Lose Belly Fat Diet

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...

Flat Belly Fix Summary


4.8 stars out of 77 votes

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

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My Flat Belly Fix Review

Highly Recommended

I started using this ebook straight away after buying it. This is a guide like no other; it is friendly, direct and full of proven practical tips to develop your skills.

This ebook does what it says, and you can read all the claims at his official website. I highly recommend getting this book.

Flat Belly Detox System

Fat Belly Detox is a program created to enable the use of natural methods in the reduction of the belly fat with just a little trick in the morning. This weight- loss programs encourages the users to engage in this trick as early as possible before they move out for their day to day activities. It is planned towards the dropping of stubborn body fats and the prevention of any heart attack, stroke and deadly disease. From discovery, its main is help in the removal of hidden hormonal glitch. The plan was not created to be a quick fix, which do not rely on rely food. In fact, like every belly fat programs, it requires the user's full attention. The methods employed in this book are natural ones that have been tested scientifically. The system comes in two formats with emphasis on the E-books. The videos are only meant to aid the reduction of belly fat but are not the primary means of reducing the belly fats. The E-book has different plans to help in the reduction of Belly Fats. The user will discover the exact herbs and spices they should add to their detox throughout the day. These will help them to flush out the harmful and dangerous toxins that lurk inside their belly and intestines, which has made belly fat loss virtually impossible. Read more...

Flat Belly Detox Summary

Contents: Ebook
Author: Josh Houghton
Official Website: flatbellydetox.com
Price: $46.00

Definition of Metabolic Syndrome

MetS is a commonly occurring cluster of clinical phenotypes that are individually and collectively strongly related to cardiovascular disease.2 MetS is characterized by disturbed carbohydrate and insulin metabolism, and is clinically defined by threshold values applied to indices of central obesity, dysglycemia, dyslipidemia, and or elevated blood pressure, which must be present concurrently in any one of a variety of combinations.2'3 The cardinal feature of MetS is abdominal obesity, as quantified most directly by increased waist circumference.4,5 Biochemically, MetS is characterized by insulin resistance - hyperinsulinemia - and by dyslipidemia - most typically raised triglycerides and or reduced HDL cholesterol. Additionally, a range of biochemical abnormalities have been secondarily associated, including increased serum concentrations of apolipoprotein B, fibrinogen, free fatty acids, C-reactive protein (CRP), tumor necrosis factor (TNF)-a, interleukin-6, and plasminogen activator...

Genes and the Metabolic Syndrome Monogenic Disorders

In addition to identifying genes for 'garden-variety' MetS, careful characterization of patients with rare monogenic disorders that recapitulate features of MetS have led to important insights that can be translated to the more common complex form. For instance, familial partial lipodystrophy (FPLD) syndromes are autosomal dominant disorders that occur with a frequency of perhaps 1 100 000 individuals in the general population.37-39 There are three distinct forms FPLD1, FPLD2, and FPLD3, of which the latter two have been found to be due to mutations, respectively, in the LMNA gene, encoding nuclear lamin A C and the PPAR-g gene, encoding peroxisome proliferator-g activated receptor (PPAR-g). Both FPLD2 and FPLD3 feature a loss of fat tissue in peripheral depots such as the extremities and gluteal region, with preservation of central and visceral fat stores. The infinite ratio of visceral to peripheral subcutaneous fat creates an extreme form of common visceral obesity, which leads to...

Whole body fat distribution subcutaneous and visceral fat

Even though the total fat mass determines the plasma pool of FFA and thereby the FFA flux from adipose to non-adipose tissue (Lewis et al. 2002), there are differences in the relationship of subcutaneous and visceral fat depots to features of peripheral and hepatic insulin sensitivity (Misra et al. 1997). Visceral fat cells are more sensitive than subcutaneous fat cells to the lipolytic effect of catecholemines and less sensitive to the antilipolytic and fatty acid re-esterification effects of insulin (Kahn & Flier 2000). Furthermore, the venous effluent of visceral fat depots leads directly into the portal vein, resulting in greater FFA flux to the liver. This makes the visceral fat depots more efficient than subcutaneous fat in influencing the carbohydrate metabolism in the human body (Kissebah 1996). Whole-body MRI and CT are the methods of choice for the quantitation of visceral fat accumulation and whole-body fat distribution. Their noninvasive nature and easy-to-follow clinical...

