Diet to Shed Belly Fat Naturally

Flat Belly Fix

In Flat Belly Fix program, you learn the easy, tested and trusted method that saved the creator of this program (Todd Lamb) beautiful wife Tara from a life battling Type 2 Diabetes and experiencing possibly death. It was a very nasty experience with the couple during those times, but with the determination of Todd, he labored ceaselessly to finding a way out for his depressed and unhappy wife. Now they live together both happy and contented. Having used the same technique for people around (seeing the wonders it did to his wife) and also recording so much success, Todd Lamb wants to relate this secret to the world, to create this same atmosphere of joy produced in his immediate environment. Hence, he was motivated to put together this workable program. You also get to learn the secret to having a flat belly, and a healthy and fit body that has been hidden from you for so long now. The creator if this program is positive about the efficacy of this program and is so excited for you to personally experience what happens when you apply The 21 Day Flat Belly Fix in your life. Read more here...

Flat Belly Fix Summary


4.8 stars out of 218 votes

Contents: Ebooks, Videos
Author: Todd Lamb
Official Website:
Price: $37.00

Access Now

My Flat Belly Fix Review

Highly Recommended

Of all books related to the topic, I love reading this e-book because of its well-planned flow of content. Even a beginner like me can easily gain huge amount of knowledge in a short period.

Overall my first impression of this book is good. I think it was sincerely written and looks to be very helpful.

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...

Defining the Metabolic Syndrome

The first broadly utilized definition of the metabolic syndrome evolved from the work of Reaven (1988) who described a group or clustering of metabolic abnormalities associated with insulin resistance including glucose intolerance, hyperinsulinemia, dyslipidemia, and hypertension. Several refinements have been proposed in the definition of the metabolic syndrome, which has also been referred to as syndrome X, metabolic syndrome X, insulin resistance syndrome, and cardiometabolic syndrome. Although differences exist in the definitions used (see below), the major utility of the metabolic syndrome classification has been to identify persons with increased risk of future cardiovascular and or diabetic complications. Diagnosis of the metabolic syndrome should initiate management of the condition, primarily through lifestyle interventions, to reduce future CVD and diabetes risk. There are several published definitions of the metabolic syndrome, and while similar, each specifies distinct...

Epidemiology of Obesity and the Metabolic Syndrome

The prevalence of the metabolic syndrome is also increasing in the United States and throughout the world however, the prevalence estimates depend upon the definition of the syndrome used. In addition, factors such as gender, ethnicity, and age greatly affect prevalence, as well as socioeconomic status and lifestyle habits (Cornier et al, 2008). Estimates of metabolic syndrome prevalence across all Americans have varied between 24 and 39 (Cornier et al, 2008), but it has been pointed out that this global statistic may not be useful because the prevalence of the metabolic syndrome increases dramatically with age (Cassells and Haffner, 2006 Ogden et al, 2006). The metabolic syndrome prevalence increases with each decade of life, paralleling age-related increases in obesity and central adiposity and based on National Health and Nutrition Examination Survey (NHANES) data, reaches 50-60 by 60-69 years of age (Cornier et al, 2008). Metabolic syndrome prevalence is highest in Hispanics and...

Pathophysiology of the Metabolic Syndrome

No specific etiology is known to account for the metabolic syndrome, nevertheless, subjects with the syndrome exhibit a variety of metabolic abnormalities associated with the individual components of the syndrome. Most notable are obesity and insulin dysregulation, which are the most frequently occurring metabolic syndrome components (Ervin, 2009). Multiple metabolic abnormalities could additively or synergistically influence the progression of CVD and diabetes. Increased circulating FFA has been hypothesized to lead to tissue-specific lipotoxicity (Kusminski et al, 2009 Unger, 2003). Elevated FFA levels inhibit insulin-stimulated skeletal muscle glucose uptake and increase hepatic glucose production (Boden, 1999), thus contributing to peripheral insulin resistance. Further, the increase in FFA levels promotes increased hepatic triglyceride synthesis and storage, and the excess triglycerides are secreted as very low-density lipoproteins (VLDL) (Lewis, 1997), which lead to an increased...

