Prevalence of Metabolic Syndrome and Associated Risk Factors in Medical Students of Universidad Central Del Ecuador

It is known that obesity increases cardiovascular risk and metabolic syndrome in children [2], adolescents and adults [3]. It is also known that inflammation plays an important role in scientific and technical development of these diseases [4]. Changes in lifestyle caused by the evolution of our era have been listed as one of the determining factors that trigger this condition [5]. In children and adolescents, obesity seems to be the most important cause of insulin resistance, which makes them a risk group for developing Metabolic Syndrome (MS) [6]. Some authors attribute these percentages of overweight and obesity to the lack of physical activity that is becoming more common in younger children. Physical activity was inversely associated with various metabolic indicators such as lipid profile, insulin resistance and High Blood Pressures (HBP), components of MS. However, physical activity must meet certain conditions (type, intensity, frequency and duration), in order to be efficient [7]. Sedentary people were found to have abnormalities in their lipid profile, including high triglycerides, low HDL cholesterol, elevated nonHDL cholesterol and Apo B, all those associated with an increased cardiovascular risk [8].


Introduction
Nowadays, adolescent obesity is a serious public health problem.In developed countries, there are about 110 million young people suffering from overweight or obesity [1].
It is known that obesity increases cardiovascular risk and metabolic syndrome in children [2], adolescents and adults [3].It is also known that inflammation plays an important role in scientific and technical development of these diseases [4].Changes in lifestyle caused by the evolution of our era have been listed as one of the determining factors that trigger this condition [5].In children and adolescents, obesity seems to be the most important cause of insulin resistance, which makes them a risk group for developing Metabolic Syndrome (MS) [6].Some authors attribute these percentages of overweight and obesity to the lack of physical activity that is becoming more common in younger children.Physical activity was inversely associated with various metabolic indicators such as lipid profile, insulin resistance and High Blood Pressures (HBP), components of MS.However, physical activity must meet certain conditions (type, intensity, frequency and duration), in order to be efficient [7].Sedentary people were found to have abnormalities in their lipid profile, including high triglycerides, low HDL cholesterol, elevated non-HDL cholesterol and Apo B, all those associated with an increased cardiovascular risk [8].
Until recently, adipose tissue was considered only as an energy storage site, but it is now known to be an active metabolic tissue that releases a number of bioactive mediators called adipokines.Some of these mediators (TNF-alpha, IL-6, IL-1) induce a systemic low-grade inflammation in people with excessive corporal fat [9].serum determination of these mediators in adolescents is an effective tool to predict and prevent cardiovascular diseases [14][15][16].
Several studies have shown the sensitivity of IL-6 in relation to increases in body weight, for that reason it is considered an excellent marker of metabolic syndrome [17].
Moreover, features exhibited by IL-6 suggest that it functions as a potent inducer of the acute phase in the inflammatory process in young obese people [17].
C-reactive protein (CRP) is an acute phase protein produced by the liver in response to factors that are released by adipocytes.This protein increases in the same pattern as IL-6 in acute and chronic inflammatory diseases and is an independent predictor of myocardial infarction, arterial disease, and sudden cardiac death, even in healthy people [18].CRP levels reflect inflammation and this relates to the lifestyle of a person, including dietary and physical activity.It has also been associated with insulin resistance and atherosclerosis in adults [19].
CRP is considered a strong indicator of future heart disease [20], elevated serum concentrations found in obese adolescents show the higher risk of cardiovascular events that these young individuals have [21].Several studies have also shown that, along with the elevation of CRP and cytokines in these patients, resistance to the action of insulin is also increased [16,22].
Combined analysis, including anthropometry and computerized tomography studies have shown a strong association between waist circumference (WC)and abdominal fat, so it has given the WC a discriminatory capacity, higher than the Body Mass Index (BMI) and waist-hip ratio, considering it a risk marker of chronic diseases such as hypertension, diabetes mellitus type 2 and cardiovascular disease [23].
In Ecuador, the follow-up given to the diagnosis of MS to predict the risk of cerebrovascular disease and diabetes mellitus is limited.Although there is significant, but sporadic evidence to justify the study of MS, there are few publications about it.Perhaps the most significant is that reported in a study conducted on a sample of male population, between the ages of 30 and 60, from the Ecuadorian highlands, in which the MS prevalence was 13.4% according to ATP III criteria and 33.1% according to IDF [24].There are not studies on MS and its risk factors in young people.Data published in the National Health and Nutrition Examination Survey (ENSANUT-ECU) 2011-2013, indicate that the prevalence of overweight and obesity in Ecuadorian adolescents between the age 12 to 19 is 26% while in individuals over 19 years old rises to 62.8%.It was higher in women (65.5%) than men (60%) [25].Other authors found an overweight and obesity prevalence of 13.7% in women and 7.5% in men [26].We work with medical students between 17 and 25 years old giving us a prevalence of 7.58% metabolic syndrome, 22.24% pre obesity and 3.14% obesity [27].
Nutritional recommendations for the MS aim to improve insulin sensitivity and prevent or treat metabolic disorders.Although some of the nutrients in the diet can influence insulin sensitivity, more benefits are obtained with weight loss [28].Several studies recommend reducing consumption of saturated fatty acids and trans fatty acids, and increase consumption of Mono Unsaturated Fatty Acids (MUFA) and Poly Unsaturated Fatty Acids (PUFA) [29].The MUFA and PUFA consumption helps control blood pressure (BP), clotting, endothelial function and insulin resistance, therefore, having beneficial effects in preventing and treating MS [30].
Students attending university have a tendency to adopt unhealthy eating habits, sedentary habits and a lifestyle characterized by stress and long schedules that results in the consumption of less nutritious food, irregular meal times and lack of exercise and obesity [31,32].
This investigation presents the results of the study on the prevalence of metabolic syndrome and associated risk factors in medical students of the first three semesters of faculty of Medical Sciences of the Universidad Central Del Ecuador (UCE) and the relation between insulin resistance and metabolic syndrome components.