Etiology of Metabolic Syndrome The Search for the Single Causal Mechanism

The recognition of the cluster of disorders characterizing MetS has sparked an ongoing examination of the potential for a single causal mechanism underlying the syndrome. This search for etiological mechanisms has largely focused on either the central role of insulin resistance and or the hormonal biochemical consequences of visceral obesity. The other major focus in the search for the single causal mechanism underlying MetS has been the cause consequences of visceral obesity. These relate to both hormonal and metabolic consequences of obesity. The impact of several adipocytokines has been examined for their roles as etiological factors in MetS. These include leptin, adiponectin, and resistin as well as inflammatory hormones (TNF-a) and additionally nonesterified free fatty acids.36 The pattern of endothelial dysfunction and sympathoadrenal activation has been linked to these mediators as well as the inflammatory phenotype characteristic of patients with MetS.

Obesity Overweight and Metabolic Syndrome

Include alterations in diet and nutrition and physical inactivity, both of which are also risk factors for CVD. Obesity not only increases the risk for the development of CVD but also for the development of type 2 diabetes. Thus, the risk factors for CVD can actually synergize with each other and produce greater changes in morbidity and mortality. The concept of synergy in combined risk factors is further reinforced when the metabolic syndrome is considered This disorder actually combines obesity, diabetes, and high blood pressure in such a way that an individual exhibiting two of the three of these disorders would be considered as part of the metabolic syndrome population. Additional discussion of the metabolic syndrome and the management of this complex disorder is available in this volume (see 6.17 Obesity Metabolic Syndrome Overview). While the obesity epidemic occurs worldwide, it is heavily concentrated in North America9 and especially in the USA where it is estimated that over...

Scope of the Metabolic Syndrome Epidemic Prevalence and Risk

Estimates of MetS prevalence vary according to age, country, and ethnic group. Interpopulation comparisons have been complicated by the fact that it is probably inappropriate to use single threshold values for the defining quantitative traits. Abdominal obesity appears to be the most frequently found MetS component observed in a number of population-based studies, irrespective of ethnicity.8-10 There has been recent consideration of the appropriateness of uniform cutoff points for abdominal obesity, drawing attention to the need for ethnic-specific guidelines.11 Some investigators have already employed modified MetS criteria in order to identify better Asian individuals with MetS,12 yet clearly more investigation is required in this respect. Interestingly, other components, such as blood pressure, show distinctive variability between ethnic groups, being dominant features in African-American populations10 and Korean males.10 adults16 and in children with severe obesity.18 More...

HsCRP Metabolic Syndrome and Type 2 Diabetes Mellitus

Another reason for clinical interest in adding hsCRP to current risk algorithms derives from the fact that inflammation may play a key role in processes associated with metabolic syndrome, a condition that confers increased cardiovascular risk (72). hsCRP levels are correlated positively with components of metabolic syndrome commonly measured in Fig. 8. Cardiovascular event-free survival according to baseline level of hsCRP among individuals with metabolic syndrome. (Adapted from ref. 75.) Fig. 8. Cardiovascular event-free survival according to baseline level of hsCRP among individuals with metabolic syndrome. (Adapted from ref. 75.) Data from the Women's Health Study also show that hsCRP levels 3 mg L successfully differentiated women with metabolic syndrome into low-, moderate-, and high-risk groups (Fig. 8) (75). In analyses comparing the predictive ability of hsCRP alone ( 3 vs

Metabolic syndrome

Effects for drugs that are used chronically. However, metabolic syndrome, including abdominal obesity, dyslipidemia, hypertension, and insulin resistance, have an increased prevalence in schizophrenics63 which may be genetically related. Weight gain in schizophrenics has been associated with the histamine H1 receptor affinity of antipyschotic medications86 with clozapine and olanazepine being the most potent of the current medications (Ki 1nM) and haloperidol (Ki 1800 nM, the least). The CATIE study55 noted that olanzapine, of the four atypical antipsychotics studied, was associated with the greatest incidence of weight gain (0.9 kg month_ 1) with greater increases in glycosylated hemoglobin, total cholesterol, and triglycerides, effects consistent with the development of metabolic syndrome.

