Le syndrome métabolique : une entité à haut risque métabolique et cardiovasculaire

The association between abdominal obesity, insulin-resistance, type 2 diabetes, arterial hypertension and dyslipidemia has been known for many years. Metabolic syndrome has been recently recognized by both WHO and NCEP ATP III with the definition including a cluster of metabolic abnormalities. Metabolic syndrome is common with its prevalence increasing with age. Metabolic syndrome represents an averse metabolic state since it confers an increased risk for both type 2 diabetes and cardiovascular disease. Targeting physical inactivity and obesity with lifestyle changes is the cornerstone of the prevention and treatment of the metabolic syndrome. Further studies are warranted to better determine the value of therapies directed specifically at insulin-resistance in individuals with metabolic syndrome.     

Obesity: a main factor of metabolic syndrome?

The metabolic syndrome (MS) is a common metabolic disorder that has been recently related to the increasing prevalence of obesity. The disorder is defined in various ways, but in the near future a new definition(s) will be applicable worldwide. The pathophysiology has been largely attributed, in the past years, to insulin-resistance, even if several epidemiological and pathophysiological data are attractive to indicate visceral obesity as a main factor in the occurrence of the MS, promoting new definitions and re-evaluation of the pathogenesis of this syndrome. In this review, we have analyzed the role of visceral obesity in the new definition of the MS such as the pathophysiological role of the abnormal fat distribution in the occurrence of this syndrome. In view of this, relationships between visceral obesity, free fatty acids, dyslipidaemia and insulin-resistance have been reported. In addition, the effects of some adipocytokines and other proinflammatory factors produced by fat accumulation on the appearance of the MS have been also emphasized. Finally, according to recommendations of several international societies, the role of the life-style change and of the weight loss in the prevention and treatment both of obesity and of other associated risk factors has been analyzed.     

Insulin resistance and the metabolic syndrome-a challenge of the new millennium

The term metabolic syndrome is used for describing a cluster of cardiovascular risk factors comprising abdominal obesity, glucose intolerance/type 2 diabetes mellitus, dyslipidaemia and hypertension. A concomitant presentation of all components of the syndrome is rare, therefore, in the view of most experts three out of the four main components are sufficient for defining the syndrome. Another recently identified component of high clinical significance is the impairment of the fibrinolytic system which is now frequently mentioned in extended definitions. This clustering of metabolic risk factors has been described in various combinations and given different names including insulin resistance syndrome or syndrome X. Unfortunately, there is no generally accepted definition so far. The original mentioning of the syndrome goes back to the late sixties, when the metabolic syndrome was described as a 'disorder of genetic adaptation becoming manifest following unrestricted food intake and/or muscular inacitvity'. In its modern meaning this term was propagated by Hanefeld and Leonhardt and by Kaplan, who also called the syndrome the 'deadly quartet' to emphasize its high atherogenic potential.     

The metabolic syndrome: a cluster of vascular risk factors

The metabolic syndrome is a cluster of several vascular risk factors (impaired glucose metabolism, dyslipidaemia, hypertension and central adiposity). The prevalence of the metabolic syndrome is high, varying between 10 and 40% depending on age and sex. This prevalence will increase in the years to come due to the increased prevalence of overweight/obesity. To identify the metabolic syndrome, there is a readily applicable definition for daily clinical practice, i.e. the presence of three or more of the following characteristics: hyperglycaemia, hypertension, low plasma HDL cholesterol level, high plasma triglyceride level and central adiposity. The underlying pathophysiology is not fully clarified, but insulin resistance plays an important role in this syndrome. The metabolic syndrome is associated with increased cardiovascular morbidity and mortality and an increased risk for the development of diabetes mellitus type 2. In subjects with one or two components of the metabolic syndrome and in patients with manifest vascular disease, it seems advisable to be alert to the presence of the other components in order to either diagnose or exclude the metabolic syndrome. Although clinical evidence is lacking, from a pathophysiological point of view it seems reasonable to focus the treatment on reducing insulin resistance, which can be achieved by weight reduction and an increase in physical activity. Treatment of the individual risk factors may also be considered, depending on the degree of vascular risk.     