Obesity and Waist Circumference

Each of the metabolic syndrome definitions includes a measure of increased body weight or adiposity using waist circumference as a surrogate measure. Decision points for waist circumference in ATP III have been standardized ( 102 cm for men and 88 cm for women), while the IDF criteria depend not only on gender but also on ethnicity to account for differences in stature and body type. In contrast, the WHO criteria utilize either the waist to hip ratio (0.9 for men and 0.85 for women) or a BMI greater than 30 kg m2. Each of the metabolic syndrome definitions utilizes slightly different locations for determination of the waist circumference. By ATP III guidelines, the waist circumference is measured immediately above the iliac crest. For WHO and IDF criteria, the waist circumference is measured at the midpoint between the inferior margin of the last rib and the crest of the ileum. The difference in measurement sites has been evaluated in several studies, and although there is generally...

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...

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 fasting...

Lifestyle Modification of the Metabolic Syndrome Type 2 Diabetes and CVD

Diabetes, a number of randomized clinical trials (RCTs) have been conducted around the world to examine whether behavioral interventions can influence the progression of this disease. More specifically, it was hypothesized that weight loss and or increased physical activity or exercise may favorably alter metabolic processes, thereby preventing type 2 diabetes. In addition, several follow-up studies have examined whether these lifestyle modifications also influence preclinical markers of morbidity and mortality due to CVD. Although there have also been long-term lifestyle intervention trials to treat hypertension, and shorter term trials directed at dyslipidemia, as yet there is no evidence that lifestyle interventions for the metabolic syndrome prevent CVD. A subsequent DPP follow-up study (Orchard et al, 2005) examined the prevalence of the metabolic syndrome at baseline and as a result of the lifestyle modification and metformin intervention. It was reported that at baseline 53 of...

The Metabolic Syndrome Obesity and Insulin Resistance

Energy-dense foods high in saturated fats and sugars and reduced physical activity. Obesity is interrelated with a cluster of metabolic variables including insulin resistance, impaired glucose tolerance, dyslipidemia, and hypertension (Cornier et al, 2008) that when present together has been referred to as the metabolic syndrome. It has been shown that the metabolic syndrome can increase the risk of type 2 diabetes and CVD and that lifestyle interventions designed to reduce body weight, increase physical activity, and attenuate the metabolic syndrome components are associated with reductions in the incidence of disease.

Genetic and Physiological Influences

Based on the extensive evidence relating central nervous system (CNS) serotonin function to the expression of psychosocial factors like hostility and the potentially pathogenic biobe-havioral characteristics that are found in persons with high hostility, Williams (1994) proposed that reduced CNS serotonin function is one brain mechanism that could account for the clustering of hostility and biobehavioral factors that increase disease risk. Using the prolactin response to fenfluramine citalopram challenge as an index of CNS serotonin function, Manuck's research group has provided extensive evidence supporting this hypothesis, showing that lower CNS serotonin function is associated with increased aggressiveness (Manuck et al, 1998, 2002), increased expression of the metabolic syndrome (Muldoon et al, 2006), and even increased carotid arteriosclerosis (Muldoon et al, 2007). They have also used cerebrospinal fluid (CSF) levels of the major serotonin metabolite 5HIAA to index CNS serotonin...

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...

Clinical manifestation

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. The study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM), a large cross-sectional analysis of HIV-positive and control men, reported that peripheral lipoat-rophy was more frequent in HIV-positive men than in controls (38.3 vs. 4.6 , p 0.001), whereas central lipohypertrophy was less frequent (40.2 vs.55.9 , p 0.001). Among HIV-positive men, the presence of central lipohypertrophy was not positively associated with peripheral lipoatrophy (odds ratio 0.71, 95 CI 0.47 to 1.06, p 0.10). HIV-positive men (age 33-45 years) both with and without lipoatrophy had less subcutaneous adipose tissue (SAT) than controls, with legs and lower trunk more affected than...