Fat Mass and Distribution Changes Total Adipose Tissue

Little is known about age-related changes in body fatness in elderly adults. Most studies have documented increases up to 50-60 years of age, after which body fatness appears to stabilise 13-16 . In a cross-sectional survey, Baumgartner et al. 6 suggest that body fatness (in terms of both absolute FM and percent body fat) may be relatively stable in elderly men, but may decrease with age in elderly women. In their study, the distribution of body fat, as assessed by DEXA, did not appear to change with age beyond 65 years, leading to the conclusion that the accumulation of abdominal and visceral fat with age (in both men and women) occurs primarily in middle age, while FM remains constant or increases slightly in subsequent decades. In a longitudinal observation of body composition in older adults, as determined using hydrodensitometry, Hughes et al. 17 found an overall increase in adipose tissue in an older cohort, but this increase was attenuated with advancing age in women, whereas...

Pathophysiology of Lipodystrophy Mechanisms of Lipodystrophy The Effects of Protease Inhibitors

Different hypotheses have been put forward to explain the putative mechanism of HAART drugs in the development of lipodystrophy syndrome 116-120,122-124,126,134,141,147-152 . The first postulates that PIs primarily block cytochrome P450, which is involved in fat metabolism. The second postulates an interaction between PIs and human proteins. HIV protease has a sequence homology of 12 amino acids with two human proteins playing an important role in fat metabolism, namely, LDL-receptor-related protein (LRP) and cytoplasmic retinoic-acid-binding protein type-1 (CRABP-1). PIs inhibit both HIV protease and these two proteins. Inhibition of LRP leads to a reduction in the absorption of fatty acids by capillary endothelium and liver cells. This causes elevated serum triglycerides, visceral fat accumulation, buffalo humps, bull neck, insulin resistance, type II diabetes, breast hypertrophy, etc. Inhibition of CRABP-1 and cytochrome P450 3A isoform results in decreased cell differentiation and...

Other Potential Therapeutic Targets

Protein tyrosine phosphatase-1B (PTP1B) dephosphorylates the insulin receptor, thus blunting its ability to initiate the signal transduction cascade upon insulin binding.92 Genetically modified mice that lack PTP1B protein expression and animals treated with a specific PTP1B antisense oligonucleotide inhibit PTP1B and thereby restore activity to the insulin receptor, resulting in increased insulin sensitivity, improved glycemic control, and resistance to diet-induced obesity. PTP1B inhibition also reduces adipose tissue storage of triglyceride under conditions of overnutrition, and was not associated with any obvious toxicity. The effects of the loss of PTP1B in vivo were also remarkably specific for components of the insulin action cascade, in spite of cell studies suggesting that PTP1B may exert a regulatory influence on a variety of other signaling pathways. Overall, these studies have paved the way for the commercial development of PTP1B inhibitors, which may serve as a novel type...

Computed Tomography CT

Signal intensity in the CT images corresponds to the linear attenuation coefficient, which depends on physical properties (including density) of tissue within the volume of interest. Signal intensity is expressed in so-called computed tomography numbers or Hounsfield units (HU), which range from -1,000 to +3,095 (4,096 values). Based on their density and the resulting differences in X-ray attenuation, muscle and fat tissue display different ranges of intensity (-190 to -30 HU for fat and 0 to 100 HU for muscle), resulting in muscle fat contrast on the CT image (Figure 13.3). Recorded fat accumulation (for subcutaneous and visceral fat depots) is thus based on volumetric measurements (Dixon 1983 Tokunaga et al. 1983 Busetto et al. 1992). For ectopic (intrahepatic, intramyocellular) lipid accumulation, measurements are based on comparison of X-ray attenuation in liver tissue and spleen (Figure 13.4) or in muscle and fat tissue (bone marrow or external phantom (Goodpaster et al. 2000a))....

Magnetic Resonance Imaging MRI and spectroscopy

Figure 13.3 Assessment of Abdominal Fat Storage by Computed Tomography (CT) Representative cross-sectional abdominal CT scans of a lean (A) and an obese (B) research volunteer, demonstrating the fat muscle CT contrast shown with demarcations of visceral (large arrowheads), deep subcutaneous (open arrows) and superficial subcutaneous (closed arrows) adipose tissue (AT) depots. The fascia (small arrowhead) within subcutaneous abdominal AT was used to distinguish superficial from deep depot. In the two CT scans shown, the area of superficial subcutaneous AT was similar (144 vs 141 cm2), whereas areas of deep subcutaneous (126 vs 273 cm2) and visceral (84 vs 153 cm2) AT were quite different. Insulin-stimulated glucose metabolism was 6.1 and 4.0 mg min-1 kg FFM-1 in lean and obese volunteers, respectively (FFM fat-free mass). Reproduced from Kelley D E et al. (2000) Am J Physiol Endocrinol Metab 278 (5) E941-E948. Courtesy of the American Physiological Society. Figure 13.3 Assessment of...

