Oxidative damage and associated inflammatory risk factors in obese Emirati women. Body mass index versus waist circumference.

OBJECTIVES: To establish whether body mass index (BMI) or waist circumference (WC) is a better predictor of cardio metabolic risk factors that are associated with increased visceral fat among obese women from the United Arab Emirates (UAE).
METHODS: In this  cross-sectional study, 333 obese subjects visiting community health centers in Al Ain city, UAE, were recruited between 2012 and 2015. After a written consent subjects had anthropometric, clinical and biochemical measurements.  Fasting serum and plasma samples were collected for the measurement of markers of oxidative damage, antioxidants and inflammation.  Outcome measures were compared between 4 equal BMI and WC quartiles.
RESULTS: We observed significantly higher blood pressure, c-reactive protein levels, IL6 levels, and protein carbonyls contents and lower β-carotene levels in the fourth quartile than in the first quartile for both BMI and WC (p less than 0.01). Glutathione peroxidase and adiponectin both decreased and TNF-α increased with increasing WC quartiles but not BMI quartiles; however, the results were statistically significant only for TNF-α (p=0.032). 
Conclusion: Both elevated BMI and elevated WC are associated with increased cardio metabolic risk factors in obese Emirati women; however, WC is a stronger predictor than is BMI.

Obesity is a known risk factor for chronic diseases including type 2 diabetes, hypertension and cardiovascular disease (CVD).1-3 In the Gulf region, the prevalence of obesity is increasing, and in some countries such as the United Arab Emirates (UAE), obesity is a major public health problem.1-4 Recent studies suggest that abdominal/visceral obesity as determined by waist circumference (WC) is closely related to chronic diseases associated with obesity, especially in the Middle East.5-9 An International study that included subjects from the Middle East assessed the relationships of BMI and WC to CVD reported that globally, the waist-to-hip is strongly related to the risk of myocardial infarction.8,9 If increased WC was used to assess the risk of CVD in the Middle East, the number of people classified as obese would increase significantly.8 Furthermore, the results suggested that BMI was uninformative for assessing CVD risk in the Arabs, highlighting the need for the present study.8,9 A number of inflammatory cytokines secreted by visceral fat have been implicated in obesity-related complications.3,10 Oxidative damage and inflammation are possible mechanisms linking obesity to diabetes and CVD risk. For example, oxidative stress has been found to correlate with increased inflammation in obese patients, and this may be the mechanism underlying obesity-related insulin resistance. Although the UAE has one of the highest rates of obesity and related diabetes mellitus in the world, the factors that affect obesity and associated diseases in this region, remain unclear. In this cross-sectional study, we examined whether BMI or WC is a better predictor of metabolic risk factors including oxidative damage, endothelial dysfunction, and inflammatory markers among obese women from the UAE.

Methods

Overweight and obese female subjects (BMI >25) visiting community health centers in the city of Al Ain, UAE, between 2012 and 2015 were invited to take part in the study. After informed written consent was obtained from the eligible subjects, the subjects underwent baseline assessment, which included anthropometric measurements and 10-ml fasting blood samples collected to measure markers of antioxidants, oxidative damage and inflammation. Other related biochemical variables, including endothelial dysfunction, were also measured. The exclusion criteria were severe chronic disease and use of anti-obesity medications. Al Ain Medical District Human Research Ethics Committee approved the study (protocol number 09/70), and written consent was obtained from each subject recruited to the study.

Measurements

All participants underwent baseline clinical assessment to record medical and clinical data, including history of chronic disease, medications and smoking history. The Tanita body composition analyzer was used to assess height, body weight, and fat mass. Waist circumference was measured using a flexible plastic tape to the nearest 0.1 cm.

Blood samples

Blood samples were taken in tubes containing potassium EDTA and anticoagulant, thoroughly mixed at room temperature and immediately transferred to the laboratory. Following centrifugation for 10 min at 4000 rotations/minutes, both plasma and serum tubes were stored at -80°C.

Antioxidants

Vitamin E and beta-carotene analyses were carried using HPLC [Waters (Milford, MA) system gradient liquid chromatography pump (model 515)]. Commercially available Cayman’s colorimetric assay kits from USA-Kit numbers 706002, 707002, and 703102 were used to measure antioxidant enzymes, including glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase. Inflammatory markers (TNF, IL6 and adiponectin) and markers of endothelial dysfunction vascular cell adhesion molecule-1 (v-CAM) and intracellular adhesion molecule (i-CAM) were measured using enzyme-linked immunosorbent assay (ELISA) kits.

Lipid peroxidation

The lipid peroxidation product thiobarbituric acid-reactive substances (TBARS) was measured using an assay kit “no. 10009055” (Cayman, 1180 E. Ellsworth Rd., Ann Arbor, MI 48108.

Protein oxidation

Protein oxidation was assessed measuring protein-bound carbonyls calorimetrically using a reagent kit (no. 10005020) from Cayman Chemical. Circulating levels of renal and liver functions, lipids, high sensitivity C-reactive protein (hsCRP), vitamin B12 and serum folate were measured using an Integra 400 Plus automated analyzer (Roche Diagnostics, Mannheim, Germany).

The Statistical Package for the Social Sciences (IBM Corp., Armonk, NY) version 19 was used for statistical analyses. BMI and WC were divided into 4 equal quartiles. For within and among-group differences we used One-way ANOVA or Kruskal-Wallis H depending on data distribution, and a p value < 0.05 was considered significant.

