Exercises to Lose Weight From Your Stomach in 2 Weeks

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

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Lean Belly Breakthrough

This product designed by a great doctor in Germany breaks the conventional media knowledge of health improvement and weight loss by introducing a simple 2-minute ritual daily to be on your way for a life full of happiness and fewer worries about health. The program was also co-created by Bruce who is a knownsuccessfulexperienced personal trainer who coached celebrities and was hosted on TV shows to discuss health issues. He combined his knowledge of training into heinrick's methods of health and weight loss to get people to lose up to dozens of deadly weight. The final product includes a set of books and videos created to help you boost your health. It will also help you reverse diabetes, discover of you will have a heart attack and evade, boost sex drive and youthfulness. Moreover, this program includes herbs and minerals to consume daily so you watch your body fat melt away by the day. You do not have to worry about the ordering procedure as this method will offer easy instructions and instant access to the material in no time. Your life ahead will be fullof joy and less of health anxiety. Furthermore, you won't have to buy those expensive supplements and take in sessions with personal trainers that know nothing. Read more here...

Lean Belly Breakthrough Summary

Contents: Ebooks, Videos, Audios
Author: Bruce Krahn
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The Metabolic Syndrome

The metabolic syndrome is a recently defined constellation of known risk factors that has been associated with an increased risk of cardiovascular disease as well as the development of diabetes. While many of the cardiometabolic risk factors have the tendency to cluster in patients, the components of the metabolic Table 7.5 NCEP ATP III criteria for the metabolic syndrome. From reference 33, with permission Increased waist circumference (in men 40 inches ( 102 cm) syndrome occur together with great frequency. Several definitions of the metabolic syndrome exist including ones from the NCEP ATP III, the WHO, and the International Diabetes Federation. In general, most definitions endorse the following basic criteria a measure of abdominal adiposity, hypertriglyceridemia, low HDL cholesterol levels, hypertension, and evidence of impaired glucose metabolism. The NCEP ATP III defines the metabolic syndrome as any three of the following elevated triglycerides (a 150 mg dL), low HDL...

Impaired Glucose Metabolism and Metabolic Syndrome

The metabolic syndrome is characterized by the concurrence of several cardiovascular risk factors central obesity, dyslipidemia, elevated blood pressure, and high fasting glucose levels. Insulin resistance, a common pathogenetic factor underlying these risk factors, may lead to the development of DM-2 and increased risk of CVD. Intra-abdominal adiposity, sedentary lifestyle, and a genetic predisposition are prime etiologic factors 9 . In the Amsterdam Growth and Health LongitudinalStudy the prevalence of the metabolic syndrome among young subjects (mean age 36 years) was 18.3 in men and 3.2 in women. Individuals with the metabolic syndrome showed reduced distensibility and compliance of the carotid and femoral arteries compared to those without risk factors. Stiffness ofthe muscular femoral artery was greater than that of the elastic carotid artery 9 . Other studies of the metabolic syndrome are in agreement with these findings 10-13 . In middle-aged Japanese men the number of...

Long Term Health Consequences of PCOS

Insulin resistance is associated with diabetes, hypertension, dyslipidemia, endothelial dysfunction, a procoagulant state, and cardiovascular disease (see Chapters 28 and 29). Recently, the National Cholesterol Education Program Adult Treatment Panel defined the metabolic syndrome as the presence of three of the five following risk factors waist circumference greater than 88 cm in females fasting serum glucose 110 mg dL or more, fasting serum triglycerides greater than 150 mg dL serum high-density lipoprotein cholesterol less than 50 mg dL and blood pressure greater than 130 85 mmHg (60). The metabolic syndrome has been found to be present in 43-46 of women with PCOS, a twofold higher prevalence compared with women in the general population of the same age (61,62).