Functional Anatomy of White Adipose Tissue

Over time, other molecules were reported to be WAT secretion products (adipokines), and the relationship between their excessive secretion and the severe complications of obesity became increasingly apparent. Especially interesting was the correlation between secretion of tumour necrosis factor (TNF)-a, resistin and adiponectin and diabetes between angiotensinogen and min-eralocorticoid-releasing factors and arterial hypertension 21 and between plasminogen activator inhibitor (PAI 1) and coagulation problems 22 . These data contributed to clarify the molecular mechanism underpinning the early clinical observation that androgenic obesity (i.e. central adiposity with a greater accumulation of visceral fat) carries more dangerous complications than gynoid obesity (peripheral adiposity with a greater accumulation of subcutaneous fat), because of the inhomogeneous secretion of adipokines across depots. An especially close relationship was described for adiponectin and diabetes.

Changing Patterns of Cachexia in the HAART

With the introduction of potent antiretroviral combination treatments, including nucleoside and non-nucleoside reverse transcriptase inhibitors (NRTI, NNRTI) and protease inhibitors (PIs), which have prolonged patient survival, the incidence of the previously described changes has been dramatically reduced. Since 1996, when HAART was introduced, the number of patients who died of AIDS and opportunistic infections has decreased by two-thirds, although wasting remains a clinical problem for patients 114,115 . In addition, new disorders involving lipids, glucose metabolism, and body fat have acquired greater clinical importance 116-120 . The changes are characterised by hyperlipidaemia, generalised, central, or peripheral fat redistribution, and hormonal disturbances 116,120-124 , and have been named lipodystrophy syndrome, HIV-associated adipose redistribution syndrome (HARS) 125 , or metabolic syndrome-X (Tables 5,6,7).

Reduction in Testosterone Growth Hormoneand IGF1

It is clear that a reduction in the testosterone concentration in healthy young individuals will result in a loss of fat-free mass and muscle strength 15 . It is also well-known that there is a reduction in testosterone of at least 1 per year after the age of 50 in normal healthy men 4 . Furthermore, it has been reported that reduced testosterone concentrations are related to reduced fat-free mass, appendicular skeletal muscle mass, and muscle strength in elderly individuals 16-19 . Additionally, growth hormone decreases with age. This results in a reduction in fat-free mass and an increase in visceral fat mass in the abdominal region 20-22 . An additional manifestation of the reduction in growth hormone is a reduction in circulating insulin-like growth factor (IGF)-1. Statistically significant inverse correlations have been observed between increasing age and IGF-1 concentrations 23 . It is believed that the effects of growth hormone on fat-free mass and fat mass are mediated through...

Clinical Trial Issues

While BMI is the most commonly used measure to assess the degree of overweight, there are concerns about how well it defines adiposity among different body types, between the genders, and among different racial and age groups. Since BMI does not really measure body composition, obesity trials may include other measures. For example, accumulation of central or visceral fat might be a better index of the overall association of obesity with morbidity, and therefore, a measure of waist-to-hip ratio may be appropriate in addition to calculating BMI. Noninvasive methods of measuring body composition in humans are available, e.g., DEXA and hydrostatic weighing. However, these can add substantially to trial costs and may not be readily available at most clinical trial sites.

Dual Energy Xray Absorptiometry DXA

Several studies have shown some correlation between DXA and CT measurements of body compositions and abdominal obesity (Kelley et al. 2000 Park et al. 2002 Snijder et al. 2002). But methodological limitations linked to the effect of hydration on X-ray attenuation (Pietrobelli et al. 1996, 1998 Lohman et al. 2000) and distortions of planar projections when scanning the thicker tissue of obese or overweight patients (Roubenoff et al. 1993 Brownbill & Ilich 2005) (Figure 13.2) make DXA model dependent and less accurate than CT or MRI.

