Karen A. Donato

Diagnosis and Management of the Metabolic Syndrome: An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement

The metabolic syndrome has received increased attention in the past few years. This statement from the American Heart Association (AHA) and the National Heart, Lung, and Blood Institute (NHLBI) is intended to provide up-to-date guidance for professionals on the diagnosis and management of the metabolic syndrome in adults. The metabolic syndrome is a constellation of interrelated risk factors of metabolic origin— metabolic risk factors —that appear to directly promote the development of atherosclerotic cardiovascular disease (ASCVD).1 Patients with the metabolic syndrome also are at increased risk for developing type 2 diabetes mellitus. Another set of conditions, the underlying risk factors , give rise to the metabolic risk factors. In the past few years, several expert groups have attempted to set forth simple diagnostic criteria to be used in clinical practice to identify patients who manifest the multiple components of the metabolic syndrome. These criteria have varied somewhat in specific elements, but in general they include a combination of both underlying and metabolic risk factors. The most widely recognized of the metabolic risk factors are atherogenic dyslipidemia, elevated blood pressure, and elevated plasma glucose. Individuals with these characteristics commonly manifest a prothrombotic state and a pro-inflammatory state as well. Atherogenic dyslipidemia consists of an aggregation of lipoprotein abnormalities including elevated serum triglyceride and apolipoprotein B (apoB), increased small LDL particles, and a reduced level of HDL cholesterol (HDL-C). The metabolic syndrome is often referred to as if it were a discrete entity with a single cause. Available data suggest that it truly is a syndrome, ie, a grouping of ASCVD risk factors, but one that probably has more than one cause. Regardless of cause, the syndrome identifies individuals at an elevated risk for ASCVD. The magnitude of the increased risk can vary according to which components of the syndrome are …

Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity.

A cluster of risk factors for cardiovascular disease and type 2 diabetes mellitus, which occur together more often than by chance alone, have become known as the metabolic syndrome. The risk factors include raised blood pressure, dyslipidemia (raised triglycerides and lowered high-density lipoprotein cholesterol), raised fasting glucose, and central obesity. Various diagnostic criteria have been proposed by different organizations over the past decade. Most recently, these have come from the International Diabetes Federation and the American Heart Association/National Heart, Lung, and Blood Institute. The main difference concerns the measure for central obesity, with this being an obligatory component in the International Diabetes Federation definition, lower than in the American Heart Association/National Heart, Lung, and Blood Institute criteria, and ethnic specific. The present article represents the outcome of a meeting between several major organizations in an attempt to unify criteria. It was agreed that there should not be an obligatory component, but that waist measurement would continue to be a useful preliminary screening tool. Three abnormal findings out of 5 would qualify a person for the metabolic syndrome. A single set of cut points would be used for all components except waist circumference, for which further work is required. In the interim, national or regional cut points for waist circumference can be used.

2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: A report of the American College of cardiology/American Heart Association task force on practice guidelines and the obesity society

Harmon S. Jordan, ScD, Karima A. Kendall, PhD, Linda J. Lux, Roycelynn Mentor-Marcel, PhD, MPH, Laura C. Morgan, MA, Michael G. Trisolini, PhD, MBA, Janusz Wnek, PhD Jeffrey L. Anderson, MD, FACC, FAHA, Chair , Jonathan L. Halperin, MD, FACC, FAHA, Chair-Elect , Nancy M. Albert, PhD, CCNS, CCRN,Obesity is a chronic, multifactor disease with sizeable socio sanitary and economic consequences and is an issue in public health, mostly in developing countries. It causes or exacerbates a large number of health problems: diabetes, coronary heart disease, hypertension, and the incidence of certain cancers. It has been linked to a greater risk of cardiovascular mortality, a higher prevalence of psychopathology disorders and social maladjustment with a higher health care cost and shorter life-expectancy. In Spain, nowadays, the prevalence of overweight and obesity is nearly 50% of population. SEEN has developed a Clinical Practice Guide on diagnosis, evaluation and treatment of overweight and obesity in adult people with two sections: 1) Definition and classification of adult obesity, its epidemiology, etiopathogeny, complications, benefits of weight reduction and clinical evaluation of patients with overweight or obesity, and 2) Identification of patients with obesity risk subsidiary to weight reduction treatment, therapy goals and therapeutical strategies available to achieve them indicating as well the degree of recommendation based upon scientific evidence on each aspect. Although obesity is a disease which is supposed to involve not only medical but also political authorities, social agents, educators and food industry among others, SEEN decided to develop this Guide taking into account the evident endocrinological and metabolical aspects of this disorder. The Guide contains scientific evidencebased recommendations intended to help doctors making decisions on diagnose, evaluations and treatment of adult overweight so that a more homogeneous attendance with settled quality can be

