High prevalence of vitamin D insufficiency or deficiency in young adolescents in Korea

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1 Eur J Pediatr (2012) 171: DOI /s ORIGINAL ARTICLE High prevalence of vitamin D insufficiency or deficiency in young adolescents in Korea Youn Ho Shin & Ki Eun Kim & Choae Lee & Hye Jung Shin & Myung Suh Kang & Hye-Ree Lee & Yong-Jae Lee Received: 23 January 2012 /Revised: 9 April 2012 /Accepted: 11 April 2012 /Published online: 6 May 2012 # Springer-Verlag 2012 Abstract Recent studies suggest that vitamin D insufficiency or deficiency is not only a problem of older generations anymore but also an important health concern among younger generations. However, comprehensive data are lacking in Korean adolescents. We investigated the vitamin D (25-hydroxy vitamin D [25(OH)D]) status, the prevalence of vitamin D insufficiency or deficiency, and the association between vitamin D levels and insulin resistance and lipid profiles in a sample of 188 Korean adolescents aged years who participated in a general health check-up at a tertiary hospital. Vitamin D deficiency was considered as serum concentrations <20 ng/ml (50 nmol/ L);alevelof21 29 ng/ml (52 72 nmol/l) was considered to indicate vitamin D insufficiency, whereas a level of 30 ng/ml or greater (>75 nmol/l) was considered sufficient or optimum. In this cross-sectional study, vitamin D insufficiency or deficiency was found in 98.9 % of boys and 100 % of girls, whereas only 1.1 % of boys and 0 % of girls had a serum 25(OH)D level of Youn Ho Shin and Ki Eun Kim contributed equally to this work. Y. H. Shin : K. E. Kim : C. Lee Department of Pediatrics, CHA University School of Medicine, Seoul, South Korea H. J. Shin Department of Pediatrics, The National Medical Center, Seoul, South Korea M. S. Kang Department of Laboratory Medicine, CHA University School of Medicine, Seoul, South Korea H.-R. Lee : Y.-J. Lee (*) Department of Family Medicine, Yonsei University College of Medicine, 225 Geumhakno, Cheoin-gu, Yongin-si, Gyeonggi-do, South Korea ukyjhome@yuhs.ac greater than 30 ng/ml. In multivariate linear regression analysis, HOMA-IR, triglyceride, and LDL cholesterol were inversely associated with 25(OH)D concentrations. We found that vitamin D insufficiency or deficiency is a very common health problem in Korean adolescents, particularly in girls, and that serum 25 (OH)D levels are inversely associated with insulin resistance and lipid profiles. These results suggest that more time spent in outdoor activity for sunlight exposure and higher vitamin D intake may be needed in younger adolescents in South Korea. Keywords Vitamin D. Adolescents. Prevalence Introduction Vitamin D plays an important role in bone and mineral metabolism with its deficiency closely associated with osteomalacia and skeletal deformities in children and osteoporosis and fracture risk in adults [21]. Increasing evidence suggests that vitamin D is associated with a wide variety of nonskeletal diseases including cardiovascular diseases [12, 16], metabolic syndrome [6], diabetes mellitus [35], cancers [17, 25], infection [15], allergy [24], and autoimmune diseases [26]. Recent studies suggest that vitamin D insufficiency or deficiency is important in children and adolescents, not just in older people [2, 10, 14, 37]. It is estimated that between 36 % and 100 % of communityliving men and women have vitamin D deficiency [3 5, 7, 10, 14, 18, 20, 23, 27, 29 31, 33, 38]. Some researchers have reported the prevalence of vitamin D insufficiency to be approximately 50 % of healthy adolescents [37], but comprehensive data are lacking in Korean adolescents. Therefore, we investigated vitamin D status and prevalence of vitamin D insufficiency or deficiency and that serum 25(OH)D levels are inversely associated with insulin