Supplemental Reading

Luyckx FH, Scheen AJ, Desaive C, et al. Parallel reversibility of biological markers of the metabolic syndrome and liver steatosis after gastroplasty-induced weight loss in severe obesity. J Clin Endo Metab 1999 84 4293. Marchesini G, Bugianesi E, Forlani G, et al. Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology 2003 37 917-23.

Potential Therapeutic Indications

Several lines of evidence implicate elevated 11p-HSD1 activity in the etiology and or maintenance of type 2 diabetes and metabolic syndrome. There is a higher level of 11p-HSD1 mRNA and activity in adipose tissue of obese humans 11,12,14,39 and rodents 40 . Chronic high-fat feeding decreases 11 b-HSD1 activity and mRNA in fat of C57Bl 6J mice, suggesting that this serves as an adaptive mechanism attempting to protect against the adverse metabolic consequence of high-fat feeding 41 . Interestingly, A J mice chronically fed a high-fat diet become obese but are less hyperinsulinemic than C57Bl 6J mice, and this is associated with lower basal adipose tissue 11 p-HSD 1 activity and mRNA and a more pronounced decrease in activity with high-fat feeding 41 . This suggests that lower local synthesis of active glucocorticoid in A J mice confers protection from dysregulated glucose homeo-stasis due to high-fat feeding. Transgenic overexpression of 11p-HSD1 in adipose tissue of mice produces...

Low Highdensity Lipoprotein Levels

While much of the current focus of therapy for dys-lipidemia centers on management of high LDL cholesterol, low HDL cholesterol levels have also been established as a major cardiovascular risk factor. In fact, the pattern of low HDL cholesterol levels with normal LDL cholesterol levels appears to represent a significant percentage of patients with coronary artery disease when compared with isolated high LDL cho-lesterol32. Low HDL cholesterol levels are also an important part of the criteria for the metabolic syndrome, which includes a constellation of other risk factors that place patients at a markedly increased risk for cardiovascular events. Low HDL cholesterol is defined by the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol Based on these data, patients should be assessed for low HDL cholesterol as both an independent risk factor for cardiovascular disease and an important component...

Endothelial Dysfunction

Studies have investigated which components of the metabolic syndrome are closely linked with endothe-lial dysfunction as assessed by changes in coronary flow in response to an agonist (Figure 6.17)26. Specifically waist circumference, systolic blood pressure, and insulin resistance were significantly negatively correlated with coronary vasodilatation. This suggests the greater the extent of obesity, the higher the blood pressure and the greater the extent of insulin resistance the worse the degree of endothelial dys-function26.

Identification of Associated Morbidities

Once the diagnosis (specific or functional) is established, related morbidities should be identified. For example, PCOS and the HAIR-AN syndrome are associated with important metabolic dysfunction, including the metabolic syndrome. As such, it is recommended that patients diagnosed with these disorders undergo measurement of fasting lipids and insulin and glucose levels following an oral glucose load (75 g).

Mechanism Linking Obesity and PCOS

Hyperandrogenism is postulated to result from either or both increased adrenal and ovarian androgen production. The predominance of abdominal obesity, insulin resistance, glucose intolerance, hypertension, and other conditions suggests that the metabolic syndrome may be more common in PCOS, and indeed this has been reported by a number of investigators (7). It is therefore obvious that for adequate treatment of patients with androgen excess, there needs to be a reduction in hyperinsulinemia and insulin resistance as well as in obesity per se. Both weight reduction and increases in physical activity are highly effective in increasing insulin sensitivity. These interrelated and yet separate issues are the focus of the following discussion.

