The worked performed so far comprehend individual level data collection, safety storage, cleaning, and variable harmonization across the different studies. Data included questionnaire, clinical, genotype and register data information. We further used publicly available genome-wide summary level data. We applied various methodological analyses in order to analyze the data and report the results to answer the research questions including, among others, various regression models, genome wide level scans, Mendelian randomization and time-to-event analysis for disease risk assessment.
We found evidence that higher physical activity and decrease sedentary time associated with lower body weight and fat percentage in general. Meaning that physical inactivity was associated with lower body weight. We further provide bidirectional evidence of causality for the association between higher sedentary time and higher adiposity. This means that decreasing sedentary time is beneficial for weight management, but also that weight loss may help reduce sedentary time, forming a reinforcing loop. However, we found no clear evidence that higher physical activity associated with improve body fat distribution, meaning that we could not explain the hypothesis that higher fat expandability was associated with a healthier lifestyle.
In relation to smoking, our findings suggested that tobacco smoking associated with higher abdominal fat and that this came at the cost of lower gluteofemoral fat. Further that the effects were coming mostly from increase abdominal visceral adipose tissue rather than subcutaneous. Thus, our findings suggest that smoking has poor fat expandability properties. Thus, we speculate that a plausible explanation for the deleterious effects from smoking on cardiometabolic diseases may be due to a decrease fat expandability.
One of the aims of this proposal was to examine whether the genetic predispositions to higher fat expandability predict a metabolically healthy obese state in middle age and whether this state was sustained after 5-year period. Our analysis in this regard was inconclusive, most likely due to low statistical power. Thus, we could not conclude that higher genetic predisposition to higher fat expandability did not associate with metabolically healthy obese.
We show that children with low body size in childhood that then have a high body size as adults had the highest risk for type 2 diabetes. As expected, high body size in adulthood was a major risk factor for cardiometabolic disease, however body size in childhood was a risk determinant for type 2 diabetes, but not for cardiovascular disease. We speculate that lean children may have an increased susceptibility for type 2 diabetes because of a limited capacity for triglyceride storage in the adipose tissue (lower fat expandability), which may lead to metabolic complications upon weight gain due to lipotoxicity in adipose tissue and systematically.
