Our study demonstrated that the prevalence of the MS was associated with degree of overweight and the insulin resistance index HOMA, and had a wide range (6–39%) using the different proposed definitions. Only 9% of the children fulfilled all the definitions of the MS for children and adolescents, pointing to a low degree of overlap between the different proposed definitions for the MS. These findings are in concordance with one small study in childhood.16
Therefore, a comparison between studies using different definitions of the MS is not meaningful in childhood. To compare different populations and studies, an internationally accepted practical uniform definition of the MS has to be established for children and adolescents.
Not only did the prevalence of the MS vary widely between the different definitions, but also the impact of puberty on the prevalence of the MS varied widely as well. De Ferranti and Cook reported a 3–5‐fold higher prevalence of the MS in pubertal adolescents compared with prepubertal children.13,15
Using their definition, we also found a higher prevalence of the MS in pubertal adolescents but only in boys and not in girls. Conversely, the other definitions of the MS proposed for childhood and adolescence demonstrated no influence of pubertal stage on the MS. The proposed definitions of the MS for children and adolescents differed widely in their criteria and the thresholds of their components. These facts likely explained the difference in frequencies of the MS and the different effect of pubertal stage on the MS.
PCA demonstrated that total cholesterol, triglycerides and waist circumference explained most of the variance between the analysed children and adolescents. Therefore, inclusion of these criteria in the definition of the MS helps to differentiate the children.
One major difference between the proposed criteria for the MS was the definition of insulin resistance. Insulin levels without respect to glucose concentrations are not a good predictor of insulin resistance.27
Furthermore, values of fasting insulin levels are limited by great intra‐ and interindividual variability.27
Accurate assessment of insulin resistance as suggested by the WHO requires a complicated test (eg, the hyperinsulinaemic euglycyaemic clamp technique).7
Its application in children is invasive and impractical, so clinicians prefer simple tools such as fasting glucose. Conversely, only 1% of the overweight children demonstrated impaired fasting glucose even if we used the new WHO definition.25
However, the insulin resistance index HOMA was associated with the MS in all definitions for children and adolescents. Moreover, previous longitudinal studies reported that insulin resistance was more closely related to components of the MS as compared with degree of overweight.4,28
Furthermore, central obesity is one major element in the definition of the MS in adults7,8,9,10
and not the degree of overweight as used in some proposals for children.12,14
However, the cut‐offs of the waist circumference percentiles for European children do not seem to be very specific since the majority of our overweight children had waist circumferences above the proposed thresholds.
Most importantly, the entire concept of the MS is controversial.4,11
A major concern in the definition of the MS refers to the use of cut‐off points for the various risk factors, thus implying that the values above the specified thresholds are associated with an excess risk, yet the rationale for the different cut‐off points has never been delineated.11
Moreover, the dichotomous use of continuous data such as lipids, waist circumference and blood pressure values, seems inaccurate since they are not all‐or‐nothing values. In fact, the relationship is not even linear which makes it all the more difficult and opens up the issue of how risk in this conglomeration of the “syndrome” might be weighted more appropriately.
Finally, the MS is based on the concept that the clustering of risk factors is predictive for CVD above and beyond the risk associated with its individual components. In overweight children, dyslipidaemia, hypertension and disturbed glucose metabolism were related to intima‐media thickness (IMT) of the common carotid artery,29,30
which is predictive and related to the severity of CVD.31,32
Therefore, the integration of these factors in the definition of the MS seems meaningful. However, it has not yet been determined whether the clustering of these risk factors is associated with an increased of CVD in childhood above the risk of the individual components. Without evidence of an increased risk in the MS beyond the sum of its parts, it may be better to pay individual attention to the well documented individual risk factors.
The frequencies of the cardinal factors of the MS (disturbed glucose metabolism, hypertension and dyslipidaemia) were similar to those found in previous studies in Caucasian children.2,3,33,34
Most overweight and obese children had one or two of these cardiovascular risk factors. It was found that 6–14% children and adolescents fulfilled the criteria for the different definitions of the MS used in adulthood, underlining the fact that the components of the MS are already present in some children.
The overall prevalence of the MS was lower in our overweight children and adolescents as compared with the studies of Weiss (39% vs 12%) and Viner (33% vs 18%).12,14
However, in our sample the overall prevalence of the MS was similar to that found in the study of Cook (29% vs 21%) and more frequent than that reported by De Ferranti (10% vs 39%).13,15
Different age ranges, races, degrees of overweight, referral practices, geographical variation in obesity and epigenetic factors might explain these differences. While the subjects in our study and those of Viner and Weiss were recruited in specialised obesity/endocrine clinics, which probably meant the frequency of the MS was overestimated, the cohorts of Cook and De Ferranti originated from general populations and had a tendency to a lower prevalence of the MS. We analysed only Caucasian children, while the studies with the highest prevalence of the MS also included subjects of Hispanic, African and Asian origin, who are suggested to have a higher frequency of the MS.12,14
This study has a few potential important limitations. Data from clinical samples may not be representative of the general population, and selection and referral bias may have influenced our estimate of the prevalence of the MS. Furthermore, oGTT was not performed in every child. Finally, consideration of pubertal stage instead of dividing children into prepubertal, pubertal and late/postpubertal groups would be the ideal way to analyse the effect of puberty on the prevalence of the MS. Conversely, performing such a study needs a very large sample size since children have not only to be divided according to different pubertal stage but also according to gender. Additionally, division into groups according to pubic hair and breast stages partially depends on the investigator.
In summary, definitive criteria for the MS for childhood and adolescence have not yet been determined. The MS was related to insulin resistance and weight status, and was independent of the pubertal stage in most definitions. The prevalence of the MS was quite different depending on the proposed definitions for children and adolescents. An internationally accepted uniform definition of the MS is needed to allow comparisons between different studies and populations. Furthermore, the concept of the MS that the clustering of risk factors is predictive for CVD above and beyond the risk associated with its individual components has to be proven in childhood and adolescence.
What is already known on this topic
- Multiple definitions for the metabolic syndrome (MS) in childhood and adolescence have been suggested.
- The variation of prevalence between the different definitions is unknown.
What is this study adds
- Since the prevalence of the MS varies widely (6–39%) between the different proposed definitions, an internationally accepted uniform definition of MS is necessary.
- The concept of the MS that the clustering of risk factors is predictive for cardiovascular disease above and beyond the risk associated with its individual components has to be proven for children and adolescents.