Glucose Insulin and Potential Mechanisms of Vascular Stiffening

Among patients with diabetes 15 or the metabolic syndrome, arterial stiffening is observed across all age groups. In children with severe obesity, arterial wall stiffness and endothelial dysfunction are accompanied by low plasma apolipoprotein A-I levels, insulin resistance, and android fat distribution, changes that may be the main risk factors for the early events leading to atheroma formation 16 . The positive correlation between insulin resistance and central arterial stiffness and the close relationship between the extent of metabolic changes and the degree of arterial stiffness suggest that insulin resistance is a primary underlying factor. In animal models of insulin-resistant diabetes, chronic hyperglycemia and hyperinsulinemia increase local angio-tensin II production and expression of vascular Ang II type I receptors via stimulation of TGF- 1, upregulate plasminogen activator inhibitor-1, and downregulate matrix metalloprotease activity, all of which play a critical role in...

Lifestyle Modification in the Infertile Patient With PCOS

Obesity is a very common feature of women with PCOS, with an estimated prevalence of 35-63 among women with the disorder (3). Ghrelin homeostasis and measures of hunger and satiety are significantly impaired in subjects with PCOS, although not affected by dietary composition (4). Abdominal obesity, characterized by a waist-to-hip ratio of more than 0.8, has been reported in 63 of women with PCOS whether they are obese or not (5,6). Obesity, particularly abdominal, is often associated with insulin resistance and hyperinsulinemia, which stimulates the biosynthesis of androgens and the decreased hepatic production of sex hormone-binding globulin (SHBG). Other factors such as increased estrogen production rate, increased activity of the opioid system and of the hypothalamic-pituitary-adrenal axis, and, possibly, high dietary lipid intake may be mechanisms by which obesity worsens the degree of hyperandrogenism and ovulatory function in PCOS (7). Obesity is associated with a reduced chance...

Arterial Stiffness and Coronary Artery Calcification

Finally, two larger studies (reported as abstracts) have reported strong associations between coronary calcification and cfPWV. First, in a study of 484 older adults (aged 70-96) from the Cardiovascular Health Study, the association between aortic stiffness (cfPWV) and both coronary and aortic calcification was evaluated. Among the older women (mean age 79 years), higher aortic stiffness was associated with higher quartiles of both coronary and aortic calcification after adjustment for age and mean arterial pressure 22 , The absence of an association among these older men may also be due to a survival bias. Second, in a cross-sectional analysis of 477 overweight postmenopausal women (aged 52-62) with no history of coronary heart disease, the prevalence of any coronary calcium was higher among those with higher levels of arterial stiffness (cfPWV) 23 . A 1-SD increase in cfPWV was associated with a 38 increase in odds of coronary calcification. These associations remained significant...

Anovulation Is A Characteristic Feature Of Pcos. It Manifests As Menstrual Disturbance 80 Amenorrhoea Oligoamenorrhea

Patient With Hyperandrogenism

Weight gain that is primarily centripetal, especially if associated with extremity wasting, purple striae, easy bruisability, moon facies, and rubor, suggests the presence of Cushing's syndrome, and these patients should be appropriately screened using 24-hour urinary-free cortisol levels or a cortisol level following an overnight dexamethasone suppression test. Other information that should be sought includes the patient's awareness of her body fat distribution, as women with PCOS have a greater prevalence of abdominal obesity (29). Weight gain may also be associated with carbohydrate craving and evidence of postprandial reactive hypoglycemia, particularly in mid-afternoons. For example, Holte and colleagues found that although insulin resistance in obese women with PCOS was reduced by weight loss to similar levels as BMI-matched controls, these patients continued to demonstrate an increased early insulin response to glucose, which could stimulate appetite and persistent weight gain...

Metformin Weight Loss and PCOS

One of the best studies relating to metformin use in androgen excess was that by Pasquali et al. (12). They randomized patients with PCOS or obesity alone who were weight index-matched to a lifestyle-modification program including diet plus metformin or placebo. After 6 months the frequency of menstrual cycles was better with metformin, and metformin was superior to placebo alone in the loss of weight, reduction in waist circumference and visceral fat, and reduction in testosterone. There was no differential benefit of metformin on fasting serum glucose, insulin, or SHBG. Patients with androgen excess responded better than matched patients with obesity to metformin with respect to reduction of visceral fat and testosterone, but not in terms of weight loss, weight circumference, fasting serum glucose, or insulin. In a placebo-controlled, double-blind study, Tang et al. (17) randomized 143 oligo- amenorrheic obese women with PCOS to metformin (850 mg) or placebo twice daily for 6...

