HHS Public Access Author manuscript Author Manuscript
Obesity (Silver Spring). Author manuscript; available in PMC 2017 February 01. Published in final edited form as: Obesity (Silver Spring). 2016 February ; 24(2): 408–416. doi:10.1002/oby.21378.
Adiposity Trajectory and Its associations with Plasma Adipokine Levels in Children and Adolescents – A Prospective Cohort Study Shenghui Li1,2, Rong Liu3, Lester Arguelles3, Guoying Wang4, Jun Zhang1,2, Xiaoming Shen1,2, and Xiaobin Wang4
Author Manuscript
1MOE
- Shanghai Key Laboratory of Children’s Environmental Health, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China 2School
of Public Health, Shanghai Jiao Tong University, Shanghai, China
3Mary
Ann & J. Milburn Smith Child Health Research Program, Northwestern University Feinberg School of Medicine and Ann & Robert H. Lurie Children’s Memorial Hospital of Chicago and Stanley Manne Children’s Research Institute (formerly Children’s Memorial Hospital and Children’s Memorial Research Center), Chicago, IL, USA
4Center
on the Early Life Origins of Disease, Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA
Abstract Author Manuscript
Objective—This study aimed to examine the associations of longitudinal adiposity measures with two adipokines, leptin and adiponectin, and their ratio in children and adolescents. Methods—A total of 953 children and adolescents participated in a 6-year longitudinal study. Body mass index (BMI), percentage body fat (%BF), and fat mass index (FMI) were used to assess adiposity status.
Author Manuscript
Results—After adjusting for possible confounders, our regression models revealed that BMI, %BF, and FMI, in both the baseline and follow-up survey, were independently associated with a higher level of leptin and the leptin/adiponectin ratio at the follow-up survey, whereas the significant association with adiponectin only partly existed in adiposity measures at the follow-up visit. Moreover, the longitudinal change in adiposity measures was found to be a significant predictor for follow-up plasma adipokine levels. Compared with the low→low group, the medium→medium group, up-trend group, and high→high group all showed a significantly increased level of leptin and leptin/adiponectin ratio. The up-trend group and high→high group also had significantly decreased adiponectin levels. Conclusions—Our findings highlight the importance of adiposity surveillance and the utility of adipokines as biomarkers for adverse metabolic consequences of childhood adiposity.
Corresponding author and person to whom reprint requests should be addressed: Xiaobin Wang, MD, ScD, Center on the Early Life Origins of Disease, Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health. 615 N. Wolfe Street, E4132, Baltimore, MD 21205-2179, USA, Phone: +01-410-955-5824, Fax: +01-410-502-5831, [email protected]. Disclosure: The authors have nothing to disclose.
Li et al.
Page 2
Author Manuscript
Keywords Adiposity trajectory; Leptin; Adiponectin; Cohort study
Introduction
Author Manuscript
Given the rapid increase in the prevalence of obesity worldwide during the past few decades, it is now recognized as a high-priority public health challenge.(1,2) Of particular concern is that the majority of childhood obesity can persist into adulthood.(3) As such, childhood obesity is significantly linked to the development of numerous adulthood co-morbidities, including type 2 diabetes, hypertension, dyslipidemia, cardiovascular disease, endothelial dysfunction, and metabolic syndrome. (4–6) Considerable effort and attention is needed to better understand the underlying biological mechanisms linking adiposity and its related comorbidities. This need is further highlighted by the fact that limited information is available in children and adolescents, the most important target population for obesity prevention and intervention. Over the past several years, mounting evidence has shown that adipokines, a series of bioactive peptides and proteins secreted by white adipose tissue, are implicated in the pathogenesis of obesity-associated complications. (7–9) As a molecular mediator, adipokines may link obesity to its associated complications. (7–10) Leptin and adiponectin are the two uniquely related adipokines because these two hormones are almost exclusively secreted by the adipocytes (9,10).
Author Manuscript
Previous studies have found that higher leptin levels contribute to the states of dyslipidaemia, insulin resistance, endothelial dysfunction, and prothrombin deficiency. (7– 11) In contrast, adiponectin appears to exert insulin sensitizing and antiatherogenic effects. (7–9,12,13) The dysregulation of leptin and adiponectin may lead to multiple metabolic disorders, such as those that are implicated in the development of both type 2 diabetes and subsequent cardiovascular events. (7–13) Thus, leptin and adiponectin may be clinically significant candidates to evaluate the risk for developing obesity-associated complications.