2 1476 Eur J Pediatr (2012) 171: resistance and lipid profiles in a sample of Korean adolescent population aged years. Materials and methods Study subjects Two hundred twenty four adolescents aged 12 to 13 years old living in Seoul, Korea visited a health-screening center (The National Medical Center, Seoul, Korea) between May and July of 2009 for Student Health Examinations. The BMI percentiles for age and gender according to 2007 Korea Growth Charts for assessment of obesity were utilized [34]. Subjects meeting any of the following criteria were excluded (n036): any missing covariate information; a medication history of steroids, insulin, glucose regulators, or antihypertensive drugs; those who had not fasted for at least 12 h prior to blood sampling. After these exclusions, 188 subjects (91 boys and 97 girls) were included in our final analysis. The Hospital Ethics Committee reviewed and approved the study, and a written informed consent was obtained from study subjects or their guardians. Data collection Health examinations were performed by the same physician according to a standardized procedure. Body weight and height were measured in subjects to the nearest 0.1 kg and 0.1 cm, wearing light indoor clothing and without shoes using an automatic height weight scale. Waist circumference was measured to the nearest 0.1 cm using a steel measuring tape placed level with the iliac crest at the end of a normal expiration. A certified technician measured blood pressure (BP), a maximum of three times on the right arm in seated subjects after a 5-min rest with an automatic BP recorder. The average of all of the available measurements was used for analysis. BMI was calculated as the ratio of weight (kilogram)/height (square meter). Following a 12-h overnight fast, blood samples were obtained from the antecubital vein of each subject, and blood samples were obtained by venipuncture and immediately centrifuged, aliquoted, and frozen to 20 C. The frozen serum and plasma samples were stored at 70 C until analysis. Fasting plasma glucose, total cholesterol, triglyceride, and high density lipoprotein cholesterol (HDL-C) were measured by enzymatic methods using the Hitachi automated chemistry analyzer (Hitachi, Tokyo, Japan). Levels of low density lipoprotein cholesterol (LDL-C) were calculated using the following formula: LDL-C0total cholesterol HDL-C (TG/5). Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were also measured. Fasting insulin levels were measured by electroluminescence immunoassay (Roche, Indianapolis, IN, USA). Insulin resistance was estimated using the homeostatic model assessment of insulin resistance (HOMA-IR) and calculated using the following formula: HOMA-IR0[fasting insulin (μiu/ml) fasting glucose (mg/ dl)/18]/22.5 [32]. Serum 25(OH)D levels were measured by a chemiluminescence immunoassay (Roche, Indianapolis, IN, USA). Diagnostic criteria of vitamin D insufficiency or deficiency To categorize serum 25(OH)D concentrations in our sample population, we used the cutoffs reported in a review published by Holick in 2008 [22]. Vitamin D deficiency was considered as those of <20 ng/ml (50 nmol/l); a level of ng/ml (52 72 nmol/l) was considered to indicate vitamin D insufficiency, whereas a level of 30 ng/ml (>75 nmol/l) or greater was considered sufficient or optimum [8, 21, 31]. Statistical analysis All continuous variables are presented as mean values with standard deviation. Chi-square test was used to examine the statistical differences in distribution of the 25(OH)D levels between boys and girls. To examine independent correlates Table 1 Characteristics of the study population Boys (n091) Girls (n097) P value a Age (years) 12.2± ± Height (cm) 159.1± ± Weight (kg) 57.8± ± Waist circumference (cm) 78.1± ± BMI (kg/m 2 ) 22.7± ± Systolic blood pressure (mmhg) 109.8± ±12.3 <0.001 Diastolic blood pressure (mmhg) 66.8± ± Serum 25(OH)D levels (ng/ml) 14.5± ±3.1 <0.001 Fasting plasma glucose (mg/dl) 87.5± ± Total cholesterol (mg/dl) 143.6± ± Triglyceride (mg/dl) 93.8± ± HDL-C (mg/dl) 49.5± ± LDL-C (mg/dl) 75.3± ± AST (IU/L) 26.5± ± ALT (IU/L) 20.4± ± Insulin (μiu/ml) 10.8± ± HOMA-IR 2.3± ± BMI body mass index, AST aspartate aminotransferase, ALT alanine aminotransferase, HDL-C high density lipoprotein-cholesterol, LDL low density lipoprotein-cholesterol, HOMA-IR homeostasis model of assessment insulin resistance Data are expressed as the mean±sd a P values were calculated by independent two-sample t test