Materials and Methods
This is an epidemiological, analytical, cross-sectional study in which the risk factors associated and the prevalence of metabolic syndrome was determined.
It included all students enrolled in first, second and third semester of the School of Medicine, Faculty of Medical Sciences of the UCE, period October 2014 -March 2015, that decided to participate voluntarily before signing an informed consent (Approved by the Ethics Committee of the Faculty of Medical Sciences of the UCE).883 students were incorporated.All tests were performed in a special office prepared for that purpose in the Faculty of Medical Sciences of UCE.All students answered a survey in which information on personal data, personal medical history, family medical history, eating habits, alcohol consumption, smoking habits, and exercise habits were collected.
Students were weighed and measured in light clothing and with no shoes using a SECA weighting scale (new, factory calibrated), BMI was determined.The abdominal and hip circumferences were measured with a tape measure, according to international standards.The BP was measured using a Riestermercury sphygmomanometer (new, factory calibrated) by a single researcher previously trained to avoid measurement bias.BP was measured after at least a 5-minute break with the student in sitting position, placing the sleeve on the left arm.If there was any concern with the BP measurement the student's BP was retested for a second time after a 10 minutes rest.The value used was the average between the two measures.
All students were scheduled for specific times in the morning after a 12-hour fasting, we took a sample of venous blood (from the elbow crease), from which the plasma was separated.The data collected was: Blood chemistry which included urea, glucose, creatinine, uric acid, lipid profile: Total cholesterol (TC), triglycerides, HDL, using a Roche Modular analyzer with P-800 enzymatic colorimetric method, LDL was calculated using the equation Friedewall.They were taken as cutoff points for each variable established by WHO and IDF [5,33].
A data sample of serum was stored at -70 degrees Celsius for further processing to determine high-sensitivity CRP, IL-6 and insulin.CRP (Latex) HS (Tina quant® C-reactive protein) was quantified in a Modular analyzer Evo P800 using the immunoturbidimetric method: latex particles Acs monoclonal mouse anti-CRP with a detection limit of quantification of 0.1 mg / L; Interleukin 6 (IL-6) was determined using the Immulite 2000 Immunometric sequential chemiluminescent solid phase method with a quantification limit of 2 pg / ml and insulin was measured using an Evo Modular E170 analyzer, using the method ECLIA / Anti-Insulin antibody (Biotin) Acs Acs anti-insulin-Ru, with a limit of quantification of 0.20 US / ml.HOMA-IR index, described by Matthews et al. [34] and validated by several authors for epidemiological studies, that is the product of fasting insulin (microU / ml) and the glucose in blood was used for the assessment of insulin resistance Fasting (mmol / L) divided by 22,5.35As cutoff HOMA-RI ≥ 2,5 was used [35,36].
For determination of IL-6 and insulin, we included all students who were overweight or obese and as a control group an equal number of students with normal weight based on BMI were included randomly.
Students who do not perform physical activity at least 3 times (days) a week were classified as sedentary people.
A database in Microsoft Excel 2010 and statistical analysis was done using SPSS 21.The results are presented in the tables and graphs below.Statistical tests used were: measures of central tendency, confidence intervals at 95%, chi x2, T test and Mann Whitney, ANOVA, Pearson correlation and association measures Odds Ratio, with its values of p, Cut off points court were taken from WHO, IDF and laboratory reference values to perform the sample analysis.

