Calculated adiposity and lipid indices in healthy Arab children as influenced by vitamin D status

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Original Article

Calculated adiposity and lipid indices in healthy Arab children as influenced by vitamin D status Q13

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Nasser M. Al-Daghri, PhD*, Shaun Sabico, Yousef Al-Saleh, Omar S. Al-Attas, Abdullah M. Alnaami, Marwan M. AlRehaili, Mohammed Al-Harbi, Hanan Alfawaz, George Chrousos, Majed S. Alokail Biomarkers Research Program Biochemistry Department, College of Science, King Saud University, Riyadh, Saudi Arabia (Drs Al-Daghri, Sabico, Al-Attas, Alnaami, AlRehaili, Chrousos, and Alokail); Prince Mutaib Bin Abdullah Chair for Biomarkers Research on Osteoporosis, King Saud University, Riyadh, Saudi Arabia (Drs Al-Daghri, Sabico, Al-Saleh, Al-Attas, Alnaami, AlRehaili, Alfawaz, Chrousos, and Alokail); King Abdulaziz Medical City, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia (Dr Al-Saleh); Diabetes Centers and Units Administration, Ministry of Health, Riyadh, Saudi Arabia (Dr Al-Harbi); Department of Food Science and Nutrition, College of Food Science and Agriculture, King Saud University, Riyadh, Saudi Arabia (Dr Alfawaz); and First Department of Pediatrics, Athens University Medical School, Athens, Greece (Dr Chrousos) KEYWORDS: Vitamin D deficiency; Body adiposity index; HDL cholesterol; Arab children; Obesity

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BACKGROUND: Both childhood obesity and vitamin D deficiency are common in the Middle East. This study aims to determine whether the associations of vitamin D status to traditional anthropometric parameters hold true for nonconventional measures of adiposity, such as body adiposity index (BAI), a measure of body fat percentage, waist-to-hip ratio, waist-to-height ratio (WHtR), and lipid indices, in apparently healthy Arab children. METHODS: A total of 4183 apparently healthy Saudi school students (1906 boys; 2277 girls) aged 12 to 17 years were recruited in this cross-sectional study. Anthropometrics were obtained. Fasting blood glucose and lipids were measured routinely. Serum 25(OH)D was measured using chemiluminescence. RESULTS: In all subjects, age, BAI, waist-to-hip ratio, and high-density lipoprotein cholesterol (HDL-C) accounted for 4% of the variance in serum 25(OH)D (P , .001). All adiposity indices were inversely associated with 25(OH)D, with WHtR being the most inferior in terms of strength of association. Vitamin D deficiency significantly increased risk for low HDL-C in all subjects (odds ratio [95% confidence interval]: 1.70 [1.24-2.3]; P , .001). CONCLUSION: BAI is significantly associated with 25(OH)D levels in Arab children. WHtR is inferior than other anthropometric measures of obesity regarding the strength of association with 25(OH)D. Risk for or low HDL-C is significantly increased with vitamin D deficiency. Interventional studies may determine the potential cardioprotective effects of vitamin D correction in this population. Ó 2016 National Lipid Association. All rights reserved.

* Corresponding author. Prince Mutaib Bin Abdullah Chair for Biomarkers Research on Osteoporosis, Biochemistry Department, College of Science, King Saud University, PO Box, 2455, Riyadh 11451, Kingdom of Saudi Arabia. E-mail address: [email protected] Submitted November 17, 2015. Accepted for publication February 6, 2016.

