PREDICTION OF CARDIOMETABOLIC RISK IN CHILDREN

Abstract

Background: Three decades of clinical research have demonstrated that the risks of atherosclerotic cardiovascular disease (ACVD: coronary disease and ischaemic stroke), and the closely related type 2 diabetes (T2D) are established and influenced by events during childhood. This is at least partly because childhood obesity usually leads to adult adiposity; so, the currently high prevalence of adult cardiometabolic disease, means that obesity needs to be identified as early as possible, ideally in childhood. Screening for obesity largely relies on anthropometric measurements like body mass index (BMI), however this has many limitations including its inability to distinguish lean from fat mass. There is therefore a need for other reliable predictors of AVCD and T2D Aim: The focus of this doctoral study was to investigate the ability of various measures of adiposity, nutrition, and metabolomic biomarkers to predict cardiometabolic risk at age 16y. Methods: A systematic review was conducted to determine the existing evidence on the role of anthropometry in determining future risk of CVD. A continuous metabolic risk score was calculated as a composite of insulin resistance, total/high-density lipoprotein cholesterol ratio, fasting triglycerides, and mean arterial blood pressure. Initial exploratory analysis was conducted followed by longitudinal analyses which included mixed effects modelling when appropriate Findings: The systematic review indicated that childhood BMI predicts the risk of dysglycaemia, abnormal carotid-intima medial thickness (CIMT), and AVCD events in adulthood; however, its ability to predict hypertension was weak. A metabolic risk score was designed and utilised in these analyses because there is no universal definition of the metabolic syndrome and in children and adolescents, the prevalence rate of the latter is very low. The score identified those with high adiposity and was also able to detect those most likely to have the metabolic syndrome. The analysis also showed that simple anthropometric measures of adiposity were at least as effective as fat mass measured by dual energy x-ray absorptiometry in detecting those at an elevated risk of developing cardiometabolic disease in the future Higher intake of energy and certain macronutrients were predictive of the trajectory of metabolic risk and some of its components, but not of adiposity. Insulin resistance, Triglycerides, Metabolic risk score, were higher in those who consumed greater energy, lower fibre, higher sugar, and higher saturated fat at 8y. Also, this unique longitudinal study of homogenous cohort of children and adolescents showed that those who had a high metabolic risk score at 16y had higher levels of specific products of branch-chain amino acid metabolism. Further studies are required to keep following this cohort to confirm the association of the score with adult-diagnosed metabolic syndrome, type 2 diabetes, and CVD events.