Sex and racial/ethnic differences in the association between childhood attention-deficit/hyperactivity disorder symptom subtypes and body mass index in the transition from adolescence to adulthood in the United States.

BACKGROUND: While attention-deficit/hyperactivity disorder (ADHD) has been associated with higher body mass index (BMI), little research has focused on how this association differs by sex or race/ethnicity. OBJECTIVE: To investigate the association between ADHD and BMI by sex and race/ethnicity (ie, European [EA], African [AA], and Hispanic American [HA]). METHODS: Data came from the National Longitudinal Survey of Adolescent to Adult Health Waves II to IV (n = 13 332, age: 12-34 years). On the basis of self-reported childhood ADHD symptoms between the ages of 5 and 12 years, participants were categorized into: ADHD predominantly hyperactive/impulsive (ADHD-HI); ADHD predominantly inattentive (ADHD-I); ADHD combined (ADHD-C; a combination of ADHD-HI and ADHD-I symptoms); and non-ADHD. RESULTS: The patterns of ADHD-BMI associations in the transition period between adolescence and young adulthood differed by sex and race/ethnicity. Compared with non-ADHD, ADHD-HI was associated with higher BMI among EA males and females, while ADHD-I was associated with higher BMI among EA females. ADHD-C was associated with higher BMI for HA females. We found no evidence of an association among AA males and females and HA males. CONCLUSION: These study results suggest that the association between ADHD subtypes and BMI might differ across population subgroups in the United States.

Diet quality and its association with type 2 diabetes and major cardiometabolic risk factors among adults in China.

AIM: We examined the association between diet quality and diabetes and major cardiometabolic risks among adults in China. METHODS AND RESULTS: We developed the China Dietary Guideline Index (CDGI) based on the 2007 Chinese dietary guidelines and tailored the Alternate Healthy Eating Index 2010 (which we call the tAHEI) to assess diet quality. Our analysis linked the dietary intake and covariates measured in 2006 with CM risk factors measured in 2009. We used diet data the longitudinal China Health and Nutrition Survey 2006 collected in 3 consecutive 24-h recalls from 4440 adults aged 18 to 65 to calculate both the tAHEI and the CDGI scores. We performed multivariable logistic regressions to analyze the association of each 2006 score with diabetes, abdominal obesity, elevated blood pressure, and lipid-related cardiometabolic risk factors in 2009. After we adjusted for potential confounders, adults in the top quintile compared with the bottom quintile of the tAHEI scores showed 36% lower odds of high low-density lipoprotein cholesterol (LDL-C) (odds ratio [OR] 0.64; 95% confidence interval [CI] 0.46, 0.90] in men and 33% lower odds (OR 0.67; 95% CI 0.49, 0.91) in women, while the CDGI scores showed 35% lower odds of high LDL-C (OR 0.65; 95% CI 0.46, 0.92) in men only. Further, the CDGI scores indicated 55% lower odds of diabetes in the top versus the bottom quintile (OR 0.45; 95% CI 0.23, 0.87) in men only, whereas a null association was observed for the tAHEI scores for both sexes. Both index scores showed null associations with other cardiometabolic risk factors. CONCLUSIONS: Chinese diets that scored high on both the CDGI and the tAHEI showed similarly negative associations with high LDL-C risk, whereas only CDGI score was negatively related to diabetes risk in men.

Concordance of haemoglobin A1c, blood pressure and C-reactive protein between children and their parents in Chinese households.

