cholesterol particle size, it may be considered a useful therapeutic option for the treatment of dyslipidaemia in such cases (Ito 2004). The potential for niacin to induce insulin resistance, however, may affect its use in practice.


The increasing prevalence of the obesity in the young is one of the most pressing public health problems facing us at present. With obesity comes the cluster of risk factors we call the metabolic syndrome. There is no question that, in younger subjects, weight management to deal with the multiple risk factors, and thus to decrease long-term risk, is the preferred approach. However, there is an inconsistent relationship between obesity and the components of the metabolic syndrome, particularly in the elderly. Many people who are obese do not develop diabetes and do not develop hypertension. Other factors, including the aging process itself and the endocrine and inflammatory changes that accompany it, are also important. There is now compelling evidence that not only obesity per se but weight gain, particularly A full review of dietary interventions cannot be undertaken here. In relation to glucose tolerance and the metabolic syndrome, there has been a move away from traditional low-fat...

The Phenotypes

Obesity is characterized by excess body mass or body fat without any particular reference to the concentration of fat in a given area of the body. Many obese individuals are characterized by an excess amount of subcutaneous fat on the trunk, particularly in the abdominal area, the so-called android obesity, or male type of fat deposition. Another type is characterized by an excessive amount of fat in the abdominal visceral area and has been labeled abdominal visceral obesity. The last is known as gluteofemoral obesity and is observed primarily in women (gynoid obesity). Thus, excess fat can be stored primarily in the truncal-abdominal area or in the gluteal and femoral area. This implies that a given body fat content, say, 30 or 30 kg, may exhibit different anatomical distribution characteristics. Figure 2 Common variance between three body fat phenotypes. Percent fat estimated from underwater weighing truncal-abdominal fat assessed from skinfolds or CT scans abdominal visceral fat...

Future Combinations

All classical HAART regimens have to date included a backbone consisting of two nucleoside or nucleotide analogs. This mainly has historical reasons nucleo-side analogs were the first available drugs against HIV, and by the time NNRTIs and PIs were under development, treatment with two nucleoside analogs was standard. With growing knowledge of the mitochondrial toxicity of nucleoside analogs, experts have increasingly questioned this concept. Nuke sparing, i.e. complete omission of nucleoside analogs, is a slogan that is being discussed more and more. PI-only combinations are already being used frequently today in salvage therapy (see corresponding chapter). But for initial therapy Since the combination of indi-navir+efavirenz fared quite badly in the 006 Study (Staszewski 1999), nuke sparing initially seemed to be a thing of the past. But nucleoside analogs are increasingly under fire. Long-term observations from an initial long-term study, in which 65 PI-naive patients intensified...

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