2013 AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults

Loria, Barbara E. Millen, Cathy A. Nonas, F. Xavier Pi-Sunyer, June Stevens, Victor J. Stevens, Karen A. Donato, Frank B. Hu, Van S. Hubbard, John M. Jakicic, Robert F. Kushner, Catherine M. Michael D. Jensen, Donna H. Ryan, Caroline M. Apovian, Jamy D. Ard, Anthony G. Comuzzie, Practice Guidelines and The Obesity Society Report of the American College of Cardiology/American Heart Association Task Force on 2013 AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults: A Print ISSN: 0009-7322. Online ISSN: 1524-4539 Copyright

Diagnosis and Management of the Metabolic Syndrome An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement: Executive Summary

This Executive Summary is a synopsis of the full scientific statement from the American Heart Association (AHA) and the National Heart, Lung, and Blood Institute (NHLBI), which is intended to provide up to date guidance for professionals on the diagnosis and management of the metabolic syndrome in adults. The metabolic syndrome has received increased attention in the past few years. It consists of multiple, interrelated risk factors of metabolic origin that appear to directly promote the development of atherosclerotic cardiovascular disease (ASCVD). This constellation of metabolic risk factors is strongly associated with type 2 diabetes mellitus or the risk for this condition. The metabolic risk factors consist of atherogenic dyslipidemia (elevated triglycerides and apolipoprotein B, small LDL particles, and low HDL cholesterol [HDL-C] concentrations), elevated blood pressure, elevated plasma glucose, a prothrombotic state, and a proinflammatory state. At present, it is not clear whether the metabolic syndrome has a single cause, and it appears that it can be precipitated by multiple underlying risk factors. The most important of these underlying risk factors are abdominal obesity and insulin resistance. Other associated conditions include physical inactivity, aging, hormonal imbalance, and genetic or ethnic predisposition. Prospective population studies show that the metabolic syndrome confers an &2-fold increase in relative risk for ASCVD events, and in individuals without established type 2 diabetes mellitus, an &5-fold increase in risk for developing diabetes as compared with people without the syndrome. This finding implies that the metabolic syndrome imparts a relatively high long-term risk for both ASCVD and diabetes. In the absence of diabetes, the absolute short-term (10-year) risk for major coronary heart disease (CHD) events is not necessarily high. In the Framingham Heart Study data, the 10-year risk for CHD depends on other risk factors in addition to the metabolic syndrome components contained in Framingham scoring …

Diagnosis and management of the metabolic syndrome An American Heart Association/National Heart, Lung, and Blood Institute scientific statement