3 Eur J Pediatr (2012) 171: P <0.001 Table 3 Correlation between 25(OHD) concentrations and various parameters 25(OH)D levels (ng/ml) of serum 25(OH)D concentrations, a multivariate linear regression analysis was conducted with 25(OH)D levels as the dependent variable. All statistical analyses were performed with PASW statistical software (version 19.0; PASW Statistics; Chicago, IL, USA). All statistical tests were two-sided and statistical significance was determined at a P value <0.05. Results Boys Girls Fig. 1 The mean values of serum 25(OH)D in boys and girls (bars mean standard deviation. P value was calculated by independent twosample t test) The demographic and clinical characteristics of the study population are presented in Table 1. There were differences in height and waist circumference between boys and girls. There were also differences in systolic blood pressure and serum 25(OH)D, total cholesterol, LDL-C, AST, and ALT between boys and girls (Table 1). Figure 1 shows the mean values with standard deviation of 25(OH)D in boys and girls. The mean concentration of 25 (OH)D in girls was significantly lower than in boys, 14.5± 5.3 ng/ml for boys vs. 10.8±3.1 ng/ml for girls (P<0.001). Table 2 shows the distribution of boys and girls within the 25(OH)D range. In our total sample of 188 subjects, 5.3 % had 25(OH)D insufficiency (21 29 ng/ml) and 94.2 % had deficient concentrations (<20 ng/ml). Only one boy (1.1 %) had optimal concentrations of 25(OH)D and 98.9 % of boys and 100 % of girls showed vitamin D insufficiency or deficiency. Pearson s correlation results are listed in Table 3 and Fig. 2. Serum 25(OH)D levels were significantly correlated with diastolic blood pressure, total cholesterol, triglyceride, LDL-C, insulin concentrations, and HOMA-IR. In multivariate linear regression analysis, triglyceride, LDL- C, and HOMA-IR were inversely associated with 25(OH)D concentrations (Table 4). Discussion Subjects We examined the prevalence of vitamin D insufficiency or deficiency in a sample of Korean adolescent population aged years. In this cross-sectional study, we found that vitamin D insufficiency or deficiency is a very common health problem among young adolescents in Korea. Our findings are in line with current knowledge that vitamin D insufficiency or deficiency was highly prevalent in young adolescents [2, 37]. A previous study based on the Fourth Korea National Health and Nutrition Examination Surveys (KNHANES IV) conducted in 2008 found that among 3,047 males and 3,878 females aged 10 years and older from whom serum 25(OH)D levels were obtained, 86.8 % of R P value Age (year) Waist circumference (cm) Systolic blood pressure (mmhg) Diastolic blood pressure (mmhg) Fasting plasma glucose (mg/dl) Total cholesterol (mg/dl) Triglyceride (mg/dl) HDL-C (mg/dl) LDL-C (mg/dl) AST (IU/L) ALT (IU/L) Insulin (μiu/ml) HOMA-IR BMI body mass index, HDL-C high density lipoprotein-cholesterol, LDL low density lipoprotein-cholesterol, AST aspartate aminotransferase, ALT alanine aminotransferase, HOMA-IR homeostasis model of assessment insulin resistance Coefficients (r) and P value were calculated using Pearson's correlation analysis Table 2 Distribution of boys and girls across the 25 (OH) D range Data are expressed number (percentage) a P value was calculated by chisquared test between boys and girls Total Boys (n091) Girls (n097) P value a Optimal concentration 1 (0.5 %) 1 (1.1 %) 0 (0 %) (>30 ng/ml) Insufficiency 10 (5.3 %) 9 (9.9 %) 1 (1.0 %) (21 29 ng/ml) Deficiency (<20 ng/ml) 177 (94.1 %) 81 (89.0 %) 96 (99.0 %)

4 1478 Eur J Pediatr (2012) 171: Fig. 2 The relationship between serum 25(OH)D levels and HOMA-IR males and 93.3 % of females had a serum 25(OH)D level of less than 30 ng/ml, thus demonstrating that the vitamin D insufficiency or deficiency was very common in Koreans across all age groups [10]. We believe that the present study is the first to examine the prevalence of vitamin D insufficiency or deficiency and its relationship to insulin resistance and lipid profiles in Korean adolescents. It has been speculated that adolescents in the U.S. tend to consume less amount of dairy products [1] and spend disproportionately greater time indoors and less time outdoors compared with older individuals [14]. Moreover, Korean adolescents devote large amounts of time to studying, and many attend private cramming courses after school on weekends in order to do well in the entrance examinations of high-ranking high schools and universities [28]. Thus, they may not receive sufficient sunlight exposure for adequate cutaneous production of vitamin D. We speculate that these lifestyle factors are likely to have affected 25(OH)D levels in our study