BACKGROUND: China has the world's highest diabetes prevalence, which along with hypertension and inflammation continues to grow particularly among children. Little is known about the strength of the association of these cardiometabolic risk factors between parents and their children; thus, the potential of household-based strategies to reduce risk is unknown. OBJECTIVES: The objective of the study is to examine the parent-child association for haemoglobin A1c (HbA1c), blood pressure (BP) and C-reactive protein (CRP) in a large, geographically diverse Chinese sample. METHODS: In 940 parent-child pairs (children aged 7-17 years) who participated in the 2009 China Health and Nutrition Survey, we measured each individual's HbA1c and CRP using fasting blood and BP. We used sex-specific random-effects linear regression to examine the parent-child association for these risk factors, accounting for within-family clustering. RESULTS: Child's HbA1c was positively associated with parental HbA1c. Beta coefficients ranged from 0.06 (95% CI 0.03-0.12) for father-daughter to 0.43 (95% CI 0.28-0.58) for mother-son pairs. We also detected a positive mother-daughter association for BP and positive father-child associations for CRP. CONCLUSION: The statistically significant parent-child association for HbA1c, BP and CRP in Chinese families suggests that household-based interventions could be useful for confronting the high rates of diabetes, hypertension and inflammation in China.

BMI loci and longitudinal BMI from adolescence to young adulthood in an ethnically diverse cohort.

OBJECTIVE: The association of obesity susceptibility variants with change in body mass index (BMI) across the life course is not well understood. SUBJECTS: In ancestry-stratified models of 5962 European American (EA), 2080 African American (AA) and 1582 Hispanic American (HA) individuals from the National Longitudinal Study of Adolescent to Adult Health (Add Health), we examined associations between 34 obesity single-nucleotide polymorphisms (SNPs) with per year change in BMI, measured by the slope from a growth-curve analysis of two or more BMI measurements between adolescence and young adulthood. For SNPs nominally associated with BMI change (P<0.05), we interrogated age differences within data collection Wave and time differences between age categories that overlapped between Waves. RESULTS: We found SNPs in/near FTO, MC4R, MTCH2, TFAP2B, SEC16B and TMEM18 were significantly associated (P<0.0015≈0.05/34) with BMI change in EA and the ancestry-combined meta-analysis. rs9939609 in FTO met genome-wide significance at P<5e-08 in the EA and ancestry-combined analysis, respectively [Beta(se)=0.025(0.004);Beta(se)=0.021(0.003)]. No SNPs were significant after Bonferroni correction in AA or HA, although five SNPs in AA and four SNPs in HA were nominally significant (P<0.05). In EA and the ancestry-combined meta-analysis, rs3817334 near MTCH2 showed larger effects in younger respondents, whereas rs987237 near TFAP2B, showed larger effects in older respondents across all Waves. Differences in effect estimates across time for MTCH2 and TFAP2B are suggestive of either era or cohort effects. CONCLUSION: The observed association between variants in/near FTO, MC4R, MTCH2, TFAP2B, SEC16B and TMEM18 with change in BMI from adolescence to young adulthood suggest that the genetic effect of BMI loci varies over time in a complex manner, highlighting the importance of investigating loci influencing obesity risk across the life course.

Sociodemographic disparity in the diet quality transition among Chinese adults from 1991 to 2011.

BACKGROUND/OBJECTIVES: This study investigates secular trends in diet quality distribution and related socioeconomic disparity from 1991 to 2011 in the Chinese adult population. SUBJECTS/METHODS: The analysis uses the 1991-2011 China Health and Nutrition Survey data on 13 853 participants (6876 men and 6977 women) aged 18-65 with 56 319 responses. Dietary assessment was carried out over a 3-day period with 24-h recalls combined with a household food inventory. We tailored Alternative Healthy Eating Index 2010 (named as tAHEI) to measure diet quality and performed quantile regression to investigate shifts in tAHEI scores at different percentiles and used mixed-effect linear regression to examine average diet quality trend and potential sociodemographic disparity. RESULTS: The energy-adjusted mean tAHEI scores increased from 36.9 (36.7-37.1) points in 1991 to 50.3 (50.1-50.5) in 2011 for men (P<0.001) and from 35.6 (35.4-35.8) to 46.9 (46.7-47.1) for women (P<0.001). The covariate-adjusted score of polyunsaturated fatty acids increased by 6.8 (6.6, 7.0) and 7.0 (6.9, 7.2), and the score of long-chain (ω-3) fats increased by 5.3 (5.2, 5.4) and 5.3 (5.2, 5.5) in men and women, respectively, whereas the cereal fiber and red meat scores decreased slightly. Increasing tAHEI score occurred across the entire distribution, and diet quality transition varied across sociodemographic groups. CONCLUSIONS: Chinese diet quality is far from optimal, with moderate improvement over a 21-year period. Findings suggest that nutritional intervention should give priority to low-income, low-urbanized communities and southern provincial adults with low diet quality in China.