Initial Evaluation

On examination, RC appears healthy, with a BP of 128 80 mmHg and a heart rate of 102 beats min. He stands 5 ft, 10 in. weighs 190 lb and has a waist circumference is 38 in. The remainder ofhis examination is unremarkable. Fasting lab work reveals normal electrolytes and a glucose of106 mg dL. His total cholesterol is 147 mg dL, LDL-C is 92 mg dL, HDL-C is 26 mg dL, and TGs are 145 mg dL.

Heterogeneity Of Atherogenic Lipoproteins

It is well established that the cholesterol content of LDL (LDL-cholesterol LDL-C ) is a risk factor for atherosclerotic cardiovascular disease (ASCVD), and therapy that lowers LDL-C limits ASCVD events. This paradigm has spawned clinical guidelines that set convenient targets for LDL lowering (1-8). Yet many patients continue to have events despite reaching LDL-C targets, and many who have low LDL-C at baseline present with ASCVD events. Several studies suggest that even patients with optimal LDL-C levels benefit from lipid-lowering therapy. These observations have led to a search for other biomarkers that might predict risk of ASCVD events and, in particular, markers that refine the ability to forecast risk from atherogenic lipoproteins. Responding to these concerns, the Adult Treatment Panel III (ATP-III) proposed two important clinical tools to identify patients whose risk may be underestimated by traditional markers (1). First, it adopted a treatment goal based on non-HDL-C in...

And Paul M Ridker MD MPH

High-sensitivity C-reactive protein (hsCRP) is a marker of inflammation that predicts incident myocardial infarction, stroke, peripheral arterial disease, and sudden cardiac death among healthy persons without a history of cardiovascular disease, as well as recurrent events and death in patients with acute or stable coronary syndromes. hsCRP adds prognostic value at all levels of low-density lipoprotein cholesterol, Framingham coronary risk score, severity of the metabolic syndrome, and blood pressure, and in those with and without subclinical atherosclerosis. Among apparently healthy men and women, hsCRP levels of less than 1, 1 to 3, and greater than 3 mg L distinguish those at low, moderate, and high risk for future cardiovascular disease, respectively. In clinical settings, hsCRP should be used in conjunction with lipid evaluation as part of global risk assessment. Improved knowledge of cardiovascular risk should lead to better compliance with lifestyle and pharmacological...

Mechanisms of Renal Dysfunction

Inflammation is an important contributor to the renal injury and endothelial dysfunction observed in hypertension and obesity. Elevated circulating levels of IL6 and TNF-a are observed in obesity and metabolic syndrome patients. IL6 stimulates the central and the sympathetic nervous system, which may result in hypertension.30 IL6 induces increases in hepatic triglyceride secretion in rats. IL6 also stimulates the production of C-reactive protein in liver and plasma levels of this protein are a good predictor of vascular inflammation. Another cytokine linked to obesity is TNF-a. TNF-a is overexpressed in the adipose tissue of obese patients, as compared with tissues from lean individuals. A positive correlation has been found between serum TNF-a concentration and both systolic blood pressure and insulin resistance in subjects with a wide range of adiposity. TNF- a acutely raises serum triglyceride levels in vivo by stimulating very low-density lipoprotein (VLDL) production and hence it...

Plasminogen Activator Inhibitor1Tissue Type Plasminogen Activator

Prospective studies evaluating the predictive risk associated with increased plasma PAI-1 levels have been performed. In patients with acute ST-elevation MI, PAI-1 levels correlate with mortality (76). In young patients who survive MI, high PAI-1 levels have been reported in association with hypertriglyceridemia (77). Finally, in patients without a previous MI, increased PAI-1 levels in men were found to correlate with future MI (78). Future studies must consider carefully the independent prognostic value of PAI-1 levels above current clinical risk factors. A special emphasis should continue on patient populations with insulin resistance and metabolic syndrome.

Laboratory Methodology

There is relatively scant information on the effects of race on CRP concentration. Chambers et al. (25) found the geometric mean for CRP to be 17 higher in Indian Asians compared with European whites however, the difference dropped after adjustment for central obesity and insulin resistance. Data from the National Health and Nutrition Evaluation Survey (NHANES III) revealed higher CRP values for non-Hispanic blacks (particularly women) than for non-Hispanic whites or Mexican Americans (26).