新疆哈萨克族和汉族代谢综合征患者脂蛋白脂酶基因HindⅢ、S447X多态性的相关分析

目的 探讨脂蛋白脂酶(LPL)基因Hind Ⅲ、S447X多态性与新疆哈萨克族和汉族人群代谢综合征(MS)及其组分的关系.方法 应用聚合酶链反应-限制性片段长度多态法检测802名研究对象(哈萨克族和汉族MS各200名和对照各201名)的LPL基因Hind Ⅲ、S447X基因多态性.结果 (1)汉族MS组H+H-/H-H-基因型(32.50%vs.47.76%)、H-等位基因(18.00%vs.28.86%)、SX/XX基因型(8.00%vs.22.39%)、X等位基因(4.00%vs.12.44%)频率低于对照组,P值均＜0.01.(2)哈萨克族MS组H+H-/H-H-基因型(33.50%vs.45.80%)、H-等位基因(22.00%vs.28.60%)、SX/XX基因型(10.50%vs.22.90%)、X等位基因(5.50%vs.12.44%)频率低于对照组,P值均＜0.01.(3)LPL基因Hind Ⅲ、S447X基因型和等位基因频率在哈萨克族和汉族MS组间的差异无统计学意义(P值均＞0.05).(4)H+H-/H-H-基因型携带者、SX/XX基因型携带者腰围、SBP、DBP、甘油三酯、空腹血糖水平分别较H+H+基因型携带者和SS基因型携带者低,高密度脂蛋白胆固醇水平分别高于H+H+基因型携带者和SS基因型携带者,差异均有统计学意义(P值均＜0.05).(5)随着MS组分异常的增多,H+H+、SS基因型携带率均有不断增加的趋势.结论 LPL基因Hind Ⅲ、S447X多态性与MS的发病风险相关,其中H+H-/H-H-基因型、H-等位基因、SX/XX基因型、X等位基因可能是MS的保护因素,H+H-/H-H-和SX/XX基因型对MS各组分产生有益的影响,且随着MS组分异常个数的增加,H+H+、SS基因型携带率也相应增加.     

The impact of genes and pre- and postnatal environment on the metabolic syndrome. Evidence from twin studies

Our population-based Danish twin study demonstrated a genetic influence on several of the components included in the metabolic syndrome, i.e. glucose intolerance, overall obesity, systolic and diastolic blood pressure and low levels of HDL-cholesterol. Abdominal obesity, insulin resistance and hypertriglyceridaemia had, on the other hand, a relatively higher environmental aetiological component. Furthermore we demonstrated a difference in aetiology among male and female twins indicating an influence of sex on several of the components in the metabolic syndrome. Studies have demonstrated an impact of the intrauterine environment (i.e. low birth weight) for the development of the components in the metabolic syndrome. The validity of conclusions drawn from classical twin studies has therefore been questioned due to the different prenatal circumstances characterising monozygotic (MZ) and dizygotic (DZ) pregnancies. Due to a potentially more adverse intrauterine environment among MZ compared to DZ twins, MZ twins may be more prone to develop various metabolic abnormalities. Our findings of a higher glucose and insulin profiles after oral glucose ingestion, and recently lower insulin-stimulated glucose uptake--indicating glucose intolerance and insulin resistance--together with higher levels of total-cholesterol and triglycerides among MZ compared to DZ twins demonstrate an effect of zygosity (i.e. intrauterine environment) on these metabolic variables and therefore question the assumption of equal pre- and postnatal environment in MZ and DZ twins. Our studies provide further evidence for a prenatal component in the aetiology of the components included in the syndrome and question the validity of classical twin studies on phenotypes with a known prenatal aetiological component. However, our present knowledge is currently far too insufficient to discard the results from classical twin studies concerning the relative role of genes versus environment for the development of the metabolic and haemodynamic components included in the metabolic syndrome.     

The metabolic syndrome: is this diagnosis necessary?

