469 Abstract Aims To establish a unified working diagnostic tool for the metabolic syndrome (MetS) that is convenient to use in clinical practice and that can be used world- wide so that data from different countries can be compared. An additional aim was to highlight areas where more research into the MetS is needed. Participants The International Diabetes Federation (IDF) convened a workshop held 12-14 May 2004 in London, UK. The 21 participants included experts in the fields of diabetes, public health, epidemiology, lipidology, genetics, metabolism, nutrition and cardiology. There were participants from each of the five con- tinents as well as from the World Health Organization (WHO) and the National Cholesterol Education Program—Third Adult Treatment Panel (ATP III). The workshop was sponsored by an educational grant from AstraZeneca Pharmaceuticals. Consensus process The consensus statement emerged following detailed discussions at the IDF workshop. After the workshop, a writing group produced a consensus statement which was reviewed and approved by all participants. Conclusions The IDF has produced a new set of criteria for use both epidemio- logically and in clinical practice world-wide with the aim of identifying people with the MetS to clarify the nature of the syndrome and to focus therapeutic strategies to reduce the long-term risk of cardiovascular disease. Guidance is included on how to compensate for differences in waist circumference and in regional adipose tissue distribution between different populations. The IDF has also produced recommendations for additional criteria that should be included when studying the MetS for research purposes. Finally, the IDF has identified areas where more studies are currently needed; these include research into the aetiology of the syndrome. Diabet. Med. 23, 469-480 (2006)

/pdf/metabolic-syndrome-a-new-world-wide-definition-a-consensus-5amrc46uob.pdf

Metabolic syndrome--a new world-wide definition. A Consensus Statement from the International Diabetes Federation.

Obesity is becoming a global epidemic in both children and adults. It is associated with numerous comorbidities such as cardiovascular diseases (CVD), type 2 diabetes, hypertension, certain cancers, and sleep apnea/sleep-disordered breathing. In fact, obesity is an independent risk factor for CVD, and CVD risks have also been documented in obese children. Obesity is associated with an increased risk of morbidity and mortality as well as reduced life expectancy. Health service use and medical costs associated with obesity and related diseases have risen dramatically and are expected to continue to rise. Besides an altered metabolic profile, a variety of adaptations/alterations in cardiac structure and function occur in the individual as adipose tissue accumulates in excess amounts, even in the absence of comorbidities. Hence, obesity may affect the heart through its influence on known risk factors such as dyslipidemia, hypertension, glucose intolerance, inflammatory markers, obstructive sleep apnea/hypoventilation, and the prothrombotic state, in addition to as-yet-unrecognized mechanisms. On the whole, overweight and obesity predispose to or are associated with numerous cardiac complications such as coronary heart disease, heart failure, and sudden death because of their impact on the cardiovascular system. The pathophysiology of these entities that are linked to obesity will be discussed. However, the cardiovascular clinical evaluation of obese patients may be limited because of the morphology of the individual. In this statement, we review the available evidence of the impact of obesity on CVD with emphasis on the evaluation of cardiac structure and function in obese patients and the effect of weight loss on the cardiovascular system.

/pdf/obesity-and-cardiovascular-disease-pathophysiology-3oufiofv6y.pdf

Obesity and Cardiovascular Disease: Pathophysiology, Evaluation, and Effect of Weight Loss

It is now clear that PCOS is often associated with profound insulin resistance as well as with defects in insulin secretion. These abnormalities, together with obesity, explain the substantially increased prevalence of glucose intolerance in PCOS. Moreover, since PCOS is an extremely common disorder, PCOS-related insulin resistance is an important cause of NIDDM in women (Table 3). The insulin resistance in at least 50% of PCOS women appears to be related to excessive serine phosphorylation of the insulin receptor. A factor extrinsic to the insulin receptor, presumably a serine/threonine kinase, causes this abnormality and is an example of an important new mechanism for human insulin resistance related to factors controlling insulin receptor signaling. Serine phosphorylation appears to modulate the activity of the key regulatory enzyme of androgen biosynthesis, P450c17. It is thus possible that a single defect produces both the insulin resistance and the hyperandrogenism in some PCOS women (Fig. 19). Recent studies strongly suggest that insulin is acting through its own receptor (rather than the IGF-I receptor) in PCOS to augment not only ovarian and adrenal steroidogenesis but also pituitary LH release. Indeed, the defect in insulin action appears to be selective, affecting glucose metabolism but not cell growth. Since PCOS usually has a menarchal age of onset, this makes it a particularly appropriate disorder in which to examine the ontogeny of defects in carbohydrate metabolism and for ascertaining large three-generation kindreds for positional cloning studies to identify NIDDM genes. Although the presence of lipid abnormalities, dysfibrinolysis, and insulin resistance would be predicted to place PCOS women at high risk for cardiovascular disease, appropriate prospective studies are necessary to directly assess this.

Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis.

Background: The metabolic syndrome is an importantclusterofcoronaryheartdiseaseriskfactorswithcommon insulin resistance. The extent to which the metabolic syndrome is associated with demographic and potentially modifiable lifestyle factors in the US population is unknown. Methods: Metabolic syndrome–associated factors and prevalence, as defined by Adult Treatment Panel III criteria,wereevaluatedinarepresentativeUSsampleof3305 black,3477MexicanAmerican,and5581whitemenand nonpregnantorlactatingwomenaged20yearsandolder who participated in the cross-sectional Third National Health and Nutrition Examination Survey. Results: The metabolic syndrome was present in 22.8% and 22.6% of US men and women, respectively (P=.86). The age-specific prevalence was highest in Mexican Americans and lowest in blacks of both sexes. Ethnic differences persisted even after adjusting for age, body mass index, and socioeconomic status. The metabolic syndrome was present in 4.6%, 22.4%, and 59.6% of normal-weight, overweight, and obese men, respectively, and a similar distribution was observed in women. Older age, postmenopausal status, Mexican American ethnicity, higher body mass index, current smoking, low household income, high carbohydrate intake, no alcohol consumption, and physical inactivity were associated with increased odds of the metabolic syndrome.

Prevalence and Associated Risk Factor Findings in the US Population From the Third National Health and Nutrition Examination Survey, 1988-1994

Coronary heart disease (CHD) is the leading cause of death in the United States.1 Factors associated with an increased risk of developing CHD that tend to cluster in individuals include older age, high blood pressure, a low level of high-density lipoprotein (HDL) cholesterol, a high triglyceride level, a high plasma glucose concentration, and obesity.2 These associated risk factors have been called syndrome X,3 the insulin resistance syndrome,4 or the metabolic syndrome.5

The mechanisms underlying the metabolic syndrome are not fully known; however, resistance to insulin-stimulated glucose uptake seems to modify biochemical responses in a way that predisposes to metabolic risk factors.3,6,7 Insulin resistance is thought to be primarily due to obesity or an inherited genetic defect.8 As the prevalence of obesity increases in the United States, the prevalence of the metabolic syndrome may be expected to increase markedly. Estimates of the prevalence of the metabolic syndrome have varied substantially in part because of the variability of evaluated populations and of diagnostic criteria.9

The recent Third Report of the National Cholesterol Education Program Adult Treatment Panel (ATP III) included clinical diagnosis guidelines for the metabolic syndrome.10 Compared with findings from earlier studies3-5 and World Health Organization guidelines, the new ATP III defines criteria readily measured in clinical practice. These consensus-generated guidelines provide the opportunity to assess the overall prevalence of the metabolic syndrome in the US population according to an accepted standard definition. In an initial study, Ford et al11 reported un-adjusted and age-adjusted metabolic syndrome prevalences of 21.8% and 23.7%, respectively, for the US population. The objectives of this study are to examine the prevalence of the metabolic syndrome by ethnicity, age, body mass index (BMI) (calculated as weight in kilograms divided by the square of height in meters), socioeconomic status, and lifestyle factors.

https://jamanetwork.com/journals/jamainternalmedicine/articlepdf/215123/ioi20116_427_436.pdf

The Metabolic Syndrome: Prevalence and Associated Risk Factor Findings in the US Population From the Third National Health and Nutrition Examination Survey, 1988-1994

Background. Insulin resistance and the concomitant compensatory hyperinsulinemia have been implicated in the pathogenesis of hypertension. However, reports on the relation between insulin and blood pressure are inconsistent. This study was designed to investigate the possibility of racial differences in this relation. Methods. We studied 116 Pima Indians, 53 whites, and 42 blacks who were normotensive and did not have diabetes; the groups were comparable with respect to mean age (29, 30, and 31 years, respectively) and blood pressure (113/70, 111/68, and 113/68 mm Hg, respectively). Insulin resistance was determined by the euglycemic—hyperinsulinemic clamp technique during low-dose (40 mU per square meter of body-surface area per minute) and high-dose (400 mU per square meter per minute) insulin infusions. Results. The Pima Indians had higher fasting plasma insulin concentrations than the whites or blacks (176, 138, and 122 pmol per liter, respectively; P = 0.002) and lower rates of whole-body gl...

/pdf/racial-differences-in-the-relation-between-blood-pressure-27vuw30t37.pdf

Castillo C

Papers

Racial differences in the relation between blood pressure and insulin resistance.