The interaction between physical activity and obesity gene variants in association with BMI: Does the obesogenic environment matter?

Little is known about how obesity susceptibility single nucleotide polymorphisms (SNPs) interact with moderate to vigorous physical activity (MVPA) in relation to BMI during adolescence, once obesogenic neighborhood factors are accounted for. In race stratified models, including European (EA; N=4977), African (AA; N=1726), and Hispanic Americans (HA; N=1270) from the National Longitudinal Study of Adolescent to Adult Health (1996; ages 12-21), we assessed the evidence for a SNPxMVPA interaction with BMI-for-age Z score, once accounting for obesogenic neighborhood factors including physical activity amenities, transportation and recreation infrastructure, poverty and crime. Eight SNPxMVPA interactions with suggestive significance (p<0.10; three in each EA, and AA, two in HA) were observed showing attenuation on BMI-for-age Z score in adolescents with ≥5 versus <5 bouts/week MVPA, except for rs10146997 (near NRXN3). Findings were robust to the inclusion of neighborhood-level variables as covariates. These findings suggest that any attenuation from MVPA on a genetic susceptibility to obesity during adolescence is likely not operating through obesogenic neighborhood factors.

Influence of SNP*SNP interaction on BMI in European American adolescents: findings from the National Longitudinal Study of Adolescent Health.

BACKGROUND: Adolescent obesity is predictive of future weight gain, obesity and adult onset severe obesity (body mass index [BMI] ≥40 kg m(-2) ). Despite successful efforts to identify Single Nucleotide Polymorphisms (SNPs) influencing BMI, <5% of the 40-80% heritability of the phenotype has been explained. Identification of gene-gene (G-G) interactions between known variants can help explain this hidden heritability as well as identify potential biological mechanisms affecting weight gain during this critical developmental period. OBJECTIVE: We have recently shown distinct genetic effects on BMI across the life course, and thus it is important to examine the evidence for epistasis in adolescence. METHODS: In adolescent participants of European descent from wave II of the National Longitudinal Study of Adolescent Health (Add Health, n = 5072, ages 12-21, 52.5% female), we tested 34 established BMI-related SNPs for G-G interaction effects on BMI z-score. We used mixed-effects regression, assuming multiplicative interaction models adjusting for age, sex and geographic region, with random effects for family and school. RESULTS: For 28 G-G interactions that were nominally significant (P < 0.05), we attempted to replicate our results in an adolescent sample from the Childhood European American Cohort from Philadelphia. In the replication study, one interaction (PRKD1-FTO) was significant after correction for multiple testing. CONCLUSIONS: Our results are suggestive of epistatic effects on BMI during adolescence and point to potentially interactive effects between genes in biological pathways important in obesity.

Implications of iron deficiency/anemia on the classification of diabetes using HbA1c.

