logo SBA


Digital archive of theses discussed at the University of Pisa


Thesis etd-03262014-093705

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