Antihyperglycemic Agents

Given the interrelationship among inflammation, metabolic syndrome, and diabetes, it is not surprising that antihyperglycemic agents such as metformin and thiazolidinedione have been shown to lower hsCRP levels. In a 26-wk trial among patients with type 2 diabetes, rosiglitazone therapy reduced hsCRP levels and other inflammatory markers (118). Changes in hsCRP level were uncorrelated with changes in glycemic control, as measured by hemoglobin A1c (r 0.06) and fasting glucose level (r 0.06) and were only minimally correlated with changes in insulin resistance (r 0.13). Whether the ability of such agents to lower hsCRP has clinical relevance beyond improvements in glycemic control is a focus of current research.

Blood pressure level the main haemodynamic basis

In type 2 diabetes, blood pressure is usually increased with microalbuminuria, but again there is a huge overlap, and many patients with type 2 diabetes have elevated blood pressure even with normoalbuminuria and at the clinical diagnosis of diabetes 83 . This may be related to the metabolic syndrome or to simple obesity.

Molecular Mechanisms of Transdifferentiation

Transgenic mice lacking the RIIp subunit (one of the subunits regulating AMPc-dependent pro-teinphosphokinase A, abundant in adipose tissues) overexpress RIa subunit, which involves increased sensitivity of proteinphosphokinase A to AMPc in WAT, and consequent UCP1 gene activation 71 . This entails a brown phenotype of abdominal fat and resistance to obesity. Foxo2 is a gene for a transcription factor expressed exclusively in adipose tissue. Its overexpression in the adipose tissue of transgenic mice gives rise to an obesity-resistant and more insulinsensitive lean phenotype. These mice show a transformation of white into brown adipocytes 72 . Interestingly, individuals with greater insulin resistance exhibit a reduction of FOXO2 (human foxo2) in subcutaneous abdominal fat accompanied by down-regulation of other genes of the brown adipocytic phenotype.

Congenital Generalised Lipodystrophy Berardinelli Seip Syndrome or Lipoatrophic Diabetes

Congenital generalised lipodystrophy (CGLD) is an autosomal recessive, transmitted disease characterised by a pronounced loss of subcutaneous and visceral fat tissue manifested since birth. The condition is associated with acromegalic traits (Fig. 2), accelerated growth with normal hGH

Congenital Partial Lipodystrophy Type 1 Dunningam Syndrome

Atrophy of the subcutaneous fat layer usually manifests at puberty, involving the arms, legs, and buttocks. The subcutaneous adipose tissue of the face, neck, and intra-abdominal area may be preserved, giving patients a silhouette of visceral obesity. An increase in intramuscular fat has been reported. Insulin resistance, reduced glucose tolerance, overt diabetes, hypertriglyceridaemia, and low levels of HDL cholesterol are associated with Dunningam syndrome and lead to early onset of atherosclerotic vascular diseases. Acute pancreatitis and liver steatosis may complicate the clinical picture. The identification of missense mutations on chromosome 1q 21-22, involving genes encoding lamins A and C, in affected members of a family suggests the molecular basis of the disease 33 . Lamins provide structural integrity to the nuclear membrane, such that mutations in the

Cytokines and Insulin Resistance

In addition to their well-known anorectic and hypermetabolic effects, cytokines appear to be involved in obesity-related disorders such as insulin resistance and vascular diseases 65 . Epidemiological findings support the hypothesis that the metabolic syndrome, type II diabetes and cardiovascular diseases have an inflammatory component mediated by cytokines 66, 67 . Thus, overweight and obese children as well as adults

Clinical Applications of apoB see also Incorporating Lipoprotein Number Into Treatment of Lipoprotein Disorders

ApoB has gained support as a risk marker from several recent analyses that have directly compared apoB to LDL-C (34,35). Grundy outlined the advantages and disadvantages of non-HDL-C and apoB and concluded that apoB is a reasonable alternative to non-HDL-C and proposed practical cutoffs (Table 2) (28). Updated prevention guidelines from the Canadian Cardiovascular Society (CCS) (4) and Canadian Diabetes Association (41) have also introduced apoB as an alternative to LDL-C. The CCS notes that apoB is especially useful for patients with metabolic syndrome and for following patients on lipid-lowering therapy (Table 2).