Results

A total of 333 overweight or obese female subjects were recruited and included in this analysis. Their mean ±SD age was 36±11 years. Based on the WHO non-Asian population sex-adjusted cut-off points for BMI, 76 (23%) of the 333 female subjects were at high health risk [BMI 25.1-29.9], and 257 (77%) were at increased health risk [BMI ≥30]. Based on the corresponding waist circumference cut-off points, 43 (13%) subjects were at high risk [WC=81-88 cm], 257 (77%) [WC >88 cm] were at increased health risk, and 20 (6%) subjects had satisfactory WC [≤80 cm].

shows the baseline demographic and clinical characteristics of obese female subjects according to BMI and WC divided into 4 quartiles. The number of subjects who have had more education and the number in employment were significantly higher in the first quartile than in the fourth quartile of the distribution for both BMI and WC (p<0.05). Systolic and diastolic blood pressure were both significantly lower in the first quartile than in the fourth quartile of the distribution for both BMI and WC (p< 0.05).

Levels of inflammatory, endothelial dysfunction, antioxidant and oxidative damage markers according to BMI and WC quartiles are shown in (Tables 2 & 3). The levels of hs-CRP, IL6, and protein carbonyl were clearly and significantly increased and that of b-carotene was decreased at the fourth quartile relative to the first quartile of the distribution for both BMI () and WC () (p<0.01). The TNF and glutathione levels were higher and adiponectin and glutathione peroxidase levels were lower in the fourth quartile than in the first quartile of the distribution for WC (), but not BMI quartiles (); however, a significant difference was only observed for TNFa. No significant difference in endothelial dysfunction marker levels, vitamin B12 or folate was observed between the first and fourth quartiles for either WC or BMI.

Discussion

We observed increased levels of inflammation and oxidative damage markers and decreased levels of antioxidant markers with increasing BMI and WC quartile number; however, the levels of some metabolic risk markers were significantly higher at higher WC quartiles but not at higher BMI quartiles. Increased BMI is used to measure obesity; however, recent work suggests that abdominal obesity, which is more prevalent in the UAE region, is more closely associated with chronic disease.5-7 as BMI does not account for factors such as body size and body fat distribution. It is believed that a high WC, which reflects abdominal/visceral obesity, is more closely related to morbidity because visceral fat secretes several metabolically active that are involved in the diseases related to obesity.3,10, In a small, recent study, we observed trends of increasing inflammatory marker levels and decreasing antioxidant levels with increasing WC; however, these trends were significant in women only.12 Oxidative damage and inflammation are potential mechanisms that link obesity to increased risk of related chronic diseases. For example, markers of oxidative stress have been found to correlate with inflammatory markers in adipose tissue of obese patients; this might be the mechanism for obesity-related complications.13,14 Oxidative stress is defined as the imbalance between the generation of free oxygen radicals and the antioxidant defense system and is known to generate reactions that damage membrane proteins and lipids. Several recent studies have suggested close associations between oxidative stress and complications of diabetes, signifying an important role of oxidative stress in the pathology and progression of the disease.13 Furthermore, a relationship between oxidative stress and insulin resistance has been reported, suggesting that antioxidants may reduce insulin resistance.14 Dietary antioxidants may also be predictors of some risk factors in healthy subjects as evaluated by inflammatory biomarkers, blood pressure and plasma glucose.15 For example, a meta-analysis concluded that increasing dietary intake of vegetables could reduce the risk of type 2 diabetes.16 Taken together, these results suggest that increased fruit and vegetable intake may be important for mitigating the deleterious effects associated with visceral obesity.

A recent study revealed that higher consumption of red/purple fruit and vegetables, such as berries, strawberry, and red plum was associated with lower abdominal fat gain.17 Another study reported a beneficial effect of higher intake of fruits, vegetables and cereal fiber on abdominal obesity prevention.18 The effects of fruits and vegetables on visceral obesity might be mediated by a decreased inflammatory response, the mitigation of oxidative damage associated with inflammatory cytokines that favor lipolysis and lipid oxidation instead of fat storage.19,20 This is clearly an area for further research.

Although the roles of both oxidative damage and related inflammation in the development of chronic complications in obese patients are well accepted, the benefits of increased fruit and vegetable consumption in the treatment of visceral obesity and related complications, including type 2 diabetes mellitus, have not been sufficiently studied.21

In conclusion, the above results suggest that the levels of oxidative stress and inflammatory markers are higher in obese women than non-obese women and increase with increasing WC. We are not aware of any previous studies that have attempted to measure the prevalence of cardio-metabolic risk factors, for example, by measuring antioxidant enzymes and oxidative markers, in relation to BMI and WC in obese women from the Middle East. Interventions that mitigate oxidative damage and/or reduce inflammation could be essential for reducing or preventing obesity and related chronic disease. Increased intake of dietary supplements notable fruits and vegetables may be an innovative strategy for controlling and reducing the obesity epidemic. Studies on dietary factors that are known to mitigate oxidative stress and inflammation and also promote health are urgently needed in this population.

Table 1

Baseline demographic and clinical characteristics of obese female subjects according to quartiles of body mass index (BMI) and waist circumference (WC), mean (SD).

Table 2

Markers of inflammation, endothelial dysfunction, oxidative damage and antioxidants according to body mass index (BMI) divided into 4 equal quartiles.

Table 3

Markers of inflammation, endothelial dysfunction, oxidative damage, and antioxidants according to waist circumference (WC) divided into 4 equal quartiles.