1. Introduction
Type 2 diabetes mellitus (T2DM) and its long-term complications, including cardiovascular diseases, stroke, and chronic kidney failure, are global health concerns that substantially affect life expectancy and mortality [
1]. In adults, principal determinants, such as abdominal obesity, dyslipidemia, hypertension, and dysglycemia, and the clustering of these disorders have been reported [
2]. Nevertheless, some of these risk factors or their precursors are observed in childhood [
3,
4,
5], and may persist into adulthood [
6]. Metabolic syndrome (MetS) is a cluster of cardiometabolic risk factors. A longitudinal study revealed that pediatric MetS predisposes adults to a high risk of high carotid intima-media thickness and T2DM [
7]; however, the risk can be reduced to normal by resolving MetS before adulthood [
8]. These findings emphasize that preventing and resolving pediatric MetS is crucial for preventing the development of these cardiometabolic disorders in adulthood.
Parent–child dyad studies have suggested that obesity and certain cardiometabolic risk factors are shared across generations [
9,
10,
11]. A study investigating longitudinal cardiovascular risk found that obese children with an obese parent were 21.2% likely to be eligible for bariatric surgery in adulthood [
12]. However, whether children with parental MetS-related diseases are at a high risk of MetS is uncertain. If such a risk exists, whether the generational effect is associated with pediatric adiposity remains to be investigated. Lifestyle risk factors, such as unhealthy diets, physical inactivity, and excessive screen time (ST), have been associated with increased cardiometabolic risk among children and adolescents [
13,
14,
15,
16,
17]. MetS is common in obese youths [
18], and numerous unhealthy behaviors have been identified as obesogenic risk factors [
19,
20,
21]. Therefore, the mediating and/or modifying effects of obesity on the association between lifestyle risk factors and pediatric MetS warrant further investigation.
In Taiwan, childhood overweight and obesity have received extensive attention as major health concerns. According to a series of national surveys conducted by Taiwan’s Ministry of Education between 1991 and 2003, the prevalence of overweight/obesity among adolescents aged 13–18 years increased by 53.7% (from 16.4% to 25.2%) in boys and 70.8% in girls (from 8.9% to 15.2%) [
22]. With the markedly high increase in childhood overweight and obesity, the clustering of cardiometabolic risk factors among adolescents has become a critical concern in pediatric health care. The present study had two aims: first, to evaluate the effects of parental overweight and MetS-related diseases in addition to pediatric lifestyle risk factors on different degrees of clustering of cardiovascular risk factors, and second, to investigate the mediating and modifying effects of pediatric adiposity on the association between these factors and cardiometabolic disorders among Taiwanese adolescents.
3. Results
After adjusting the complex sampling design, the prevalence of pot-MetS and MetS among adolescents in Southern Taiwan was 39.3% and 3.3%, respectively (
Table 1). The MetS group had a higher percentage of males than did the non-MetS group (63.4% vs. 48.0%). No notable discrepancy was observed in the distribution of age, ethnicity, residential area, total calorie intake, alcohol drinking, and cigarette smoking across adolescents in the non-MetS, pot-MetS and MetS groups. Adolescents with a poor MetS condition tended to have decreased physical activity and an increased SSB intake, central obesity, zBMI value, waist circumference, BP, serum triglyceride, and plasma glucose and were likely to have a low HDL-C level.
The association between parental risk factors and adolescent MetS status is shown in
Table 2. Parental overweight/obesity was observed to be associated with a higher cardiometabolic prevalence ratio in adolescents (aOR = 1.5 for pot-MetS in both father and mother and 2.2 for MetS in the mother). In addition, both parents being overweight/obese predisposed adolescents to a 2.3- and 3.2-fold higher prevalence ratio of pot-MetS and MetS, respectively. Adolescents with parental diabetes and hypertension had a 1.7- and 1.5-fold aOR of pot-MetS and 5.1- and 2.7-fold aOR of MetS, respectively, compared with those whose parents had no disease history. The prevalence ratio of MetS was also higher than that of pot-MetS among adolescents with parental diabetes and hypertension (aOR ratio = 3.0 and 1.8, respectively;
p < 0.03).
Figure S1 illustrates the distribution of overweight and obesity among adolescents with different MetS status. A considerable decrease in the proportions of normal weight, overweight and obesity was observed in adolescents without any metabolic abnormality, whereas the corresponding body weight proportions notably increased in adolescents with MetS. Adolescent overweight/obesity was associated with a 3.9- and 1461.2-fold elevated prevalence ratio of pot-MetS and MetS, respectively (
Table 3). The adjusted mean of the BMI for adolescents with MetS was 7.4 kg/m
2 higher than that for adolescents with pot-MetS.