Author Manuscript
Previous epidemiological studies have consistently shown a positive relationship between obesity and plasma leptin levels both in adults and children. (14–19) However, the association between adiposity and adiponectin is still a matter of controversy. (14,17–22) Moreover, the joint effect of leptin and adiponectin, as ascertained by their ratio, has been proposed as a more reliable predictor for obesity-associated complications than adiponectin and leptin alone. (23) However, there is very limited information with respect to the association between adiposity and the leptin/adiponectin ratio. In addition, to the best of our knowledge, no prospective study has specifically assessed this association in children and adolescents. This prospective study was specifically designed to examine the longitudinal associations of adiposity and its trends with leptin, adiponectin, and their ratio among children and adolescents.
Obesity (Silver Spring). Author manuscript; available in PMC 2017 February 01.
Li et al.
Page 3
Author Manuscript
Materials and Methods Study participants Participants in this study were recruited from the Chinese Metabolic Syndrome Twin Cohort Study, which was conducted in the Anqing and Luan areas of Anhui Province, China. The baseline study was carried out from September 1998 through May 2000, and the follow-up survey was completed from August 2005 through February 2007.
Author Manuscript
Detailed information on participant enrollment was described previously. (24,25) Briefly, the baseline study recruited twins: 1) who were 6–60 years of age; 2) if both twins were available; 3) if both twins agreed to participate in the study; and 4) if there was no previous history of cardiovascular, renal, hepatic, or malignant diseases. In the follow-up study, participants were eligible if both twins participated in the baseline survey and agreed to participate in the follow-up study. Written informed consent was obtained from all participants. This report focuses on children and adolescents under 18 years of age at the baseline survey. Those who had adiposity measurements, at both the baseline and follow-up surveys, and adipokine measurements at the follow-up survey were included in the final analyses. The final sample consisted of 953 (513 males vs. 440 females) children and adolescents aged 6.0 to 15.3 years at baseline and 13.0 to 21.0 years at the follow-up survey. The study protocol was approved by the Institutional Review Boards of the Ann & Robert H. Lurie Children’s Hospital of Chicago (formerly Children’s Memorial Hospital), the Johns Hopkins Bloomberg School of Public Health, and the Institute of Biomedicine, Anhui Medical University, Hefei, China.
Author Manuscript
Questionnaire A comprehensive questionnaire was used to collect participant demographics, disease history, and lifestyle information. Physical activity was assessed using the short version of the international physical activity questionnaire (IPAQ-short) (http://www.ipaq.ki.se/ ipaq.htm), which has been validated in China. (26) Detailed information on physical activity has been described previously. (24,25) Based on the scoring system, the IPAD generates a categorical indicator (low level=1, moderate =2, and high=3) of regular physical activity. Anthropometry, DXA measures of adiposity, and Tanner stage assessment
Author Manuscript
Height and weight were measured following the standard protocols, as described previously. (25) BMI was calculated as weight (kg)/height2 (m2). A standard whole-body scan was performed by DXA (GE-Lunar Prodigy, Madison, WI) to measure total body fat (BF), as shown previously. (25) %BF was calculated as (total BF/body weight)×100, and fat mass index (FMI) was calculated as [BF (kg)/height2 (m2)] × 100. Tanner stages (I-V) were assessed by a professional physician based on visual inspection of pubic hair, genitals (boys), and breasts (girls).
Obesity (Silver Spring). Author manuscript; available in PMC 2017 February 01.
Li et al.
Page 4
Adipokine measurement
Author Manuscript
Plasma leptin and total adiponectin were measured by a sandwich immunoassay based on flow metric xMAP technology on Luminex 200 (Luminex Corp., Austin, TX). (27) In this study, the assay sensitivity for leptin and adiponectin was 138.8pg/ml and 145.4pg/ml, respectively. The intraassay coefficient of variation for leptin and adiponectin was 5.1% and 8.0%, respectively. Zygosity identification Twin zygosity was determined using DNA fingerprint technology by genotyping 10 microsatellite markers on different somatic chromosomes with high heterozygosity (>70%), as described previously. (25)
Author Manuscript
Statistical analysis Plasma leptin, adiponectin, and leptin/adiponectin ratio (calculated as leptin/adiponectin × 100) were positively skewed; a logarithmic transformation was used to normalize the data for subsequent statistical analyses. The BMI was standardized as age- and gender-specific z sores based on the China national reference data. (28) Other Adiposity measures (%BF and FMI) were also transformed to age- and gender-specific z sores using the data from the Chinese Metabolic Syndrome Twin Cohort Study. (24,25) The difference in anthropometric and adiposity measures between the baseline and follow-up surveys was examined using Generalized Estimating Equation models, stratified by gender.
