This prospective cohort study with 18.2 years of follow-up showed that the presence of MetS during adolescence, based on Cook and de Ferranti’s definitions, increased the risk of high a CIMT during adulthood. However, after adjusting for adulthood BMI, no significant association was found based on any of the MetS definitions. Moreover, adolescents with high WC/low HDL-C or high WC/HTN or high TG/high WC metabolic phenotypes had higher risks of a high CIMT. After adjusting for adulthood BMI, the high WC/low HDL-C metabolic phenotype was still significantly associated with an increased risk of adulthood high CIMT.
The importance of MetS during childhood and adolescence is a controversial issue. Several studies have suggested an association between pediatric MetS and the increased risk of MetS, type 2 diabetes, and subclinical atherosclerosis (31). On the other hand, similar predictive values have been reported for simpler screening tools, such as BMI, to identify adulthood MetS (32). Moreover, the confounding effect of adulthood BMI on the association between pediatric MetS and adulthood MetS reveals the insignificance of MetS during childhood and adolescence (11). Therefore, further research is needed on the importance of MetS during childhood and adolescence.
Different definitions of MetS have been proposed; three widely used definitions of pediatric MetS in observational studies are Cook, de Ferranti, and pediatric IDF definitions (12) (13). A previous study on the TLGS showed a positive association between metabolic phenotypes and the early adult MetS (33). Moreover, Koskinen et al. showed that MetS, based on several definitions (Cook, modified National Cholesterol Education Program (MetSNCEP75), and MetSPed), was associated with a high CIMT among adolescents > 11 years (31). Consistently, we found that the presence of MetS based on Cook and de Ferranti’s definitions increased the risk of a high CIMT incidence during adulthood. It is important to note that this association became insignificant after adjusting for adulthood BMI.
Previous studies have suggested the independent role of MetS components in children to predict cardiovascular and metabolic outcomes in adulthood. High TG and high WC have been shown to be associated with adulthood MetS (11, 34). Moreover, in the analysis of MetS components, different combinations of the components were found to predict the early adult MetS (11). Accordingly, a hypertriglyceridemic waist phenotype can be used simply to identify adolescents at a higher risk of metabolic abnormalities and CVD (35, 36). Zhao et al., in a cross-sectional study, showed that clustering of cardiometabolic risk factors predicted a high CIMT in childhood significantly better than MetS (AUC = 0.66 vs. 0.54) (37). Also, Koskinen et al., combining four cohort studies (31), reported that a high insulin level between the age of 11 and 16 years and high TG and low HDL-cholesterol levels between the age of 14 and 18 years were associated with a high CIMT. In this study, it was found that high WC/HTN, high WC/low HDL-C, and high TG/high WC metabolic phenotypes in adolescents were associated with the incidence of a high CIMT in future adulthood.
The substantial confounding effect of adulthood BMI on the association between adolescent MetS and adulthood high CIMT was found in the present study. After adjusting for adulthood BMI, all positive associations between the metabolic phenotypes and MetS became null. Also, previous studies have shown that individuals with a decreasing BMI trajectory from adolescence to adulthood (excess to normal weight) do not have an increased CIMT (38–40); highlighting the importance of tracking BMI from adolescents to adulthood. Considering the importance of final weight achieved in adulthood, irrespective of BMI status in adolescence, when we are faced with adolescents affected by MetS we can advise them to get to an appropriate BMI in future to prevent development of high CIMT in adult years.
An unexpected finding of the current study was the persistent positive association between the high WC/low HDL-C metabolic phenotype and the incidence of a high CIMT in adulthood, even after adjusting for adulthood BMI. Therefore, this phenotype can be used as a simpler alternative for MetS to predict early adulthood high CIMT. This is an interesting metabolic phenotype with genetic determinants, which can be investigated in future studies to discover possible conditions leading to this unhealthy metabolic status.
This study had several limitations. First, the serum insulin level was not measured to determine insulin resistance as a metabolic risk factor. Second, the participants were not divided into different age groups due to the low number of subjects in each age group. Finally, some possible confounders, such as puberty stage, physical activity, dietary habits, and socioeconomic status, were not considered.
To the best of our knowledge, this is the first cohort study to explore the role of metabolic phenotypes among adolescents in predicting an increased CIMT in early adulthood. The prospective design and the duration of follow-up are the main strengths of this study. Also, national definitions and cut-off points were used in this study. Finally, data were obtained by trained technicians to reduce subjective errors, and no self-report measure was used.
In conclusion, the presence of MetS, based on Cook and de Ferranti’s definitions, increased the risk of a high CIMT incidence in adulthood. Nevertheless, after adjusting for adulthood BMI, the association became insignificant. However, a specific binary combination of metabolic abnormalities (high WC/low HDL-c) had a positive association with a high CIMT, even after adjusting for adulthood BMI; this indicates the higher predictive value of this association. However, future studies with long-term follow-ups are required to clarify the relationship between metabolic phenotypes, especially high WC/low HDL-C, and the incidence of a high CIMT and other cardiovascular outcomes in adulthood.
Figure Legends:
Figure 1. Diagram showing the selection process of study participants