Values of insulin-mediated glucose disposal vary continuously throughout a population of apparently healthy persons, and a difference of > or = 600% exists between the most insulin-sensitive and the most insulin-resistant persons. Approximately 50% of this variability can be attributed to differences in adiposity (25%) and fitness (25%), with the remaining 50% likely of genetic origin. The more insulin-resistant a person, the more likely that he or she will develop some degree of glucose intolerance, high triacylglycerol and low HDL concentrations, essential hypertension, and procoagulant and proinflammatory states, all of which increase the risk of cardiovascular disease (CVD). To identify persons at greater CVD risk because of these abnormalities, the World Health Organization, the Adult Treatment Panel III, and the International Diabetes Federation created a new diagnostic category, the metabolic syndrome. Although the components of the 3 versions of the metabolic syndrome are similar, the specific values for those components that define an abnormality are somewhat different, and the manner in which the abnormalities are used to make a positive diagnosis varies dramatically from version to version. This review will summarize the similarities in and differences between the 3 versions of the metabolic syndrome, point out that the clustering of components that make up all 3 definitions of the metabolic syndrome is not accidental and occurs only in insulin-resistant persons, develop the argument that diagnosing the metabolic syndrome in a person has neither pedagogical nor clinical utility, and suggest that the clinical emphasis should be on treating effectively any CVD risk factor that is present.     

Multidimensional Disadvantages of a Gluten-Free Diet in Celiac Disease: A Narrative Review

A gluten-free diet is the mainstay method of treatment and the prevention of celiac disease complications. However, an inadequately balanced gluten-free diet can increase the risk of obesity, negatively affect glucose and lipid metabolism, and increase the risk of the metabolic syndrome. Therefore, an adequate nutritional counselling is necessary for patients diagnosed with celiac disease in order to prevent and treat the components of the metabolic syndrome.     

Metabolic syndrome after pregnancy complicated with gestational diabetes: four-year follow-up

Although clustering of cardiovascular risk factors is unquestionable, the importance of the "metabolic syndrome" as a distinct cardiovascular risk marker has been debated recently. In the authors' previous report a high frequency of glucose intolerance was described 8 years after a pregnancy complicated by gestational diabetes, often associated with other unfavorable metabolic parameters. In the present study the objective was to estimate the prevalence of metabolic syndrome in a cohort of previously gestational diabetes women, using different diagnostic criteria, 4 years after delivery. Those data were compared to a control group of 39 women with normal glucose tolerance during pregnancy. Irrespective of the criteria used, metabolic syndrome was found more frequently among women with prior gestational diabetes. The prevalence of metabolic syndrome increased by degree of deterioration of glucose tolerance in the prior gestational diabetes group. Overweight women in both group had 10-fold increased risk of metabolic syndrome compared to normal-weight women. According to our results a clustering of cardiovascular risk factors might be observed in previous gestational diabetes women, 4 yrs after delivery. These data highlight the importance of regular follow-up of these women, and the possible advantage of early and aggressive treatment of each component of metabolic syndrome.     

Metabolic syndrome, inflammation and atherosclerosis

The inflammatory component of atherogenesis has been increasingly recognized over the last decade. Inflammation participates in all stages of atherosclerosis, not only during initiation and during evolution of lesions, but also with precipitation of acute thrombotic complications. The metabolic syndrome is associated with increased risk for development of both cardiovascular disease and type-2 diabetes in humans. Central obesity and insulin resistance are thought to represent common underlying factors of the syndrome, which features a chronic low-grade inflammatory state. Diagnosis of the metabolic syndrome occurs using defined threshold values for waist circumference, blood pressure, fasting glucose and dyslipidemia. The metabolic syndrome appears to affect a significant proportion of the population. Therapeutic approaches that reduce the levels of proinflammatory biomarkers and address traditional risk factors are particularly important in preventing cardiovascular disease and, potentially, diabetes. The primary management of metabolic syndrome involves healthy lifestyle promotion through moderate calorie restriction, moderate increase in physical activity and change in dietary composition. Treatment of individual components aims to control atherogenic dyslipidemia using fibrates and statins, elevated blood pressure, and hyperglycemia. While no single treatment for the metabolic syndrome as a whole yet exists, emerging therapies offer potential as future therapeutic approaches.     

The role of Mediterranean diet in the epidemiology of metabolic syndrome; converting epidemiology to clinical practice

Metabolic syndrome is a collection of associated conditions such as dyslipidemia, high blood pressure, impaired glucose tolerance and tendency to develop fat around the abdomen. It is now well known that individuals with the metabolic syndrome are at high risk for atherosclerosis and, especially, coronary heart disease. However, it has been suggested that people with the metabolic syndrome may benefit from aggressive lifestyle modification, through diet and exercise. In this review we summarize scientific evidence regarding the effect of Mediterranean diet on the development of metabolic syndrome.     