BACKGROUND/OBJECTIVES: Nonglycemic factors like iron deficiency (ID) or anemia may interfere with classification of diabetes and prediabetes using hemoglobin A1c (HbA1c). However, few population-based studies of diabetes in areas with endemic ID/anemia have been conducted. We aimed to determine how mutually exclusive categories of ID alone, anemia alone and iron-deficiency anemia (IDA) were each associated with prediabetes and diabetes prevalence using fasting blood glucose (FBG) versus HbA1c in a population-based study of adults with endemic ID/anemia. SUBJECTS/METHODS: We used data from the China Health and Nutrition Survey, a longitudinal, population-based study across 228 communities within nine provinces of China. This analysis included 7308 adults seen in the 2009 survey aged 18-75 years. We used descriptive and covariate-adjusted models to examine relative risk of prediabetes and diabetes using FBG alone, HbA1c alone, HbA1c and FBG, or neither (normoglycemia) by anemia alone, ID alone, IDA or normal iron/hemoglobin. RESULTS: Approximately 65% of individuals with diabetes in our sample were concordantly classified with diabetes using both FBG and HbA1c, while 35% had a discordant diabetes classification: they were classified using either FBG or HbA1c, but not both. Fewer participants with ID alone versus normal iron/hemoglobin were classified with diabetes using HbA1c only. From covariate-adjusted, multinomial regression analyses, the adjusted prevalence of prediabetes using HbA1c only was 22% for men with anemia alone, but 13% for men with normal iron/hemoglobin. In contrast, the predicted prevalence of prediabetes using HbA1c only was 8% for women with ID alone, compared with 13% for women with normal iron/hemoglobin. CONCLUSIONS: These findings suggest potential misclassification of diabetes using HbA1c in areas of endemic ID/anemia. Estimating diabetes prevalence using HbA1c may result in under-diagnosis in women with ID and over-diagnosis in men with anemia.

Is waist circumference per body mass index rising differentially across the United States, England, China and Mexico?

BACKGROUND/OBJECTIVES: Little is known about whether waist circumference (WC) has increased disproportionately relative to body mass index (BMI) around the world. SUBJECTS/METHODS: Data came from the US National Health and Nutrition Examination Survey (1988-1994 and 2007-2010), Health Survey for England (1992-1993 and 2008-2009); the Mexican Nutrition Survey (1999) and the Mexican National Health and Nutrition Survey (NHNS 2012); and the China Health and Nutrition Survey (1993 and 2011). Country- and sex-stratified (for the United States, also race-/ethnicity-stratified) multivariable linear regressions were used to estimate mean difference in WC over time relative to BMI at specified overweight and obesity cutoff points, adjusting for age and survey year. RESULTS: Although mean WC and BMI shifted upward over time in all age-sex subpopulations in all four countries, trends in overweight prevalence were less consistent. However, WC relative to BMI increased at varying magnitudes across all countries and subpopulations, except US Black men. The magnitude of increase was largest for women in the youngest age group (20-29 years), particularly for women in Mexico (+6.6 cm, P<0.0001) and China (+4.6 cm, P<0.0001) (holding BMI constant at 25 kg/m(2)). For men, the increase was primarily evident among Chinese men (+4.8 cm, P<0.0001). CONCLUSIONS: WC has increased disproportionately over time relative to overall body mass across the United States, England, Mexico and China, particularly among young women, with the largest increases occurring in the middle-income countries of Mexico and China. These patterns are potentially a cause for concern especially for countries undergoing rapid economic and nutritional transitions.

Changes in waist circumference relative to body mass index in Chinese adults, 1993-2009.

BACKGROUND: Although body mass index (BMI) and waist circumference (WC) are correlated, the relationship between WC and BMI may have changed over time. OBJECTIVES: To describe temporal trends in BMI and WC distributions and quantify the increase in WC at a given BMI over time. SUBJECTS/METHODS: Data on adults aged 20-59 years from two waves (1993 and 2009) of the China Health and Nutrition Survey were used in a pooled cross-sectional analysis. Quantile regression examined age-adjusted temporal trends in the distributions of BMI and WC. Linear regression examined changes in mean WC over time, adjusting for BMI, age at survey and survey year. All models were stratified by gender. RESULTS: There was a significant increase in BMI and WC over time, particularly at the 95th quantile: on average, men had 2.8 kg m(-2) (95% confidence interval (CI): 2.4, 3.3) and women 1.5 kg m(-)(2) (95% CI: 1.1, 2.0) higher BMI in 2009 compared with their counterparts in 1993. WC increased by 9.0 cm (95% CI: 7.5, 10.1) and 5.0 cm (95% CI: 3.4, 6.6) for men and women, respectively. On average, men and women had a 3.2 cm (95% CI: 2.8, 3.7) and 2.1 cm (95% CI: 1.7, 2.5) higher WC in 2009 compared with their counterparts in 1993, holding BMI and age constant. WC adjusted for BMI increased to a larger extent among obese versus lean individuals and among younger versus older women. CONCLUSIONS: For both genders, BMI and WC increased significantly over time, with particularly greatest increase in magnitude in the upper tail of the BMI and WC distributions. Furthermore, WC at equivalent BMIs was higher in 2009, compared with their counterparts in 1993. Our findings suggest that even if BMI remained constant from 1993 to 2009, adults in 2009 might be at increased cardiometabolic risk as a result of their higher WC.