Author Manuscript
Adiposity measures (BMI, %BF, and FMI) were grouped into gender- and age-specific tertiles at the baseline and follow-up surveys (Supplemental Materials, online Table 1). The 1st, 2nd and 3rd tertiles reflected low, medium and high levels, respectively. Based on these three levels for the two surveys, the longitudinal trends of each adiposity measure were then grouped into five categories: low→low, medium→medium, high→high, up-trend (as those ranked low or medium at baseline moved up to medium or high at follow-up), and downtrend (as those medium or high at baseline became low or medium at follow-up.) Locally weighted nonparametric smoothing plots (SAS LOESS; SAS Institute, Cary, NC) were used to graphically examine the relationship of the longitudinal trend in adiposity with plasma leptin, adiponectin, and leptin/adiponectin ratio.
Author Manuscript
To quantify the associations of each adiposity measure, either at the baseline or at the follow-up, or the trend, with adipokine levels (Ln[leptin], Ln[adiponectin], and Ln[leptin/ adiponectin ratio]), Generalized Estimating Equation Regression models were applied, adjusted for age, gender, Tanner stage, zygosity [monozygotic (MZ) and dizygotic (DZ)], sleep duration, and physical activity (low, moderate, and high). We also stratified our analysis by gender and zygosity to examine whether the relationship between adiposity and adipokines differed between MZ and DZ participants or between males and females. Since the adiposity-adipokine associations were very similar between MZ and DZ and between males and females, all groups were combined together in the final analyses.
Obesity (Silver Spring). Author manuscript; available in PMC 2017 February 01.
Li et al.
Page 5
Author Manuscript
All analyses were performed using the Statistical Analysis System (SAS) for Windows, version 9.2 (SAS Institute, Cary. NC). In the presentation of the results, the statistical significance was set at a p value < 0.05 (two tailed).
Results Anthropometric measures at the baseline and follow-up surveys The present study included 953 participants (513 males vs. 440 females) with the mean age of 10.17±2.21yrs and 16.77±2.36yrs for the baseline and follow-up, respectively. Table 1 summarizes the anthropometric and adiposity measures by gender at both the baseline and follow-up. Anthropometric parameters, including height, weight, and adiposity measures, such as BMI, %BF, and FMI, were all significantly higher at follow-up than at baseline (all p
Obesity (Silver Spring). Author manuscript; available in PMC 2017 February 01. Published in final edited form as: Obesity (Silver Spring). 2016 February ; 24(2): 408–416. doi:10.1002/oby.21378.
Adiposity Trajectory and Its associations with Plasma Adipokine Levels in Children and Adolescents – A Prospective Cohort Study Shenghui Li1,2, Rong Liu3, Lester Arguelles3, Guoying Wang4, Jun Zhang1,2, Xiaoming Shen1,2, and Xiaobin Wang4
Author Manuscript
1MOE
- Shanghai Key Laboratory of Children’s Environmental Health, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China 2School
of Public Health, Shanghai Jiao Tong University, Shanghai, China
3Mary
Ann & J. Milburn Smith Child Health Research Program, Northwestern University Feinberg School of Medicine and Ann & Robert H. Lurie Children’s Memorial Hospital of Chicago and Stanley Manne Children’s Research Institute (formerly Children’s Memorial Hospital and Children’s Memorial Research Center), Chicago, IL, USA
4Center
on the Early Life Origins of Disease, Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA
Abstract Author Manuscript
Objective—This study aimed to examine the associations of longitudinal adiposity measures with two adipokines, leptin and adiponectin, and their ratio in children and adolescents. Methods—A total of 953 children and adolescents participated in a 6-year longitudinal study. Body mass index (BMI), percentage body fat (%BF), and fat mass index (FMI) were used to assess adiposity status.
Author Manuscript
Results—After adjusting for possible confounders, our regression models revealed that BMI, %BF, and FMI, in both the baseline and follow-up survey, were independently associated with a higher level of leptin and the leptin/adiponectin ratio at the follow-up survey, whereas the significant association with adiponectin only partly existed in adiposity measures at the follow-up visit. Moreover, the longitudinal change in adiposity measures was found to be a significant predictor for follow-up plasma adipokine levels. Compared with the low→low group, the medium→medium group, up-trend group, and high→high group all showed a significantly increased level of leptin and leptin/adiponectin ratio. The up-trend group and high→high group also had significantly decreased adiponectin levels. Conclusions—Our findings highlight the importance of adiposity surveillance and the utility of adipokines as biomarkers for adverse metabolic consequences of childhood adiposity.