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, a high rate of smoking among HIV patients and increased levels of tissue plasmino-gen 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 for an increased...

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...

An unkind note on sociobiology or evolutionary psychology

Many of the factors determining the frequency of use of contraceptives may also affect the waist to hip ratio. One way to avoid the bias would be to forbid the participants in our study to use contraceptives, but such an approach appears slightly unrealistic. In fact, the worldwide use of contraceptives has made impossible an unbiased study comparing the fertility of women with a waist to hip ratio of 0.70 to that of women with larger or smaller waist to hip ratios. A solution to this could be to use historical data from a time before contraceptives were introduced. Many countries have kept excellent birth registers for centuries. The only problem is that these birth registers do not normally include the waist to hip ratio. It is doubtful whether any do it. Perhaps some old photographs could be used for estimating this crucial ratio, but it is uncertain. In former times people had the unex-plainable habit of being dressed when they went to the photographer and on the occasions where...

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

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.

Clinical Characteristics of Homozygous Individuals

However, the two largest kindreds (Sindh and Itabaianinha) have many adult IGHD subjects who have not been treated with GH, allowing an analysis of lifetime lack of GH due to such mutations. Affected subjects exhibit similar phenotypic features with proportionate short stature, poorly developed muscle mass, and excessive abdominal fat accumulation. Small developmental defects have been noted in some patients, especially ear deformities.119 In addition, they have a characteristic high-pitched voice, due to the lack of GH effect on laryngeal development.144,14 Adult IGHD patients have an increased cardiovascular risk profile with increased abdominal obesity, systolic blood pressure, total and LDL-cholesterol, and C-reactive protein compared to normal subjects from the same area.153 In patients with acquired IGHD both morbidity154,155 and mortality156 are increased, and this has been attributed to such risks factors.157 Because most of these risks factors respond to GH therapy (Ref. 157...

Future Directions

Most of the studies, so far, have used BMI as a simple and inexpensive proxy measure of adiposity, which is easy to collect in large samples. More accurate measures of adiposity might further improve power, yet these are often more expensive and harder to collect. Genome-wide association studies for body fat percentage, waist circumference, extreme obesity risk and for mediating traits that underlie obesity, such as food intake and energy expenditure, may reveal new obesity susceptibility loci that are currently hidden in studies that use BMI as the main outcome. Similarly for type 2 diabetes, genome-wide association studies for fasting glucose, fasting insulin levels, HbA1C and other

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 Link Between Birth Weight and Later Health

Resources, the altered metabolism and coveting of nutrients can result in a propensity for obesity. Such a scenario sometimes occurs after adoption of a young infant from an impoverished setting to an affluent country. These children are then at greater risk for becoming overweight and developing the metabolic syndrome with glucose intolerance and atherogenic dyslipidemia and are more prone to cardiovascular disease. Clinical tests indicate that these individuals also have prothrombotic and proinflammatory profiles. In addition to the human studies supporting this line of reasoning, numerous reports on rodent and sheep models have begun to delineate the hormone mechanisms and metabolic pathways accounting for these long-term effects (Murphy et al, 2006 Wintour et al, 2003). These experiments indicate that the physiological programing includes changes in the kidney, with decreases in nephron number and or size, which contribute to the later hypertension in adulthood (Moritz et al,...

Chronic Negative Affect

Deficits in socioemotional skills may ultimately stabilize into enduring risks for emotional disorders, such as anxiety, depression, and other chronic negative emotional states. These states may act as predisposing factors for adverse physical health outcomes (Hemingway et al, 2003). For example, hostility has been tied to the development of metabolic syndrome among children and adolescents (Dembroski et al, 1985) and to an increased risk for coronary heart disease (CHD) and hypertension (Julkunen et al, 1994). Major depression, depressive symptoms, and history of depression have all been identified as predictors of cardiac events (Frasure-Smith et al, 1995), and depression is a risk factor for mortality following myocardial infarction, independent of cardiac disease severity (Frasure-Smith et al, 1995). State depression, as well as clinical depression, have been related to sustained suppressed immunity (Herbert and Cohen, 1993). Anger appears to play a significant role in the...