The association between childhood sexual and physical abuse with incident adult severe obesity across 13 years of the National Longitudinal Study of Adolescent Health.

BACKGROUND: Severe obesity has increased, yet childhood antecedents of adult severe obesity are not well understood. OBJECTIVE: Estimate adult-onset severe obesity risk in individuals with history of childhood physical and/or sexual abuse compared with those who did not report abuse. METHODS: Longitudinal analysis of participants from the US National Longitudinal Study of Adolescent Health (n = 10,774) wave II (1996; aged 12-22 years) followed through wave IV (2008-2009; aged 24-34 years). New cases of adult-onset severe obesity (body mass index [BMI] ≥ 40 kg/m2 using measured height and weight) in individuals followed over 13 years who were not severely obese during adolescence (BMI <120% of 95th percentile Centers for Disease Control and Prevention National Center for Health Statistics growth curves). RESULTS: The combined occurrence of self-reported sexual and physical abuse during childhood was associated with an increased risk of incident severe obesity in adulthood in non-minority females (hazard ratio [HR; 95% Confidence Interval] = 2.5; 1.3, 4.8) and males (HR = 3.6; 1.5, 8.5) compared with individuals with no history of abuse. CONCLUSION: In addition to other social and emotional risks, exposure to sexual and physical abuse during childhood may increase risk of severe obesity later in life. Consideration of the confluence of childhood abuse might be considered as part of preventive and therapeutic approaches to address severe obesity.

Overweight dynamics in Chinese children and adults.

China has experienced a transition from a history of undernutrition to a rapid increase in obesity. The China Health and Nutrition Survey, an ongoing longitudinal, household-based survey of urban and rural residents of nine provinces, documents these changes using measured height and weight across 53,298 observations from 18,059 participants collected from 1991 to 2011. Adult overweight (body mass index [BMI] ≥ 25 kg/m(2)) prevalence nearly tripled from 1991 (11.7%) to 2009 (29.2%), with significant cohort and age-related effects (stronger in males). Among youth, quantile regression reveals changes across the BMI distribution. By 2009, approximately 12% of children and adolescents were overweight, and 3% of 7-11-year-olds and 1% of 12-17-year-olds were obese (International Obesity Taskforce BMI 25 and 30 kg/m(2) equivalents, respectively). In 1991-2000, urbanicity was strongly and positively associated with BMI, but in 2000-2011, trends were similar across rural and urban areas. Among women, the burden has shifted to lower educated women (the reverse is true for males, as overweight was higher in men of higher education). Our findings highlight the importance of preventive measures early in the life cycle to reduce weight gain.

The emergence of cardiometabolic disease risk in Chinese children and adults: consequences of changes in diet, physical activity and obesity.

Strong secular declines in physical activity, increased fat and salt intake, and increased obesity, especially abdominal obesity, mark China's recent nutrition transition. The China Health and Nutrition 2009 Survey collected anthropometry, blood pressure and fasting blood samples from more than 9,000 individuals ≥ 7 years of age. We focus on elevated blood pressure and plasma markers of diabetes, inflammation and dyslipidemia. We used international definitions of cardiometabolic risk and estimated age- and sex-specific prevalence ratios for each outcome for high waist circumference or overweight. We used logistic regression to assess each risk factor's association with diet, physical activity, overweight and abdominal obesity. Cardiometabolic risk prevalence was high in all age groups Prevalence ratios for most risk factors were nearly doubled for overweight or high waist circumference groups. Prevalence ratios were higher in younger than older adults. Low physical activity consistently predicted higher cardiometabolic risk across most outcomes and age-sex groups. The co-occurrence of overweight and high waist circumference was highly predictive of dyslipidemia, elevated glycated haemoglobin and diabetes. High prevalence of cardiometabolic risk factors and their strong association with weight status and abdominal obesity in young adults portend increases in cardiometabolic morbidity and mortality. Early interventions will be required to reverse trends.