Impaired Glucose Tolerance Impaired Fasting Glucose Insulin Resistance And Diabetes

While diabetes has been a well-established cardiovascular risk factor, impaired glucose tolerance, impaired fasting glucose, and insulin resistance are emerging risk factors that are also associated with the metabolic syndrome as well as the development of overt diabetes. In general, impaired glucose tolerance is determined with an oral glucose tolerance test, impaired fasting glucose is detected by serum glucose after a fast, and insulin resistance is suggested by an elevated fasting serum insulin level. Figure 7.17 Hazard ratios for the incidence of cardiovascular disease associated with prehypertension and abnormalities of glucose metabolism. Hazard ratios were compared with the group of normal glucose tolerance and normal blood pressure and adjusted for age, gender, body mass index, waist circumference, low- and high-density lipoprotein cholesterol levels, triglycerides, physical activity, smoking, and alcohol use. NGT, normal glucose tolerance IGT, impaired...

Metabolism or storage

Endocannabinoid System Interaction

Receptor (knockout mice) are lean and appear to be resistant to diet-induced obesity32. Because of these observations, it was postulated that by blocking the CB1 receptor, this approach would represent an innovative approach for the management of high-risk abdominal obesity and the related cardiometabolic risk38. The results from recently completed phase III clinical trials in overweight obese patients suggests that this approach may indeed yield substantial clinical benefits6,40,41. The observations reported in animal studies appear to be quite compatible with the human condition. Specifically, an overstimulation of the endocanna-binoid system in human abdominal obesity has been suggested to lead to fat cell hypertrophy and to markedly reduced plasma adiponectin levels, which are well-described features of abdominal obesity43. Furthermore, it was reported that the low plasma adiponectin concentration observed in viscerally obese patients was a key factor responsible for their...

Classification and evolution of increased cardiometabolic risk states

Prevalence Metabolic Obesity

It has been accurately observed that certain risk factors in humans appear to 'cluster' with clinical states such as obesity and type 2 diabetes. Specifically, this risk factor clustering, and the association with insulin resistance, led investigators to propose the existence of a unique pathophysiological condition1. Many names have been provided to describe this clinical state including 'metabolic syndrome', 'syndrome X', and 'insulin resistance syndrome'1. The particular names that refer to this risk factor clustering describe the human condition characterized by the presence of co-existing traditional risk factors for cardiovascular disease (CVD), such as hypertension, dyslipidemia, glucose intolerance, obesity, and insulin resistance, in addition to non-traditional CVD risk factors, such as inflammatory processes and abnormalities of the blood coagulation system2-6. Table 1.1 lists conditions and components associated with the clustering of risk factors. As seen, the components...

Atherogenic Dyslipidemia

Insulin Nursing

Insulin resistant states such as the metabolic syndrome are commonly associated with an atherogenic dyslipidemia that contributes to significantly higher risk of atherosclerosis and cardiovascular disease. Emerging evidence suggests that insulin resistance and its associated metabolic dyslipidemia result from perturbations in key molecules of the insulin signaling Figure 5.15 Schematic of the most fundamental defect in patients with metabolic syndrome which is resistance to the cellular actions of insulin, particularly resistance to insulin-stimulated glucose uptake. Insulin insensitivity appears to cause hyper-insulinemia, enhanced hepatic gluconeogenesis and increased glucose output. Reduced suppression of lipolysis in adipose tissue leads to a high free fatty acid flux, and increased hepatic very-low-density lipoprotein (VLDL) secretion causing hypertrigly-ceridemia and reduced plasma levels of high-density lipoprotein (HDL) cholesterol Figure 5.15 Schematic of the most fundamental...

