A Study On The Relationship Between Childhood Obesity And Abnormal Metabolism Of Cardiovascular Disease And Bone Mineral Density

The association of childhood obesity and cardiometabolic risk with bone mineral denity-Results from multiple races in two nationwide cross-sectional surveys in China and the US[Background]Worldwide,the prevalence of obesity in childhood and adolescence has increased at an alarming rate in recent decades,becoming a crucial public health problem.Extensive studies have demonstrated that childhood obesity is associated with a series of metabolic disorders,which can adversely affect almost every organ system.However,the relationship between obesity and bone mineral density(BMD)is still largely debated.Some studies observed increased BMD in obese children,whereas others indicated that childhood obesity was associated with insufficient BMD and might be susceptible to bone fractures.One possible explanation to these contradictory findings is the use of body mass index(BMI)to evaluate obesity.In this case,the association between obesity and BMD would be confounded with lean mass,and the different impacts of fat depot on bones would not be reflected.Furthermore,many studies have shown that not all obese subjects are affected by adipose tissue dysfunction and related cardiometabolic disorder(CMD).Failure to discriminate different obesity and CMD subtypes in population studies may lead to conflicting results of obesity-bone relations.In addition,race,a comprehensive indicator of variation in genotype and lifestlyes,may also play a role in the relationship between obesity and BMD.But,the comparison of the obesity-bone interelations in multiple races has rarely been reported in children.Childhood and adolescence are critical periods for the accrual of bone minerals.There is a need for understanding the association of childhood obesity and related CMD with BMD in races,to prevent and manage childhood obesity and bone abnormities.In present study,utilizing data from nationwide cross-sectional surveys in China and the US,we aimed to investigate the association of childhood obesity and BMD from three aspects:(i)relationship of excessive fat accumulation and BMD,(ii)relationship of fat depot and BMD,and(iii)relationship of adipose tissue related CMD and BMD.[Objective]1.To analyze the age-related changes of childhood BMD in four races2.To explore the association of degree and types of obesity with BMD in four races3.To examine the association of CMD with childhood BMD in four races4.To determine the association of obesity-CMD subtypes with BMD in four races[Methods]The data for analysis are composed of two subsamples of children and adolescents aged 8-18 years enrolled in two nationwide cross-sectional surveys of China and the US.(i)Chinese population:a total of 7,816 Han children were selected from China Child and Adolescent Cardiovascular Health Study(CCACH)conducted during 2013-2015;(ii)American population:non-Hispanic white(n=2,216),non-Hispanic black(n=2,724),and Mexican-American(n=2,835)children were selected from the National Health and Nutrition Examination Survey(NHANES)conducted during 1999-2006.Total-body-less-head BMD,total body fat and regional fat(android fat and gynoid fat)were assessed via dual-energy x-ray absorptiometry.Obesity was defined based on being above the race-,sex-,and age-specific 75th percentiles of fat mass index(FMI),android fat mass index(A_FMI)and gynoid fat mass index(G_FMI),android fat to gynoid fat ratio(AGR)respectively.Meanwhile,four types for obesity(non-obesity,abdominal-only obesity,peripheral-only obesity,mixed obesity)were classified according to FMI and AGR levels.The race-,sex-,and age-specific 75th percentiles of blood pressure(BP),fasting plasma glucose(FPG),triglycride(TG)and 25th percentile of high-density lipoprotein cholesterol(HDL-C)were used as cut-offs to define abnormalities of these cardiometabolic risk(CMR)factors.Children with two or more abnormalities of CMR factors were defined as CMD.Additionally,subjects were stratified into four groups according to their obesity and CMD status.Data were analyzed using SPSS 20.0,SAS 9.3 and LMS Charter for t-test,chi-squared test,one-way analysis of variance,anlysis of covariance,partial correlation,Fisher-Z test,and coefficients of skewness-median-coefficient of variation to construct BMD growth curves for children in separate race and sex.