Corresponding author and person to whom reprint requests should be addressed: Xiaobin Wang, MD, ScD, Center on the Early Life Origins of Disease, Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health. 615 N. Wolfe Street, E4132, Baltimore, MD 21205-2179, USA, Phone: +01-410-955-5824, Fax: +01-410-502-5831, [email protected]. Disclosure: The authors have nothing to disclose.
Li et al.
Page 2
Author Manuscript
Keywords Adiposity trajectory; Leptin; Adiponectin; Cohort study
Introduction
Author Manuscript
Given the rapid increase in the prevalence of obesity worldwide during the past few decades, it is now recognized as a high-priority public health challenge.(1,2) Of particular concern is that the majority of childhood obesity can persist into adulthood.(3) As such, childhood obesity is significantly linked to the development of numerous adulthood co-morbidities, including type 2 diabetes, hypertension, dyslipidemia, cardiovascular disease, endothelial dysfunction, and metabolic syndrome. (4–6) Considerable effort and attention is needed to better understand the underlying biological mechanisms linking adiposity and its related comorbidities. This need is further highlighted by the fact that limited information is available in children and adolescents, the most important target population for obesity prevention and intervention. Over the past several years, mounting evidence has shown that adipokines, a series of bioactive peptides and proteins secreted by white adipose tissue, are implicated in the pathogenesis of obesity-associated complications. (7–9) As a molecular mediator, adipokines may link obesity to its associated complications. (7–10) Leptin and adiponectin are the two uniquely related adipokines because these two hormones are almost exclusively secreted by the adipocytes (9,10).
Author Manuscript
Previous studies have found that higher leptin levels contribute to the states of dyslipidaemia, insulin resistance, endothelial dysfunction, and prothrombin deficiency. (7– 11) In contrast, adiponectin appears to exert insulin sensitizing and antiatherogenic effects. (7–9,12,13) The dysregulation of leptin and adiponectin may lead to multiple metabolic disorders, such as those that are implicated in the development of both type 2 diabetes and subsequent cardiovascular events. (7–13) Thus, leptin and adiponectin may be clinically significant candidates to evaluate the risk for developing obesity-associated complications.
Author Manuscript
Previous epidemiological studies have consistently shown a positive relationship between obesity and plasma leptin levels both in adults and children. (14–19) However, the association between adiposity and adiponectin is still a matter of controversy. (14,17–22) Moreover, the joint effect of leptin and adiponectin, as ascertained by their ratio, has been proposed as a more reliable predictor for obesity-associated complications than adiponectin and leptin alone. (23) However, there is very limited information with respect to the association between adiposity and the leptin/adiponectin ratio. In addition, to the best of our knowledge, no prospective study has specifically assessed this association in children and adolescents. This prospective study was specifically designed to examine the longitudinal associations of adiposity and its trends with leptin, adiponectin, and their ratio among children and adolescents.
Obesity (Silver Spring). Author manuscript; available in PMC 2017 February 01.
Li et al.
Page 3
Author Manuscript
Materials and Methods Study participants Participants in this study were recruited from the Chinese Metabolic Syndrome Twin Cohort Study, which was conducted in the Anqing and Luan areas of Anhui Province, China. The baseline study was carried out from September 1998 through May 2000, and the follow-up survey was completed from August 2005 through February 2007.
Author Manuscript
Detailed information on participant enrollment was described previously. (24,25) Briefly, the baseline study recruited twins: 1) who were 6–60 years of age; 2) if both twins were available; 3) if both twins agreed to participate in the study; and 4) if there was no previous history of cardiovascular, renal, hepatic, or malignant diseases. In the follow-up study, participants were eligible if both twins participated in the baseline survey and agreed to participate in the follow-up study. Written informed consent was obtained from all participants. This report focuses on children and adolescents under 18 years of age at the baseline survey. Those who had adiposity measurements, at both the baseline and follow-up surveys, and adipokine measurements at the follow-up survey were included in the final analyses. The final sample consisted of 953 (513 males vs. 440 females) children and adolescents aged 6.0 to 15.3 years at baseline and 13.0 to 21.0 years at the follow-up survey. The study protocol was approved by the Institutional Review Boards of the Ann & Robert H. Lurie Children’s Hospital of Chicago (formerly Children’s Memorial Hospital), the Johns Hopkins Bloomberg School of Public Health, and the Institute of Biomedicine, Anhui Medical University, Hefei, China.