Table 3 presents the association between adolescent lifestyle factors and their MetS conditions. Compared with adolescents with a high level of PA (≥2140.5 MET·min/week), those with moderate (952.4–2140.4 MET·min/week) and low (<952.4 MET·min/week) levels of PA had a 2.5- and 4.4-fold higher aOR of MetS, respectively. Long ST (≥3 h/day) was associated with a higher MetS prevalence ratio, with adolescents with MetS having a 0.30 h/day longer ST than did non-MetS adolescents. Adolescents who consumed heavy amounts of SSB (>500 mL/day) had a 1.7- and 30.2-fold higher aOR of pot-MetS and MetS, respectively. For moderate and low levels of PA, a heterogeneous prevalence ratio was identified between pot-MetS and MetS (aOR ratio, 2.5 and 3.8, respectively). Considering SSB intake, the prevalence ratio of MetS was higher than that of pot-MetS (aOR ratio, 13.0 and 17.7 for 1–500 and >500 mL/day of SSB intake, respectively), and adolescents with MetS had a 68.1 mL/day higher SSB intake than did those with pot-MetS.
The excess prevalence ratios of pot-MetS and MetS explained by the adolescent BMI for significant risk factors are shown in
Table 4. The child BMI accounted for 66.9%–72.9% of the effect of parental overweight/obesity on pot-MetS, as well as for 23.5%–40.1% and 18.8%–50.5% of the association of parental T2DM and hypertension with pediatric pot-MetS and MetS, respectively. A high proportion of excess prevalence ratio of MetS (60.3%) associated with ≥3 h/day of ST was explained by the child BMI. For heavy SSB consumption (>500 mL/day), the child BMI separately accounted for 23.6% and 16.9% of the effect on pot-MetS and MetS. Although the prevalence ratios between pot-MetS and MetS were heterogeneous for parental T2DM, hypertension, and adolescent low PA (aOR ratio, 2.6, 1.8, and 2.6, respectively), more than 10% of the association was explained by the adolescent BMI (44.4%, 10.2%, and 41.7%, respectively).
Table 5 shows the synergistic effects of risk factors and adolescent body weight on pot-MetS and MetS. The prevalence ratio (aOR = 8.6) of pot-MetS + MetS in SSB consumers who were overweight/obese was remarkably higher than the expected combined prevalence ratio (aOR = 2.9) estimated using a multiplicative interaction model (
p = 0.009). A significantly additive synergistic effect on pot-MetS + MetS was also observed among overweight/obesity adolescents with parental T2DM (SI = 4.2, 95% CI = 1.4–12.4) and who had ≥1.5 h/day of ST (SI = 1.8, 95% CI = 1.2–2.9). No significant interactions were found across the other risk factors for pot-MetS + MetS (
Table S1).
4. Discussion
The present findings reveal the association between parental overweight, T2DM, and hypertension and pediatric adiposity and lifestyle factors with the clustering of cardiometabolic risk factors among adolescents. This study also revealed the mediating and modifying effects of pediatric overweight on the association of familial and individual factors with adolescent pot-MetS and MetS.
Family linkage studies have reported that cardiovascular risk factors, such as obesity and hyperlipidemia, incline to cluster within families [
9,
10,
11]. In a longitudinal parent–child dyad study, a 14.2-fold higher risk of eligibility for bariatric surgery was observed among obese children with an obese parent compared with children with non-obese families [
12]. This study further revealed that parental overweight/obesity may predispose children to a higher risk of pot-MetS (aOR = 1.5 in both father and mother) and MetS (aOR = 2.2 in the mother). Recently, cardiometabolic abnormalities among children have been associated with parental MetS-associated diseases [
37,
38]. In India, a higher risk of being overweight, low HDL-C, high BP, and glucose intolerance was observed in adolescents with parental T2DM [
38]. In Iran, a 4.5-fold risk of MetS was observed in adolescents with both parents having MetS. Our study revealed that a parental history of T2DM and hypertension was associated with pediatric pot-MetS and MetS, and the risk of MetS was higher than that of pot-MetS (aOR ratio, 3.0 and 1.8, respectively) in adolescents whose parents had the two MetS-related diseases.