[Results]1.Age-related changes of childhood BMD in four racesBMD increased dramatically with age and showed race differences in BMD from 8 to 18 years old,with blacks showing the highest level,and followed by whites,Mexicans and Chinese.Compared with Han Chinese,children from other races of the US had higher BMD after adjusting for age,height and lifestyle factors.2.The association of degree and types of obesity with BMD in four racesAfter adjusting for age,height,lean mass index and lifestyle factors,FMI,A_FMI and G_FMI were negatively associated with BMD in Han boys,while no statistically significant association was observed between AGR and BMD.In Han girls,positive correlations were shown between adiposity measures(including FMI,A_FMI,G_FMI,and AGR)and BMD.In both Han boys and girls,the above correlation coefficients decreased and became negative(or lack of correlation)with increase in BMI.Simlar with Han boys,all fat measures were negatively correlated with BMD in white,black and Mexican boys and girls,and their correlation coefficients were greater than those in Chinese.In Han boys,obese individuals diagnosed by each fat measures(except for AGR)had lower BMD than non-obese subjects;BMD levels were lower in peripheral-only obese and mixed obese boys than non-obese boys,but no significant difference was found among subjects with abdominal-only obesity(0.807 vs 0.799,P=0.087).For Han girls,positive relationship was found in different degree and types of obesity.For whites,blacks and Mexicans,different degree and types of obesity were negatively associated with BMD.However,compared with children with non-obesity,decreased BMD were only found in abdominal-only obesity in black and Mexican boys(Black boys:0.974 vs 0.995,P=0.033;Mexican boys:0.909 vs 0.936,P=0.004)3.The association of CMD with BMD in four racesIn Han boys and girls,population with elevated BP had higher BMD(boys:0.880 vs 0.868,P<0.001;girls:0.830 vs 0.824,P=0.008).Moreover,in Han girls,individuals with elevated FPG had lower BMD than those with normal FPG(0.823 vs 0.831,P=0.006).For US children,decreased HDL-C was negatively correlated with BMD in white boys and girls(boys:0.969 vs 0.989,P<0.001;girls:0.929 vs 0.942,P=0.017),and elevated TG was adversely associated with BMD(0.901 vs 0.925,P<0.001).The number of CMR was not correlated with BMD in Han children,while downward trends were found in white boys(μtrend=-0.010,P=0.031)and Mexican girls(βtrend=-0.007,P=0.031).4.The association of obesity-CMD subtypes with BMD in four racesFor Han Chinese children,reduced BMD was only seen in boys with obesity(diagnosed by each measure,except for AGR)and CMD,while increased BMD was shown in girls with obesity and CMD.For obesity assessed by AGR,no difference was found among boys and girls with different obesity and CMD types.By contrast,both obese children with and without CMD had declined BMD compared with healthy children in white,black and Mexican groups.[Conclusions]1.Obesity has a dual effect on bone in children,which is probably resulted from divergent weight status.Fat and BMD is positively correlated in subjects with lower BMI,but negatively correlated in subjects with higher BMI.In addition,fat is more closely correlated with BMD in children from other races of the US than that of Chinese Hans.2.Decreased BMD is associated with increase of whole-body or regional fat mass,which is differed by race and sex.In Han boys and children of other races,obese individuals diagnosed by FMI has lower BMD levels,while opposite patterns demonstrate in Han girls.In most races and sex,no difference is noted between abdominal-only obese children and non-obese chidren.3.The relationship between obesity and BMD is influenced by CMD status.Obese children and those with FMI-determined obesity and CMD have decreased BMD in all the four races,except for Chinese Han girls.Obese Chinese girls have higher BMD levels than non-obese subjects irrespective of their cardiometabolic status.Thus,attention is needed to prevent BMD declining in obese boys,especially those with cardiometabolic disorder.Long-term impact of body mass index and fat in childhood on adult bone mineral density-Results from Beijing Blood Pressure Study(BBS)[Background]Worldwide,osteoporotic fracture is one of the leading causes of disability,resulting in enormous medical,social,and economic burdens.Bone mineral density(BMD)plays an important role in osteoporosis detection and future bone fractures prediction.BMD is affected by many intrinsic and environmental factors.Extensive studies have demonstrated a strong and positive association between body weight and BMD,but it should be noted that their relationship is far from that simple.Body mass,expecially lean mass,has a protective role in BMD by providing mechanical load for stimulating bone minerals accrual.But excessive body weight may have an adverse effect on BMD for increased cytokines and altered osteoclast activity.Childhood and adolescence are critical periods in the development of lifelong bone health.During these growth periods,weight and adipose status may have long-term influence on adulthood skeletal health via sustained mechanical loading as well as potential hormonal changes.To date,data are limited regarding the association of long-term burden and trajectory patterns of childhood body mass and fat with BMD in later life.In previous pediatric cohort,single measurements of childhood body mass and fat were