Preface to the Series

The editors have chosen topics from both important therapeutic areas and from work that advances the discipline of medicinal chemistry. For example, cancer, metabolic syndrome and Alzheimer's disease are fields in which academia and industry are heavily invested to discover new drugs because of their considerable unmet medical need. The editors have therefore prioritized covering new developments in medicinal chemistry in these fields. In addition, important advances in the discipline, such as fragment-based drug design and other aspects of new lead-seeking approaches, are also planned for early volumes in this series. Each volume thus offers a unique opportunity to capture the most up-to-date perspective in an area of medicinal chemistry.

Ultrasonography US

Differences in the ultrasonic reflection and transmission coefficient between water and fat tissue enables us to visualise fat layer accumulation in the subcutaneous regions. Even though the imaging ability of the method can be limited by human anatomy and the depth of observed regions, US measurement has made its way to broad clinical applicability. Measurement schemes for the assessment of visceral fat volumes have been introduced (Armellini et al. 1990 Abe et al. 1995) and validated against measurements by computed tomography (Ribeiro-Filho et al. 2003 Hirooka et al. 2005). Using US, the distances between anatomical landmarks in the subcutaneous area and abdominal cavity (Hirooka et al. 2005) or the lower back region (Ribeiro-Filho et al. 2003) are measured, and the volume of intra-abdominal fat is calculated by empirical model equations (Figure 13.1).

Fat Tissue

Only 2 of mature adipocytes undergo mitosis, under appropriate stimulation. Therefore, adipocyte hypertrophy, rather than an increase in their number, seems responsible for the diffuse or localised increases in fatty masses 99 . There is, however, a pool of quiescent or immature adipocytes that can differentiate into mature adipocytes under hormonal and vitamin stimulation 98, 100 . During differentiation, markers such as LPL mRNA, glycerol triphosphate dehydrogenase (GPDH), hormone-susceptible lipase (HSL), perilipin, a glucose carrier (GLUT4), and p-3 receptors are acquired. Triglycerides comprise 90 of the mature adipocyte and provide a source of easily available energy through their hydrolysis to fatty acids and glycerol. Mature adipocyte expresses a-2 -adrenergic receptors (a2AR) and adipsin 98 . Adipose tissue secretes LPL, adipsin, complement C3 and B fractions, P450 aromatase, leptin, and growth factors 94, 101 . Its main metabolic functions are...

Renal Dysfunction

In addition to a role in producing the products stored in, and voided from, the bladder, the renal system is a key system in the regulation of blood pressure via its role in regulating blood volume. Diseases of the kidney encompass renal dysfunction and end-stage renal disease (ESRD), the result of the metabolic syndrome, diabetes, obesity, and hypertension (see 6.25 Renal Dysfunction in Hypertension and Obesity). Treatments to deal with these issues initiate with lifestyle changes, diet, and exercise, are progressively followed with drug regimens to treat the diabetes, obesity, and hypertension, kidney dialysis to restore normal function, and kidney transplant.


The prevalence of CAN increases with age, duration of diabetes and poor glycaemic control, and in the presence of distal symmetric polyneuropathy, microangiopathy and macroangiopathy (Ziegler 1999). Recent data suggest a correlation between the components of the metabolic syndrome and reduced HRV. In the MONICA KORA cohort we showed at the population level that age, diabetes, obesity and smoking should be regarded as primary risk factors of reduced HRV (Ziegler et al. 2004).

Cyp2c Cyp2j

Stimulation of the RAS increases sodium and water reabsorption through direct actions on renal tubular transport function 44.44 This effect is mainly due to the stimulation of AT-1 receptor by AT-II. Activation of angiotensin receptors by AT-II also stimulates synthesis of aldosterone in the zona glomerulosa of the adrenal gland. Aldosterone binds mineralocorticoid receptors expressed in the kidney and other organs leading to more salt and water retention. Aldosterone is involved in the development of obesity-induced hypertension. Plasma aldosterone levels are elevated in hypertensive patients with visceral obesity,45 and blocking mineralocorticoid receptors with the specific antagonist, eplerenone, inhibits development of high blood pressure in dogs fed a high-fat diet.46

Diagnostic Workup

The diagnosis of amyloidosis depends on the pathologic demonstration of typical congophilic deposits. The most common strategy is to take the biopsy from the most easily available tissue. Small amyloid deposits often occur in subcutaneous tissue of most people with AL or AA amyloidosis. For this reason, an abdominal fat aspirate is often used as an initial screen. However, a negative result does not exclude a diagnosis of AL, and other sites, such as rectal mucosa, marrow, and particularly the involved organ may need to be sampled.