Results
883 college students with a range of 17-25 years were included in the study, the average age was 19.3 ± 1.4, and 67% of the participants were female.
Table 1 shows the average anthropometric and biochemical variables presented by gender, by making a comparative analysis; it was found that both men and women have a similar BMI.Waist circumference average is increased in women; men have a higher Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP), women showed higher total cholesterol, while men presented higher triglyceride values.The mean difference between men and women was statistically significant (p < 0.05) in waist circumference, SBP, DBP, total cholesterol, HDL cholesterol, triglycerides and glycemia.
Table 2 shows the prevalence of risk factors for MS according to gender.In the general population, it was found that 22% were overweight and 3% obese.In women, 20.9% were overweight and 2.3% obese, while men had 24.7% and 4.6% of overweight and obesity respectively.The waist circumference was altered (women > 80 / men > 90) in 52.3% of women and 26.2% of men (p0.001).HDL cholesterol was altered in 39.7% of women versus 18.2% of men (p 0.001).BP levels were above the normal range in men more than in women (24.4% vs 9.8%, p 0.001).Total cholesterol values, LDL, triglycerides and glucose, have shown no statistically significant differences between genders.Tabaco consumption is higher in men than in women (19.8% vs 7.3%, p0.001).In relation to the sedentary lifestyle, the number of women who are not physically active is greater than that of men (92.5% vs 75%, p0.001).
The prevalence of MS was 8.2% (n = 73), where 68% were women and 32% men.The 16.08% of students had at least two risk factors for the development of MS, only 34.65% of the study population did not present any risk factors (Graph 1).
The prevalence of MS according to BMI and gender (Graph 2) was also calculated, in which 4.40% of women and 1.70% of normal-weight men had MS, overweight prevalence increased to 23.10% in females and 15.00% for men and when present obesity rises to 30.80% and 46.70% in males and females respectively.
The risk of developing MS in overweight women was 6.75 (3.66 -12.45) times that of women with normal weight (p0.001) while in the overweight or obese men the risk was 14.06 (4.63 -42.63) times more than men with normal BMI (p0.001).
In the general population categorized by BMI and presence of MS it was found statistically significant differences in the averages of all the variables studied in Table 3.In relation to fasting glucose, this parameter was plotted in a graph versus BMI (Graph 3).It is observed a slight trend for the glucose to increase when the BMI does.
Regarding the inflammatory markers, 19.4% of the general population presented CRP values between 1-3 mg / l, 7.4% of 3-9 mg / l and 7.48% had altered levels of IL6 (> 3.1 pg / ml).The average CRP was lower in students with a BMI > 25 kg / m2 in relation to the group of< 25 kg / m2, so do MS carriers where the average is lower compared to those who do not have MS.
The average values found in IL6 as BMI < 25 kg / m2 and > 25 kg / m2 show a slight increase in the values of IL6 in the group of overweight and obesity (p0.0001) and in the group with MS (p0.0001) (Table 4).
It was also found that 70.3% of the students who exercise three or more days a week and more than thirty minutes (nonsedentary), have a normal BP contrary to those who do not perform any activity (sedentary) where the percentage normal BP was of 52.27%, this difference is statistically significant.In addition, the last group was found to have an increased risk for developing a BP altered OR 1.96 (1.30 -2.97) (p0.001) (Table 5).
Regarding the BP, statistically significant differences were found in all variables when BP was high (> 135/85 mmHg) (Table 6).
Insulin resistance (HOMA-IR index) was plotted in a graph versus BMI (Graph 4).The graph does not show a clear relationship between insulin resistance and BMI.When the parameters were stratified by sex, a significant relationship was not found (Graph 5).

