How to Reduce Belly Fat Naturally

My Bikini Belly

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Prevalence Of A Large Waist Circumference

The data of the WHO MONICA population (second survey carried out between 1987 and 1992) have recently been analysed with respect to waist cut-off points (15). From this analysis it is clear that the use of these single cut-off points of the waist circumference to replace classification by BMI and waist-to-hip ratio varies greatly from country to country. The prevalence of a large waist circumference (> 102 cm in men and > 88 cm in women) and of obesity (BMI > 30 kg m2) is shown in Table 2.5. Table 2.5 Prevalence of a large waist circumference (102 cm or more in men or 88 cm or more in women) and of obesity (BMI 30 or more) in 19 centres participating in the WHO MONICA study (second round, 1987-1992). Adapted from reference 16 Table 2.5 Prevalence of a large waist circumference (102 cm or more in men or 88 cm or more in women) and of obesity (BMI 30 or more) in 19 centres participating in the WHO MONICA study (second round, 1987-1992). Adapted from reference 16

Predicting Total Body Fat from Waist Circumference and Triceps Skinfold

Subcutaneous skinfold thicknesses (2) in subjects with increased intra-abdominal fat mass, reflected by a high waist circumference or waist-to-hip ratio, including the elderly and those with type 2 diabetes. Waist circumference (Figure 4.4) has been found to correlate highly with both intra-abdominal and total fat masses (6,23), and was used on its own and with skinfold thicknesses to develop new regression equations to correct for the intra-abdominal fat mass (6). These equations were validated in a large Dutch sample from previous study of body fat distribution (3). Equations using waist circumference alone, adjusted for age (equation 3), showed good prediction of body fat in the independent Dutch sample (r2 78 ) with similar error of prediction as other equations. These equations are particularly good for estimating body fat in the elderly without the systematic underestimation of body fat that occurs in the subcutaneous skinfold method (Figure 4.6). Body fat (men) 0.567 x Waist...

Definition and diagnosis what is the metabolic syndrome

Occurrence of three or more of the following prespecified risk factors is sufficient for a positive diagnosis abdominal obesity (most common feature Fig. 1D , hypertension, hypertriglyceridemia, low plasma high-density lipoprotein cholesterol, and elevated fasting plasma glucose) (see Table 1 for defining levels) (1). Patients rarely present with all of the five factors. Each determinant can be assessed easily in clinical practice for example, measuring waist circumference (at the level of the iliac crest at the end of normal expiration) with a tape measure confirms abdominal obesity, and an oral glucose tolerance test is not needed. Because metabolic syndrome is typically asymptomatic, affected individuals will normally be identified at routine medical examinations or when presenting with other complaints. If metabolic syndrome is suspected at this consultation (e.g., because the patient is overweight and or hypertensive), screening for other components of the syndrome is warranted....

Which clinical sequela are associated with metabolic syndrome

The next challenge for the physician is to appreciate and communicate to the patient the magnitude of the inherent risks of metabolic syndrome. Cardiovascular disease is the main adverse clinical outcome. This is not surprising given that coexistence of multiple CVD risk factors carries a greater susceptibility to cardiovascular morbidity and mortality than a disturbance in just one factor. The risk of a major cardiovascular event (myocardial infarction, sudden cardiac death, unstable angina, or stroke) is about twofold greater among individuals with metabolic syndrome than those without it (13). Metabolic syndrome also predisposes to type 2 diabetes mellitus. This is important from a CVD standpoint, because diabetes is regarded as a coronary risk equivalent (1), meaning that the likelihood of a first major coronary event among patients with diabetes is as high as a recurrent event among individuals with established heart disease. Patients with diabetes and metabolic syndrome are thus...

The role of hypertension in the metabolic syndrome

Within the metabolic syndrome cluster, hypertension is defined as systolic blood pressure (SBP) > 130 mmHg and diastolic blood pressure (DBP) > 85 mmHg. It is present in 84.2 of men and 76.7 of women with metabolic syndrome (Fig. 1) (15), and contributes directly to many adverse clinical outcomes. In its early stages, hypertension-related vascular and end-organ damage is often subclinical, manifesting itself only when a catastrophic cardiovascular event occurs (such as myocardial infarction or stroke). The development of microalbuminuria may serve as an early indicator of widespread vascular damage, being not only a pressure-dependent functional phenomenon in the glomerular vessels, but reflecting permanent atherosclerotic abnormalities throughout the entire vascular system.

Abdominal Obesity Fatty Acids and Neurogenic Hypertension

As noted previously, NEFAs have been linked epidemiologically to hypertension and its genesis. NEFAs have several actions that could contribute to hypertension and help explain the link between the obesity epidemic and increasing prevalence of hypertension (37). Hypertensive patients are more likely to be overweight and obese than normoten-sive individuals. Moreover, when matched for body mass index, hypertensives are more likely to have a centralized fat pattern and a greater amount of visceral to subcutaneous abdominal fat than normotensives (38). Even within the normotensive range, abdominally obese subjects have higher blood pressures than individuals with gluteofemoral obesity, and these blood pressure differences are related to insulin resistance (39). Subjects with abdominal obesity are not only resistant to insulin-mediated glucose disposal, but they are also resistant to insulin's NEFA lowering actions (1,2,40). Moreover, resistance to insulin's effects on fatty acids during...

Genetic influences on the metabolic syndrome

Although the metabolic syndrome per se is not central to the focus of this review, we must give brief consideration to this major public health concern. The prevalence of the metabolic syndrome as defined by the NCEP-ATP III report is about 23 in the American population and rises to about 43 of elderly people in the USA, while higher prevalence rates can be observed in various ethnic groups around the world (Ford et al., 2002). This syndrome associates obesity, excessive blood pressure, high plasma glucose with disturbances of lipid homeostasis (high plasma triglycerides and low HDL cholesterol). It has long been thought that obesity precedes the metabolic syndrome, but it is now known that this syndrome can be observed in lean subjects, even if its prevalence increases in a graded fashion as body weight increases (St-Onge et al., 2004). Recent findings about the endocrine (but also paracrine and autocrine) function of adipocytes have renewed interest in the topic. Indeed, it has been...

Subgrouping Of Visceral Obesity With The Metabolic Syndrome

Visceral obesity is associated with other endocrine abnormalities than that of cortisol. Indeed, visceral obese individuals with the metabolic syndrome may have all the hormonal abnormalities of the elderly, suggesting that this condition may be a sign of premature ageing (58). The most common deficiencies are those of growth hormone (GH) and sex steroids (59). Whereas men have low testosterone levels (60), women have irregular menstrual cycles (61). Functionally, the growth axis and the reproductive axis are influenced at many levels by the HPA axis. Prolonged activation of the HPA axis thus leads to suppression of GH secretion as well as inhibition of sex steroids (23,62). These endocrine abnormalities have a profound effect on peripheral tissues. While cortisol promotes accumulation of visceral fat and insulin resistance in muscle tissue, the GH and sex steroids, often in concert, do the opposite (42). Low GH and sex steroid secretions will thereby multiply the pathogenetic effects...

Treatment On Abdominal Fat Distribution

Numerous studies have shown that the health risk associated with obesity is more closely related to visceral fat (3) than to a more peripheral fat distribution. Weight loss, independent of the therapy used, is associated with loss of visceral fat (106). As stated in Table 31.2 the ideal anti-obesity drug preferentially reduces abdominal fat mass. Visser et al. (107) investigated the effect of fluoxe-tine on visceral fat reduction, but could not demonstrate any significant effect. In a study by Marks et al. (108) treatment with dexfenfluramine in obese type 2 diabetic subjects resulted in a selective reduction of visceral fat area, measured by magnetic resonance imaging. Meta-analysis of four long-term studies with sibutramine showed a significantly greater decrease in waist circumference, as an indicator of visceral fat mass, in sibutramine-treated subjects compared with those receiving placebo (53). The same paper reported on the preliminary data on absolute changes in visceral fat,...

Measuring Central Obesity

For a comprehensive estimate of weight-related health risk it is also desirable to assess the extent of intra-abdominal or 'central' fat accumulation. This can be done by simple and convenient measures such as the waist circumference or waist-to-hip ratio. Changes in these measures tend to reflect changes in risk factors for cardiovascular disease and other forms of chronic illness. Some experts Table 1.2 Sex-specific waist circumference measurements for identification of individuals at increased health risk due to intra-abdominal fat accumulation Table 1.2 Sex-specific waist circumference measurements for identification of individuals at increased health risk due to intra-abdominal fat accumulation

Growth Hormone And Abdominal Obesity

Secretion of Growth Hormone 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 (69). Moreover, the metabolic clearance rate of GH is accelerated (70). The serum insulin-like growth factor I (IGF-I) concentration is primarily GH dependent and influences GH secretion though a negative feedback system (71). The serum levels of IGF-I are inversely related to the percentage of body fat (69). In addition, the low serum IGF-I concentration in obesity is predominantly related to the amount of visceral adipose tissue and not to the amount of subcutaneous fat mass (72). Serum free IGF-I concentration may, on the other hand, be increased in abdominal obesity (73) possibly as an effect of the concomitant insulin-induced suppression of serum IGF binding protein-1 levels. The relationship between regional fat distribution and GH secretion has only recently been...