In 1998, Giora Feuerstein joined DuPont Pharmaceuticals as the head of the Cardiovascular Disease Department leading thrombosis, cardiovascular, and metabolic syndrome programs. Razaxaban, a lead FXa inhibitor was advanced to phase II development prior to acquisition of the DPC by BMS. In 2003 Giora Feuerstein joined Merck Co, Inc, West Point as the Executive Director, cardiovascular diseases where he established a new department leading efforts in hypertension (renin inhibitors), metabolic syndrome and cardiac arrhythmias. In addition, Giora Feuerstein was appointed as member of strategic forums in cardiovascular drug development and chaired licensing and business development committees.


At baseline, RC had optimal cholesterol levels, few major risk factors, and a reassuring Framingham score. Yet he had an ominous family history, impaired fasting glucose, and a low HDL-C. The low HDL-C was the only lipid abnormality that suggested he had atherogenic dyslipidemia, but prediabetes is also an important clue. Although the standard labs hinted at subtle abnormalities, the apoB and NMR findings revealed substantial lipoprotein abnormalities that were not reflected in his LDL-C levels. In fact, the optimal LDL-C might be falsely reassuring. The ATP-III approach helps to overcome this problem by adding criteria for managing hypertriglyceridemia (and, in turn, non-HDL-C) and metabolic syndrome. Many patients with atherogenic dyslipidemia, however, do not meet criteria

Creactive protein

Many clinical conditions are associated with an inflammatory state and or profiles. Obesity 74 , especially that of the abdominal type 75 , is commonly associated with elevated CRP concentrations. The expanded abdominal fat deposits of overweight obese patients represent a source of inflammatory cytokines (interleukin IL -6 and tumour necrosis factor TNF -a) 76 . The production of CRP by the hepatocytes is stimulated by IL-6 77 , and adipose tissue is a key source of circulating IL-6 in patients with abdominal obesity 78, 79 . Intervention studies have shown that weight loss is associated with a reduction in circulating CRP concentrations, and this reduction is proportional to the extent of weight loss 80,81 . It has been shown repeatedly that endurance training can reduce CRP concentrations 85, 86 . Part of this effect seems to be mediated by the exercise-associated weight loss. The specific impact of selective loss of visceral adipose tissue 87 associated with endurance exercise...

Ldl Particle Number

No doubt, the ATP-III strategy emphasizing metabolic syndrome and following non-HDL-C will detect many individuals who warrant aggressive preventive efforts. However, the objective to better identify at-risk patients has prompted new discussion on how to measure lipoproteins (28,34,42,43). The ideal measure of dyslipidemia might be to estimate the number of lipoprotein particles, because LDL-C does not distinguish small, dense LDL, and particle number may actually correlate more closely with outcomes than level of LDL-C does (10). Direct measurement of LDL particle number has been elusive because of technical limitations. However, a technique to measure LDL particle number is now clinically available. apoB levels also correspond to the number of atherogenic lipoprotein particles. Hence, the differences between particle number and cholesterol content apply to apoB as well.


The worldwide prevalence of ED has been estimated at over 152 million males with projections for 2025 being in excess of 320 million. In older males, ED may have a physical cause, such as disease, injury, drug side effects, injury to nerves, arteries, smooth muscles, and fibrous tissues, or impaired blood flow in the penis. Other common causes of organic ED include the metabolic syndrome, diabetes, kidney disease, chronic alcoholism, multiple sclerosis, atherosclerosis, vascular disease, and neurologically related causes.9 The incidence of ED increases with age with approximately 5 of 40-year-old males and 15-25 of 65-year-old males experiencing aspects of ED. Surgery, including radical prostatectomy and bladder cancer surgery, can injure nerves and arteries near the penis, causing ED. Antihypertensives, antihistamines, antidepressants, and hypnotics can produce ED as a side effect. Psychological factors including stress, anxiety, guilt, depression, low self-esteem, and fear of sexual...

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How To Lose Your Belly Fat

How To Lose Your Belly Fat

Losing All that Excess Belly Fat and Getting a Well Toned Flat Stomach. Trimming down and toning up your entire body, from head to toe, is definitely something that many people want to do. But chances are, theres one place in particular where all that excess fat just doesnt want to seem to go away, no matter how hard you try.

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