Discussion
In this study, 8.2% were diagnosed with MS (IDF), the prevalence in women was higher (68%).Similar studies conducted in other countries such as Colombia, Chile and Venezuela showed overall prevalence of 2% (IDF), [37] 1.8% (IDF) [38] and 3.3% (NCP ATPIII) [39], respectively.Moreover a Mexican study found a prevalence of 7.8% in a similar population (NCP ATPIII) [40].An important feature to point out it that the 16.08% of students had at least two risk factors for the development of MS and about 50% at least one, same as described in a study in similar populations in Mexico [41].Only 34.65% of the study population did not present any risk factor.
In this study, 29.3% of men were overweight or obese compared with 23.3% in women, which is consistent with studies in Mexico [42,43], Venezuela [39] and Chile [38] these factors were higher in men.Data from ENSANUT-ECU conducted by the Ministry of Public Health of Ecuador reports that the prevalence of pre-obesity and obesity in adolescents between 12 to 19 years old is 26% and population of 19-60 years old 62.8% [25] In relationship to WC, women had a major alteration which is consistent with data from several studies in Latin America [37,38,40,43], but not with those found by Trujillo-Hernandez et al. who reported that the WC was preferentially altered in men [42] this agrees with the growing trend of the worldwide obesity in children and adolescents and our study group is not an exception.
Total cholesterol, LDL and glucose values are not altered in most of the sample, unlike other studies [37,39] Surprisingly, HDL alterations found in this study occurred predominantly in women   39.7%, in contrast to 18.2% for men, data similar to those found in Mexican studies.[40,43] However, this data disagrees with that found in studies from countries such as Chile and Colombia, where low levels of HDL were significantly more common in men [37,39] Triglyceride level was higher in men (12.3%)than in woman (10.6%), showing a higher level compared to the Chilean study [38].
BP levels were above the normal range more in men than in women (24.4% vs 9.8%), same results as in the studies cited previously [37,39] One thing that stands out is the probable association between the risk of developing hypertension at an early age and the presence of risk factors such as abnormal levels of triglycerides, BMI and WC.
Overall, it can be said that risk factors such as lipid profile, BP, blood glucose, BMI and WC are increase in students diagnosed with MS in relation to the healthy ones.In the same way, subjects with obesity and overweight showed values much higher than those reporting normal weight which is consistent with the literature [44].
hsCRP concentration is an independent risk factor and predictor of coronary heart disease.In adults, elevated hsCRP was significantly associated with body fat and specific components of MS [45] Adolescents and young adults' data in the field are limited.There have been some reports that levels of hsCRP and cardiovascular risk are similar to those of adults [46].
Few studies assessed the association between markers of inflammation and metabolic risk (insulin resistance, hypertension, dyslipidemia), this effect seems to be attenuated when obesity is adjusted.A study in Mexican children concludes that there is little evidence on the association between obesity, inflammation and cardiovascular risk factors [2].They found that concentrations of IL-6 correlate with BMI, but were not associated with insulin resistance when the model was adjusted for obesity and lipid concentration [2].In a study conducted in Argentina among adolescent students, the hsCRP values were not different among adolescents with and without MS [44].Other authors have reported higher levels of hsCRP in adolescents with MS.In this study hsCRP levels show a different behavior, it was found that the average hsCRP according to the WC is higher in normal subjects, this does not persist with the IL6, where the value is slightly higher in those with altered WC.For students who do not present any metabolic disorder, an increase value of hsCRP compared to those with MS was also found.The value of IL-6 is slightly higher in subjects with MS than in the healthy students.When correlated with BMI, the trend was observed again; those with normal weight reported a greater CRP value than overweight or obese.IL-6 was higher in the overweight and obese population, compared to the healthy ones with a statistically significant difference (p < 0.05).To rule out any kind of outside interference in the results of hsCRP, all subjects who reported some type of infectious disease (bacterial or viral) 15 days prior to sampling and subjects with leukocytosis were excluded (>10.000).Data were stratified according to lipid profiles to rule out that these values were responsible for the changes in CRP levels, and it was found no relationship.hsCRP data obtained in this study are not consistent with those reported by other authors, so that further studies are needed in young Ecuadorian population.If these data are repeated, it is necessary to rule out other variables such as age or genetics that are determining this type of behavior.The risk of cardiovascular events in our young people could be increased; however, it points out that the number of overweight students with altered WC and SM has lower concentrations of hsCRP than those found in normal individuals.
Regarding data from insulin resistance, there was no relationship between this parameter and BMI.This data is not consistent with the literature.The problem related with the HOMA-IR index can be attributed to the fact that insulin measure was made after, in a sample collected and saved in ultra freezing (-70 degrees Celsius) in a primary collector tube with gel separator.It is possible that the sample suffered contamination with red blood cells and this produced false low insulin levels.