Early Adversity and Health Outcomes Tests of the Model

Metabolic functioning is a complex of risk factors for coronary artery disease and diabetes and is typically defined by fasting glucose, cholesterol, triglycerides, and abdominal obesity, among other indicators. High levels of these variables contribute to metabolic syndrome, which is prognostic for heart disease, diabetes, inflammatory disorders, and all-cause mortality (see Chapter 46). The prevalence of metabolic syndrome in the United States is approximately 22 (McEwen and Seeman, 1999), making it an important contributor to chronic illness.

Biological Pathways

Metabolic syndrome describes a cluster of risk factors for cardiovascular disease. Recent research linking SES to metabolic syndrome suggests that lower parent education is also associated with multiple metabolic risks among adolescents, including higher insulin and glucose, higher LDL cholesterol, waist circumference, and BMI, as well as cumulative risks (Goodman et al, 2005).

Introduction classifying diabetes

Diabetes mellitus is a heterogeneous metabolic syndrome with several different causes characterized by chronic hyperglycaemia with partial or total lack of insulin secretion and a reduced sensitivity to the hormone in peripheral tissues. If monitored inadequately and associated with other lipid and protein disorders, long-term complications may develop in several organs and systems, resulting in both high morbidity and mortality rates. Many of the long-term complications can be attributed to microangiopathy such as retinopathy, in the worst case leading to reduced sight or blindness to nephropathy leading to insufficient kidney function and to neuropathy, leading to motor-sensitivity deficit, a predisposing factor to the formation of ulcers and articular deformations of the feet. However, the most important epidemiological and clinical complications are those derived from macroangiopathy, primarily responsible for causing cardiovascular pathologies (chronic ischaemic cardiopathy,...

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).

Dietary strategies for preventing the onset of diabetes

The association between abdominal obesity (waist circumference 102 cm in men, 88 cm in women10), high low-density lipoprotein (LDL) cholesterol, low high-density lipoprotein (HDL) cholesterol, hypertriglyceridaemia, high blood pressure, high fasting glucose (impaired glucose tolerance IGT 110mg dL and 126mg dL), and insulin resistance (known as metabolic syndrome) is highly predictive of type 2 diabetes and potential coronary disease. Recently, a large clinical trial, the 'Diabetes Prevention Program' (DPP),11 investigated whether diet and physical activity were more effective than metformin in preventing or delaying the onset of type 2 diabetes in subjects with impaired glucose tolerance and a family history of type 2 diabetes. The results of this study showed that the group that underwent lifestyle changes, intensive nutrition and exercise counselling (150 minutes a week) and behaviour modification lost 7 per cent of their body weight, with a 58 per cent reduction in the incidence of

Mortality and Morbidity

Various other chapters in this book report on evidence that social, psychological, and lifestyle factors impact on overall health outcomes. Also, meta-analyses and systematic reviews suggest that lack of social support (Lett et al, 2005), depressive symptoms (Nicholson et al, 2006), and unhealthy lifestyle behaviors such as lack of physical exercise (Oguma et al, 2002) are associated with increased risk of developing cardiovascular disease and all-cause mortality. Although these reviews do not explicitly distinguish between studies using middle-aged and older populations, it is good to realize that in fact the majority of meta-analyzed studies examining the impact of behavioral factors on general health outcomes have been conducted among older persons, simply because morbidity and mortality most commonly occur in the oldest age groups. Therefore, there is no doubt that these behavioral factors continue to impact on general health outcomes such as mortality and (cardiovascular)...