Moderate to vigorous physical activity interactions with genetic variants and body mass index in a large US ethnically diverse cohort.

BACKGROUND: Little is known about the interaction between genetic and behavioural factors during lifecycle risk periods for obesity and how associations vary across race/ethnicity. OBJECTIVE: The objective of this study was to examine joint associations of adiposity-related single-nucleotide polymorphisms (SNPs) and moderate to vigorous physical activity (MVPA) with body mass index (BMI) in a diverse adolescent cohort. METHODS: Using data from the National Longitudinal Study of Adolescent Health (n = 8113: Wave II 1996; ages 12-21, Wave III; ages 18-27), we assessed interactions of 41 well-established SNPs and MVPA with BMI-for-age Z-scores in European Americans (EA; n = 5077), African-Americans (AA; n = 1736) and Hispanic Americans (HA; n = 1300). RESULTS: Of 97 assessed, we found nominally significant SNP-MVPA interactions on BMI-for-age Z-score in EA at GNPDA2 and FTO and in HA at LZTR2/SEC16B. In EA, the estimated effect of the FTO risk allele on BMI-for-age Z-score was lower (ß = -0.13; 95% confidence interval [CI]: 0.08, 0.18) in individuals with ≥5 vs. <5 (ß = 0.24; CI: 0.16, 0.32) bouts of MVPA per week (P for interaction 0.02). Race/ethnicity-pooled meta-analysis showed nominally significant interactions for SNPs at TFAP2B, POC5 and LYPLAL1. CONCLUSIONS: High MVPA may attenuate underlying genetic risk for obesity during adolescence, a high-risk period for adult obesity.

Screen time behaviours may interact with obesity genes, independent of physical activity, to influence adolescent BMI in an ethnically diverse cohort.

BACKGROUND: There has been little investigation of gene-by-environment interactions related to sedentary behaviour, a risk factor for obesity defined as leisure screen time (ST; i.e. television, video and computer games). OBJECTIVE: To test the hypothesis that limiting ST use attenuates the genetic predisposition to increased body mass index (BMI), independent of physical activity. DESIGN: Using 7642 wave II participants of the National Longitudinal Study of Adolescent Health, (Add Health; mean = 16.4 years, 52.6% female), we assessed the interaction of ST (h week(-1) ) and 41 established obesity single nucleotide polymorphisms (SNPs) with age- and sex-specific BMI Z-scores in 4788 European-American (EA), 1612 African-American (AA) and 1242 Hispanic American (HA) adolescents. RESULTS: Nominally significant SNP*ST interaction were found for FLJ35779 in EA, GNPDA2 in AA and none in HA (EA: beta [SE] = 0.016[0.007]), AA: beta [SE] = 0.016[0.011]) per 7 h week(-1) ST and one risk allele in relation to BMI Z-score. CONCLUSIONS: While for two established BMI loci, we find evidence that high levels of ST exacerbate the influence of obesity susceptibility variants on body mass; overall, we do not find strong evidence for interactions between the majority of established obesity loci. However, future studies with larger sample sizes, or that may build on our current study and the growing published literature, are clearly warranted.

The spatial distribution of overweight and obesity among a birth cohort of young adult Filipinos (Cebu Philippines, 2005): an application of the Kulldorff spatial scan statistic.