Background Childhood obesity has been a persistent public health threat in most developed nations, and low- and middleincome countries, in modern-day times.1 Although

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significant health programs were made to address this epidemic, the global progress to fight childhood obesity and other nonchronic communicable diseases remains uneven.2 In the Kingdom of Saudi Arabia, current evidence points to a consistently high prevalence of obesity in adults; and more importantly, the already high prevalence of childhood obesity seems to further increase with time.3–5 The most common obesity risk factors identified in Saudi children recently include frequent eating in restaurants and physical inactivity.6 The same obesity risk factors are true for Saudi adults with the inclusion of marital status, level of education, and presence of other chronic, noncommunicable diseases.7 The high prevalence of childhood obesity, including the full metabolic syndrome, seems to be common within the Arab region, with countries such as Egypt reporting the same.8 These parallel obesity trends in both Saudi adults and children are consistent with the observations of Al-Daghri et al,9 in that increased adiposity and abnormal cardiometabolic patterns are highly heritable among Arab families. But aside from the genetic components of obesity, sedentary lifestyle and over nutrition are also common.10 Emerging risk factors for obesity, however, have been identified, and among them is vitamin D deficiency.11 Several cross-sectional studies done in the Kingdom of Saudi Arabia have consistently shown the extremely high prevalence of vitamin D deficiency in the country, as well as significant inverse associations of circulating 25(OH)D with body mass index (BMI) and other cardiometabolic parameters in children and adults.12,13 However, these clinically relevant associations were not compared with other novel adiposity and cardiometabolic indices that highlight body fat distribution and circulating lipid ratios. Whether vitamin D status influences other cardiometabolic indices aside from the conventional ones warrants further investigation. This is to better understand the extraskeletal and pleiotropic effects of 25(OH)D and to determine which among the obesity-related measures will improve the most from vitamin D status correction. Our study aims to determine whether other calculated adiposity and lipid indices, such as body adiposity index (BAI), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), and non– high-density lipoprotein cholesterol (HDL-C), are associated with circulating 25(OH)D in apparently healthy Arab children.

Methods A total of 4183 Saudi school students aged 12 to 17 years recruited over a 5-year period (2008–2013) were included in this cross-sectional study. Ethical approval was obtained from the Ethics Committee of the College of Medicine and the College of Science, King Saud University (KSU), Riyadh, Saudi Arabia.

Subjects All subjects were Saudi school children aged 12 to 18 years at the time of recruitment. Subject information was collected from the master database of the Biomarkers Research Program of KSU in Riyadh, Saudi Arabia. This master database is a collection of both the Biomarkers Screening in Riyadh database, a collaborative project with the Ministry of Health, which is a repository of more than 17,000 Saudi subjects aged 1 to 70 years old randomly recruited from different households, and the on-going collaborative project with the Ministry of Education involving randomly selected Saudi school children from different schools of the capital.13,14 All subjects filled a generalized questionnaire that contains demographic and medical information. Anthropometrics included height (cm), weight (kg), waist (cm), and hips (cm), as well as blood pressure (mm Hg). Fasting blood samples were also obtained. Subjects’ consent and assent (if applicable) were obtained before inclusion. All subjects were apparently healthy at the time of recruitment, and only those with acute conditions that require immediate medical attention, non-consenting, and nonambulatory subjects were excluded.

Blood analysis Fasting blood sample extraction from all subjects was done under the supervision of a registered physician and nurse who were part of the research team. Blood samples were centrifuged, and serum was placed in polystyrene tubes for immediate transport and storage (220 C) at Biomarkers Research Program, KSU. These samples were analyzed for fasting blood glucose and lipid profile (triglycerides, HDL-C, and total cholesterol) using routine standardized laboratory techniques (Konelab, Vantaa, Finland). Serum 25(OH)D was measured using DEQAS- Q7 certified COBAS e-411 automated analyzer (Roche Diagnostics, Indianapolis, IN). For serum 25(OH)D assay, the interassay and intra-assay coefficients of variation were 8.0% and 5.6%, respectively, with a detection limit of ,10 nmol/L.

