Body size trajectories and cardio-metabolic resilience to obesity

Individuals with obesity do not represent a single homogenous group in terms of cardio-metabolic health prospects. The concept of metabolically-healthy obesity is a crude way of capturing this heterogeneity and has resulted in a plethora of research linking to future outcomes to show that it is not a benign condition. By contrast, very few studies have looked back in time and modelled the life course processes and exposures that explain the heterogeneity in cardio-metabolic health and morbidity and mortality risk among people with the same body mass index (BMI) (or waist circumference or percentage body fat). The aim of the Medical Research Council New Investigator Research Grant (MR/P023347/1) ‘Body size trajectories and cardio-metabolic resilience to obesity in three United Kingdom birth cohorts’ is to reveal the body size trajectories, pubertal development patterns, and other factors (e.g. early-life adversity) that might attenuate the positive associations of adulthood obesity makers (e.g. BMI) with cardio-metabolic disease risk factors and other outcomes, thereby providing some degree of protection against the adverse effects of obesity. This work builds on the principle investigator’s previous research as part of the Cohort and Longitudinal Studies Enhancement Resources initiative and focuses on secondary data analysis in the nationally representative UK birth cohort studies (initiated in 1946, 1958, and 1970), which have life course body size and exposure data and a biomedical sweep in adulthood. The grant will provide novel evidence on the life course processes and exposures that lead to some people developing a cardio-metabolic complication or disease or dying while other people with the same BMI do not. This paper details the grant’s scientific rationale, research objectives, and potential impact

Healthy obesity: time to give up the ghost?

Healthy obesity: time to give up the ghost

Determinants of the population health distribution: an illustration examining body mass index

Most epidemiological studies examine how risk factors relate to average difference in outcomes (linear regression) or odds of a binary outcome (logistic regression); they do not explicitly examine whether risk factors are associated differentially across the distribution of the health outcome investigated. This paper documents a phenomenon found repeatedly in the minority of epidemiological studies which do this (via quantile regression); associations between a range of established risk factors and body mass index (BMI) are progressively stronger in the upper ends of the BMI distribution. In this paper, we document this finding and provide illustrative evidence of it in the 1958 British birth cohort study. Associations of low childhood socioeconomic position, high maternal weight, low childhood general cognition and adult physical inactivity with higher BMI are larger at the upper end of the BMI distribution, on both absolute and relative scales. For example, effect estimates for socioeconomic position and childhood cognition were around three times larger at the 90th compared with 10th quantile, while effect estimates for physical inactivity were increasingly larger from the 50th-90th quantiles, yet null at lower quantiles. We provide potential explanations for these findings and discuss implications. Risk factors may have larger causal effects amongst those in worse health, and these effects may not be discovered when health is only examined in average terms. In such scenarios, population-based approaches to intervention may have larger benefits than anticipated when assuming equivalent benefit across the population.. Further research is needed to understand why effect estimates differ across the BMI outcome distribution and investigate whether differential effects exist for other physical and mental health outcomes

Infant weight gain and adolescent body mass index: comparison across two British cohorts born in 1946 and 2001

Objective To investigate how the relationship of infant weight gain with adolescent body mass index (BMI) differs for individuals born during compared to before the obesity epidemic era. Design Data from two British birth cohorts, the 1946 National Survey of Health and Development (NSHD, n = 4,199) and the 2001 Millennium Cohort Study (MCS, n = 9,417), were used to estimate and compare associations of infant weight gain between ages 0-3 years with adolescent outcomes. Main outcome measures BMI Z-scores and overweight/ obesity at ages 11 and 14 years. Results Infant weight gain, in Z-scores, was positively associated with adolescent BMI Z-scores in both cohorts. Non-linearity in the MCS meant that associations were only stronger than in the NSHD when infant weight gain was above -1 Z-score. Using decomposition analysis, between-cohort differences in association accounted for 20-30% of the differences (secular increases) in BMI Z-scores, although the underlying estimates were not precise with 95% confidence intervals (CI) crossing zero. Conversely, between-cohort differences in the distribution of infant weight gain accounted for approximately 9% of the differences (secular increases) in BMI Z-scores, and the underlying estimates were precise with 95% CI not crossing zero. Relative to normal weight gain (change of -0.67 to +0.67 Z-scores between ages 0-3 years), very rapid infant weight gain (> 1.34), but not rapid weight gain (+0.67 to +1.34), was associated with higher BMI Z-scores more strongly in the MCS (β = 0.790; 95% CI = 0.717, 0.862 at age 11 years) than the NSHD (0.573; 0.466, 0.681); p < 0.001 for between-cohort difference. The relationship of slow infant weight gain (< -0.67) with lower adolescent BMI was also stronger in the MCS. Very rapid or slow infant weight gain were not, however, more strongly associated with increased risk of adolescent overweight/ obesity or thinness, respectively, in the more recently born cohort. Conclusions Greater infant weight gain, at the middle/ upper-end of the distribution, was more strongly associated with higher adolescent BMI among individuals born during (compared to before) the obesity epidemic. Combined with a secular change toward greater infant weight gain, these results suggest that there are likely to be associated negative consequences for population-level health and wellbeing in the future, unless effective interventions are developed and implemented