Metabolic Syndrome

The years leading up to frank type 2 DM will decrease the likelihood of subsequent clinical events. The metabolic syndrome, first described by Reaven, has been proposed as a ''disease'' that includes many of the clinical, biological, and vascular abnormalities observed in non-insulin-requiring DM patients. The metabolic syndrome includes hyperinsulinemia (impaired glucose tolerance) an abnormal lipid profile characterized by elevated triglycerides, low levels of high-density-lipoprotein (HDL) cholesterol, and increased low-density-li-poprotein (LDL) cholesterol, hypertension, and central obesity with an increased waist-to-hip ratio. Many cross-sectional studies have indicated that insulin resistance is associated with ultrasonographically or angiographically demonstrable atherosclerosis, even in the absence of other risk factors for CAD. However, controversy still exists about the mechanisms by which the metabolic syndrome induces or accelerates atherogenesis. Some have proposed that...

The Nature Of Complications

The discovery that metabolic consequences of type 1 diabetes (insulin deficiency attributable to failure of pancreatic beta cells, generally induced by autoimmune phenomena) could be corrected by administration of pancreatic extracts and ultimately purified insulin gave rise to a powerful belief system in which insulin deficiency is embraced as the cause of diabetes under all circumstances. We now know that more than 90 of individuals with diabetes have type 2 diabetes, a condition in which insulin resistance is among the primary defects. However, the evolution of diabetes is such that at any given level of insulin resistance the pancreatic compensatory mechanism is inadequate to meet demands and insulin deficiency is a relatively late manifestation of the disorder. Surprisingly, this dichotomy was anticipated in the 1930s. Himsworth was interested in the causes of hyperglycemia in patients with diabetes and performed what Gerald Reaven described as ''a series of simple, but elegant...

Cardiovascular Disease In Type 2 Diabetes

Type 2 diabetes is very different from type 1 diabetes in its underlying etiology and its natural history. Insulin resistance, which is defined as a less than normal effect of insulin on in vivo glucose uptake and metabolism, occurs in a high proportion of the population of societies embracing western culture (10,26). Factors responsible for the development of insulin resistance are only partially understood. Fetal malnutrition predisposes to insulin resistance in postnatal life (27). Excess calorie intake and reduced physical activity lead to exaggerated lipid deposits and obesity. The proportion of excess calories deposited as lipids in subcutaneous adipose tissue relative to visceral adipose tissue is both genetically and hormonally determined (28). An increase in visceral adiposity but not subcutaneous adiposity is highly correlated with insulin resistance and the components of the metabolic syndrome (29,30). There is a significant correlation between visceral adiposity and both...

Highrisk Groups for Weight Gain

In many industrialized countries, minority ethnic groups are especially liable to obesity and its complications. Some researchers believe that this is the result of a genetic predisposition to store fat which only becomes apparent when the individuals are exposed to a positive energy balance promoted by modern lifestyles. Central obesity, hypertension and NIDDM are very common in urban Australian Aborigines, but can be reduced or even eliminated within a very short time by simply reverting to a more traditional diet.

Economic Growth and Modernization

Poor growth and development of the unborn baby can increase the risk of abdominal fatness, obesity and related illness in later life. 'Adiposity rebound' describes a period, usually between the ages of 5 and 7, when BMI begins to increase rapidly. This period coincides with increased autonomy and socialization and so may represent a stage when the child is particularly vulnerable to the adoption of behaviours that both influence and predispose to the development of obesity. Early adiposity rebound may be associated with an increased risk of obesity later in life. This is a period of increased autonomy which is often associated with irregular meals, changed food habits and periods of inactivity during leisure combined with physiological changes. These promote increased fat deposition, particularly in females. Early adulthood is often associated with a marked reduction in physical activity. This usually occurs between the ages of 15 and 19 years in women but as late as the early 30s in...

Conclusions And Therapeutic Implications

Then the primary goal should be to treat to and maintain the fasting and postprandial plasma glucose as close to normal as possible, while minimizing the develop- -g ment of visceral obesity. Such a strategy, if it can be implemented, should main- < j tain atherosclerosis progression at the prediabetic level.

Classification Of Obesity And Fat Distribution

Much research over the last decade has suggested that for an accurate classification of overweight and obesity with respect to the health risks one needs to factor in abdominal fat distribution. Traditionally this has been indicated by a relatively high waist-to-hip circumference ratio. Recently it has been accepted that the waist circumference alone may be a better and simpler measure of abdominal fatness (3,4). Table 2.2 gives some tentative cut-points for the waist circumference. These are again based on data in white populations. In June 1998 the National Institutes of Health (National Heart, Lung and Blood Institute) adopted the BMI classification and combined this with waist cut-off points (6). In this classification the combination of overweight (BMI between 25 and 30kg m2) and moderate obesity (BMI between 30 and 35 kg m2) with a large waist circumference (> 102 cm in men or 88 cm in women) is proposed to carry additional risk.

Obesity Body Composition

Excessive accumulation of fat in the upper body's abdominal area is referred to as ''truncal'' or ''central'' obesity. Central obesity appears to be a better predictor of morbidity than excess fat in the lower body, the so-called lower body segment obesity (72,74,75). Such types of body composition have been clinically separated based on a waist-to-hip circumference ratio (WHR) and individuals are referred to as having apple- or pear-shaped bodies, based on having an elevated or decreased WHR, respectively. The importance of body composition was first reported over 40 years ago by Vague, who noted that the incidence of metabolic complications among equally obese subjects varied depending on their physique (76). Morbidity was clearly shown to be higher in ''android-type'' obesity than in ''gynoid-type'' obesity and this heterogeneity was supported by results in several studies suggesting regional differences in adipose tissue metabolism (77-79). The heterogeneity of fat distribution...

Weight Monitoring for Schizophrenia

In this age of second-generation antipsychotic medications, we need to routinely ask patients if they notice a change in their waist size or increased appetite, and intervene early, when weight gain is modest (i.e., 5 pounds). Prevention in this case may be the greatest cure. Physicians should routinely measure weight at each visit, and BMI should be recorded. The National Heart, Lung and Blood Institute (NHLBI) has posted a useful, free BMI calculator for Palm operating system-based PDAs on its Web site (hin.nhlbi.nih.gov bmi_palm.htm). An even more important predictor of diabetes and the dysmetabolic syndrome (also known as syndrome X, a quartet of symptoms including hypertriglyceridemia, diabetes, hypertension, and abdominal obesity) (Groop and Orho-Melander 2001) is waist circumference, a reflection of visceral adiposity (Park et al. 2001). Central adiposity is more highly associated with diabetes, the dysmetabolic syndrome, and subsequent increased risk of coronary artery...

Anthropometric Assessment Of Body Fat Distribution

The ratio of waist-to-hip circumferences (Figure 4.4) was the first anthropometric method developed from epidemiological research as an indicator of fat distribution in relation to metabolic diseases. Waist-to-hip ratio is related more closely to the ratio of intra-abdominal fat extra-abdominal fat mass than the absolute amount of intra-abdominal fat mass (32), and has been shown to relate to mortality from coronary heart disease and type 2 diabetes independent of BMI (28,29). Most of the value in indicating body fat is derived from waist circumference, the hip circumference probably reflecting several other body tissues such as bones and muscles. The waist-to-hip ratio may have some particular value in reflecting diseases which involve muscle reduction as well as fat deposition, e.g. type 2 diabetes (33).

Markers of inflammation in cardiovascular disease

Prospective studies reported that CRP is an independent predictor of risks of future myocardial infarction, stroke, and peripheral vascular disease (144,149-151). In a recent study, a cohort from the Framingham Heart Study, in which the participants were free of cardiovascular disease, the relationship between CRP and coronary calcification was evaluated (152). The authors found that CRP levels were associated with epicardial coronary calcification, even after adjustment for age and the traditional risk factors. The clinical utility of CRP has also been assessed to predict future risk of sudden cardiac death in apparently healthy men who have no clinical evidence of coronary heart disease (144,149,151). In addition to its predictive value for cardiovascular events, CRP has been associated with the development of type II diabetes, metabolic syndrome, and hypertension (153-155). Taken together, these clinical data further support a role for inflammation in cardiovascular disease and...

Withindepot Sitespecific Properties And Obesity

The synergism between certain cytokines and the sympathetic nervous system agonist noradrenaline (Figure 13.3), and the fact that stimulation of the perinodal adipose tissue in one popliteal depot induces detectable changes in the mesenteric and omental adipose tissue (33), suggest that a pathway by which frequent activation of the immune system could promote lipolysis in the intra-abdominal depots. Repeated activation over many years could contribute to the development of intra-abdominal obesity, as does chronic overstimulation of the hy-pothalamo-pituitary-adrenal endocrine axis (52).

Causes Of Insulin Resistance

Insulin resistance may be caused by rare genetic defects that alter insulin binding to its cellular receptors or cause defects in receptor or postreceptor signal trans-duction (1). Recently, defects in the nuclear receptor, PPARy, have also been linked to syndromes of severe insulin resistance (2). In addition, some endocrine-metabolic syndromes, such as Cushing's syndrome, acromegaly, and polycystic ovary syndrome, are associated with insulin resistance because of the hormonal imbalances associated with these conditions. However, in the most common forms of insulin resistance, single gene defects have not been identified and the development of insulin resistance represents a complex interaction among a poorly understood array of predisposing genetic factors and acquired environmental factors that modify insulin sensitivity. Among the latter, the most prominent are obesity (particularly intra-abdominal obesity), physical inactivity, and increasing age. It is also now well documented...