Calculations and cutoffs used BMI was calculated as weight (kg)/height (m)2. WHR was calculated as waist (cm) divided by hip (cm) circumferences. WHtR was calculated as the waist (cm) over height (cm) ratio. BAI was calculated based on the formula Q8 proposed by Bergman et al15 (hip circumference [cm] divided by height [m] 1.5 2 18). Low-density lipoprotein cholesterol (LDL-C) was calculated using the Friedman equation [total cholesterol2HDL-C2triglycerides/2.2], and non–HDL-C was calculated as the difference between total cholesterol and HDL-C as previously used in the same cohort.14

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Adiposity and lipid indices vs 25(OH)D in children

(mmol/L), BMI, systolic blood pressure, diastolic blood pressure, total cholesterol, glucose, and log triglycerides as independent variables. Bonferroni-corrected P values were calculated and applied in the regression analysis. Multinomial logistic regression was done to identify the risk based on the different cutoffs as previously mentioned. All P values were 2-tailed, and P values ,.05 were significant unless otherwise specified.

Obesity was defined based on age- and gender-specific cutoffs proposed by Cole et al.16 Cutoffs for BAI, WHtR, and WHR were determined using the 90th percentile values obtained from the cohort. Abnormal lipids were diagnosed based on the proposed cutoffs by the American Academy of Pediatrics for children and adolescents (elevated triglycerides . 1.47 mmol/L; low HDL-C , 1.03 mmol/L; high non–HDL-C . 3.75 mmol/L).17 Finally, vitamin D status was defined as follows: deficiency (,50 nmol/L), insufficiency (50–74.9 nmol/L), and sufficiency ($75 nmol/L).18

Results

Data analysis

Vitamin D deficiency was seen in 3464 (82.8%) subjects, vitamin D insufficiency in 590 subjects (14.1%), and vitamin D sufficiency in 129 (3.1%) subjects (not shown in tables). Table 1 summarizes the general characteristics of boys and girls and showed no significant difference in the mean age. With regard to BAIs, girls had significantly higher BMI, waist and hip circumference, and BAI than boys (P values ,.001). Boys, on the other hand, had significantly higher mean WHR than girls (P , .001). Mean systolic blood pressure and mean blood glucose were also significantly higher in boys than girls (P values ,.001), whereas girls had significantly higher mean diastolic blood pressure than boys. Among the lipid indices, only mean triglycerides was higher in boys than girls, having a borderline significance (P 5 .046), whereas the rest of the mean lipid values (total cholesterol, HDL-C, LDL-C, and non–

Data analyses were done using the SPSS 22.0 (SPSS Inc, Chicago, IL). Data were expressed as mean 6 standard deviation. Kolmogorov–Smirnov test was performed to test continuous variables for normality. All non-Gaussian parameters were logarithmically transformed before correlations and linear regression analyses. Independent Student’s t-tests were used to compare means between groups of normally distributed data and Mann-Whitney U test for non-normal data. Pearson correlation was used to determine relations between 25(OH)D and age, BMI, waist circumference, hip circumference, WHR, WHtR, BAI, systolic blood pressure, diastolic blood pressure, glucose, triglycerides, total cholesterol, LDL-C, HDL-C, and non– HDL-C. Stepwise multiple linear regression analysis was done using log-transformed 25(OH)D concentrations as the dependent variable and age, BAI, WHR, HDL-C

Table 1

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General characteristics of subjects P value

Parameters

Boys

Girls

N (%) Age (y) Adiposity indices BMI (kg/m2) BMI z-score Waist circumference (cm) Hip circumference (cm) Waist-to-hip ratio (WHR) Waist-to-height ratio (WHtR) Body adiposity index (BAI) Clinical indices Systolic blood pressure (mm Hg) Diastolic blood pressure (mm Hg) Glucose (mmol/L) Lipid indices and vitamin D Triglycerides (mmol/L)* Total cholesterol (mmol/L) LDL cholesterol (mmol/L) HDL cholesterol (mmol/L) Non-HDL cholesterol 25(OH)D (nmol/L)*