Of Physiological Stress Mechanisms in the Oldest

Consequently, not considering the possibility of reduced cortisol levels among depressed older persons might lead to erroneous conclusions. Results of the InCHIANTI study among 800 community-dwelling older persons showed that only hypercortisolemic depressed persons showed an increased prevalence of the metabolic syndrome (Vogelzangs et al, 2007b). Lastly, high cortisol levels are also considered a central mechanism in the effects of psychosocial

Biological Indicators of Health or Resistance to Disease

CHD, and depression (Dekker et al, 2008 Herbert et al, 2006 Raison et al, 2006). Cortisol also contributes to memory function across the life span, with evidence that long-term exposure to high levels of glucocorticoids is associated with memory impairments and reduced hippocampal volume in the aging brain (Lupien et al, 2005). Until the advent of salivary assays, cortisol was primarily measured in blood or urine. Since cortisol secretion has a pronounced diurnal rhythm, this resulted in difficulty in accurately capturing representative cortisol levels in population studies, as the timing of data collection required standardization. Nevertheless, two studies showed that a single sample recorded early in the day was predictive of future clinical depression in adolescents or adults at high risk (Goodyer et al, 2000 Harris et al, 2000). A high cortisol testosterone ratio was found to predict incident CHD in a longitudinal study in South Wales, UK, probably through influences on the...

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...

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...

The Sympatho AdrenalMedullary System

Affects resting metabolic rate, lipolysis, and thermogenesis SNS overactivity is associated to visceral obesity (Tentolouris et al, 2006). Through actions on ascending vagal afferents, elevated systemic levels of epinephrine may possibly affect cognitive processes, such as memory and attention. An inverted U shape of catecholamine actions has been proposed, with moderate levels being beneficial, while low or high levels impairing cognitive performance (Lundberg, 2000 Roozendaal et al, 2009).

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...

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

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

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...

Project Title Social And Occupational Influences On Health And Illness

Summary The inverse gradient in Coronary Heart Disease (CHD) by socioeconomic status is one of the major unsolved puzzles in epidemiology. Whitehall II is a longitudinal cohort study of 10,308 female and male British Civil Servants set up in 1985 to test the hypothesis that psychosocial factors and differences in nutrition might explain this inverse gradient. NHLBI has been instrumental in supporting the measurement of psychosocial characteristics, in particular the psychosocial work environment and social support. There have now been four phases of data collection in the study, of which two have involved clinical screening with measurement of blood pressure, ECG and a blood sample. Five year incidence data, based on self-report coronary endpoints suggest that standard coronary risk factors explain no more than a third of the gradient, but factors in the psychosocial environment and height appear to explain the major part of the social gradient in CHD. There are also clear social...

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...

Search Strategy and Selection Criteria

We identified and conducted a review of systematic reviews of behavioral intervention trials targeting lifestyle risk factors related to the prevention and or management of circulatory and related conditions. Suitable reviews were identified by conducting an electronic search with the Database of Systematic Reviews of the Cochrane Library (Issue 3, 2009) and by crossing the keywords 'diet,' 'eating,' 'physical activity,' 'exercise,' 'smoking,' 'nutrition,' 'lifestyle,' 'behavior,' 'change,' 'smoking,' 'obesity,' 'overweight,' and 'adiposity.' These were crossed separately with 'cardiovascular,' 'heart disease,' 'coronary,' 'metabolic syndrome,' 'type 2 diabetes,' 'pre-diabetes,' and 'chronic disease.' Last, the search was combined with 'intervention' or 'trial.' We identified 165 reviews published between 1997 and 2009. We selected only reviews that were published in English and related to adults aged 18 or above. Reviews were excluded if they were (1) related to medical conditions...

Intervention Outcomes

Small improvements were found in weight, BMI, and waist circumference (Table 62.1, SR11-13), although statistical heterogeneity for these outcomes was high and effects were minimized by significant weight loss in the comparison groups (Norris et al, 2005a). Modest, but statistically significant improvements were shown on many physiological and anthropomet-ric outcomes. Both reviews on prevention of type 2 diabetes reported statistically significant reductions in the incidence of type 2 diabetes, but only one provided a pooled effect (Orozco et al, 2008).