The Insulin Resistance Syndrome

Insulin resistance and hyperinsulinemia are frequently associated with a cluster of clinical and biochemical abnormalities that have been described with increasing detail and given a variety of names including deadly quartet, syndrome X, insulin resistance syndrome, metabolic syndrome, and cardiovascular dysmeta-bolic syndrome (9-13). Many prefer to call it insulin resistance syndrome because insulin resistance and the resulting hyperinsulinemia appear to be the underlying abnormalities from which the other features of the syndrome are derived (see Chap. 7). The hallmarks of insulin resistance syndrome are obesity, particularly central or intra-abdominal obesity, glucose intolerance, or type 2 diabetes mellitus, hypertension, a dyslipidemia characterized by elevated triglycerides, low HDL cholesterol and small dense LDL cholesterol, a hypercoagulable state

Relationship Between Obesity And Type 2 Diabetes Mellitus

Trowell and Burkitt's studies of epidemiological changes in modernizing societies showed that obesity is the first of the 'diseases of civilization' to emerge in the longitudinal picture (78). As such obesity is clearly the earliest target for intervention to halt a wide range of non-communicable diseases of modern and modernizing societies. Gracey has termed this defined cluster of diseases the New World syndrome (79), and has included within its sphere obesity, type 2 diabetes, hypertension, dys-lipidemia, and cardiovascular disease (also termed the metabolic syndrome X (80)) (with the addition of cigarette smoking and alcohol abuse).

Regional Adiposity And Coronary Artery Atherosclerosis In Females

We examined the relationship between social status, social stress, and central obesity in a series of studies of social group-living cynomolgus monkeys. In all of the experiments discussed below, adult monkeys were fed a moderately atherogenic diet that contained between 0.25 and 0.39 mg cholesterol calorie and 40 of calories from fat (primarily saturated fat). These monkeys were housed in small social groups of four to six animals of the same gender.

Regional Adiposity And Metabolic Aberrations

Female cynomolgus monkeys with high central fat have higher glucose and insulin concentrations in an intravenous glucose tolerance test than females with relatively low central fat. They also have higher blood pressure and total plasma cholesterol concentrations, and lower HDL cholesterol concentrations compared to low central fat females (50). In women, central obesity has been linked with a metabolic syndrome consisting of impaired glucose tolerance, raised serum triglycerides and low levels of HDL cholesterol (51).

Social Stress And Regional Adiposity In Males

The monkeys were assigned to treatment groups using a method of stratified randomization that matched the groups for pretreatment plasma cholesterol concentrations. Pretreatment anthropo-metric measures were used to control for small (non-significant) differences in adiposity that were present prior to treatment. Computed tomography was used to measure intra-abdominal and subcutaneous abdominal fat in forty monkeys and regional skinfold thicknesses were also measured (55). Males that lived in the stress condition produced by repeated social reorganization had significantly higher ratios of intra-abdominal subcutaneous (IA SQ) abdominal fat (56).

Summary of evidence from human studies

Findings from human studies are contradictory and it is yet to be confirmed whether, and to what extent, dietary fat quantity and or quality may affect insulin action in humans. There is a paucity of studies that have measured insulin sensitivity using direct, rather than indirect or surrogate, measures. Where direct measurements have been made, comparisons are complicated by differences in methods of measurement of insulin sensitivity, study duration and dietary composition. Critically there have been no reported studies in which the effects of dietary fat substitution (SFA MUFA or SFA PUFA) on insulin sensitivity have been studied in subjects with the metabolic syndrome. Lipgene is a multicentre, 5-year pan-European project that will address this gap in our knowledge. This study will investigate the impact of dietary fat quality, and diet-sensitive genotypes, on insulin sensitivity and risk markers for the metabolic syndrome. RISCK is another ongoing multicentre, 4-year, UK-based...

Conclusions fatty acids and insulin sensitivity

Studies are contradictory in some cases, there does appear to be consistent evidence to support an adverse role for SFA in maintenance of normal insulin sensitivity. Less consistent, though suggestive, is the evidence that unsaturated fatty acids may have beneficial effects on insulin sensitivity. This latter question is one which is important to answer to enable policy makers to draw conclusions regarding the relative benefits of low-fat versus fat-substituted diets in the prevention of insulin resistance, metabolic syndrome and type 2 diabetes. Until this question is adequately addressed through controlled human studies, it is not possible to provide adequate guidance to agriculturalists and food manufacturers concerning the optimal compositions of oils to be produced and used in food manufacturing and processing.

Obesity Cortisol Metabolism

It is, however, apparently not possible to explain why cortisol secretion is particularly elevated in centrally localized obesity, since an elevated cortisol secretion along this mechanism would be expected to be dependent on total mass of adipose tissue irrespective of its localization. Furthermore, if cortisol is rapidly inactivated in the peripheray, this would not be expected to result in peripheral consequences of hypercortisolism, as seen in central obesity. Local elevations of the HSD1, which has been reported to occur in visceral fat depots, might have local effects but it seems difficult to imagine that a secretion of cortisol from visceral fat would have systemic effects, due to the small mass of this tissue. Cortisol from such elevated secretion would presumably also be inactivated peripherally. It is also difficult to understand the relationships, if any, between mechanisms, working on the regulatory centres of the HPA axis, described in the preceding section, and...

Obesity Perinatal Factors

Perinatal factors are likely to be involved in the problem of centralization of body fat stores. This idea originates from studies by Barker (25), who found that children born small for gestational age frequently develop centralization of body fat and associated metabolic syndrome, 'the small baby syndrome'. Although originally based on statistical observations from populations where intrauterine undernutrition was suspected, this hypothesis has gained considerable support from the results of recent studies. It is thus apparent that perinatal factors are critical for the development of obesity and centralization of body fat stores with its metabolic associates in adult life. Evidence suggests that this might at least partly be mediated via programming of the regulation of the HPA axis. It will be of interest in the future to find out to what extent 'the small baby syndrome' is involved in the overall prevalence of centralization of body fat and the metabolic syndrome in adult life.

Psychosocial And Socioeconomic Factors

Psychosocial factors have been found to be associated with an elevated WHR in both men and women. The relationships seem stronger in men, with factors such as living alone and divorce. Socioeconomic handicaps are also involved, including poor education, physical type of work, low social class and low income (50,51). This has also recently been observed in the Whitehall studies with strong inverse relationships between socioeconomic status on the one hand and an elevated WHR associated with the metabolic syndrome on the other (52). In a similar treatment of our data we find the same relationships, which are associated with perturbations of the HPA axis. In addition, exposure time for such handicaps seems to worsen the symptoms (53). It seems likely that exposure to such socioeconomic and psychosocial handicaps provides a background which would frequently expose such individuals to a stressful environment, and activate the stress systems in the lower part of the brain, followed by the...

Endocrine Deficiencies

Men with low testosterone, women after menopause and both men and women with growth hormone deficiency without involvement of HPA axis perturbations tend to have abdominal obesity (49). These hormones prevent accumulation of body fat in intra-abdominal depots, and deficiency would then be expected to be followed by enlargement of these depots. The mechanisms whereby this occurs have been largely elucidated, and substitution with the deficient hormone is followed by a specific decrease of visceral fat as well as improvement of the factors included in the metabolic syndrome (6). The prevalence of such conditions seem to be in the order of 10 in the middle-aged male population (56).

Definition and Epidemiology of Pediatric Human Immunodeficiency Virus

Therapy for HIV infection includes three major drug categories nucleoside reverse transcriptase inhibitors, protease inhibitors, and non-nucleoside reverse transcriptase inhibitors. Studies in adults show that protease inhibitors are associated with increases in abdominal fat deposition and elevated serum triglyceride levels.4 In addition, numerous other medications are often used for the prophylaxis or treatment of secondary infections. These intensive drug therapies may induce side effects such as nausea, vomiting, and diarrhea that can have an impact on the child's nutritional state. Table 18-1 lists common causes of malnutrition seen in pediatric AIDS.

Lipidgene interactions diet and health

During the last century, new techniques for the production of food facilitated an exponential increase in population and the lengthening of average lifespan. However, this improvement in food availability, along with changes in lifestyles toward less physical activity, but perhaps with more 'stress', was also accompanied by substantial changes in dietary patterns. Indeed, at least in industrialized countries, energy intake increased, and the contribution of dietary fat (40-50 energy), especially saturated fatty acids, became more and more important. At the same time, the prevalence of metabolic diseases (obesity, metabolic syndrome, diabetes and subsequently cardiovascular diseases) dramatically increased. Because of the economic costs of these conditions, we have been driven to ask whether changes in diets, and dietary fat more particularly, could, at least in part, be responsible for this significant rise in metabolic diseases. acids, then to dietary cholesterol and finally the...

What is the goal of blood pressure management

The ultimate goal of antihypertensive therapy is to delay, prevent, or reverse blood pressure-related end-organ vascular damage. To achieve this most effectively, blood pressure should be reduced to target levels specified in the current guidelines. The current (seventh) report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure (JNC7) recommends a goal of < 140 90 mmHg in the general population (16). However, a substantial proportion of patients with metabolic syndrome have diabetes or chronic kidney disease JNC7 and the American Diabetes Association recommend a goal of < 130 80 mmHg for such individuals (16,17). Thus, the physician is challenged to be bold enough to adopt an intensive blood pressure management strategy to achieve and maintain goal blood pressure and protect the patient against future morbidity and mortality. A survey utilizing the Framingham algorithm to evaluate coronary risk in NHANES III subjects with...