Conclusions
Some studies have shown an association between the presence of MS in children and adolescents in the long term, especially due to the morbidity and mortality that these can cause.This morbidity and mortality have increased in younger ages and prospective studies are needed to clarify the true diagnostic value of MS in young people.
The prevalence of metabolic syndrome was 8.2% and only 34% of the population presented no risk factors for MS. 1 out of 4 students have some degree of overweight or obesity.A significant percentage of students presented alterations in plasma lipid levels and blood pressure.While most students are still in lowrisk categories, authors should continue doing this type of studies that will allow increasing awareness of the presence of risk for chronic non transmissible diseases and diagnosing and treating properly the MS patients.
Our results confirm the need to establish primary prevention programs of non-infectious diseases, it should be considered as a priority in health matters in populations like ours that are facing nutritional problems.

Limitations
A limitation of the study was the fact that insulin levels were measured in a saved sample, and for these reasons the obtained values have to be interpreted with caution.
A new study to measure the real values of insulin is now being developed by the authors.We believe this new study will clarify the data regarding insulin resistance.
NETLAB SA, clinical laboratory accredited under ISO 15189 international standards and certification Standardization LIPIDS PROGRAM CDC Atlanta.

Table 1 :
Average anthropometric and biochemical variables according to the gender

Table 2 :
Prevalence of risk factors evaluated in relation to gender.

Table 3 :
Average anthropometric and biochemical variables as BMI and presence of MS.

Table 4 :
Average of inflammatory markers in relation to the presence of MS, WC and BMI.

Table 5 :
Days a week that physical activity is performed according to BMI and PA.

Table 6 :
BP high or normal risk factors studied.