participants. However, we did not obtain information on each subject's amount of sunlight exposure. A previous study suggested that those who usually work indoors were predisposed to vitamin D insufficiency compared with those who work outdoors and thus have relatively higher serum levels of vitamin D [14]. In the multivariate linear regression model, serum 25 (OH)D levels were inversely associated with HOMA-IR, triglyceride, and LDL-C. These findings are in line with current knowledge regarding vitamin D levels, insulin resistance, and metabolic syndrome in children and adults [6, 9, 11, 13, 36]. Vitamin D may directly regulate insulin secretion by binding to pancreatic β-cell vitamin D receptors [35]. Also, vitamin D may indirectly affect pancreatic β- cell function by regulating extracellular calcium concentrations [35]. Moreover, a recent study involving a representative sample of French-Canadian children and adolescents (878 boys and 867 girls) reported a positive correlation between 25(OH)D concentrations and some lipid profiles such as total cholesterol, apolipoprotein A1, apolipoprotein B, and triglyceride [11]. These findings suggest that public health interventions such as outdoor activity and vitamin D supplementation may be needed to improve vitamin D status in adolescents with insulin resistance and dyslipidemia. Our study has some limitations. Firstly, we did not inquire into each individual's amount of sunlight exposure. We only assumed that since they were all junior high school students they would have spent most of their daytime indoors. Thus, we could not estimate how the level of sunlight exposure actually differs among the individuals. Secondly, we did not obtain data regarding behavioral factors that could affect cutaneous synthesis of vitamin D such as sunscreen use, degree of skin pigmentation, or coverage of skin by clothing. Much debate has taken place over the definition of vitamin D deficiency. Most agree that a 25(OH)D concentration, <50 nmol/l or 20 ng/ml, is an indication of vitamin D deficiency, whereas a 25(OH)D concentration of nmol/l or ng/ml is considered to indicate insufficiency; concentrations>75 nmol/l or 30 ng/ml are considered to be sufficient [8, 21, 31]. This is based on the observation that intestinal calcium absorption is maximized above 80 nmol/l or 32 ng/ml in postmenopausal women [19] and that parathyroid hormone (PTH) concentrations in adults continue to decline and reach their nadir at nmol/l or ng/ml [8, 23, 38]. It has been assumed that children have the same requirement as adults; however, limited studies have been carried out on intestinal calcium transport or PTH levels in children. Table 4 Results of multivariate linear regression analysis to assess independent relationships between 25(OH)D concentrations and clinical variables Variables Parameter, β SE P value Age (year) Waist circumference (cm) Systolic blood pressure (mmhg) Fasting plasma glucose (mg/dl) Triglyceride (mg/dl) HDL-C (mg/dl) LDL-C (mg/dl) HOMA-IR Multivariate linear regression analysis included age, waist circumference, systolic blood pressure, fasting plasma glucose, triglycerides, HDL cholesterol, LDL cholesterol, and HOMA-IR as independent variables HDL-C high density lipoprotein-cholesterol, LDL-C low density lipoprotein-cholesterol, HOMA-IR homeostasis model of assessment insulin resistance

5 Eur J Pediatr (2012) 171: In conclusion, we found that vitamin D insufficiency or deficiency is highly prevalent in Korean adolescents, particularly in girls, and that there is a significant association between 25(OH)D levels and insulin resistance and lipid variables in these young adolescents. Our results suggest that more time spent in outdoor activity for sunlight exposure and higher vitamin D intake may be needed to improve vitamin D status in younger adolescents in South Korea. Acknowledgements The authors would like to thank Dr. Jong-Seok Kim for his help in editing the manuscript. Conflict of interest The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. References 1. (2000) Osteoporosis prevention, diagnosis, and therapy. NIH Consens Statement 17: Absoud M, Cummins C, Lim MJ et al (2011) Prevalence and predictors of vitamin D insufficiency in children: a Great Britain population based study. 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