Endocannabinoid System

Insulin Resistance Obesity

A recently characterized physiologic system that plays a major role in modulating energy metabolism is the endocannabinoid-CB1 receptor system (Figure 4.9)31'32. The discovery of this system represents a significant advance in understanding mechanisms contributing to the development of obesity and as such, provides targets for new pharmacological approaches to target abdominal obesity and its related metabolic

Ziv E And Shafrir E Nutritionally Thrifty Gene Background

9 Grundy SM, Brewer HB Jr, Cleeman JI, Smith SC Jr, Lenfant C, American Heart Association National Heart, Lung, and Blood Institute Definition of metabolic syndrome Report of the National Heart, Lung, and Blood Institute American Heart Association conference on scientific issues related to definition. Circulation 2004 109 433-438. 10 Ferreira I, Henry RM, Twisk JW, van Mechelen W, Kemper HC, Stehouwer CD The metabolic syndrome, cardiopulmonary fitness, and subcutaneous trunk fat as independent determinants of arterial stiffness the Amsterdam Growth and Health Longitudinal Study. Arch Intern Med 2005 165 875-882. 12 Scuteri A, Najjar SS, Muller DC, et al Metabolic syndrome amplifies the age-associated increases in vascular thickness and thickness. J Am Coll Cardiol 2004 43 1388-1395. 15 Tomiyama H, Koji Y, Yambe M, Motobe K, Shiina K, Gulnisa Z, Yamamoto Y, Yamashina A Elevated C-reactive protein augments increased arterial stiffness in subjects with the metabolic syndrome....

Reflections

Aging is the dominant process altering vascular stiffness, wave reflections, and PP. There is however an extreme variability of the age-mediated changes 21 . This variability is influenced by the histopathological particularities of arterial tissue (muscular or musculo-elastic), and mostly by the presence of other CV risk factors inside the microenvironment. In subjects with middle-age hypertension, when other CV risk factors (tobacco consumption, diabetes mellitus, dyslipidemia, obesity ) are not or minimally present, high MAP contributes dominantly to the increase of arterial stiffness, whereas MAP-independent structural and functional changes in stiffness play a more important role in older subjects, as described earlier 3, 21 . MAP-independent increase of arterial stiffness largely predominates in subjects with endothelial dysfunction as observed prematurely in the evolution of patients with diabetes mellitus, metabolic syndrome, obesity, end-stage renal disease or finally with...

Obesity

Lished that hyperinsulinemia, insulin resistance, and other obesity-related metabolic abnormalities are significantly associated with overall accumulation of fat in the body, there is now substantial evidence that the specific distribution of fat is important as outlined in Chapter 3. Excessive accumulation of fat in the upper body's so-called truncal region, or central obesity, is a better predictor of morbidity than excess fat in the lower body, the so-called lower body segment obesity10,12,13.

Creactive Protein

Several studies have shown that there is a significant relationship between individual components of the metabolic syndrome and CRP. The exact relationship varies from component to component (Figure 6.4), but broadly there is a positive relationship with blood pressure, glucose, insulin resistance, obesity, and triglycerides, and a negative relationship with HDL. That CRP levels correspond with individual components of the metabolic syndrome is consistent with the hypothesized role of inflammation in several processes critical to the development of atherothrombosis. Furthermore, several cross-sectional studies have demonstrated that there is a positive relationship between the number of components of the metabolic syndrome and CRP6,7 (Figure 6.5). Among healthy populations such as the Women's Health Study the average CRP levels are higher among subjects with the metabolic syndrome (average range 3.01-5.75 mg L) compared with those without (average range 0.68-1.93 mg L). Thus, some...