used,which had lower statistical power to identify measurement errors and individual variations,causing inconsistent associations with adulthood measures.In addition,body weight and fat tracks from childhood to adulthood,suggesting that childhood weight and fat might affect bone health in later life through connection of childhood and adulthood weight/fat(mediation).To date,the degree of the mediation effect of adult weight/fat on the childhood weight/fat-adult BMD association has been largely unknown.In present study,we aimed to estimate the impact of growth patterns and cumulative burden of body weight and fat during childhood on adult BMD and explore quantitatively the potential roles of adult BMI on these associations utilizing data from Beijing Blood Pressure Study(BBS).[Objective]1.To investigate the relationship between trajectory patterns of childhood bodyweight/fat and adult BMD2.To examine the long-term burden and trend of childhood body weight/fat on adult BMD.3.To quantify the mediation effect of adult weight and body composition on theassociation of childhood body weight/fat with adult BMD.[Methods]The longitudinal study consisted of 397 adults(54.4%males),who had been examined for body mass index(BMI)and subscapular skinfold(SSF)4-8 times during childhood(6-19 years)and BMD in adulthood(29-37 years).Adult BMD,body fat mass and lean mass were assessed via dual-energy x-ray absorptiometry.Low BMD were defined by the sex-and age-specific 20th percentile of BMD at different sites.Childhood BMI and SSF growth curves were constructed using a random-effects mixed model.The area under the curve(AUC)was calculated to represent long-term burden of childhood BMI and SSF;incremental AUC(iAUC)represented the longitudinal trends during childhood.[Results]1.The relationship between trajectory patterns of childhood body weight/fat and adult BMDChildhood BMI and SSF were fitted quadratic functions of age.The normal BMD group had higher childhood BMI and SSF than the low BMD group,with the intercepts of BMI and SSF at age of 12.7(the mean age centered to)being significantly lower in the low BMD group than normal BMD group at all three sites.2.The long-term burden and trend of childhood body weight/fat on adult BMD.Significant and positive associations were noted between AUCof BMI/SSF and adult BMD at three sites after adjustment for adult covariates(sex,age,height,physical activity,smoking and alcohol drinking).The regression coefficients were 0.019(0.005)and 0.013(0.005)for association of AUCBMI and AUCSSF with whole body BMD,0.023(0.007)and 0.013(0.007)for association of AUCBMI and AUCSSF with spine BMD,0.038(0.007)and 0.026(0.007)for association of AUCBMI and AUCSSF with hip BMD.For longtitudinal trends of BMI and SSF during childhood,only iAUC of BMI was positively correlated with adult BMD at hip(0=0.023,P<0.001).3.The mediation effect of adult weight and body composition on the association of childhood body weight/fat with adult BMD.When adult BMI was included for additional adjustment,associations between childhood BMI and adult BMD were substantially attenuated.Significantly positive regression coefficients were only found in associations of whole-body BMD with childhood AUC of BMI(β=0.017,P=0.009).The mediation effect of adult BMI was significant on the association of childhood AUC of BMI with hip BMD(mediation effect=79.1%,P<0.001);but it was borderline significant for the association with spine BMD(mediation effect=49.8%,P=0.068).After BMI was divided into fat mass index(FMI)and lean mass index(LMI),marked mediation effects(～67%)of adult LMI was noted on the childhood BMI-adult BMD association at the hip and whole body.For FMI,it was found to be a significant mediator of the association between childhood AUC of BMI and whole-body BMD(mediation effect=-54.7%,P<0.001).Similar with the results on the ’childhood BMI-adult BMD’ relations,a positive correlation was only found between AUC of SSF and whole-body BMD(β=0.013,P=0.026)after adjusting adult FMI.Mediation effects(75.5%)of adult FMI were significant for the association of childhood AUC of SSF with adult hip BMD.[Conclusion]1.These findings suggest that the impact of body weight and fat on adult BMD originates from childhood.Maintaining an adequate weight from childhood is important for the achievement of higher subsequent bone density.2.Divergent associations of childhood body weight and fat with adult BMD accur at different sites.The associations at the site of hip are stronger than those at spine and whole body.3.Due to the significant tracking correlation between childhood and adulthood body weight and fat,childhood body weight/fat affected adult BMD through adult weight/fat connection.Specifically,adult LMI,not FMI,was an important mediator of the ’childhood BMI/fat-adult BMD’ relationship,emphasizing the importance of increased concurrent lean mass in establishing and maintaining optimal BMD.