Dietary patterns and metabolic syndrome--a review of epidemiologic evidence

Metabolic syndrome is associated with increased risk of coronary heart disease and type 2 diabetes, and appears to be widely prevalent in both developed and developing countries. While lifestyle modification is recommended for management of the syndrome, the dietary pattern most beneficial for patients is yet to be ascertained. Original research papers from the Medline database were examined for dietary patterns that may be associated with the syndrome. Three large-scale epidemiological studies were found fitting our criteria. Dietary patterns high in fruit and vegetable content were generally found to be associated with lower prevalence of metabolic syndrome. Diet patterns with high meat intake were frequently associated with components of metabolic syndrome, particularly impaired glucose tolerance. High dairy intake was generally associated with reduced risk for components of metabolic syndrome with some inconsistency in the literature regarding risk of obesity. Minimally processed cereals appeared to be associated with decreased risk of metabolic syndrome, while highly processed cereals with high glycaemic index are associated with higher risk. Fried foods were noticeably absent from any dietary pattern associated with decreased prevalence of metabolic syndrome. The conclusion of this review is that no individual dietary component could be considered wholly responsible for the association of diet with metabolic syndrome. Rather it is the overall quality of the diet that appears to offer protection against lifestyle disease such as metabolic syndrome. Further research is required into conditions, such as overweight and obesity, which may influence the effect of diet on the development of metabolic syndrome.     

陕西省秦岭以北地区成人尿酸与代谢综合征关系的横断面研究

目的 了解陕西省秦岭以北地区成人血清尿酸和代谢综合征(MS)及其组分的关系,为有效预防和控制MS提供科学依据.方法 于2007年10月至2008年4月,分层随机抽取陕西省秦岭以北地区3 298名居民作为调查对象,对尿酸、血脂、血糖水平等进行检测,对血压、身高、体重、腰围、臀围等进行测量,并对个人医疗史以及生活方式等进行问卷调查,分析尿酸水平与MS之间的关系.结果 调查人群高尿酸血症和MS的粗患病率分别为6.22％和16.89％,男性均高于女性,差异有统计学意义(P＜005).随着尿酸水平的升高,MS检出率及其组分(体质指数、血压、总胆固醇、甘油三酯、低密度脂蛋白胆固醇、餐后30和120 min血糖)水平逐渐升高,差异有统计学意义(P＜0.01).随着MS组分数目的增加,高尿酸血症的检出率呈上升趋势,经趋势x2检验,有统计学意义(P＜0.01).并且随着尿酸水平的升高,MS的检出率也呈增高趋势,趋势x2检验有统计学意义(P＜0.01).以尿酸水平第1分位区间(＜199 μmol/L)人群作为参照,第2、3、4分位区间(199～、249～、≥309 μmol/L)人群患MS风险(OR,95％ CI)分别为1.235(0.979～1.559)、1.884( 1.472 ～2.410)、3.569(2.704～4.711)倍.结论 血尿酸升高与MS及其各组分密切相关.     

Age of menarche and the metabolic syndrome in China

OBJECTIVES: In western populations, young age of menarche is associated with increased cardiovascular risk. Little is known about the potential impact of menarche on the metabolic syndrome (as a proxy for cardiovascular risk) in rapidly economically developing populations where age of menarche is falling. We sought to determine the relation between age of menarche and the metabolic syndrome in a rapidly developing Chinese population. METHODS: We carried out a retrospective historical cohort study of 7349 women from the Guangzhou Biobank Cohort Study, China, enrolled in 2003-2004. Cardiovascular risk factors were obtained from physical examination; age of menarche was obtained from self-report. The main outcome measure was the metabolic syndrome and its components. RESULTS: Adjusted for age, education, and number of pregnancies, young age of menarche (<12.5 years) compared with age of menarche > or =14.5 years was associated with a higher risk of the metabolic syndrome (odds ratio = 1.49; 95% confidence interval = 1.22-1.82), central obesity (1.35; 1.10-1.65), raised blood pressure (1.34; 1.09-1.65), raised fasting glucose (1.40; 1.15-1.71), and higher triglyceride levels (1.36; 1.12-1.67). Further adjustment by waist circumference attenuated these effects, but the odds ratios remained elevated. CONCLUSIONS: Earlier age of menarche experienced by younger women in China today, now 12.5 years on average in urban populations, may contribute to an increase in the metabolic syndrome and thereby an increase in cardiovascular disease as these women age. These results further highlight the importance of childhood antecedents of adulthood disease.     