PHSD1 Inhibitors

Early inhibitors of 11p-HSD1 were natural product analogs that generally had low 11p-HSD1 potency and poor selectivity over 11p-HSD2. Compounds such as carbenoxolone demonstrated modest in vivo effects on markers of metabolic syndrome, but were generally poor pharmacological tools because of issues such as selectivity. These inhibitors, as well as early work on thiazole analogs, were reviewed in 2003 53 . Subsequently, more in vivo results and several new chemical entities have been published in both the peer-reviewed and patent literature 54 . Thiazoles, triazoles, amides, and some miscellaneous derivatives have all demonstrated 11p-HSD1 potency as well as selectivity over 11p-HSD2. This review will focus on recent advances and compounds with published pharmacological data 55 .

Conclusions

The importance of the concept of assessing overall cardiometabolic risk is highlighted by the fact that cardiovascular risk factors do not occur in isolation of each other and that some predispose patients to other risk factors. The majority of patients present with multiple cardiometabolic risk factors, and their cardiovascular outcomes are driven by combinations of these risk factors which are often more potent than suggested by their sums. Cardiometabolic risk encompasses emerging risk predictors, such as the metabolic syndrome and markers of inflammation, that may be present in patients without other more traditional risk factors. An evaluation that only assesses for traditional risk factors may fail to identify patients at elevated risk for adverse cardiovascular outcomes. Therefore, assessment and knowledge of all the cardiometabolic risk factors and associated risks have become a crucial part of cardiovascular risk assessment.

Diabetes Mellitus

Diabetes mellitus is a metabolic syndrome characterized by chronic hyperglycemia due to insulin deficiency, insulin resistance or both. Diabetes is a chronic illness that requires long-term continuing medical care and patient self-management education in order to reduce the risk of acute complications. Diabetic patients can have a reasonably normal lifestyle if they comply with the appropriate medical and educational guidelines aimed to maintain healthy blood glucose levels and reduce the likelihood and progression of adverse macrovascular complications, e.g., CAD, stroke, and peripheral vascular disease and microvascular complications, e.g., retinopathy, nephropathy, and neuropathy.

Epidemiological Data

The possibility that insulin resistance is independently associated with increased arterial stiffness was first suggested by cross-sectional analysis of ARIC (Atherosclerosis Risk in Communities) data. This study explored the relationship between insulin resistance (measured using fasting insulin concentrations) and arterial stiffness measured with ultrasound in 4,701 white and black subjects 9 . In the entire study group, arteries appear to become stiffer at increasing concentrations of fasting glucose and insulin, independent of race or gender. The relationship between glucose and insulin concentrations and stiffness remained significant after adjustment for classic cardiovascular risk factors. This was also true within the non-diabetic subjects, which comprised 95 of the study subjects 9 . In 2,488 adults participating in the Health ABC study, increased serum insulin concentrations and visceral fat volume measured with computed tomography were associated with increased aortic...

Hypertriglyceridemia

Hypertriglyceridemia shares similarities with low HDL cholesterol levels in that it is both an important independent risk factor for cardiovascular disease and part of the criteria for the metabolic syndrome. Hypertriglyceridemia is generally diagnosed when triglyceride levels are elevated above 150mg dL33. In a meta-analysis of several large prospective trials, the effect of hypertriglyceridemia on the incidence of cardiovascular disease was investigated56. Hypertriglyceridemia was associated with nearly a 30 increase in the relative risk of cardiovascular disease among men and a 75 increase among women56. Although the relative risk increases attenuated after adjustment for HDL cholesterol levels and other risk factors, a statistically significant increase in risk persisted for both men and women suggesting that hypertriglyceridemia was an independent risk

Microalbuminuria

Suggest that the prevalence in middle-aged non-diabetics is as high as 10-15 . In a cross-sectional study of approximately 3500 Chinese subjects, the waist-to-hip ratio, systolic and diastolic pressure, serum triglyceride level, fasting plasma glucose, and homeostasis model assessment-insulin resistance (HOMA-IR) were all significantly increased in those subjects with microalbuminuria compared with normal subjects31. The prevalence of microalbuminuria was also significantly increased with an incremental rise in the number of components of the metabolic syndrome (p for trend