Reducing blood pressure through lifestyle changes

Therapeutic lifestyle changes focusing on weight reduction, exercise, and healthy eating (restricted sodium intake, the dietary approaches to stop hypertension DASH eating plan, and moderate alcohol consumption) is the foundation of hypertension management in persons with metabolic syndrome (Table 3) (16). Individuals should also be counseled to stop smoking to reduce their overall CVD risk. A realistic weight loss target is 10 of initial weight over 6 mo. Losing 22 lbs (10 kg) reduces SSP by 5-20 mmHg in a large proportion of overweight individuals (16). Lifestyle interventions also prevent the development of diabetes, an important consideration in patients with metabolic syndrome. A program comprising weight loss and physical activity reduced the onset of diabetes by almost 60 vs placebo and was significantly more effective than metformin in prediabetic individuals with elevated fasting and postload plasma glucose levels (18). Lifestyle modifications also reduce the overall CVD risk...

Use of antihypertensive drugs

Once a decision has been made to adopt a pharmacological approach to hypertension management, the challenge is to select the most appropriate drug. According to JNC7, thiazide diuretics, -blockers, ACE inhibitors, angiotensin receptor blockers (ARBs), and calcium channel blockers are suitable for reducing blood pressure and preventing hypertensive complications in patients with metabolic syndrome (16). Antihypertensive drug selection should be tailored to the individual, taking into account the metabolic syndrome determinants present and any comorbid conditions, such as renal disease, that are compelling indications for specific agents.

Calcium Channel Blockers

Because calcium channel blockers have neutral effects on lipid and glucose metabolism, they are appropriate for patients with metabolic syndrome. Clinical outcome trials, such as the hypertension optimal treatment (HOT) trial (20) and the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT) (21) showed that calcium channel blockers are safe and effective in controlling blood pressure and reducing CVD events in patients with diabetes. Side effects associated with vasodilatation, such as flushing, headache, and ankle edema, can be troublesome.

Microalbuminuria and Antihypertensive Medication

Microalbuminuria (urinary albumin excretion 30-300 mg d) clusters with metabolic syndrome, the prevalence being significantly higher among those with than without metabolic syndrome (12.3 vs 4.7 p 0.004) (31). In many patients, microalbuminuria is attributable to diabetic nephropathy. The presence of microalbuminuria demands attention because it is associated with a 50 increase in cardiovascular risk in the general population (32), suggesting that it reflects more widespread vascular damage. Of the individual metabolic syndrome components, microalbuminuria confers the strongest risk of cardiovascular death (33).

Fatty acids and cardiovascular risk clinical epidemiology

Abdominal obesity is linked to increased non-esterified fatty acid (NEFA) concentrations and turnover that are resistant to suppression by insulin (1,2). Similarly, physical activity and maximal oxygen consumption, a marker of physical fitness, are inversely associated with plasma NEFA concentrations measured as the area under-the-curve during a standard 2-h oral glucose tolerance test (3). Familial combined hyperlipidemia, a relatively common autosomal dominant trait, is associated with high plasma NEFAs as well as greater and more prolonged elevation of NEFAs following a fat load (4). Obesity, sedentary lifestyles, and familial combined hyperlipidemia are associated with high blood pressure, abnormal glucose and lipid metabolism, and more cardiovascular events including sudden death (5-7). NEFAs may be a common denominator linking diverse entities such as central obesity, physical inactivity, and familial combined hyperlipidemia to elevated blood pressures and greater cardiovascular...

Fatty Acids and Endothelial Function

High-fat meals impair flow-mediated dilation, a marker of endothelial function (19). Endothelial function is also impaired in patients with insulin resistance including abdominal obesity and diabetes mellitus (20). The adverse effects of high-fat meals, central obesity, and diabetes on endothelial function may be mediated by NEFAs. NEFAs, especially cis-unsaturated fatty acids, produce a concentration dependent inhibition of Ca2+-calmodulin dependent nitric oxide synthase activity in endothelial cells (21,22). Moreover, short-term elevations of plasma NEFAs produced by simultaneous infusion of intralipid, a source of triglycerides, and heparin, which activates endothelial lipo-protein lipase, also reduce endothelial cell nitric oxide production and impair responses to endothelium-dependent vasodilators such as metacholine and acetylcholine (23). In addition to suppressing endothelial nitric oxide synthase activity, NEFAs also enhance Fig. 1. Selected target organ system and cellular...

Fatty Acids and Signaling in Selected Target Cells

As noted, cis-unsaturated NEFAs suppress Ca2+-calmodulin dependent nitric oxide synthase activity in endothelial cells under basal and stimulated conditions (22). The diminution in nitric oxide synthase activity is associated with reduced Ca2+ signaling and with enhanced production of superoxide. Unsaturated NEFAs also enhance PAI-1 production by endothelial cells. The effects of unsaturated fatty acids including oleic, linoleic, and linolenic acids on endothelial PAI-1 production appear to be mediated by activation of PPARa and or PPARy (25). Oleic acid also stimulates endothelin-1 expression in cultured endothelial cells. The latter effects of oleic acid are mediated by activation of PKC, especially the Ca2+-dependent isoforms a and PII, and NF-kB (24). Collectively, these studies implicate elevations of unsaturated NEFAs in the endothelial dysfunction that accompanies many insulin resistant states, which include patients with abdominal obesity, diabetes mellitus, familial combined...

The Pancreas and Diabetes

Type 2 diabetes mellitus, also called adult-onset or non-insulin-dependent diabetes mellitus (NIDDM), accounts for about 90 of diabetes cases. Type 2 diabetes is initiated by cellular resistance to insulin. Feedback stimulation of the pancreatic islets leads to overproduction of insulin and then to reduced insulin production by the overworked cells. Metabolic syndrome (also called syndrome X or insulin resistance syndrome) is the term now used to describe a state of hyperglycemia caused by insulin resistance in association with some metabolic disorders, including high levels of plasma triglycerides (fats), low levels of high-density lipoproteins (HDLs), hypertension, and coronary heart disease.

Introductionepidemiology

Human obesity is characterized by a wide variation in the distribution of excess body fat, and the distribution of fat affects the risks associated with obesity as well as the kinds of comorbidities that result. In the 1920s the idea emerged, under Kret-schmer's influence (1), that the pychnic type of body build was associated with abdominal obesity, gout, apoplexia and impaired glucose tolerance. Vague extended these observations further and labelled obesity types android (male-type) and gynoid (female-type), and noted that, although gender-specific in general, women might have android obesity and vice versa (2). Nevertheless, the android type of obesity carries a greater risk for disease in both men and women. In addition to the pioneering attempts by Kret-schmer and Vague to categorize obesity, recent developments have confirmed the higher prevalence of dyslipidaemia, insulin resistance and hypertension in abdominal, central obesity in comparison with the more peripherally...

Methodological Comparisons

Centralization of body fat is most likely an effect of cortisol, as clearly seen in Cushing's syndrome, exhibited as severe truncal obesity. After successful therapy, the somatic features of Cushing's syndrome disappear (39). This provides evidence that cortisol may have a most potent stimulatory effect on central, visceral fat accumulation. Further evidence suggests that cortisol, in the presence of insulin, activates the main gateway for lipid accumulation in adipocytes, the lipoprotein lipase (LPL) enzyme, by actions on the processes of transcription and post-translation (40,41). Moreover, under these conditions the activity of the lipid mobilization system is low (41). These metabolic processes are mediated throughout the GR in adipose tissue. High activity in the lipid accumulating pathway together with low activity of lipid mobilization, exerted by cortisol, will be most pronounced is visceral fat depots due to the high density of GR (42). In light of this clinical and...

Johannes D Veldhuis MD Ali Iranmanesh MD and Daniel Keenan PhD

The aging process is marked by a relatively subtle short-term decline in reproductive hormone outflow in men. However, the nominal 0.8-1.3 annual fall in systemic bioavailability of testosterone results in a reduction of 30-50 by the sixth through eighth decades of life. Low testosterone concentrations forecast relative sarcopenia, osteopenia, visceral fat accumulation, detectable cognitive impairment, and variable mood depression. Accordingly, the mechanisms driving progressive androgen deprivation are important to understand. To this end, age-associated alterations in three dominant sites of physiological control, namely the hypothalamus, pituitary gland, and testis, are highlighted. The cognate signals are gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH), and testosterone, which jointly determine androgen availability via feedback and feedforward adaptations. According to this emergent notion, no single gland acts in isolation to maintain homeostasis. An integrative...

Stages Of The Hpa Axis Functional Status

The above subgroups of the functional status of the HPA axis represent extremes in terms of the resiliency of the HPA axis. Although strongly genetically determined (71), environmental and social factors also affect the circadian rhythm of the HPA axis (72). The question arises whether there are time- and stress-related changes in patterns of HPA axis activity and regulation, and if it is possible to tentatively define stages of such HPA axis affliction. A first stage then would be a normal function of the HPA axis, defined as a normal circadian rhythm with high morning and low afternoon-evening cortisol levels, and normal feedback control of GRs. Total cortisol output is regulated within the normal range and this is associated with optimal health. A second stage is seen upon acute stress where central regulation of HPA axis rhythm is maintained as well as the feedback control. The growth and reproductive axes are not affected. Cortisol secretion will, however, be elevated with...