1906 (45.6) 14.3 6 1.9

2277 (54.4) 14.3 6 2.1 4.8 1.0 12.2 13.0 0.1 0.1 5.8

,.001 ,.001 ,.001 ,.001 ,.001 .003 ,.001

115.6 6 14.0 69.4 6 9.7 5.2 6 0.7

113.1 6 13.6 70.0 6 9.6 5.0 6 0.6

,.001 .06 ,.001

1.0 (0.6) 4.0 6 0.8 2.5 6 0.7 0.9 6 0.3 3.0 6 0.8 36.6 (23.6)

1.0 (0.5) 4.2 6 0.9 2.7 6 0.7 1.1 6 0.3 3.1 6 0.8 27.2 (16.4)

.046 ,.001 ,.001 ,.001 ,.001 ,.001

21.4 0.06 61.7 83.0 0.9 0.5 25.0

6 6 6 6 6 6 6

5.1 1.0 23.0 16.9 0.1 0.1 7.6

22.0 0.05 71.1 91.0 0.8 0.47 30.0

6 6 6 6 6 6 6

.92

BMI, body mass index; HDL, high-density lipoprotein; LDL, low-density lipoprotein. Data presented as mean 6 standard deviation for normal variables, whereas median (interquartile range) is used for non-normal variables. *Non-normal variables; P value significant at P , .05.

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HDL-C) were significantly higher in girls than boys (P values ,.001). Finally, mean serum 25(OH)D was significantly higher in boys than girls (P , .001). Table 2 summarizes the bivariate associations of serum 25(OH)D to the metabolic indices measured in boys and girls. In boys, significant inverse associations were observed in age, BMI, hip circumference, WHtR, blood pressure (systolic and diastolic), glucose, and triglycerides. Only HDL-C was positively associated with serum 25(OH) D in boys. Similar to boys, the same significant inverse associations between serum 25(OH)D and adiposity indices were observed in girls, with the addition of WHR. However, contrary to the significant inverse associations observed in boys and with the exception of triglycerides, all the lipid indices were positively associated with serum 25(OH)D in girls. Furthermore, blood pressure (systolic and diastolic) and glucose were not associated with serum 25(OH)D in girls. Neither gender was BAI associated with serum 25(OH)D. Significant predictors for serum 25(OH)D are summarized in Table 3 using all the anthropometric and metabolic indices as independent variables and serum 25(OH)D as dependent variable. In boys, age, triglycerides, and BMI cumulatively accounted for 8% in the variances observed in serum 25(OH)D (P , .001). Significant predictors in girls included age, total cholesterol, and HDL-C, as well as WHR, predicting 4% of the variances perceived in serum 25(OH)D. Among all subjects, age, BAI, WHR, and HDL-C accounted for 4% of the variance in serum 25(OH)D (P , .001).

Table 2 Correlations between 25(OH)D (nmol/L) and assessed parameters Parameters

All

Boys

Girls

Age (y) Adiposity indices BMI (kg/m2) Waist circumference (cm) Hip circumference (cm) Waist-to-hip ratio (WHR) Waist-to-height ratio (WHtR) Body adiposity index (BAI) Clinical indices Systolic blood pressure (mm Hg) Diastolic blood pressure (mm Hg) Glucose (mmol/L) Lipid indices Triglycerides (mmol/L)‡ Total cholesterol (mmol/L) LDL cholesterol (mmol/L) HDL cholesterol (mmol/L) Non-HDL cholesterol

20.11*

20.19*

20.07*

20.12* 20.14* 20.19* 0.13* 20.08* 20.15*

20.15* 20.02 20.16* 0.04 20.10* 20.05

20.08* 20.14* 0.11* 20.05† 20.10* 20.04

20.03 20.02 20.01

20.16* 20.06† 20.06†

0.01 0.02 20.03

20.03 0.04† 0.01 0.07* 0.02

20.08* 20.01 20.02 0.15* 20.03

0.005 0.13* 0.10* 0.17* 0.09*

Data represented in terms of Pearson correlation coefficient for Logged Transform 25(OH)D and Spearman correlation for non-normal 25(OH)D levels. *Indicates P value ,.01 significance level. †Indicates P value ,.05 significance level. ‡Represents non-normal variable.