Figure 336

Diagnosis of primary systemic amyloidosis based on the presence of amyloid in tissue in an 11-year study at the Mayo Clinic. The initial diagnostic procedure should be an abdominal fat aspirate 11 . The diagnosis will be confirmed in 80 of patients. Experience in the staining technique and interpretation of the fat aspirate is important before routine use. A bone marrow aspirate and bone marrow biopsy specimen should be obtained to determine the degree of plas-macytosis, and results of amyloid stains are positive in more than half of patients. Either the abdominal fat aspirate or bone marrow biopsy specimen is positive in 90 of patients. When amyloid is still suspected and the test results of these tissues are negative, one should proceed to performing a rectal biopsy, which is positive in approximately 80 of patients. The specimen must include the submucosa. When the test results for these sites are negative, tissue should be obtained from an organ with suspected involvement. (From...

Figure 58

Acute renal failure may be present at the time of initial diagnosis. In others, it may occur at any time during the disease. Renal failure can be due to diverse mechanisms. The light chains produced by the monoclonal B lymphocytes may be nephrotoxic 28 . While the toxicity of the light chains leads to a variety of tubular transport disorders, including Fanconi's syndrome, the intratubular precipitation of these proteins causes light-chain cast nephropathy and acute renal failure. The light chains (usually lambda) may be transformed into Congo-red-positive amyloid fibrils and deposited diffusely throughout the body 29 . Deposition of amyloid in renal tissue results in the nephrotic syndrome and, often, renal failure. Biopsy of the kidney, abdominal fat pad, or rectal mucosa is useful in the diagnosis of AL amyloidosis. Light chains may also be deposited in a granular pattern along the basement membranes of blood vessels in a variety of organs. In the kidney, these deposits are noted in...

Cushings Syndrome

Physical characteristics of Cushing's syndrome. A, Side profile of a patient with Cushing's syndrome demonstrating an increased cervical fat pad (so-called buffalo hump), abdominal obesity, and thin extremities and petechiae (on the wrist). The round (so-called moon) facial appearance, plethora, and acne cannot be seen readily here. B, Violescent abdominal striae in a patient with Cushing's syndrome. Such striae also can be observed on the inner parts of the legs in some patients.

Results

Hypertension is one of the most common medical disorders associated with obesity. Resolution or improvement of diastolic hypertension occurs in approx 70 of individuals, but occurs more commonly in those patients with a lower postoperative BMI. The severity of cardiac dysfunction decreases, as does the degree of dyspnea associated with congestive heart failure. Arthralgia in major joints such as knee, hips, and vertebrae improves rapidly and most significantly with weight loss. There is a clear correlation of these improvements with the chronicity of the condition and the amount of weight loss. Infertility has been corrected with weight loss in a significant number of females. Last, it has been shown that bariatric surgery is the long-term procedure of choice for severely obese patients with pseudotumor cerebri. It has been shown to have a much higher rate of success than cerebrospinal fluid-peritoneal shunting reported in the literature. It is thought that the resolution of...

Medical Assessment

The physical examination may be somewhat limited when the patient is morbidly obese, but it can yield evidence of endocrine causes and detect complicating conditions. It is necessary to obtain not only an accurate weight and height for calculation of the BMI but also the simple tape measurement of the waist circumference, an important modifier of the risk in obesity, as previously noted. Laboratory evaluations should serve to screen for the complications of obesity. Blood chemistries should include, in particular, counts of fasting serum glucose, cholesterol, and triglycerides and liver function tests.A thyroid stimulating hormone level should be obtained, as well as other endocrine and metabolic tests if a problem is suspected.