OBJECTIVES: The objectives of the study were to test for spatial clustering of obesity in a cohort of young adults in the Philippines, to estimate the locations of any clusters, and to relate these to neighborhood-level urbanicity and individual-level socioeconomic status (SES). SUBJECTS: Data are from a birth cohort of young adult (mean age 22 years) Filipino males (n=988) and females (n=820) enrolled in the Cebu Longitudinal Health and Nutrition Survey. METHODS: We used the Kulldorff spatial scan statistic to detect clusters associated with unusually low or high prevalences of overweight or obesity (defined using body mass index, waist circumference and body fat percentage). Cluster locations were compared to neighborhood-level urbanicity, which was measured with a previously validated scale. Individual-level SES was adjusted for using a principal components analysis of household assets. RESULTS: High-prevalence clusters were typically centered in urban areas, but often extended into peri-urban and even rural areas. There were also differences in clustering by both sex and the measure of obesity used. Evidence of clustering in males, but not females, was much weaker after adjustment for SES.

PNPLA3 gene-by-visceral adipose tissue volume interaction and the pathogenesis of fatty liver disease: the NHLBI family heart study.

BACKGROUND: Fatty liver disease (FLD) is characterized by increased intrahepatic triglyceride content with or without inflammation and is associated with obesity, and features of the metabolic syndrome. Several recent genome-wide association studies have reported an association between single-nucleotide polymorphism rs738409 in the (patatin-like phospholipase domain-containing protein 3) PNPLA3 gene and FLD. Liver attenuation (LA; hounsfield units, HU) by computed tomography is a non-invasive measure of liver fat, with lower values of HU indicating higher liver fat content. Clinically, a LA value of 40 HU indicates moderate-to-severe hepatic steatosis. OBJECTIVE: We investigated whether missense rs738409 PNPLA3 interacted with abdominal visceral adipose tissue (VAT) volume (cm) to reduce LA (that is, increased liver fat) in 1019 European American men and 1238 European American women from the Family Heart Study. METHODS: We used linear regression to test the additive effect of genotype, abdominal VAT, and their multiplicative interaction on LA adjusted for age, body mass index, high-density lipoprotein-cholesterol, insulin resistance, serum triglycerides, abdominal subcutaneous adipose tissue and alcohol intake. RESULTS: In men and women combined, the interaction between each copy of the rs738409 variant allele (minor allele frequency 0.23) and 100 cm/150 mm slice VAT decreased LA by 2.68±0.35 HU (P<0.01). The interaction of 100 cm VAT and the variant allele was associated with a greater decrease in LA in women than men (-4.8±0.6 and -2.2±0.5 HU, respectively). CONCLUSIONS: The interaction between genotype and VAT volume suggest key differences in the role of PNPLA3 genotype in conjunction with abdominal VAT in liver fat accrual. The stronger association of the PNPLA3 genotype and liver fat in women suggests that women may be more sensitive to liver fat accumulation in the setting of increased visceral fat, compared with men. The presence of the PNPLA3 variant genotype, particularly in the context of high VAT content may have an important role in FLD.

Estimation of genetic effects on BMI during adolescence in an ethnically diverse cohort: The National Longitudinal Study of Adolescent Health.

OBJECTIVE: The contribution of genetic variants to body mass index (BMI) during adolescence across multiethnic samples is largely unknown. We selected genetic loci associated with BMI or obesity in European-descent samples and examined them in a multiethnic adolescent sample. DESIGN AND SAMPLE: In 5103 European American (EA), 1748 African American (AfA), 1304 Hispanic American (HA) and 439 Asian American (AsA) participants of the National Longitudinal Study of Adolescent Health (Add Health; ages 12-21 years, 47.5% male), we assessed the association between 41 established obesity-related single-nucleotide polymorphisms (SNPs) with BMI using additive genetic models, stratified by race/ethnicity, and in a pooled meta-analysis sample. We also compared the magnitude of effect for BMI-SNP associations in EA and AfA adolescents to comparable effect estimates from 11 861 EA and AfA adults in the Atherosclerosis Risk in Communities study (ages 45-64 years, 43.2% male). RESULTS: Thirty-five of 41 BMI-SNP associations were directionally consistent with published studies in European populations, 18 achieved nominal significance (P<0.05; effect sizes from 0.19 to 0.71 kg m(-2) increase in BMI per effect allele), while 4 (FTO, TMEM18, TFAP2B, MC4R) remained significant after Bonferroni correction (P<0.0015). Of 41 BMI-SNP associations in AfA, HA and AsA adolescents, nine, three and five, respectively, were directionally consistent and nominally significant. In the pooled meta-analysis, 36 of 41 effect estimates were directionally consistent and 21 of 36 were nominally significant. In EA adolescents, BMI effect estimates were larger (P<0.05) for variants near TMEM18, PTER and MC4R and smaller for variants near MTIF3 and NRXN3 compared with EA adults. CONCLUSION: Our findings suggest that obesity susceptibility loci may have a comparatively stronger role during adolescence than during adulthood, with variation across race/ethnic subpopulation.