Coronary Heart Disease 21 Risk Factors

The leading cause of death worldwide is CHD (WHO, 2008). Although atherosclerosis, the preclinical antecedent of CHD, begins in childhood, the clinical manifestations of CHD occur in adulthood and include angina pectoris, MI, heart failure, and sudden death. Major cardiovascular risk factors are those that independently influence the development of atherosclerosis and CHD. More than a half century ago the Framingham Heart Study identified cigarette smoking, elevated serum cholesterol, hypertension, and advancing age as major risk factors (Dawber et al, 1951). Since then, conventional wisdom has come to accept that four modifiable traditional cardiovascular risk factors (i.e., smoking, hypertension, hypercholesterolemia, type 2 diabetes mellitus) account for only 50 of the risk for CHD (Braunwald, 1997 Hennekens, 1998). However, some investigators have contended that the 50 figure is a myth and that traditional risk factors account for far more than half the prevalence of CHD (Canto...

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.

Insulin and the Pancreas

Insulin, a peptide hormone produced in P-cells of the islets of Langerhans in the pancreas, strongly modulates the metabolism, facilitating the uptake of glucose in the liver, muscle, and fat tissue. Insulin facilitates the storage of glucose as glycogen in the liver and muscle and inhibits the use of fat as an energy source. The HPA axis and the sympatho-adrenal-medullary system interact with insulin actions, and chronic stress exposure is associated with insulin resistance, diabetes mellitus 2, and the metabolic syndrome (Kyrou et al, 2006 for detail see also Chapter 46).

Insulin Resistance and Hyperglycemia

The WHO definition of the metabolic syndrome is the only one that utilizes a measure of insulin resistance as a required component, although elevated fasting glucose levels, specified by the ATP III and IDF definitions, are often associated with an insulin-resistant state. Insulin resistance can be defined as the condition in which normal amounts of insulin are inadequate to produce a normal insulin response from fat, muscle, and liver cells. In mild cases of insulin resistance, increased insulin secretion by pancreatic P cells results in hyperinsulinemia to maintain eug-lycemia. As insulin resistance worsens, individuals whose increased pancreatic insulin secretion is unable to compensate for the reduced insulin action develop impaired glucose tolerance and hyperglycemia.

Risk factors diseases and comorbidities

Important ED risk factors coexist frequently in HIV patients, including excessive alcohol consumption, smoking and other recreational drug use metabolic disorders (hyperlipidemia, diabetes mellitus) and cardiovascular disease, with hypertension being of particular importance. Pathophysiologically, most cases of ED are caused by neuronal (polyneuropathy) and vascular (micro- and macroangiopathy) changes however, ED can also be an early sign of a metabolic syndrome.

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...

Stress and Allostatic Overload Related Illnesses

When it comes to metabolism, the effects of chronically high glucocorticoids are enigmatic. Food intake is inhibited by exposure to high levels of glucocorticoids. This effect may be mediated by the increase in corticotrophin releasing hormone (CRH) acting as a catabolic signal (Kellendonk et al, 2002). However, in other situations of high glucocorticoids, such as in hypercortisolemia, obesity can result (Marin et al, 1992 Nieuwenhuizen and Rutters, 2008 Pasquali et al, 1996 Rosmond et al, 1998). Hypercortisolism, such as is found in Cushing's disease, is also associated with increases in free fatty acids that contribute to insulin resistance. This then can exacerbate the increase in visceral fat accumulation, augment sympathetic activation, and can result in hypertension (Brindley and Rolland, 1989). However, in most animal models, chronic restraint or immobilization stress results in reduced weight gain (Lucas et al, 2007 Magarinos and McEwen, 1995a, b

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.

Components from skimmed milk and weight loss 121 Calcium and weight loss

Yogurt, resulted in a larger decrease in body fat, body weight, waist circumference and trunk fat when compared to a non-dairy control. Trunk fat loss was 81 greater than the control samples and also resulted in a significant decrease in waist circumference (-0.58 versus -3.99 cm). Other researchers have specifically focused on calcium and implications in weight loss (Zemel, 2001, 2003a, 2003c, 2004, Zemel and Miller, 2004, Schrager, 2005).

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.

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.


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 multicenter...