Cb1r Antagonists

The endocannabinoid system consists of endogenous ligands (i.e., anandamide and 2-arachidonoyl glycerol) that bind to and activate either of two receptor subtypes, CB1R or CB2R, that are distributed throughout the periphery (gut, liver, spleen, immune cells) and the CNS 4,5 . Endocannabinoids and exogenous can-nabinoids (notably A9-tetrahydrocannabinol, the principal active constituent in Cannabis sativa L., or marijuana) have been shown to stimulate appetite 6 . CB1R was hypothesized to play a role in the regulation of appetite because of its location in the hypothalamus. This was confirmed using a combination of CB1R selective ligands and CB1 knockout (KO) mice 7-11 . Recently, 2-year clinical efficacy data with rimonabant, a selective CB1R antagonist, have been published, claiming rimonabant-treated patients had significantly reduced waist circumference and plasma triglycerides and an increase in HDL cholesterol and adi-ponectin concentrations in addition to significant and...

Increased

Reverse Cholesterol Transport

HDL consists of a heterogeneous class of lipoproteins containing approximately equal amounts of lipid and protein (Figure 5.10)9. The various HDL subclasses vary in quantitative and qualitative content of lipids, apolipoproteins, enzymes, and lipid transfer proteins, resulting in differences in shape, density, size, charge, and antigenicity. Beyond reverse cholesterol transport HDL is believed to have other beneficial effects including improving endothelial function (Figure 5.11). HDL also attenuates expression of adhesion molecules and inflammatory cytokines which promote leukocyte extravasation into the vessel wall. Infusion of HDL has been shown to increase nitric oxide synthetase activity promoting vasodilatation. HDL also inhibits the oxidation of LDL and the formation of lipid hydroperoxides which reduce inflammation. Sujects with metabolic syndrome have low levels of HDL which is believed to contribute to their cardiometabolic risk. The biological effects of HDL are...

Info

Sex hormone levels are also influenced by the degree of overweight. women with PCOS have lower sex hormone-binding globulin (SHBG) levels, with more pronounced SHBG reduction in obese women with PCOS, especially if they present with abdominal obesity (6). Lower SHBG levels increase the bioavailability of sex hormones, and therefore increase hyperandrogenemia in obese PCOS women. Both total and free testosterone levels are increased in obese PCOS compared to normal-weight women with PCOS because of the combination of increased androgen production and lower SHBG (6). Many studies have confirmed that low birthweight is associated with central obesity and insulin resistance after adjustment for BMI. Hofman et al. (31) showed that prematurity or being small for gestational age was related to diminished insulin sensitivity measured at 4-10 years old. In the Nurses Health Study, low birthweight was associated with higher risk of type 2 diabetes, even after adjustment for BMI and all the...

Flutamide

Some studies reported that this drug is more effective than spironolactone or finasteride in the treatment of hirsutism. However, differences were small, and all these medications gave similar results in a controlled comparative trial (18). Anecdotal evidence suggests that flutamide is more effective than other drugs in treating androgen-dependent acne, although no controlled study has been specifically designed to assess this aspect. Some studies reported that this drug might have favorable effects on visceral fat and on the lipid profile in patients with PCOS (22,23). These effects are of great interest in subjects who frequently show abdominal obesity, insulin resistance, and multiple metabolic abnormalities.

Glucose metabolism

Hyperinsulinemia Euglycemia Therapy

Abnormalities in glucose tolerance are commonly noted in individuals with central obesity. As outlined in Chapter 1, it is now well accepted that the presence of insulin resistance in an individual will need to be compensated for by hyperinsulinemia in order to maintain normal glucose tolerance. In those individuals who develop diabetes, a progressive loss of the insulin secretory capacity fails to compensate for the insulin resistance and results in a progressive hyper-glycemia (see Chapter 1). Thus, an individual with obesity and insulin resistance, depending on the stage of compensation for the insulin resistance, may have euglycemia, impaired fasting glucose, impaired glucose tolerance, or overt hyperglycemia confirming the diagnosis of type 2 diabetes.

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