Risk for obesity as defined by the different adiposity indices and risk for abnormal lipid profile according to vitamin D status are summarized in Table 4. Both vitamin D insufficiency and deficiency were not significantly associated with increased risk for obesity and other adiposity indices in both boys and girls. On the other hand, increased risk for low HDL-C, by as much as 2 folds, Q9 in both boys (odds ratio [OR]: 1.81; confidence interval [CI]: 1.17–2.8; P , .01) and girls (OR [CI]: 2.04 [1.42– 2.9]; P , .01) was significantly linked to vitamin D deficiency. The same increased risk in low HDL-C for boys, but not in girls, was seen in vitamin D insufficiency (OR 1.7 [1.24–2.3]; P , .01). Finally, both vitamin D insufficiency and deficiency seem to confer protection against high non–HDL-C, but only in girls (see Table 4). Figure 1 shows the decreasing mean values of all adiposity indices with respect to increasing 25(OH)D levels in all subjects, specifically BMI, waist and hip circumferences, and BAI (P values ,.001).

Discussion Our study extended the influence of vitamin D status in childhood obesity with the use of nonroutine calculated adiposity and lipid indices such as BAI, WHR, WHtR, and non–HDL-C in Arab children. Our study is also one of the few to use BAI in children, as most of the studies in this population focuses on BMI-percentile for age and gender, as well as waist circumference for truncal obesity. BAI has been documented to directly estimate body fat percentage without the necessary routine adjustments for age and gender.14 The significance of BAI as a predictor for vitamin D status in children only appeared without gender stratification, as splitting into boys and girls resulted in other anthropometric predictors: BMI as a significant predictor of 25(OH)D in boys, and WHR in girls. Consequently, WHtR, although inversely associated with 25(OH)D, seemed inferior to other anthropometric indices with respect to the strength of association. The significant inverse associations of 25(OH)D to all the anthropometric parameters used in the study are consistent with recent findings on children and adolescents,13,19–21 including the study of Dong et al, which showed an inverse association between 25(OH)D and total body fat mass in black youth.22 This inverse association, however, is not seen in all populations,23,24 indicating possible ethnic influence or differences in confounding factors. Furthermore, this inverse association of 25(OH)D to adiposity observed in cross-sectional studies does not translate to improved anthropometric indices in some 25(OH)D correction intervention trials.25 Possible explanations include increased vitamin D sequestration in the adipose tissue and volumetric dilution.25 Bioavailable 25(OH) D levels were observed to be the same for obese and lean children, with differences seen in the concentration of vitamin D binding protein.26 Findings from our study also

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Table 3

Adiposity and lipid indices vs 25(OH)D in children

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Multivariate stepwise regression analysis of log-transformed 25(OH)D vs all variables measured

Gender

Predictors

b

SEM

Adjusted R2

P value

Boys

Age Triglycerides Body mass index Age HDL cholesterol Total cholesterol Waist-to-hip ratio (WHR) Age Body adiposity index WHR HDL cholesterol

20.04 20.26 20.01 20.02 0.23 0.04 20.41 20.02 20.01 0.54 0.15

0.01 0.09 0.003 0.01 0.04 0.01 0.17 0.005 0.002 0.13 0.03

0.08

3.08213*

0.04

1.70213*

0.04

3.34223

Girls

All subjects

HDL, high-density lipoprotein; SEM, standard error of mean. Waist and hip circumference, WHR, low-density lipoprotein cholesterol, and non-HDL cholesterol were removed from the regression model due to multicollinearity; P value significant at ,.05. *Denotes Bonferroni-adjusted P value.