Multilevel examination of diabetes in modernising China: what elements of urbanisation are most associated with diabetes?

AIMS/HYPOTHESIS: The purpose of this study was to examine the association between urbanisation-related factors and diabetes prevalence in China. METHODS: Anthropometry, fasting blood glucose (FBG) and community-level data were collected for 7,741 adults (18-90 years) across 217 communities and nine provinces in the 2009 China Health and Nutrition Survey to examine diabetes (FBG ≥7.0 mmol/l or doctor diagnosis). Sex-stratified multilevel models, clustered at the community and province levels and controlling for individual-level age and household income were used to examine the association between diabetes and: (1) a multicomponent urbanisation measure reflecting overall modernisation and (2) 12 separate components of urbanisation (e.g., population density, employment, markets, infrastructure and social factors). RESULTS: Prevalent diabetes was higher in more-urbanised (men 12%; women 9%) vs less-urbanised (men 6%; women 5%) areas. In sex-stratified multilevel models adjusting for residential community and province, age and household income, there was a twofold higher diabetes prevalence in urban vs rural areas (men OR 2.02, 95% CI 1.47, 2.78; women, OR 1.94, 95% CI 1.35, 2.79). All urbanisation components were positively associated with diabetes, with variation across components (e.g. men, economic and income diversity, OR 1.42, 95% CI 1.20, 1.66; women, transportation infrastructure, OR 1.18, 95% CI 1.06, 1.32). Community-level variation in diabetes was comparatively greater for women (intraclass correlation [ICC] 0.03-0.05) vs men (ICC ≤0.01); province-level variation was greater for men (men 0.03-0.04; women 0.02). CONCLUSIONS/INTERPRETATION: Diabetes prevention and treatment efforts are needed particularly in urbanised areas of China. Community economic factors, modern markets, communications and transportation infrastructure might present opportunities for such efforts.

The expanding burden of cardiometabolic risk in China: the China Health and Nutrition Survey.

China faces a major increase in cardiovascular disease, yet there is limited population-based data on risk factors, particularly in children. Fasting blood samples, anthropometry and blood pressure were collected on 9,244 children and adults aged ≥7 years in late 2009 as part of the national China Health and Nutrition Survey. Prevalent overweight, elevated blood pressure, and cardiometabolic risk factors: glucose, HbA1c, triglycerides (TG), total cholesterol (TC), high- and low-density lipoprotein cholesterol (HDL-C and LDL-C), and C-reactive protein (CRP) are presented. We found that 11% of Chinese children and 30% of Chinese adults are overweight. Rates of diabetes, dyslipidaemia, hypertension and inflammation are high and increased with age and were associated with urbanization. Approximately 42% of children have at least one of the following: pre-diabetes or diabetes, hypertension, high TC, LDL-C, TG, and CRP and low HDL-C, as do 70% men and 60% women aged 18-40 years and >90% of men and women ≥60 years. In sum, the HbA1c findings suggest that as many as 27.7 million Chinese children and 334 million Chinese adults may be pre-diabetic or diabetic. The high prevalence in less urban areas and across all income levels suggests that cardiometabolic risk is pervasive across rural and urban China.