Does a diagnosis of metabolic syndrome have value in clinical practice?

"The metabolic syndrome" is the name for a clustering of risk factors for cardiovascular disease and type 2 diabetes that are of metabolic origin. These risk factors consist of atherogenic dyslipidemia, elevated blood pressure, elevated plasma glucose, a prothrombotic state, and a proinflammatory state. There are 2 major, interacting causes of the metabolic syndrome-obesity and endogenous metabolic susceptibility. The latter typically is manifested by insulin resistance. The metabolic syndrome is accompanied by a 2-fold increase in the risk of cardiovascular disease and a 5-fold increase in the risk of type 2 diabetes. A clinical diagnosis of the metabolic syndrome is useful because it affects therapeutic strategy in patients at higher risk. However, there are 2 views about the best therapeutic strategy for patients with the metabolic syndrome. One view holds that each of the metabolic risk factors should be singled out and treated separately. The other view holds that greater emphasis should be given to implementing therapies that will reduce all of the risk factors simultaneously. The latter approach emphasizes lifestyle therapies (weight reduction and increased exercise), which target all of the risk factors. This approach is also the foundation of other therapies for targeting multiple risk factors together by striking at the underlying causes, as in the development of drugs to promote weight reduction and to reduce insulin resistance. Treating the underlying causes does not rule out the management of individual risk factors, but it will add strength to the control of multiple risk factors.     

Alcohol consumption and the metabolic syndrome in Korean adults: the 1998 Korean National Health and Nutrition Examination Survey

BACKGROUND: The metabolic syndrome is associated with a high risk of cardiovascular disease morbidity and mortality. Light and moderate alcohol consumption have been associated with reduced cardiovascular disease morbidity and mortality. OBJECTIVE: This study was performed to examine the association between alcohol consumption and the metabolic syndrome. DESIGN: The study sample comprised 7962 Korean adults (3597 men, 4365 women) who had participated in the 1998 Korean National Health and Nutrition Examination Survey. RESULTS: The prevalence of the metabolic syndrome was 20.8% in men and 26.9% in women. The adjusted odds ratio for the metabolic syndrome in the group consuming 1-14.9 g alcohol/d was 0.71 (95% CI: 0.53, 0.95) in men and 0.80 (95% CI: 0.65, 0.98) in women. Alcohol consumption had a significant inverse relation with the odds ratio for low HDL cholesterol in all alcohol groups. Heavy alcohol consumption (> or =30 g/d) was associated with significantly higher odds ratios for high blood pressure and high triacylglycerol in men and high fasting blood glucose and high triacylglycerol in women. Odds ratios for the metabolic syndrome and its components tended to increase with increasing alcohol consumption. The dose-response relation of the odds ratio between alcohol consumption and the clustering of > or =3 risk factors was significant in both the high and low HDL-cholesterol groups. CONCLUSIONS: Although alcohol consumption had a significant inverse relation with the odds ratio for low HDL cholesterol in all alcohol groups, an increasing dose-response relation was found between alcohol consumption and the odds ratio for the metabolic syndrome. This might be due to the opposite relation of alcohol consumption to other components of the metabolic syndrome.     

Prevalence of Metabolic Syndrome and Associated Cardiovascular Risk Factors in Guatemalan School Children