Environmental Factors Influencing The Hpa Axis

Traits of anxiety and depression have a predictive association with visceral obesity in both men and women (55,56). Furthermore, alcohol consumption and smoking are common among subjects with elevated WHR (51,52). In addition, we have recently identified a number of psychosocial and socioeconomic handicaps in this condition (51,52). The most prominent factors are divorce, solitude, poor economy and low education, unemployment, and problems at work when employed. Interestingly, socioeconomic inequality and low educational have recently been shown to be associated with elevated stress-related cortisol secretion as well as visceral obesity (95). Moreover, we have identified a subgroup of elevated WHR and D, where a blunted dexamethasone response is found, associated with traits of anxiety and depression as well as personality disorders (57,96). It has been suggested that persistent psychosocial and socioeconomic handicaps constitute a base for stress, resulting in frequent challenges of...

Risk Factors For Type 2 Diabetes

Table 24.2 presents the known modifiable and non-modifiable risk factors or aetiological determinants associated with type 2 diabetes (27). The overall risk of type 2 diabetes must be assessed on the basis of all of these. Because of the additive effect of different risk factors and determinants, individuals with high levels of non-obesity risk may develop type 2 diabetes without becoming obese, while in other cases obesity alone may be sufficient to lead to diabetes. Generalized and central obesity are just two of the interrelated risk factors associated with type 2 diabetes, and of the modifiable lifestyle factors are probably the most important in terms of size and consistency of effect. Other components of the metabolic syndrome Pregnancy-related determinants (parity, gestational diabetes, diabetes in offspring of women with diabetes during pregnancy, intrauterine environment) Abdominal fat, especially the visceral rather than subcutaneous depots, is strongly associated with the...

Lymphoproliferative disorders

Amyloid arthropathy attributed to deposition of AL protein is associated with dysproteinemias, such as multiple myeloma. It occurs in up to 5 of myeloma patients and is more common in men and those with l light chains. This arthropathy can mimic RA and is associated with carpal tunnel syndrome, shoulder pad sign, and nodules. Erosions are rarely noted. Additional clinical clues that warrant consideration of amyloidosis are hepatosplenomegaly, congestive heart failure, macroglossia, pinch purpura, raccoon eyes, and nephrosis. Biopsy sites to establish a tissue diagnosis include abdominal fat, rectum, synovium, and bone marrow. (see Chapter 51, section I.)

Cardiovascular Disease

The relationship between obesity per se and CHD therefore appears doubtful when the measure of adiposity is expressed with a classical anthropo-metric variable such as weight and BMI, which may be inadequate surrogates for adiposity itself. As previously mentioned, the association between obesity and CHD becomes more robust when the distribution of fat is considered. Although Gillum et al. (34) and Hodgson et al. (91) found that the increased risk for ACVD present in abdominal adiposity is indirectly mediated by the presence of the other classical risk factors, several subsequent papers confirmed that the abdominal distribution of fat is an independent risk for CHD. Clark et al. found that, at least in black women, the strongest predictor for CHD is WHR > 0.85 followed by a family history of CHD and cigarette smoking (92). From forensic autopsy evaluations, Kortelainen and Sarkioja found that abdominal accumulation of fat is associated with the severity of coronary atherosclerosis...

Localized amyloidosis

Radiographs will often show subchondral radiolucent bone cysts consisting of amyloid deposits and erosion. Systemic deposits are rare, and specimens obtained by abdominal fat pad aspiration (the simplest screening test) are usually negative for amyloid deposits. In patients with chronic renal failure, other conditions, such as secondary hyperparathyroidism, aluminum overload, and apatite crystal deposition, may occasionally play a contributory role in arthropathy, and such conditions should be identified.

Role Of Hypocretin In Sleep Regulation

Narcoleptic patients have a tendency to grow obese. This had already been observed more than 70 years ago.63 Recent studies point to a specific role of hypocretin in the genesis of this obesity. A first hint came from the observation that narcoleptic patients with measurable hypocretin levels (a small minority of the total patient population) tended to be less obese than patients with undetectably low levels.16 A subsequent study in a large group of typical narcoleptic patients, known to have undetectable hypocretin-1 in more than 90 of cases, and comparably sleepy patients with idiopathic hypersomnia (who have normal hypocretin levels), confirmed this impression and suggests that hypocretin deficiency per se promotes body weight gain.29 Hypocretin-deficient narcoleptics were significantly heavier than age- and sex- matched controls, and the percentage of obese patients (BMI > 30kg m2) was significantly higher in the narcoleptic group. In addition, waist circumference and the...

Pulmonary Function and Mechanics

Fat deposition in the neck, upper airway, chest wall and abdomen can impair the mechanical function of the respiratory system. In general, the effects of obesity alone are mild and are typically in proportion to the degree of obesity (1-3). Reduced lung volumes are seen, with falls in the expiratory reserve volume (ERV) and the functional residual capacity (FRC) the commonest findings. Reductions in vital capacity and total lung capacity are generally only seen when the body mass index (BMI) exceeds 40kg m2. Reductions in lung volumes below 70 predicted are rarely due to obesity alone. Measurements of central obesity may correlate more closely than BMI with abnormalities of lung function (4,5). Patients with obesity-hypoventilation syndrome (OHS) tend to have more impaired respiratory function than patients without sleep-disordered breathing, despite identical degrees of obesity. The reasons for this are not clear. subcutaneous neck fat may be the critical factor causing upper airway...

Vascular effects of et1

ET-1 generation is modulated by shear stress that downregulates its release by endothelial cells (10). NO production, stimulated by shear stress, is an important inhibitor of ET-1 release (11), and may thus be a mediator of this effect. Hypoxia, epinephrine, thrombin, Ang II, vasopressin, cytokines, insulin, and growth factors such as TGF- 1 stimulate endothelial release of ET-1. Leptin has also been shown to upregulate ET-1 production by endothelial cells (12), which could explain in part increases of ET-1 in obesity. This may represent a mechanism that relates obesity to frequently associated cardiovascular conditions including hypertension and atherosclerosis, or that contributes to the evolution of the metabolic syndrome toward type 2 diabetes. Peroxisome proliferator-activated receptors (PPARs) are nuclear factors involved in adipocyte differentiation and insulin sensitivity that have been recently shown to exhibit potent anti-inflammatory and antigrowth properties (13-15). Both...

Carbohydrate metabolism

For years, the development of type 2 diabetes mellitus, metabolic syndrome and insulin resistance have been found to be related to high caloric intake, especially saturated fatty acids (SFAs), and it is usually associated with excess weight and obesity (Reaven, 2003). For this reason, research in the 1960s, pointed out that a diet higher in CHO (up to 60-70 of total energy), complemented by a reduction in the daily intake of cholesterol and an increase in the consumption of fibre, could be used by people with diabetes. The studies have usually shown that substituting total fat (with high content of SFA) with CHO results in an improvement in mediated-glucose disposal and insulin secretion (Brunzell et al., 1971 O'Dea et al., 1989 Borkman et al., 1991). In summary, there is substantial evidence that in patients with type 2 diabetes mellitus, metabolic syndrome and insulin resistance, diets with a relatively high

General Pharmacological Aspects

Although the ideal weight loss drug does not exist yet, a series of characteristics should be considered in qualifying a molecule for human use (Table 31.2). It is important that drugs are effective in reducing body fat, visceral fat in preference, without displaying any major health risks (13,22). In addition, the effect of the drug should be long lasting. In this context, the effect of the drug on the maintenance of achieved weight loss is as important as the initiation of weight loss. It is not the case that a drug designed for weight loss does not have any effect once a phase of weight stabilization after weight loss has been reached. In this situation, discontinuation of the drug treatment will most probably result in weight regain (23).

Female Sex Steroid Hormones

Previous studies have demonstrated that increasing androgenicity in women, as reflected by low SHBG concentration, or an increase in the percentage of free testosterone, is associated with visceral obesity (7,39). Menopause seems to be associated with increasing body fat and with an increasing proportion of abdominal body fat distribution (40). It may be conceivable that these changes in body fat and its distribution are related to the marked decrease in oestrogen and progesterone levels associated with menopause. Consequently, it may therefore be hy- Visceral fat Waist circumference

Differences in Regulation of TAG Storage and Mobilization between Visceral and Subcutaneous Adipocytes

Individuals with peripheral obesity possess fat distribution subcutaneously in glu-teofemoral areas and the lower part of the abdomen, and are at little risk of metabolic complications, such as NIDDM. Conversely, individuals with upper-body obesity accumulate fat in subcutaneous and visceral deposits and are more susceptible to metabolic problems, in particular when visceral fat deposits are abundant. Visceral fat deposits, located in the body cavity, are composed of the omental and mesenteric fat, and comprise the minor component of total body fat, representing 20 and 5-8 of total body fat in men and women, respectively. In upper-body obesity, fat excess is present in the visceral abdominal regions but also in the subcutaneous abdominal regions. There are several explanations but no clear proof why upper-body obesity is more at risk of developing metabolic disease than lower-body obesity 499 . Since the visceral deposit is in direct contact with the liver through the portal...

Cefalu Wt 2000. Insulin Resistance In Medical Management. Of Dm. New York. Marcel Dekker Inc Pp 57 76.