It is interesting to look through the citation records of classic papers such as this – Bulbring & Lin (1958). It serves as a whos who in serotonin research and catalogues the development of our understanding of the role that 5-HT plays in sensory signalling from the gut lumen. Bulbring had already shown in early publications that the peristaltic reflex was entirely mediated by neural mechanisms within the bowel wall since degenerative section of the extrinsic innervation had no effect on reflex activity (Bulbring et al. 1958). They had also demonstrated that the peristaltic reflex could be triggered by distension, but required a sensory mechanism within the mucosa since it was lost after removal of the mucous membrane or following topical application of local anaesthetic. It was also evident that there was a rich source of 5-HT in the gastrointestinal tract and that this was mainly within the mucosal epithelium (Feldberg & Toh, 1953). However, there was also something of a dilemma. Carcinoid syndrome, in which there is massive outpouring of 5-HT from mucosal enterochromaffin cells, is characterized by increased intestinal activity and diarrhoea. In contrast, when 5-HT was applied to isolated intestinal segments in an organ bath it inhibited or abolished the peristaltic reflex (Kosterlitz & Robinson, 1957). Bulbring and Lin therefore set out to ask the beautifully simple question – what happens if 5-HT is applied not to the serosa but to the mucosa? Their hypothesis was that this would mimic release of endogenous 5-HT which in turn would activate receptors associated with mucosal sensory mechanisms. This classic paper describes the methodological developments that were necessary to record the propulsion of luminal contents by pressure-evoked peristalis in the guinea-pig ileum (and rabbit jejunum) during application of 5-HT to the lumen, and gives a detailed account of experiments designed to unravel the role of 5-HT in sensory signalling. First, a word or two about the available methodology. Reading again about kymographs and ‘home-made’ piston and float recorders to monitor pressure and volume contrasts with modern descriptions of solid-state electronics, digital devices and computer analysis. Limited pharmacological tools reflect the lack of appreciation at the time of the range of 5-HT receptor subtypes that are now known to be expressed in the gut mucosa and which influence sensory signalling. Assay for endogenous 5-HT was based on strips of rat stomach, uterus and colon rather than HPLC or amperometry. The paper is also very descriptive so that the reader can get a real feel for the whole study design, problems that were encountered and overcome, variability in responses and theres not a P value in sight. Yet, with cleverly designed protocols and enormous insight Bulbring and Lin established a concept for control that still holds 50 years later. Their major findings can be summarized as follows. In the guinea-pig ileum peristalsis was triggered initially by a pressure rise of just 1–1.5 cmH2O, rising to about 2 cmH2O after an hour or so. Adding 5-HT to the lumen dose-dependently decreased threshold with a threshold concentration around 1 nm. Application of 5-HT to the bath invariably caused inhibition of peristalsis, even when this was already stimulated by intraluminal 5-HT. Removing the mucosa from the loop of intestine or luminal application of cocaine or procaine abolished the peristaltic reflex and under these conditions luminal 5-HT had no effect. LSD and 2-bromo-d-LSD were used as 5-HT antagonists. Applied to the lumen they blocked the effect of co-administered 5-HT. However, when applied alone the antagonist raised the peristaltic threshold suggesting that it prevented the action of locally released 5-HT. However, peristalsis was not abolished indicating that 5-HT release is not an essential prerequisite for activation of the peristaltic reflex but is necessary to set the threshold. 5-HT overflow into the lumen increased in response to distension, an observation consistent with pressure-evoked release contributing to peristalsis. The increase was proportional to the degree of distension but declined rapidly over time. Again peristalsis was still evident even when 5-HT levels had fallen to very low levels and is therefore not essential for reflex activation to occur. The amount of 5-HT released and the decline over time could be pharma-cologically manipulated. Inhibiting 5-HT breakdown with a luminal agent to inhibit amine oxidase (1 isonicotinyl-2-isopropylhydrazine) slowed the decline in 5-HT output over time. Addition of the 5-HT precursor, 5-HTP, increased the release of 5-HT and augmented peristalsis. Procaine, which abolished peristalsis, did not prevent 5-HT release in response to distension. Bath applied hexamethonium also abolished the peristaltic reflex but, again, 5-HT release into the lumen was preserved. In contrast luminal acetylcholine (at low concentrations) stimulated peristalsis. Finally, with current interest in the role of 5-HT receptor subtypes in mucosal signalling, it is important to see that phenyldiguanide, which is now known to be a 5-HT3 receptor agonist, also stimulated peristalis when applied to the lumen. These observations are interesting in light of subsequent studies that place Enterochromaffin cells in a pivotal role in sensory signalling both for enteric reflexes and in extrinsic afferent activation. Many studies since have demonstrated that 5-HT receptor blockade can reduce or prevent reflex activation by mechanical stimulation of the mucosa or following application of chemicals to the mucosal epithelium, particularly bacterial toxins (Gershon, 1999). 5-HT receptors are present on the terminals of both enteric and extrinsic sensory neurones and convey information related to the luminal mechanical and chemical environment to enteric reflex circuits and to reflex centres in the brainstem (Hillsley & Grundy, 1998; Hillsley et al. 1998; Bertrand et al. 2000). Such observations have enormous clinical relevance. The treatment of nausea and vomiting triggered by cancer chemo- and radiotherapy has been revolutionized by the discovery that the underlying mechanism involves EC cell activation and 5-HT acting on vagal mucosal afferents (Costall & Naylor, 2004). 5-HT ligands have also been shown to have clinical efficacy in treating patients with constipation predominant and diarrhoea predominant irritable bowel syndrome (IBS) (Camilleri et al. 2002). There is growing evidence that bioavailability of 5-HT is altered in some patients with IBS, particularly those whose symptom onset is related to an acute inflammatory insult. EC cell numbers are increased and the transport mechanisms that take up 5-HT following release are reported to be blunted although this is controversial (Dunlop et al. 2005). Bulbring and Lins observations on the consequence of altering 5-HT metabolism are particularly relevant in this context. Current interest in altered 5-HT bioavailability in visceral hypersensitivity following changes in the serotonin transporter can also be traced back to their observations on the effects of increasing precursor availability and decreasing breakdown. It is also now clear that there is an elaborate arrangement of receptors and ion channels on EC cells that regulate 5-HT release. 5-HT release is modulated by a variety of neuromodulators acting on adrenoreceptors, nicotinic and muscarinic cholinoreceptors and 5-HT3 receptors (Racke et al. 1996). Bulbring and Lins observations with luminal acetylcholine and phenyldiguanide, which mimicked the effect of luminal 5-HT, may have arisen because of a common action on endogenous 5-HT release. There therefore exists a bidirectional communication between EC cells and sensory mechanisms on the one hand and enteric reflexes influencing EC cell function on the other. The work coming from Edith Bulbrings laboratory in the late 1950s was the foundation for this modern day concept.