highlight gender differences in terms of associations between 25(OH)D and adiposity indices measured. This is in line with our previous observation that sexual dimorphism exists in the physiology of vitamin D not only at the clinical phenotypic level but more so in the serum proteomic level.27 Moving on to the lipid indices, circulating 25(OH)D levels were found to be significantly associated with HDL-C in both boys and girls and was a significant predictor of 25(OH)D levels. Moreover, low HDL-C was associated with increased risk for vitamin D deficiency, in both boys and girls. These findings are consistent with other studies that highlight the significant relations of unfavorable lipid profile and vitamin D deficiency in children.28,29 Unlike the adiposity indices, lipids, particularly HDL-C and triglycerides, are more sensitive to changes in

25(OH)D levels, strengthening the premise that vitamin D correction is cardioprotective in terms of improving the lipid profile of vitamin D deficient subjects at least in adults.30 Whether this cardioprotective effect is also true for children needs to be proven in interventional studies that specifically target dyslipidemia through vitamin D correction. The authors acknowledge several limitations. Information on sunlight exposure and physical activity, both significant confounding factors on vitamin D status, was not included in the study. Furthermore, other calculated adiposity indices and other lipid ratios were removed as advanced statistical analyses revealed multi-collinearity. Nevertheless, this is the first study to address that 25(OH)D levels in Arab children influence body adiposity, regardless of its distribution and lipids with preponderance to HDL-C.

Table 4 Multinomial logistic regression analyses using the different adiposity and lipid indices as dependent variables and 25(OH)D status as independent variable

Parameters Adiposity indices Obese (age and gender equivalent) WHR (.0.94) BAI (.36.54) WHtR (.0.56) Lipid Indices Elevated triglycerides (.1.47) Low HDL cholesterol (,1.03) High non-HDL cholesterol (.3.75)

Sufficient ($50 nmol/L)

Insufficient (between 25 and 50 nmol/L)

Deficient (,25 nmol/L)

Boys

Girls

Boys

Girls

1.0

1.91 (0.90–4.05)

0.64 (0.32–1.29)

1.54 (0.61–3.88)

1.20 (0.60–2.38)

1.0 1.0 1.0

1.12 (0.77–1.63) 1.15 (0.42–3.13) 1.55 (0.73–3.31)

1.04 (0.34–3.18) 1.77 (0.85–3.67) 1.19 (0.54–2.65)

0.91 (0.55–1.52) 2.04 (0.63–6.61) 1.30 (0.49–3.43)

1.74 (0.58–5.17) 1.06 (0.50–2.22) 1.45 (0.66–3.19)

1.0

1.07 (0.71–1.61)

1.07 (0.66–1.75)

1.04 (0.62–1.75)

1.22 (0.75–1.99)

1.0

1.70 (1.24–2.3)**

1.35 (0.94–1.93)

1.81 (1.17–2.8)**

2.04 (1.42–2.9)**

1.0

0.93 (0.57–1.51)

0.61 (0.41–0.90)*

1.42 (0.77–2.62)

0.61 (0.41–0.91)*

BAI, body adiposity index; HDL, high-density lipoprotein; WHR, waist-to-hip ratio; WHtR, waist-to-height ratio.

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web 4C=FPO

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Figure 1

Mean adiposity indices (standard error) vs vitamin D status in all subjects.

In conclusion, calculated adiposity indices, including BAI, a gross measure of body fat percentage, are inversely associated with circulating 25(OH)D levels in Arab children. WHtR, although also associated with 25(OH)D levels, is inferior to other anthropometric measures relative to strength of association. Vitamin D deficiency is associated with low HDL-C in Arab children. Interventional studies are needed to determine the potency of the potential cardioprotective effects of vitamin D correction in this population.

Acknowledgments

Q10

The authors thank the Deanship of Scientific Research, Prolific Research Group Program (PRG-1436-15), Vice Rectorate for Graduate Studies and Scientific Research in King Saud University (KSU), Riyadh, Saudi Arabia, for funding the study. The authors are also grateful to Mr Malak Nawaz Khan Kattak and Mr Syed Danish Hussain for the statistical analysis of the data.

Financial disclosure Q11

N.M.A.-D. has nothing to disclose.

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Adiposity and lipid indices vs 25(OH)D in children

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