Life-course epidemiology of early life adversity, obesity, and cardiometabolic health

Background

The world has been facing an obesity epidemic for many years, which represents a public health issue because obesity is associated with an increased predisposition for several chronic diseases, namely cardiovascular risk. However, those with obesity display heterogeneity in their cardiometabolic profiles and disease risks, as do normal weight individuals. Those with obesity who have a healthier metabolic profile (i.e., 0-2 cardiometabolic risk factors) versus a less healthy metabolic profile (>2 cardiometabolic risk factors) may be defined as displaying cardiometabolic resilience to obesity or as being metabolically healthy obese (MHO). Poorer cardiometabolic health within individuals of the same weight class category is associated with increased disease and mortality risks. There is limited literature on the life-course mechanisms and processes investigating what leads to differing cardiometabolic risk within different weight categories. Understanding and identifying factors of potential intervention across the life course is of public health benefit to potentially delay and prevent cardiometabolic risk, even among those obese. Cardiometabolic risk later in life may be linked to individuals’ history of adiposity exposure. However, there is limited research investigating obesity histories and cardiometabolic risk in different weight groups, and the literature that does exist does not consider exposure to central adipose tissue in addition to overall adiposity. Early life adversity is a proxy of stress exposure, which in turn has been consistently linked to cardiovascular disease and obesity. However, the literature linking early life adversity with an adverse cardiometabolic profile in adulthood is equivocal. There is evidence that early life adversity is linked to increased cardiometabolic risk amongst those obese, however, cumulative exposure to early life adversity and cardiometabolic risk amongst different weight categories has not yet been explored.

Aim This thesis aims to elucidate the relationships between early life adversity, obesity histories, and cardio-metabolic health in overweight/obesity and normal weight individuals. The following objectives were outlined to achieve this aim: 1) To systematically review the literature on the life course factors (i.e., body size, pubertal development, body composition, lifestyle behaviours, psychosocial stress, socioeconomic position and stress response measures) associated with MHO, 2) To investigate the association between BMI and WC history and cardiometabolic health amongst normal weight and overweight/obese groups in the Whitehall II cohort, 3) To investigate how early life psychosocial and socioeconomic adversity are related to cardiometabolic health among normal weight and overweight/obese groups in the National Survey for Health and Development (NSHD) 1946 cohort, and 4) To investigate the relationship between exposure to early life psychosocial adversity and later life inflammation (using c- reactive protein as a proxy) and cortisol regulation (using measures such as morning cortisol, diurnal slope, cortisol awakening response, and evening cortisol) in the National Survey for Health and Development 1946 cohort.

Methods

To address objective one a systematic review was conducted. Three databases were searched using a trialled search strategy, and 2,506 publications were screened according to eligibility criteria, of which 30 studies were included in the review and summarised using a narrative synthesis. To address objective two secondary data analysis was conducted using data from the Whitehall II cohort study. To address objectives three and four secondary data analysis was conducted using data from the 1946 National Survey for Health and Development (NSHD) cohort study.

Key Findings

1) The most investigated exposures in relation to MHO include body size. Higher birth weight was associated with cardiometabolic resilience to obesity in childhood to early adulthood, and higher adulthood BMI and WC in adulthood were associated with later reduced cardiometabolic resilience to obesity. Despite body size being the most investigated exposure, little is known about exposure to body size histories (i.e., WC and BMI) over time and MHO. Overweight/obesity exposures were minimally studied, and measures of such were crude. Alcohol intake had the most agreement among findings for lifestyle exposures (smoking, alcohol intake, physical activity, and nutrition). Increased alcohol intake was associated with reduced risk of MHO versus MUO. Smoking was also generally associated with a reduced risk of MHO versus MUO. There was no consensus that increased physical activity was related to later reduced risk of MHO versus MUO. 2) In the Whitehall II cohort, higher average BMI and WC over twenty years was associated with an increased risk of being metabolically unhealthy later in adulthood in both normal weight and overweight/obese groups. A high duration of central or general obesity was associated with an increased risk of poor cardiometabolic health in normal weight and overweight/obese groups. In addition, there was some evidence for greater variability in BMI and WC across 20 years being associated with increased risk of poor cardiometabolic health in both normal weight and overweight/obese groups. The strongest risk factor for being metabolically unhealthy versus healthy in normal weight and overweight/obese groups was a history of persistent central obesity. Results also showed that greater exposure to excess adiposity only partly explain the elevated disease risk factors of unhealthy (compared to healthy) normal weight adults and overweight/obese adults.

3) In the NSHD 1946 cohort, independent of socioeconomic early life adversity, children exposed to the highest level of psychosocial early life adversity had an increased risk of being metabolically unhealthy at ages 60-64 years in both normal weight and overweight/obese groups. However, the highest level of socioeconomic early life adversity was only associated with an increased risk of being metabolically unhealthy in the overweight/obese group.

4) In the NSHD 1946 cohort, individuals who experienced the highest level of childhood psychosocial adversity had lower waking cortisol at 60-64 years and had a lower decline in cortisol across the day (i.e., a less negative diurnal slope). Thus, indicating that psychosocial ELA may be associated with a dysfunctional stress response later in life. Secondly, there was tentative evidence that the highest level of childhood psychosocial adversity was associated with greater CRP at 60-64 years in females.

Conclusions

Future research is required to elucidate the life-course processes and mechanisms that explain why some overweight/obese individuals do not develop the typical cardiometabolic risk factors associated with overweight/obesity. Lower exposure to adiposity across 20 years in adulthood may reduce cardiometabolic risk in those normal weight and overweight/obese individuals. Specifically, the most important risk factor for increased cardiometabolic risk in adulthood may be a history of persistent central obesity, even in those of normal weight. Results, hence, highlight the importance of maintaining optimum and stable BMI and WC, both in adults who become and do not become overweight/obese. Independently of socioeconomic early life adversity, psychosocial adversity in childhood may be associated with an increased cardiometabolic risk in both normal weight and overweight/obese adults. However, higher socioeconomic early life adversity exposure may be associated with greater cardiometabolic risk in overweight/obese individuals only. This may be because high psychosocial ELA captures exposure to toxic stress, which may cause a biological embedding of the neuroendocrine, metabolic, and immune systems. Thus, there may be a predisposition for increased cardiometabolic risk irrespective of weight status. Although further research is required to elucidate this specific pathway. There may be sex differences between psychosocial ELA exposure and later inflammation; again, however, further research is required to elucidate if and why this may be present.