Prevention Conference VII Obesity, a Worldwide Epidemic Related to Heart Disease and Stroke: Group IV: Prevention/Treatment

Obesity is a worldwide problem, not just an issue for industrialized nations. Therefore, we need to examine opportunities for prevention and treatment from a global perspective.

Executive summary: Guidelines (2013) for the management of overweight and obesity in adults

In 2008, the NHLBI initiated these guidelines by sponsoring rigorous systematic evidence reviews for each topic by expert panels convened to develop critical questions (CQs), interpret the evidence, and craft recommendations. In response to the 2011 report from the Institute of Medicine on the development of trustworthy clinical guidelines (1), the NHLBI Advisory Council recommended that the NHLBI focus specifically on reviewing the highest-quality evidence and partner with other organizations to develop recommendations (2,3). Accordingly, in June 2013 the NHLBI initiated collaboration with the ACC and AHA to work with other organizations to complete and publish the guidelines noted above and make them available to the widest possible constituency. Recognizing that the expert panels/work groups did not consider evidence beyond 2011 (except as specified in the methodology), the ACC, AHA and collaborating societies plan to begin updating these guidelines starting in 2014.

Community Resources for Promoting Youth Nutrition and Physical Activity

Abstract Childhood obesity is a national public health crisis. The National Diabetes Education Program (NDEP), the National Institutes of Health and Kaiser Permanente have developed community tools and resources for children and families to lower their risk for obesity through healthier, active lifestyles. The authors describe innovative practices and community mobilization case studies from the NDEP “Move It! and Reduce Your Risk for Diabetes” program and the NIH We Can!TM - Ways to Enhance Children’s Activity and Nutrition, and programs from Kaiser Permanente for the promotion of healthier lifestyles for children and families. Replication of these creative programs can be modified to be implemented in communities throughout the United States.

Executive summary: Guidelines (2013) for the management of overweight and obesity in adults: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Obesity Society Published by the Obesity Society.

In 2008, the NHLBI initiated these guidelines by sponsoring rigorous systematic evidence reviews for each topic by expert panels convened to develop critical questions (CQs), interpret the evidence, and craft recommendations. In response to the 2011 report from the Institute of Medicine on the development of trustworthy clinical guidelines (1), the NHLBI Advisory Council recommended that the NHLBI focus specifically on reviewing the highest-quality evidence and partner with other organizations to develop recommendations (2,3). Accordingly, in June 2013 the NHLBI initiated collaboration with the ACC and AHA to work with other organizations to complete and publish the guidelines noted above and make them available to the widest possible constituency. Recognizing that the expert panels/work groups did not consider evidence beyond 2011 (except as specified in the methodology), the ACC, AHA and collaborating societies plan to begin updating these guidelines starting in 2014.