Subclasses of Glucose Trajectories in Early Childhood Stratified the Risk of Abnormal Glucose Tolerance in Adolescence and Young Adulthood

Abstract

Early-life exposures may shape long-term effects on glucose regulation. This study aimed to stratify long-term abnormal glucose tolerance (AGT) risk from early childhood. A total of 906 children were enrolled at baseline and reevaluated in adolescence and young adulthood. By using the latent class trajectory analysis, glucose trajectories of children were measured via five–time point oral glucose tolerance tests and then grouped into three latent subclasses: mild excursion–normal reversion (MN), moderate excursion–delayed reversion (MD), and severe excursion–delayed reversion (SD). Logistic regression was performed to estimate the risk of AGT and associations between cardiometabolic factors and subclasses. In adolescence, compared with the MN subclass, the risk of AGT was 1.7-fold in the MD subclass and 5.5-fold in the SD subclass, after adjusting for age, sex, BMI, and Tanner stage. In young adulthood, the adjusted risk of AGT was 3.6-fold and 11.6-fold in the MD and SD subclasses, respectively. During the full natural history of glucose tolerance, the risk of AGT was 3.6-fold in the MD subclass and 18.1-fold in the SD subclass, after adjusting for childhood covariates. MD and SD subclass membership was strongly associated with childhood hypertension, maternal gestational diabetes, and maternal hypertension during pregnancy. Glucose trajectory subclasses in early childhood effectively stratified the long-term risk of AGT. The association between maternal cardiometabolic health and childhood subclass membership highlighted that prenatal exposures may influence metabolic outcomes in offspring. Article Highlights Abnormal glucose tolerance (AGT) in youth has become an alarming global public health issue; however, approaches to identify high-risk population among young people have not been well-established. Can the long-term risk of AGT be stratified by the subclasses of glucose trajectories defined in childhood? Subclasses defined in childhood can efficiently stratify the risk of AGT in adolescence and young adulthood. The subclass membership was strongly associated with cardiometabolic disorders in childhood and maternal cardiometabolic disorders during pregnancy. This subclass method provides a potential strategy to identify those at risk of later cardiometabolic disorders from childhood for more intensive evaluation of intervention. The close relationship between maternal cardiometabolic disorders and subclass membership of children highlighted the potential influence of gestational cardiometabolic health on the development of cardiometabolic disorders in offspring.