Author Manuscript
Questionnaire A comprehensive questionnaire was used to collect participant demographics, disease history, and lifestyle information. Physical activity was assessed using the short version of the international physical activity questionnaire (IPAQ-short) (http://www.ipaq.ki.se/ ipaq.htm), which has been validated in China. (26) Detailed information on physical activity has been described previously. (24,25) Based on the scoring system, the IPAD generates a categorical indicator (low level=1, moderate =2, and high=3) of regular physical activity. Anthropometry, DXA measures of adiposity, and Tanner stage assessment
Author Manuscript
Height and weight were measured following the standard protocols, as described previously. (25) BMI was calculated as weight (kg)/height2 (m2). A standard whole-body scan was performed by DXA (GE-Lunar Prodigy, Madison, WI) to measure total body fat (BF), as shown previously. (25) %BF was calculated as (total BF/body weight)×100, and fat mass index (FMI) was calculated as [BF (kg)/height2 (m2)] × 100. Tanner stages (I-V) were assessed by a professional physician based on visual inspection of pubic hair, genitals (boys), and breasts (girls).
Obesity (Silver Spring). Author manuscript; available in PMC 2017 February 01.
Li et al.
Page 4
Adipokine measurement
Author Manuscript
Plasma leptin and total adiponectin were measured by a sandwich immunoassay based on flow metric xMAP technology on Luminex 200 (Luminex Corp., Austin, TX). (27) In this study, the assay sensitivity for leptin and adiponectin was 138.8pg/ml and 145.4pg/ml, respectively. The intraassay coefficient of variation for leptin and adiponectin was 5.1% and 8.0%, respectively. Zygosity identification Twin zygosity was determined using DNA fingerprint technology by genotyping 10 microsatellite markers on different somatic chromosomes with high heterozygosity (>70%), as described previously. (25)
Author Manuscript
Statistical analysis Plasma leptin, adiponectin, and leptin/adiponectin ratio (calculated as leptin/adiponectin × 100) were positively skewed; a logarithmic transformation was used to normalize the data for subsequent statistical analyses. The BMI was standardized as age- and gender-specific z sores based on the China national reference data. (28) Other Adiposity measures (%BF and FMI) were also transformed to age- and gender-specific z sores using the data from the Chinese Metabolic Syndrome Twin Cohort Study. (24,25) The difference in anthropometric and adiposity measures between the baseline and follow-up surveys was examined using Generalized Estimating Equation models, stratified by gender.
Author Manuscript
Adiposity measures (BMI, %BF, and FMI) were grouped into gender- and age-specific tertiles at the baseline and follow-up surveys (Supplemental Materials, online Table 1). The 1st, 2nd and 3rd tertiles reflected low, medium and high levels, respectively. Based on these three levels for the two surveys, the longitudinal trends of each adiposity measure were then grouped into five categories: low→low, medium→medium, high→high, up-trend (as those ranked low or medium at baseline moved up to medium or high at follow-up), and downtrend (as those medium or high at baseline became low or medium at follow-up.) Locally weighted nonparametric smoothing plots (SAS LOESS; SAS Institute, Cary, NC) were used to graphically examine the relationship of the longitudinal trend in adiposity with plasma leptin, adiponectin, and leptin/adiponectin ratio.
Author Manuscript
To quantify the associations of each adiposity measure, either at the baseline or at the follow-up, or the trend, with adipokine levels (Ln[leptin], Ln[adiponectin], and Ln[leptin/ adiponectin ratio]), Generalized Estimating Equation Regression models were applied, adjusted for age, gender, Tanner stage, zygosity [monozygotic (MZ) and dizygotic (DZ)], sleep duration, and physical activity (low, moderate, and high). We also stratified our analysis by gender and zygosity to examine whether the relationship between adiposity and adipokines differed between MZ and DZ participants or between males and females. Since the adiposity-adipokine associations were very similar between MZ and DZ and between males and females, all groups were combined together in the final analyses.
Obesity (Silver Spring). Author manuscript; available in PMC 2017 February 01.
Li et al.
Page 5
Author Manuscript
All analyses were performed using the Statistical Analysis System (SAS) for Windows, version 9.2 (SAS Institute, Cary. NC). In the presentation of the results, the statistical significance was set at a p value < 0.05 (two tailed).
Results Anthropometric measures at the baseline and follow-up surveys The present study included 953 participants (513 males vs. 440 females) with the mean age of 10.17±2.21yrs and 16.77±2.36yrs for the baseline and follow-up, respectively. Table 1 summarizes the anthropometric and adiposity measures by gender at both the baseline and follow-up. Anthropometric parameters, including height, weight, and adiposity measures, such as BMI, %BF, and FMI, were all significantly higher at follow-up than at baseline (all p