Additive influences of maternal and paternal body mass index on weight status trajectories from childhood to mid-adulthood in the 1970 British Cohort Study

This study aimed to (i)describe the weightstatus trajectories from childhood to mid-adulthood and (ii) investigate the influence ofmaternal and paternal body massindex (BMI) onoffspring’s trajectories in a nationally representative study inGreat Britain. Thesample comprised 4,174 (43% male) participantsfrom the 1970 British Cohort Study withcompleteBMI data at ages 10, 26, 30, 34, and 42years. Individuals’ weight status was categorised as overweight/obese or non-overweight/obese at eachage, and trajectories of weightstatus from 10 to42 years of age were assessed. Sex-stratified multinomial logistic regressionmodels were used to assess associations of maternal andpaternal BMI with trajectory group membership, adjusting for potential confounders (e.g.socioeconomicposition and puberty). Thirty per cent ofindividuals were never overweight/obese (reference trajectory),6%, 44%and 8%hadchildhood, early- and mid-adulthood onset of overweight/obesity (respectively), and 12% other trajectories. In fully adjusted models,highermaternal and paternal BMI significantlyincreased the risk of childhood (relativerisk ratio: 1.2-1.3) and early adulthood onset(1.2) of overweight/obesity in both sexes. Relative risk ratios were generall higher formaternal than paternal BMI in females but similar in males. Earlypuberty also increasedtherisk ofchildhood (1.8-9.2 and early-adulthoodonset (3.7-4.7)of overweight/obesity. Results highlight the importance of primary prevention, as mostindividuals remained overweight/obese after onset. Maternal and paternal BMI had additive effects on offspring weight status trajectories across 32 years of the life course,suggesting thatprevention/interventionprogrammes should focuson the whole famil

Improving risk estimates for metabolically healthy obesity and mortality using a refined healthy reference group

Objective: We aimed to re-examine mortality risk estimates for metabolically healthy obesity by using a ‘stable’ healthy non-obese referent group. Design: prospective cohort study. Methods: Participants were 5,427 men and women (aged 65.9 ± 9.4 years, 45.9% men) from the English Longitudinal Study of Ageing. Obesity was defined as body mass index ≥ 30 kg/m2 (vs. non-obese as below this threshold). Based on blood pressure, HDL-cholesterol, triglycerides, glycated haemoglobin, and C-reactive protein, participants were classified as ‘healthy’ (0 or 1 metabolic abnormality) or ‘unhealthy’ (≥ 2 metabolic abnormalities). Results: 671 deaths were observed over an average follow up of 8 years. When defining the referent group based on 1 clinical assessment, the unhealthy non-obese (Hazard ratio = 1.22; 95% CI, 1.01, 1.45) and unhealthy obese (1.29; 1.05, 1.60) were at greater risk of all-cause mortality compared to the healthy non-obese, yet no excess risk was seen in the healthy obese (1.14; 0.83, 1.52). When we re-defined the referent group based on 2 clinical assessments, effect estimates were accentuated and healthy obesity was at increased risk of mortality (2.67; 1.64, 4.34). Conclusion: An unstable healthy referent group may make ‘healthy obesity’ appear less harmful by obscuring the benefits of remaining never obese without metabolic dysfunction

Patterns of BMI development between 10-42 years of age and their determinants in the 1970 British Cohort Study

Background Mixture modelling is a useful approach to identify sub-groups in a population who share similar trajectories. We aimed to identify distinct BMI trajectories between 10-42 years and investigate how known early-life risk factors are related to trajectories. Methods Sample: 9,187 participants in the 1970 British Birth Cohort Study, with BMI observations between 10-42 years and data on birth-weight, parental BMI, socioeconomic status (SES), breastfeeding and puberty. Latent growth mixture modelling in Mplus was used to model age-related BMI trajectories and test associations of risk factors with trajectory membership. Results A three latent class model was most credible; 1) Normative: 92%: started normal weight but gradually increased BMI to become overweight in adulthood; 2) Childhood onset persistent obesity (COP): 4%: persistently high BMI from childhood; 3) Adolescent and young adulthood onset obesity (AYAO): 4%: normal weight in childhood but had a steep ascending trajectory. Higher maternal and paternal BMI and early puberty increased the probability of being in either the COP or the AYAO classes compared with the normative class. Conclusion Most individuals gradually increased BMI and became overweight in mid-adulthood. Only 8% demonstrated more severe BMI trajectories. Further research is needed to understand the underlying body composition changes and health risks in the COP and AYAO classes

Socioeconomic inequalities in childhood-to-adulthood BMI tracking in three British birth cohorts