Carriers of biallelic GHRHR mutations present a proportionate dwarfism with severe growth retardation, together with very low serum GH and IGF-1 levels. They have abnormal lipid profile and abdominal fat accumulation, and they respond well to GH therapy and reach target height if the treatment is started early in life. There are no reports of anti-GH antibody development and the success of GH therapy suggests that it is an unlikely possibility. A mild phenotype has been shown for heterozygous carriers of GHRHR mutations. 153. Barreto-Filho JA, Alcantara MR, Salvatori R, Barreto MA, Sousa AC, Bastos V, et al. Familial isolated growth hormone deficiency is associated with increased systolic blood pressure, central obesity, and dyslipidemia. J Clin Endocrinol Metab 2002 87 2018-23.


In view of the prolonged use of antiretroviral medication, long-term renal side effects are to be expected. Similar to experiences with diabetes mellitus and diabetic nephropathy, the principles of therapy should be particularly emphasized adjustment of blood pressure values to 130 80 mm Hg and no smoking. However, they have not yet been scientifically investigated in relation to HIV infection. The consequent adjustment of diabetes mellitus or change of therapy to avoid a metabolic syndrome are in principle advantageous and will probably have a long-lasting positive side effect on renal function.

Testosterone Decline

The decline in testosterone with age puts a greater number of elderly men at risk for developing hypo-gonadism. Rhoden and Morgentaler estimated that between two and four million men in the United States alone suffer from hypogonadism (defined as serum total testosterone levels lower than 325 ng per deciliter) (Rhoden et al., 2004). More alarmingly though, the same study reported that only 5 of these men are getting treatment for their symptoms, which include decreased libido and erectile dysfunction, loss of muscle mass and strength, weight gain, and declining cognitive function. Hypogonadism is also associated with type II diabetes, musculoskeletal frailty, cardiovascular disease, and the metabolic syndrome.


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...


Common components to all definitions of the metabolic syndrome are elevated triglycerides and low HDL-C (Table 46.1). These measures are standardized (Myers et al, 1989), can be determined by most reference laboratories, and are directly comparable among most studies. The high triglyceride low HDL-C phenotype is often associated with elevated levels of LDL-cholesterol, presence of atherogenic small dense LDL, and elevated postprandial hyperlipidemia. Each of these factors has been shown to independently elevate CVD risk (Grundy, 1998b).

Blood Pressure

Although none of the metabolic syndrome definitions provide explicit guidelines for accurate blood pressure measurement, it is clear that standardized methodology should be used. The AHA scientific statement for blood pressure measurement (Pickering et al, 2005) recommends the auscultatory technique utilizing a trained observer and mercury sphygmomanome-ter. While many variables can affect blood pressure readings, observer error accounts for the

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.

Sleep Continuity

Fewer studies have used objective measures of sleep continuity to evaluate relationships among sleep and health. In two separate cross-sectional studies, Hall and colleagues reported that the metabolic syndrome was more prevalent in individuals with decreased sleep efficiency, as measured by in-home PSG and after adjusting for symptoms of depression, sleep disordered breathing, and other relevant covariates (Hall, Okun et al, under review Hall, Matthews et al, under review). As shown in Fig. 49.3, the metabolic syndrome was more prevalent in mid-life women (n 340 age range 46-57 years) with PSG-assessed sleep efficiency values below 80 , compared with participants with sleep efficiency values of 80 or higher (Hall, Okun et al, under review). Similar results were observed in a sample of 219 mid- to late-life men and women (age range 46-78 years) also shown in Fig. 49.3 (Hall, Matthews et al, under review) Other cross-sectional studies have reported significant associations among PSG-or...

Sleep Architecture

Bi-directional relationships among components of sleep architecture and physiological processes important to health and functioning, including metabolic, endocrine, autonomic, and immune mechanisms (e.g., Hall et al, 2004 Opp, 2006 Rasch et al, 2007 Tasali et al, 2008a). In the only study of its kind conducted to date, Tasali and colleagues (2006) demonstrated that selective suppression of slow-wave sleep in healthy, lean adults resulted in marked decreases in insulin sensitivity. Changes in insulin sensitivity were strongly associated with EEG spectral power in the slow-wave delta band and were unaffected by sleep duration. These results are consistent with three observational studies that reported cross-sectional associations among the metabolic syndrome and decreased sleep depth, as measured by decreased visually scored slow-wave sleep or increased EEG spectral power in the fast-frequency beta band after adjusting for age, sleep apnea, and other relevant covariates (Hall, Okun et...