This study revealed that the adolescent BMI accounted for a majority of the effects of parental overweight/obesity on pediatric pot-MetS and MetS (66.9%–72.9% for pot-MetS in both parents and 95.6% for MetS in the mother). This emphasizes the potential effect of a shared obesogenic environment across generations. Although adolescent BMI also accounted for 18.8%–50.5% of the increased risks of parental T2DM and hypertension on pediatric MetS, the generational effect of the two MetS-associated diseases remained significant (zBMI-adjusted OR = 2.6 and 2.4, respectively;
p < 0.03), implying the existence of non-obesity-mediated mechanisms. These results were consistent with those of a recent study, in which many cardiometabolic risk factors significantly correlated between parents and children even after adjustments for their BMIs [
10]. Unhealthy lifestyle factors are the major determinants of obesity, diabetes, and cardiovascular diseases [
20,
39]. Considering these findings that reveal the clustering of cardiometabolic risk factors and diseases within families, establishing a family-based healthy lifestyle is crucial for preventing and resolving the clustering of MetS components within families. Our study identified a notable modifying effect of parental T2DM on the risk of pot-MetS + MetS for adolescent overweight/obesity by using an additive interaction model (combined aOR = 23.8). This indicates that overweight adolescents with parental T2DM are a high-risk group for the clustering of cardiometabolic abnormalities and are the primary target to be intervened with a healthy lifestyle.
Consistent with our findings, a previous study revealed the detrimental effect of a low level of PA on cardiometabolic disorders [
13]. A recent study suggested that, independent of PA levels, screen-based sedentary behavior is an emerging risk factor for adiposity and cardiometabolic diseases among children and youth [
40]. In a 12-year follow-up study, a higher ST in childhood was observed to be associated with a higher level of BMI, triglycerides, and MetS
Z-score in early adulthood [
14]. In a longitudinal study with multiple life course investigations, an increased number of life periods of frequent TV viewing during adolescence and early adulthood increased the cardiometabolic risk in mid-adulthood [
41]. Similarly, our study revealed that adolescents with ≥3 h/day of ST had a 2.2-fold higher risk of MetS; however, an increase of 60.3% in the risk was explained by the child BMI. In a prospective study with mediation analysis, low PA was identified to partially mediate the adverse effect of ST on adiposity, and adiposity was observed to strongly mediate the association between ST and the total-to-HDL-C ratio (a cardiometabolic marker) [
42]. ST is a modifiable lifestyle factor, which may promote PA- and adiposity-mediated effects on the cardiometabolic risk. Directing public health efforts toward reducing this sedentary behavior is a crucial concern in adolescent cardiometabolic health care.
Our study revealed that adolescents who consumed >500 mL/day of SSB had elevated parental risk factors and child BMI- and total calorie intake-adjusted MetS risk (aOR = 15.2 and 22.5, respectively, compared with adolescents with pot-MetS and non-MetS adolescents,
Table 4). The association between a high consumption of SSB and the development of hypertension, dyslipidemia, dysglycemia, insulin resistance, and hyperuricemia have been reported in recent epidemiological studies in adolescents [
4,
24,
43,
44,
45,
46]. Despite specific controversies, some mechanisms have been proposed to support the argument that excess sugar consumption increases cardiometabolic risk. The direct pathway is associated with disordered hepatic uptake and unregulated fructose metabolism, and the indirect pathway is associated with weight gain and fat accumulation [
47]. Moreover, this study revealed that the risk of pot-MetS + MetS associated with SSB consumption was multiplicatively enhanced among adolescents with overweight/obesity (
p for multiplicative interaction < 0.05), supporting the hypothesis that weight gain is associated with the development and aggregation of cardiometabolic risk factors in a mechanistic manner and thus increasing the effect of added sugar in beverages.
Passive smoking has been associated with an increased risk of MetS and a few cardiometabolic risk factors among adolescents [
48,
49]. In the 2007–2010 National Health and Nutrition Examination Survey, the joint risk of adolescent MetS from high exposure to passive smoking and low levels of vitamin E or omega-3 polyunsaturated fatty acids was higher than that expected from the individual risks [
50]. However, in this study, no significant effects of parental smoking on adolescent MetS were identified.
This study has several strengths. First, according to our review of relevant literature, this study is the first to evaluate the associations of parental and pediatric risk factors with the clustering of cardiometabolic risk factors among Taiwanese adolescents; moreover, a large representative data set was used. Second, because highly trained staff members cautiously explained the data filling protocol and because participants were unaware of the research hypothesis, reporting bias should be limited; even if it exists, the association measure should be biased toward the null. However, this study has several limitations. First, although anthropometric measurements and lifestyle factors were obtained three weeks before collecting clinical blood samples, the cross-sectional study design prevents any cause–effect determination. Second, parental blood samples were not collected, thus limiting the valuation of familial aggregation for all MetS components. Finally, participants with pot-MetS and MetS were combined because of the low prevalence of MetS, thus limiting interaction assessments between risk factors for adolescents with MetS.