Background: Body mass index (BMI) tracks from childhood to adulthood, but the extent to which this relationship varies across the distribution and according to socio-economic position (SEP) is unknown. We aimed to address this using data from three British cohort studies. Methods: We used data from: 1946 National Survey of Health and Development (NSHD, n=2,470); 1958 National Child Development Study (NCDS, n=7,747); 1970 British Cohort Study (BCS, n=5,323). BMI tracking between 11 and 42 years was estimated using quantile regression, with estimates reflecting correlation coefficients. SEP disparities in tracking were investigated using a derived SEP variable based on parental education reported in childhood. This SEP variable was then interacted with the 11-year BMI z-score. Results: In each cohort and sex, tracking was stronger at the upper end of the distribution of BMI at 42 years. For example, for men in the 1946 NSHD, the tracking estimate at the 10th quantile was 0.31 (0.20, 0.41), increasing to 0.71 (0.61, 0.82) at the 90th quantile. We observed no strong evidence of SEP inequalities in tracking in men in the 1946 and 1958 cohorts. In the 1970 cohort, however, we observed tentative evidence of stronger tracking in low SEP groups, particularly in women and at the higher end of the BMI distribution. For example, women in the 1970 cohort from low SEP backgrounds had tracking coefficients at the 50th, 70th, and 90th quantiles which were 0.05 (-0.04; 0.15), 0.19 (0.06; 0.31), and 0.22 (0.02; 0.43) units higher, respectively, than children from high SEP groups. Conclusion: Tracking was consistently stronger at the higher quantiles of the BMI distribution. We observed suggestive evidence for a pattern of greater BMI tracking in lower (compared to higher) SEP groups in the more recently born cohort, particularly in women and at the higher end of the BMI distribution

Do socio-economic inequalities in infant growth in rural India operate through maternal size and birth weight?

Background 3·1 million young children die every year from undernutrition. Greater understanding of associations between socio-economic status (SES) and the biological factors that shape undernutrition are required to target interventions. Aim To establish whether SES inequalities in undernutrition, proxied by infant size at 12 months, operate through maternal and early infant size measures. Participants and Methods The sample comprised 347 Indian infants born in 60 villages in rural Andhra Pradesh 2005-2007. Structural equation path models were applied to decompose the total relationship between SES (standard of living index) and length and weight for age Z-scores (LAZ/ WAZ) at 12 months into direct and indirect (operating through maternal BMI and height, birthweight Z-score and LAZ/WAZ at 6 months) paths. Results SES had a direct positive association with LAZ (Standardized coefficient = 0.08, 95% CI = 0.02, 0.13) and WAZ at age 12 months (Standardized coefficient = 0.08, 95%CI = 0.02, 0.15). It also had additional indirect positive associations through increased maternal height and subsequently increased birthweight and WAZ/LAZ at 6 months, accounting for 35% and 53% of the total effect for WAZ and LAZ respectively. Conclusion Findings support targeting evidence based growth interventions towards infants from the poorest families with the shortest mothers. Increasing SES can improve growth for two generations

Socioeconomic inequalities in childhood and adolescent body-mass index, weight, and height from 1953 to 2015: an analysis of four longitudinal, observational, British birth cohort studies

Background Socioeconomic inequalities in childhood body mass index (BMI) have been repeatedly documented in high income countries, yet there is uncertainty regarding how they have changed across time, how inequalities in the composite parts of BMI have changed (weight and height), and whether inequalities differ in magnitude across the outcome distributions. We investigated socioeconomic inequalities in childhood/adolescent weight, height, and BMI from 1953 to 2015 using British birth cohorts born in 1946, 1958, 1970, and 2001. Methods Associations between childhood social class and anthropometric outcomes at age 7, 10/11 and 14/16 years were examined to assess socioeconomic inequalities in each cohort using gender-adjusted linear regression models. Multilevel models were used to examine if these inequalities widened or narrowed from childhood to adolescence; quantile regression was used to examine whether the magnitude of inequalities differed across the outcome distribution. Findings Lower social class was associated with lower childhood/adolescent weight in earlier-born cohorts (1946-1970), yet with higher weight in the 2001 cohort. Lower social class was associated with shorter height in all cohorts, yet the absolute magnitude of this difference narrowed across generations. There was little inequality in childhood BMI in the 1946–1970 cohorts, yet inequalities were present in the 2001 cohort, and in all cohorts at 14/16 years (p<0.05 age x social class interactions). BMI and weight inequalities were larger in the 2001 cohort and systematically larger at higher quantiles—eg, in the 2001 cohort at 11 years there was a 0.98kg/m2 difference (0.63, 1.33) in median BMI (lowest to highest social class), yet 2.54kg/m2 (1.85, 3.22) difference at the 90th BMI percentile. Interpretation In the later 20th and early 21st centuries, socioeconomic inequalities in weight reversed, those in height narrowed, while inequalities in BMI and obesity emerged and widened. These drastic changes highlight the powerful impact of societal changes on child-adolescent growth and the insufficiency of previous policies in preventing obesity and its socioeconomic inequality. New and effective policies are required to reduce BMI inequalities in current and future children and adolescents. Without effective interventions, it is anticipated these inequalities will widen further throughout adulthood