Armellini F, Zamboni M, Rigo L, Bergamo-Andreis IA, Robbi R, De Marchi M, Bosello O. Sonography detection of small intra-abdominal fat variations. Int J Obes 1991 15 847-852. 81. Armellini F, Zamboni M, Rigo L, Todesco T, Bergamo-Andreis IA, Procacci C, Bosello O. The contribution of sonography to the measurement of intra-abdominal fat. J Clin Ultrasound 1990 18 563-567. 84. Cefalu WT, Wang ZQ, Werbel S, Bell-Farrow A, Crouse JR, Hinson WH, Terry JG, Anderson R. Contribution of visceral fat mass to the insulin resistance of aging. Metabolism 1995 44 954-959. 86. Grundy SM. Small LDL, atherogenic dyslipidemia, and the metabolic syndrome. Circulation 1997 95 1-4. 88. Grundy SM. Hypertriglyceridemia, insulin resistance, and the metabolic syndrome. Am J Cardiol 1999 83 25F-29F.

Methods For Anthropometric Measurements

Mri Abdominal Intra Abdominal Fat

Waist Circumference Waist circumference is measured midway between the lower rib margin and iliac crest, with a horizontal tape at the end of gentle expiration (Figure 4.4), with feet kept 20-30 cm apart. Subjects should be asked not to hold in their stomach, and a constant tension spring-loaded tape device reduces errors from over-enthusiastic tightening during measurement. Waist circumference measurement reflects body fat and does not include most of the bone Figure 4.8 Subcutaneous and intra-abdominal fat images obtained from magnetic resonance imaging. (a, above) Male (b, opposite) female. Light areas indicate fat Maximum hip circumference is measured with a horizontal steel tape at the widest part of the trochanters at horizontal position (Figure 4.4) with feet kept 20-30 cm apart. It is related more closely to subcutaneous fat than to intra-abdominal fat mass. Hip circumference has limited value on its own in body composition estimation. The circumference of the hip is...

Regulation Of Adipose Tissue Distribution In Humans Bjorntorp

Stress-related cortisol in men Relationships with abdominal obesity and endocrine, metabolic and hemodynamic abnormalities. J Clin Endocrinol Metab 1998 83 1853-1859. 19. Bjorntorp P. Abdominal fat distribution and disease An overview of epidemiological data. Ann Med 1992 24 15-18. 22. Rosmond R, Bjorntorp P. Endocrine and metabolic aberrations in men with abdominal obesity in relation to anxio-depressive infirmity. Metabolism 1998 47 1187-1193. 35. Bjorntorp P, Holm G, Rosmond R, Folkow B. Hypertension and the metabolic syndrome. Closely related central origin Blood Press. 2000 9 71-82. 46. Thakore JH, Richards PJ, Reznek RH, Martin A, Dinan TG. Increased intra-abdominal fat mass in patients with major depressive illness as measured by computed tomography. Biol Psychiatry 1997 41 1140-1142. 48. Ljung T, Ahlberg A-C, Holm G, Friberg P, Andersson B, Eriksson E, Bjorntorp P. Treatment of men with abdominal obesity with a serotonin reuptake inhibitor....

Testosterone Shbg And Obesity

Determine whether visceral fat is more closely linked to low testosterone than is total body fat, but results have been conflicting (26). Glass et al. (25) also first noted that low testosterone levels in obese men could be partly explained by a decrease in SHBG, but whether SHBG is more highly correlated with abdominal obesity or with body mass index remains controversial. A summary of several studies reporting cross-sectional correlations between SHBG and body mass index and waist-to-hip ratio (WHR) is found in Table 2. In massively obese men, weight loss after bariatric surgery can reverse the SHBG abnormalities when near-normal body weight is achieved (27). Men with Cushing's syndrome have central obesity and are generally hypogonadal (41). Glucocorticoids suppress GnRH transcription (42), suggesting that the hypogo-nadotropic hypogonadism of obese men could also be explained by hypercortisolemia. However, studies of cortisol production in obese men have produced mixed results...

Other Lifestyle Dietary Factors Affecting the Adult Male

Cryptorchidism Human Males

Via effects on sex hormone-binding globulin (SHBG) (61). There is a well-established relationship between obesity, insulin resistance, and SHBG secretion (62,63), but probably the most important pathways by which obesity affects testosterone levels are at the hypothalamic-pituitary level (57) and or at the testicular level (64). The latter study, as well as animal studies, have indicated a role for leptin in directly suppressing testosterone production by Leydig cells, so the inverse relationship between leptin and testosterone levels in obese and nonobese men (64,65) is perhaps indicative of cause and effect. For certain, there is an intriguing relationship emerging between sex steroids (particularly estradiol), fat stores obesity, insulin resistance, and leptin levels (63,65-67), but the precise cascade of events is unclear (see Chapter 17). Once this is better understood, it will hopefully shed more light on the relationship between increased abdominal obesity and lowering of...

Mechanisms by Which the Atypical Antipsychotic Agents May Cause Diabetes Mellitus

Central obesity is a significant risk factor for the development of type II diabetes mellitus in schizophrenic patients as well as in the general population. The risk for the development of type II diabetes in mildly obese individuals has been reported as 2-fold, in moderately obese individuals

Field Anthropometric Methods

Biceps Triceps Subscapular Suprailiac

Using an underwater weighing method to predict body fat is impractical for large field studies, requiring facilities and the cooperation of subjects and expertise of the investigators. Proxy anthropometric methods (Table 4.1) have been employed including skinfolds (2), body mass index (BMI) (3), and skinfolds combined with various body circumferences (4-6) to predict body fat estimated by underwater weighing. Body fat predicted from these equations shows high correlations with body fat measured by underwater weighing and relatively small errors of prediction. However, there have been few major validations of these equations in independent populations to test their generalizabil-ity or applicability in special population subgroups. The most widely used field method for total fat has been the four-skinfold methods (Figure 4.3), derived from underwater weighing (2). Recognizing possible errors of predicting body fat in subpopulations with altered fat distribution, regression equations...

Recent New Experience With Antiobesity Drugs

Orlistat Body Weight Eucaloric

Ramine helped greater proportions of patients to maintain > 100 , > 50 , or 25 of weight loss following a very low calorie diet and was associated with decreases in waist circumference (66). Sibutramine is, in some preliminary studies at least, also able to stimulate thermogenesis (69) and to reduce significantly the amount of visceral fat (70). Energy expenditure was significantly increased during the 5-hour period after administration of sibutramine 30 mg compared with placebo in healthy volunteers (71). Energy expenditure, as measured by indirect calorimetry, was increased during the fasted and the fed states by 152 and 34 versus placebo, respectively. These sibutramine-in-duced increases were accompanied by increases in plasma catecholamines and glucose concentrations, heart rate and diastolic blood pressure. Resting energy expenditure was decreased from baseline values by about half as much with sibutramine 10mg as with placebo (by 5.3 vs. 9.4 not statistically significantly...

Procoagulant Activity

PAI concentrations are higher in patients with hypertriglyceridemia, hypertension, and CHD, suggesting that PAI-1 concentrations are related to insulin resistance and or compensatory hyperinsulinemia. Epidemiological evidence in sup- -o port of this view comes from the European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study, indicating that PAI-1 concentrations were S significantly associated with hyperinsulinemia, hypertriglyceridemia, and hypertension in 1500 patients with angina pectoris. Furthermore, insulin-resistant < j hyperinsulinemic women have a higher PAI-1 concentrations, associated with J higher TG and lower HDL cholesterol concentrations, than insulin-sensitive women matched for age, body mass index, and abdominal obesity. Thus, high concentrations of PAI-1 are another manifestation of syndrome X.

Human Breast Cancer Cell Line Mda-ms231

D. (2004) Abdominal obesity and dyslipidemia in the metabolic syndrome importance of type 2 diabetes and familial combined hyperlipidemia in coronary artery disease risk. J. Clin. Endo. Metab. 89, 2601-2607. 43. Hennes, M. M., O'Shaugnessy, I. M., Kelly, T. M., Labelle, P., Egan, B. M., and Kissebah, A. H. (1996) Insulin resistant lipolysis in abdominally obese hypertensives role of the renin-angiotensin system. Hypertension 28, 120-126.

Risk Factors For Atherosclerotic Cardiovascular Disease In Obesity

Clerotic cardiovascular disease (ACVD), obese people often present well-recognized coronary risk factors such as hypertension, lipid abnormalities, and type 2 diabetes (Table 25.2). There is now evidence that fat distribution rather than excess fatness is more commonly associated with these risk factors for ACVD. Abdominal fat deposition, which is principally observed in males and in postmenopausal females, is not only independently associated with ischaemic heart disease, but is a clinical condition in which the traditional risk factors for atherosclerosis are determined by the presence of insulin resistance which has likewise been associated with increased cardiovascular risk (11). The clinical aggregation of all these risk factors is also called the '(pluri)meta-bolic syndrome or syndrome X'. Regardless of these linguistic bagatelles, these patients will be exposed throughout their life to an excess risk for ACVD. More recently it has been shown that lipoprotein abnormalities are...

Blood Lipids and Lipoproteins

Low HDL-C is often found in individual patients in association with other metabolic risk factors, including elevated very low-density lipoprotein (VLDL) and small, dense low-density lipoprotein (LDL), hypertriglyceridemia, and glucose intolerance (136). Insulin resistance may underlie this clustering of metabolic abnormalities, which has been referred to as the metabolic syndrome (150). Many of these metabolic changes promote the development of atherosclerosis and risk of cardiovascular events. All components of the metabolic syndrome have been related to low testosterone and SHBG in epidemiologic studies (14,65,87,138-140,142-144,146). Whether these relationships are truly causal or indirect must be evaluated further. An association of testosterone and SHBG with at least some components of the metabolic syndrome has been attributed to insulin resistance (65).