Sleep Quality

The majority of studies that have evaluated subjective sleep quality and indicators of health have been cross-sectional. For example, patients with hypertension, diabetes, kidney disease, polycys-tic ovary syndrome, and cancer report greater subjective sleep quality complaints than do age- and sex-matched healthy controls (e.g., Alebiosu et al, 2009 Haseli-Mashhadi et al, 2009 Knutson et al, 2006 Liu et al, 2009 Sabbatini et al, 2008 Tasali et al, 2006). In a community-based study of mid-life adults without clinical cardiovascular disease, Jennings and colleagues reported that higher PSQI-assessed sleep quality complaints were associated with increased prevalence of the metabolic syndrome (Jennings et al, 2007). Although these data preclude attributions of causality, sleep quality is likely related to health in complex and sometimes indirect ways. For example, evidence that sleep quality improves with treatment of the primary medical disease (e.g., allergic rhinitis, hypertension,...

Energy balance

Both overall and abdominal obesity have deleterious effects on insulin sensitivity and insulin secretion and are risk predictors of impaired glucose tolerance and clinical type 2 diabetes (reviewed in Feskens 1992 Virtanen & Aro 1994 Costacou & Mayer-Davis 2003). Already a small, sustained decrease in weight improves insulin sensitivity and decreases the risk of type 2 diabetes (Tuomilehto et al. 2001 Diabetes Prevention Program Research Group 2002). The putative effects of dietary factors other than energy overload (such as fibre, glycaemic load, proportion of fat, type of dietary fatty acids) in the aetiology of overall and abdominal obesity remain to be settled.


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...

Measurement Model

SEM measurement models are also more common in psychology than in behavioral medicine. Shen and colleagues (2006) used a second-order model to examine the structure of the metabolic syndrome. My colleagues and I (Llabre et al, 2006) also used a second-order model to separate estimates of reliability and validity in measures of medication adherence.


Obesity is a risk factor for cardiovascular diseases, diabetes mel-litus, gallbladder disease, and some malignancies (particularly endometrial and breast cancer). The distribution of fat in the body is also important there is a greater risk of cardiovascular disease when the distribution of fat produces a high waist-to-hip ratio, or an apple shape, as compared to a pear shape. This is because the amount of intra-abdominal fat in the mesenteries and greater omentum is a better predictor of a health hazard than is the amount of subcutaneous fat. In terms of the risk of diabetes mellitus, the larger adipocytes of the apple shape are less sensitive to insulin than the smaller adipocytes of the pear shape. Obesity in childhood is due to an increase in both the size and number of adipocytes. Weight gain in adulthood is due mainly to an increase in adipocyte size in intra-abdominal fat, although the number of adipocytes elsewhere in the body can increase through activation of the PPARy...

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...

Sleep Duration

Strong cross-sectional associations also have been observed for extremes of sleep duration and multiple indices of health and functioning, including increased blood pressure, elevated levels of inflammatory markers, and the metabolic syndrome (e.g., Hall et al, under review Hall et al, 2008b Knutson et al, 2009 Steptoe et al, 2006). With respect to temporal precedence, self-reported short and or long sleep duration have been prospectively associated with weight gain, diabetes, hypertension, coronary artery disease, myocardial infarction, and stroke in several population-based studies (Ayas et al, 2003a, 2003b Chen et al, 2008 Gangwisch et al, 2007 Hasler et al, 2004 Patel et al, 2006). For example, short sleep duration (

Lose The Belly Fat

Lose The Belly Fat

50 Ways To Lose That Belly Fat Without Yo-yo Dieting So You Can Be On Your Way To A Flat Belly Starting Today!

Get My Free Ebook