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Tesi etd-03262014-093705


Thesis type
Tesi di dottorato di ricerca
Author
CHEDRAUI, PETER
URN
etd-03262014-093705
Title
CLINICAL, BIOCHEMICAL - MOLECULAR AND ETIOLOGICAL ASPECTS OF THE METABOLIC SYNDROME AFTER THE MENOPAUSE
Settore scientifico disciplinare
MED/40
Corso di studi
NEUROSCIENZE E SCIENZE ENDOCRINOMETABOLICHE
Commissione
tutor Prof. Simoncini, Tommaso
Parole chiave
  • sindrome metabolica
Data inizio appello
03/03/2014;
Consultabilità
completa
Riassunto analitico
The metabolic syndrome (METS) is a cluster of lipid and non-lipid factors that increase<br>cardiovascular risk [1]. The National Cholesterol Educational Program and its Third Adult<br>Treatment Panel (NCEP ATP-III) have established diagnostic criteria for the METS, which<br>are met when three or more of the following are present: abdominal obesity, decreased highdensity<br>lipoprotein cholesterol (HDL-C) levels and increased serum triglycerides (TG), fasting<br>glucose and/or blood pressure levels [2].<br>A. Prevalence<br>Prevalence of the METS is higher in women, especially those of Latin America ancestry [3],<br>with an increased frequency observed in relation to age and the menopausal status. Indeed,<br>during the menopausal transition there is an emergence of features related to the METS:<br>obesity, dyslipidemia, diabetes, hyperinsulinism, hypertension and co-morbid conditions [4],<br>possibly but not totally related to increasing estrogenic deficiency [5]. Rates may also vary<br>according to the studied population from 22% [6] to 34% as determined in seven crosssectional<br>studies of non-diabetic Europeans [7]. This syndrome increases cardiovascular<br>morbidity and mortality and the risk of developing diabetes [8].<br>B. The effect of the menopause over female weight<br>The prevalence of abdominal obesity is nearly double that of general obesity, with rates in<br>North American women calculated for 2008 in 65.5% (aged 40-59 years) and 73.8% (60<br>years or more)[9]. It has been suggested that body mass index (BMI) but not menopausal<br>status determines central adiposity in postmenopausal women. However, there is substantial<br>evidence that the perimenopause is associated with a more rapid increase in fat mass and<br>redistribution of fat to the abdomen, resulting in a transition from a gynoid to an android<br>pattern of fat distribution and an increase in total body fat [10]. Moreover, postmenopausal<br>women have greater amounts of intra-abdominal fat as compared to premenopausal ones,<br>as determined with several radiological modalities [11]. Waist circumference represents both<br>5<br>subcutaneous and visceral adipose tissue depot size and correlates closely with the risk for<br>cardiovascular disease. In women, it is also closely associated with dyslipidemia [12].<br>Abdominal fat is considered an endocrine organ as it has the capacity to secrete<br>adipokines and other active substances closely related to metabolic diseases: insulin<br>resistance, type 2 diabetes and the METS [13]. Both, the menopausal transition and aging,<br>are associated with changes in adipose tissue metabolism, which contribute to the<br>accumulation of body fat after menopause [14]. Deleterious changes in inflammatory markers<br>and adipokines correlate strongly with increased visceral adiposity after the menopause [15].<br>Waist circumference significantly changes in relation to the time since final menstrual<br>period. Moreover, significant increases in central abdominal fat have been reported from<br>longitudinal studies in Caucasian and Asian women [16]. It has been observed that when<br>non-obese premenopausal women are followed-up for several years, significant increases in<br>total, percentage and truncal and visceral fat mass occur [16]. Women who later became peri<br>or postmenopausal displayed a significant increase in visceral fat compared with baseline<br>[16].<br>C. The impact of increased weight over menopausal symptoms<br>Severity and prevalence of menopausal symptoms relate several factors. These include<br>not only the hormonal changes imposed by the transition, but also psychosocial factors. As<br>weight increased during the menopausal transition, so do menopausal symptoms. Obesity is<br>an independent risk factor for more severe menopausal symptoms [17,18].<br>Reduction of weight, BMI and abdominal circumference have been associated with a<br>significant reduction in vasomotor symptoms women who are overweight and obese [19].<br>The combination of dietary modification and exercise also has positive effects on health<br>related quality of life (HRQOL) and psychological health, which may be greater than that from<br>exercise or diet alone [20]. Improvements in weight, aerobic fitness and psychosocial factors<br>may mediate some of the effects of these interventions on HRQOL [20]. Weight loss in<br>6<br>overweight and obese women improves psychological wellbeing, HRQOL, self-esteem and<br>health practices [21]. In addition, dietary weight loss and exercise exert a positive effect over<br>insulin resistance in postmenopausal women, which together with a decrease in menopausal<br>symptoms may potentially decrease cardiovascular risk.<br>D. The METS a state of pro-inflammation and endothelial dysfunction<br>The METS is associated with increased inflammation, endothelial dysfunction, oxidative<br>stress and abnormalities in both the macro- and microvasculature [22]. Adipocytes and<br>adipose-tissue macrophages are involved in the production of IL-6, which is one of the main<br>mediators of chronic inflammation [23]. Elevated IL-6 is an established risk factor for<br>cardiovascular events in women after the menopause; thus, it is interesting to find that the<br>presence of METS, rather than the menopause itself, relates to increased IL-6 levels. IL-6<br>serum levels are associated with visceral adipose tissue and can influence insulin levels [24].<br>On the other hand, it has been reported that IL-6 polymorphisms may play a role in the<br>pathogenesis of the METS through the modulation of IL-6 levels [25].<br>F. Endothelial dysfunction during pregnancy as a model for future METS risk<br>Preeclampsia is a leading cause of maternal mortality and morbidity worldwide [26].<br>Epidemiological data indicate that women complicated with preeclampsia are more likely to<br>develop future cardiovascular disease (CVD). Population-based studies<br>relate preeclampsia to an increased risk of later chronic hypertension (RR, 2.00 to 8.00) and<br>cardiovascular morbidity/mortality (RR, 1.3 to 3.07), compared with normotensive pregnancy<br>[27]. Women who develop preeclampsia before 36 weeks of gestation or have multiple<br>hypertensive pregnancies are at highest risk (RR, 3.4 to 8.12). The underlying mechanism<br>for the remote effects of preeclampsia is complex and probably multifactorial. Many risk<br>factors are shared by CVD and preeclampsia, including endothelial dysfunction, obesity,<br>hypertension, hyperglycemia, insulin resistance, and dyslipidemia. Therefore, it has been<br>proposed that the METS may be a possible underlying mechanism common to CVD<br>7<br>and preeclampsia. Follow-up and counseling of women with a history of preeclampsia may<br>offer a window of opportunity for prevention of future disease [27].
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