Clinical Presentation

One of the earliest signs in most all patients with CS (including CD) is obesity in growing children this is combined with growth deceleration or arrest (9-12). The accumulation of visceral fat in patients with CS, a result of excess cortisol and insulin secretion, is associated with the full expression of the metabolic syndrome X (hypertension, hyperlipidemia, hypercoagulation, insulin resistance) and its long-term (cardiovascular) sequelae. Typical signs of glucocorticoid excess are fat accumulation in the face (especially temple area and cheeks), neck (buffalo hump, supraclavicular fossae), trunk, abdomen, and epidural fat, with sparing of the limbs (8,13,14). Connective tissue atrophy leads to thin fragile skin, violaceous striae, and easy bruising. Hirsutism and a variable degree of acne (depending on the individual sensitivity to glucocortioids and androgens) can also be seen. Although mild to moderate hypertension often are present in patients with CD, hypokalemia and...

Blood Coagulation and Fibrinolytic Proteins

Bonithon-Kopp et al. (156) examined the cross-sectional relationships between endogenous testosterone and hemostatic factors in 251 middle-aged men without ischemic heart disease who were not taking medications that influence sex steroid hormones or hemostatic function. There was no association between total testosterone and fibrinogen concentrations in multivariate analyses that controlled for body mass, cigarette smoking, alcohol consumption, and other cardiovascular risk factors. On the other hand, lower levels of total testosterone were associated with higher concentrations of another key component of the blood coagulation system factor VII. In another report of 64 healthy men aged 18 to 45 yr, lower levels of free testosterone were associated with higher concentrations of fibrinogen and factor VII, independent of age, central obesity, fasting insulin and glucose, and other cardiovascular risk factors (157). Several studies have also reported an association between...

Effects of Increased Intra Abdominal Pressure on Laparoscopic Surgery in Severe Obesity

Laparoscopic surgery has become very popular for the treatment of severe obesity. Obesity can be distributed in either an android fashion, primarily within the abdominal area or centrally as seen primarily in male patients, or in a gynoid manner, in the hips and buttocks, peripherally as seen primarily in female patients. Many of our severely obese female patients have both peripheral and central obesity. We have found that central obesity is associated with a significant increase in intra-abdominal pressure and this pressure is as high or higher than the pressure seen in patients with an acute abdominal compartment syndrome (Fig. 5.1). Data support the finding that this increase in intra-abdominal pressure is associated with a number of obesity related co-morbidity problems leading to the development of a chronic abdominal compartment syndrome. These co-morbidities include obesity hypoventilation syndrome with its high cardiac filling pressures, gastroesophageal reflux disease,...

Laparoscopic Adjustable Silicone Gastric Banding

Lap Band Journal

Steep reverse Trendelenburg positioning is required in the morbidly obese patient as a significant amount of intra-abdominal fat may obscure visualization of the proximal stomach, particularly omentum hanging from the greater curvature of the stomach. Occasionally we have placed a long suture through the superior-most 'tongue' of fat and brought it out through a left lateral trocar in order to facilitate this retraction. In order to safely tilt the OR table into such steep positions, a foot board must be placed and the legs and feet securely positioned and padded for protection to prevent the disastrous consequences of an obese patient sliding off the end of the table.

Testosterone Effects On Fat Metabolism

Percent body fat is increased in hypogonadal men (76). Induction of androgen deficiency in healthy men by administration of a GnRH agonist leads to an increase in fat mass (47). Some studies of young, hypogonadal men have reported a decrease in fat mass with testosterone replacement (46,76), whereas others (77,78) found no change. In contrast, long-term studies of testosterone supplementation of older men are consistent in demonstrating a significant decrease in fat mass (79). Epidemiological studies (80,81) have found lower serum testosterone levels in middle-aged men with visceral obesity. Serum testosterone levels correlate inversely with visceral fat area and directly with plasma high-density lipoprotein (HDL) levels. Testosterone replacement of middle-aged men with visceral obesity improved insulin sensitivity and decreased blood glucose and blood pressure (82). Testosterone is an important determinant of regional fat distribution and metabolism in men (82). In our dose-response...

What is Beauty

Beauty institutes have understood this for a long time and enthusiastically apply it. Do we not read in women's magazines ladies have beautiful breasts, a flat stomach and good legs, but are they also firm The firmness and elasticity of tissue are fundamental qualities of a child's skin and a part of their beauty. Beauty is costly. It is easy for wealthy people to get jewelry and beauty accessories, but these are more difficult to acquire without money. This is one explanation of the popularity of aesthetic medicine and surgery among the less well-off and among those who cannot please merely with their natural gifts or with the artificial resources of the wealthy. As they are only able to please with their body, the less wealthy will more pay readily for an operation to remove acquired or existing supposed defects so that they can continue to be admired.

Infants and Children

Figure 4.4 Measuring waist circumference midway between iliac crest and lowest rib margin, and hip circumference at the level of the greater trochanters Figure 4.4 Measuring waist circumference midway between iliac crest and lowest rib margin, and hip circumference at the level of the greater trochanters

Illness

Conventional anthropometric prediction equations break down with altered relative body composition. For example, patients with advanced tuberculosis and cancer or with benign oesophageal stenosis may have similar BMIs as a result of weight loss, but muscle loss is likely to be greater in a cachectic inflammatory condition. Errors will therefore result from using the same body composition prediction equations. Illnesses that result in considerable loss of minerals or specific tissues, e.g. muscle wasting in patients with acquired immune deficiency syndrome (AIDS), may result in an overestimation of body fat using conventional prediction equations. In contrast, in patients with non-insulin-dependent diabetes mellitus (NIDDM) (Type 2 diabetes) who have increased intra-abdominal fat, there is underestimation of body fat using skinfold methods, which increases with the amount of central fat deposition (20). There is a problem in measuring body composition of amputees whose substantial...

Obesity

The association between truncal obesity and the metabolic syndrome, or syndrome X, which comprises a cluster of abnormalities including abdominal obesity, dyslipidemia with elevated triglycerides and low HDL cholesterol, hypertension, hypercoagulability, and evidence of insulin resistance (with or without overt glucose intolerance) (Bard et al. 2001 Grundy 1999). An estimated 22 of adults in the United States meet criteria for the metabolic syndrome, making this an intense focus of research among epidemiologists and clinicians (Ford et al. 2002).

Conclusions

Looking at the association between obesity and type 2 diabetes, many indications suggest that a high-risk strategy may be worthwhile, not only from an individual standpoint, but also from a population perspective. The role of screening programmes is to identify and treat these high-risk individuals. The question from a cost-effective point of view, when screening for obesity, is not how to find these high-risk individuals, whether by using mass screening, opportunistic screening or screening by educating people to seek advice and support from the health care system when BMI or waist circumference is above a certain level. The costs for the detection of obesity in screening programmes will be within reasonable limits, irrespective of screening methods used. A potential danger is that many high-risk individuals from low socioeconomic groups will abandon the screening activities. We must remember that the central issue, with respect to obesity, is to find an acceptble treatment open to...

Type 2 Diabetes

Several mechanisms may be implied in the involvement of inflammatory cytokines in the pathogenesis of the disease. For instance, both IL-6 and IL-1 P act on the liver to produce the characteristic dyslipidemia of the metabolic syndrome, with increased very low-density lipo-proteins high-density lipoproteins.62 Carriers of the G SNP at -174 at 5-upstream of IL-6, characterized by high IL-6 plasma levels, appear to be prone to develop lipid abnormalities and Accordingly, in the Leiden 85-Plus Study66 it has been demonstrated that low production of IL-10 by stimulated peripheral blood cells, associates with the metabolic syndrome and type 2 diabetes. It was found that individuals with raised blood glucose tended to have a low capacity to produce IL-10. A similar association was shown between high plasma triglyceride concentrations and low production capacity of IL-10. Even if this study does not consider the possibility that the elevation of blood glucose concentration itself could have...

Summary

In primates, abdominal obesity is associated with low social status, the metabolic syndrome, and increased risk of morbidity and mortality due to depression and cardiovascular disease. Data from studies of monkeys suggest that social stress may be an underlying cause. We hypothesize that the stress of social subordination or social instability causes increased sympathetic nervous and HPA function. The chronic stimulation of these two systems leads to increased blood pressure and heart rate, and imbalances in sex steroid production which result in injury to the artery wall, and deposition of fat in the viscera. Visceral fat depots in turn exacerbate the metabolic effects of stress. Some of these physiological stress responses affect the function of the brain, resulting in depression.

Hypertension

There is now considerable evidence indicating that primary hypertension is frequently associated with centralization of body fat mass (33) and the metabolic syndrome (34,35). From the statistical correspondence between elevated blood pressure and insulin arose the suggestion that elevated blood pressure might be caused by hyperinsulinaemia or its precursor, insulin resistance. This contention is supported by experimental work showing that the central sympathetic nervous system is activated by insulin (36).