Guatemala is experiencing a nutritional and lifestyle transition. While chronic malnutrition is prevalent, overweight, obesity and chronic diseases have increased substantially in the country. This study was conducted to investigate the prevalence of metabolic syndrome and the associated cardiovascular risk factors in the pre-adolescent Guatemalan population. A cross-sectional study was conducted among 302 Guatemalan children (8–13 years old) attending public and private schools in the Municipality of Chimaltenango. Demographic data and anthropometric and blood pressure measurements were collected. A blood sample was taken after an 8 h overnight fast and analyzed for glucose, triglyceride and high-density lipoprotein cholesterol levels. The data were analyzed to identify factors associated with metabolic syndrome and with its components. The prevalence of metabolic syndrome in the study population was 2.0 %. However, approximately 54 % of the children had at least one component of metabolic syndrome, while none had four or five of the components. The three most prevalent risk factors were high triglycerides (43.4 %), low HDL cholesterol (17.2 %) and obesity (12.3 %). Boys were more likely to be obese than girls and rural children were more likely to have higher triglyceride levels than urban children. Although the prevalence of metabolic syndrome is low, the fact that majority of the children already have at least one component of metabolic syndrome is cause for concern since components of metabolic syndrome can continue into adulthood and increase the risk for chronic diseases later in life. Therefore, immediate action should be taken to address the problem.     

Metabolic syndrome in childhood and adolescence

Metabolic syndrome has an outstanding impact on public health due to its increasing prevalence and poor prognosis. The development of insulin resistance, as a consequence of obesity, can be demonstrated even in childhood which has a pivotal role in the pathomechanism of the syndrome. Besides obesity, low birth weight, increased gain in body mass in early childhood, decreased pubertal insulin sensitivity and clinical markers of insulin resistance (acanthosis nigricans, polycystic ovarian syndrome, premature adrenarche) confer risk of metabolic syndrome. Currently, there are no consistent and consensus based diagnostic criteria of metabolic syndrome in children and adolescents. The most recent definition of the International Diabetes Federation [central obesity plus any two of four factors (raised triglyceride, reduced high-density lipoprotein-cholesterol, raised blood pressure and raised fasting plasma glucose)] is not approved for children and epidemiology data are not yet available. Applying the modified version of the most commonly used Adult Treatment Panel III diagnostic system for children and adolescents, the prevalence is given as 4.2% in the literature. As the components of the syndrome, frequency were as follows: 9.8-17.9% for abdominal obesity, 21.0-23.4% for elevated triglyceride, 18.3-23.3% for reduced high-density lipoprotein-cholesterol, 4.9-7.1% for elevated blood pressure and 0.8-1.7% for impaired fasting glucose. High frequency of morphological and functional disturbances of the vascular and endothelial systems seen frequently among children with signs of metabolic syndrome suggests early cardiovascular events and underlines the clinical significance of this entity. The most effective tool for prevention of metabolic syndrome is to avoid the development of childhood obesity. In case of established disease, the effective treatment should address the different components of the syndrome. The authors emphasize the need of elaboration of consensus based pediatric diagnostic criteria, national prevalence data, protocols for prevention, early recognition and effective treatment.     

Whole-grain intake is inversely associated with the metabolic syndrome and mortality in older adults

BACKGROUND: Whole-grain intake has been inversely associated with the metabolic syndrome in middle-aged populations, but the association has not been investigated in older adults. The metabolic consequence of consuming high whole-grain diets may differ in elderly persons, who are prone to greater insulin resistance and impaired glucose tolerance. OBJECTIVE: The aim of the present study was to examine the cross-sectional association between whole- and refined-grain intake, cardiovascular disease risk factors, prevalence of the metabolic syndrome, and the incidence of cardiovascular disease mortality in the same cohort of older adults. DESIGN: The nutritional status of 535 healthy persons aged 60-98 y was determined from 1981 to 1984. The subjects kept a 3-d food record and had their blood tested for metabolic risk factors. The metabolic syndrome was defined based on criteria set by the third report of the National Cholesterol Education Program. The vital status of the subjects was identified in October 1995. RESULTS: The results showed a significant inverse trend between whole-grain intake and the metabolic syndrome (P for trend = 0.005) and mortality from cardiovascular disease (P for trend = 0.04), independent of demographic, lifestyle, and dietary factors. Fasting glucose concentrations and body mass index decreased across increasing quartile categories of whole-grain intake (P for trend = 0.01 and 0.03, respectively), independent of confounders, whereas intake of refined grain was positively associated with higher fasting glucose concentrations (P for trend = 0.04) and a higher prevalence of the metabolic syndrome (P for trend = 0.01). CONCLUSION: Whole-grain intake is a modifiable dietary risk factor, and older and young adults should be encouraged to increase their daily intake to > or = 3 servings/d.