Mental Depression

Much to our initial surprise we found in population studies that subjects with traits of depression and anxiety often had centralized fat depots (39). This has also been found in our most recent studies in both men and women (22, and data in preparation). These traits are depressed moods, frequent use of antidepressant drugs and anxiolytics as well as various sleeping difficulties (39-41). This has now also been confirmed from other laboratories (42). As is almost invariably the case, this centralization of body fat is followed by the metabolic syndrome, as well as frequently, by hypertension. These findings are of interest from at least two aspects. Full-blown melancholic depression is a condition with severe perturbations of several neuroendocrine axes, including activation of the HPA axis with poor suppression of cortisol secretion by dexamethasone, elevated activity of the sympathetic nervous system and inhibition of the hypotalamic-gonadal axis and growth hormone secretion (43)....

Cancer

Cancer is also predicted by increased proportions of the central fat stores. This was first reported in a small number of endometrial carcinomas (57), and has subsequently been reported also for breast carcinoma (58) and confirmed in a larger study of endometrial carcinomas (59). Since these reports seem to suggest that the carcinomas predicted are localized to tissues which are sensitive to sex steroid hormones, one might speculate that the abnormalities of steroid hormone secretion found in abdominal obesity are also involved in this problem. Elevated androgens are closely associated with centralization of fat in women (21,60) as discussed in a preceding section, and probably originate from the adrenals as a consequence of a central drive of the HPA axis. Such abnormalities indicate disturbed secretions of sex steroid hormones which in an unknown way might be associated with these endocrine dependent carcinomas.

General Summary

This overview has attempted to summarize briefly the multitude of conditions in which central, visceral fat is accumulated in excess. In all these situations there seems to be a neuroendocrine background affecting the HPA as well as other central hormonal axes, often coupled to the autonomic nervous system. This parallel activation is characteristic of an arousal reaction of centres in the lower parts of the brain, constructed for adaptation to surrounding pressures in order to maintain homeo-stasis or allostasis. The widespread occurrence of elevated central body fat masses suggests by itself that vital, common pathways are activated. The associations between central fat and such diverse conditions as heart disease, stroke, diabetes, obesity, hypertension, cancer, depression, anxiety, endocrine disturbances, personality aberrations, alcohol abuse, socioeconomic and psychosocial handicaps etc., suggest some kind of common pathogenetic denominator. It seems likely that this denominator...

Thiazide Diuretics

Thiazide diuretics are widely regarded as the cornerstone of antihypertensive drug therapy. JNC7 recommends initial therapy with a thiazide diuretic in patients with uncomplicated hypertension, either alone or combined with drugs from other classes. At high doses, however, diuretics may cause untoward metabolic disturbances (e.g., hypokalemia, hyperuricemia, impaired glucose control, and increased insulin resistance), which are of concern in metabolic syndrome patients. Combining a low dose of diuretic with another antihypertensive agent provides additive blood pressure- lowering efficacy and minimizes drug-related, dose-dependent side effects. Diuretic-induced potassium depletion can be offset by coadministering an ARB or ACE inhibitor.

Pathogenetic Aspects

These statistical observations imply a major, fundamental, systematic pathogenetic background to abdominal, visceral fat accumulation and its associated multiple comorbidities. From a clinical point of view, there is a perceptible resemblance between this condition and that of Cushing's syndrome. In fact, subjects with abdominal, visceral obesity share many of the metabolic, hormonal, circulatory and behavioural findings observed in Cushing's syndrome. It may therefore be suspected that the regulation of cortisol secretion is involved in the syndrome of visceral obesity (5,14).

Overview

Androgen deficiency in men is associated with reduced physical stamina, relative sarcopenia, osteopenia, visceral obesity, sexual dysfunction, depressed mood, reduced sense of well-being, and detectable cognitive impairment (1-10). Impoverished testosterone production in the older male has been affirmed by (1) direct sampling of the human spermatic vein, (2) meta-analysis of cross-sectional epidemiological data (11), and (3) longitudinal investigations in healthy populations (12-15). For example, the European SENIEUR and Massachusetts Male Aging Cohort studies inferred that bioavailable (non-sex hormone-binding globulin SHBG -bound) testosterone concentrations decline by 0.8-1.3 annually (13,16), and, a 15-yr prospective analysis in New Mexico observed that total testosterone concentrations fall by 110 ng dL per decade in men after age 60 (14,17). Surgery, trauma, stress, systemic illness, medication use, and chronic institutionalization exacerbate androgen depletion in elderly...

Genetic Aspects

A dose-response study of inhibition by dex-amethasone administration has shown that feedback regulation in subjects with visceral obesity is diminished (33), in parallel with a blunted function of GR in adipose tissue (Ottosson et al., unpublished data). The latter study indicates the possibilities of both a decreased responsiveness and sensitivity of the GRs. Consequently, the GR gene (GRL), located in chromosome 5 and consisting of 10 exons with a minimum size of 80 kilobases (kb) (79), has been partially sequenced. However, no abnormalities in the DNA-binding (exon 2) or steroid binding (exon 9) domains of the GRL have been revealed (unpublished data). Nevertheless, the recent discovery that a BclI GRL polymorphism is associated with elevated cortisol concentrations in response to metabolic stress has raised the possibility that mutations may decrease the sensitivity to cortisol feedback (46). With the restriction enzyme BclI two alleles with fragment lengths of 4.5 and 2.3 kb are...

TAG in Lipoproteins

Man apolipoprotein C-I leads to hyperlipidemia accompanied by decreased visceral fat depots and lack of subcutaneous WAT in mice 113 . Conversely, overexpression of apoA-II, the second most abundant HDL component, increases adiposity and insulin resistance in relation to decreased skeletal muscle glucose utilization 114 . In the capillaries of skeletal muscle and adipose tissue at the luminal face of endothelial cells, LPL catalyses the rate-limiting step in the hydrolysis of TAG from circulating VLDL and chylomicrons. Thus LPL plays an important role in directing fat partitioning. In fact, complete LPL deficiency in mice results in minimal amounts of tissue lipids, leading to neonatal death due to marked hypoglyce-mia and hypertriglyceridemia 115 . In heterozygotes only mild hypertriglyceride-mia with impaired LDL clearance and mild hyperinsulinemia accompanied by an approximately 20 decrease in fasting glucose concentrations were observed. Exclusive LPL deficiency in adipose tissue...

Blood pressure

There are a growing number of studies indicating that antioxidants may be responsible for some of the protective effects of virgin olive oil (Moline et al., 2000 Giugliano, 2000). In concordance with this hypothesis, Perona et al. (2004) have suggested that dietary virgin olive oil compared with sunflower oil proved to be helpful in reducing the systolic pressure of treated hypertensive elderly subjects. Recently, Esposito et al. (2004) have demonstrated, in a randomized, single blind trial, conducted among 180 patients with the metabolic syndrome, that the consumption of a Mediterranean-style diet was associated with a significant reduction of blood pressure. With this information we are led to believe that diets rich in MUFA may induce a hypotensive effect that is more potent than that observed for in other unsaturated enriched diets. Nevertheless, more intervention trials are needed before we can ascertain to what extent they are beneficial and in which subgroups they would be most...

Energy balance

Body fatness is probably the principal modifiable risk factor for the development of diabetes and metabolic syndrome. Traditionally, hypocaloric diets intended for weight loss are high in CHO and low in fat. A common perception is that dietary fat of any kind is fattening, while low-fat diets have slimming properties.

Body Composition

Concomitant with the increases in muscle mass after androgen substitution in hypogonadal men, there are decreases in fat mass and percent fat measured by DEXA or visceral fat measured by abdominal computed tomography (CT) or magnetic resonance imaging (MRI) scan. The decreases in fat mass have been demonstrated with injectables and transdermals but not with the sublingual testosterone (16,17,38-40), which may be related to the amount of testosterone delivered to the body. A dose-response study showed that the decrease in fat mass is inversely related to the serum testosterone level and the dose of testosterone administered (21). Decreases in fat mass are also observed in middle-aged or older men administered testosterone (18,30,42). The decrease in visceral fat observed in some studies has been suggested to result in decrease in insulin resistance. Testosterone and its esters have no significant effects on glucose metabolism and insulin sensitivity in younger men (43). In older men,...

Concluding Remarks

The experimental evidence for involvement of aberrant (with regard to amount and or localization) intracellular storage of TAG in LD of various tissues (muscle, liver, heart and pancreas) and dysregulated mobilization of FA from TAG in LD of adipose tissue in the development of the metabolic syndrome and further on to frank NIDDM is increasing steadily. Consequently, the appropriate down-regulation of unrestrained TAG mobilization seems to represent a promising mode of action for future antidiabetic drugs which encompass three different levels of molecular mechanisms, each engaging several potentially interesting molecular targets as discussed in the preceding chapters

Glucocorticosteroids

Weight gain is a common adverse effect of long-term pharmacological treatment with glucocor-ticoids in patients not suffering from adrenal insufficiency (104-106). In a 12-month study of 109 patients with polymyalgia rheumatica giant cell arteritis, a steroid-related dose-dependent weight increase of between 2 and 13 kg occurred in more than 50 of all patients (104). In a large retrospective study with 774 patients examined before and after liver transplantation, mean body mass index (BMI) increased from 24.8 kg m2 initially to 28.1 kg m2 in the second year after the operation (105). Of the 320 patients who were not obese before transplantation more than 20 became obese later. Interestingly, both donor and recipient BMIs were found to be risk factors for weight gain together with a high cumulative prednisolone dose. Other studies have suggested that intermittent use of glucocorticoids may diminish the weight gain (107), but data are not overwhelming. Glucocorticoid treatment also...

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