Analysis of the association of leptin and adiponectin concentrations with metabolic syndrome in children: Results from the IDEFICS study

https://doi.org/10.1016/j.numecd.2017.04.003Get rights and content

Highlights

  • Adipokines may link obesity to its co-morbidities, including the metabolic syndrome.

  • Limited evidence exists about this relationship in childhood.

  • In the European IDEFICS population, higher leptin levels are associated with metabolic syndrome, independently of body mass.

  • In the age range under investigation, the association of adiponectin with metabolic syndrome is mediated by body fat.

  • The measurement of leptin could discriminate overweight/obese children at higher risk of cardio-metabolic complications.

Abstract

Background and aims

Adipokines may play a role in the pathogenesis of the metabolic syndrome (MetS) in children. We aimed to evaluate the association of leptin, adiponectin, and its ratio (L/A ratio) with the metabolic syndrome (MetS) in a subsample of the IDEFICS (Identification and prevention of Dietary- and lifestyle-induced health EFfects In Children and infantS) cohort.

Methods and results

Leptin, adiponectin and MetS parameters were measured in a subsample of 1253 children (3–9.9 years) participating to the IDEFICS study, grouped as: Non-OW (underweight/normal weight) and OW/Ob (overweight/obese). MetS was defined using the sex- and age-specific cut-offs based on the distribution of MetS components in the IDEFICS cohort.

The prevalence of the MetS among OW/Ob was 24.8% and 27.1% in boys and girls respectively, whereas ≤2% among Non-OW. OW/Ob had significantly higher leptin and L/A ratio as compared to Non-OW. Significantly higher leptin was found in OW/Ob with MetS as compared with OW/Ob without MetS. Significantly lower adiponectin was observed only in OW/Ob girls as compared to Non-OW. A 1SD increase in leptin and L/A ratio z-scores or a 1SD decrease in adiponectin z-score were significantly associated with higher risk of MetS. After adjustment for BMI or body fat mass (BFM) the association remained significant only for leptin.

Conclusion

We showed that in European children, higher leptin concentration is associated with MetS, even after adjusting for BMI or BFM, confirming an early role of leptin in MetS, while the association of adiponectin with MetS seems be mediated by body fat in this age range.

Introduction

The metabolic syndrome (MetS) is a cluster of metabolic abnormalities, including hypertension, insulin resistance/glucose intolerance, abdominal obesity and dyslipidaemia, which are often associated with an increased risk to develop cardiovascular diseases and diabetes [1]. The prevalence of MetS has increased considerably in the recent years in adults [2] and its prevalence in children and adolescents has become a public health problem worldwide [3].

Although the interest in childhood MetS has noticeably increased, a clear and unique definition for its diagnosis is still lacking [4]. Indeed, the literature review by Ford & Li published in 2008 found 40 different definitions of MetS in 27 paediatric studies [5]. It seems that the main limitation of the majority of definitions is the choice of the cut-off points used to define the different components of the MetS. Recently, Ahrens et al. [6] have proposed a new definition of MetS in healthy European children aged 2–10.9 years, considering the reference standards obtained in the IDEFICS (Identification and prevention of Dietary- and lifestyle-induced health Effects in Children and infantS) study. This definition is based on age- and sex-specific percentiles of each single component of the MetS in healthy children from 8 European countries, instead of absolute values, taking into account child growth variation.

The pathophysiology of the MetS is not completely clear and the several pathogenic mechanisms proposed are still under investigation. Among the involved factors, the adipokines profile seems to be crucial for the development of the adverse metabolic phenotype typical of individuals who develop the syndrome [7], [8].

Leptin has been identified as a key factor in the long-term regulation of body weight [9]. Impairment of leptin transport and signalling may result in leptin resistance, probably a primary risk factor for obesity [10]. About twenty years ago, Zimmet et al. already hypothesized a role of leptin resistance in the cascade of metabolic disturbances clustered under the definition of metabolic syndrome [11].

Adiponectin, another member of the adipokine family, is involved in pathogenetic mechanisms leading to obesity-related insulin resistance and related disorders [12]. Lower adiponectin concentration was observed in obese subjects than in lean subjects [13]. Apart from negative correlations with measures of adiposity, Lindberg et al. recently reported that low adiponectin concentration predicts the development of the metabolic syndrome in healthy adults [14].

Since an increasing body of evidence indicates that both leptin and adiponectin are involved in the pathophysiology of obesity-related insulin resistance [12], their ratio (leptin to adiponectin ratio – L/A ratio) has been investigated as a possible predictor of metabolic disorders, including metabolic syndrome [15], [16], in adult population samples. Few studies evaluated on relatively small samples of children whether this index could be a better biomarker of metabolic disorders than either leptin or adiponectin alone [17], [18], [19]. The evidence provided by these studies is conflicting.

Although a possible role of adipokines in the metabolic sequelae of obesity in children has been suggested a decade ago [20], the association between leptin, adiponectin and L/A ratio with MetS in children has been scarcely examined up to now [21], [22], [23]. In particular, Papoutsakis et al. [23] showed that adiponectin and leptin predicted the number of MetS features in a large paediatric population in Greece. However, the finding was no longer significant after adjustment for BMI.

Aim of the present analysis is to simultaneously evaluate the association of leptin, adiponectin, and its ratio, with MetS in a large and well-characterised population-based sample of European school children, using the novel definition of metabolic syndrome developed in the framework of the IDEFICS project [6]. This definition is based on the sex- and age-specific cut-offs derived from the distribution of all MetS components in the healthy children of the IDEFICS cohort [6].

Section snippets

Study sample

The IDEFICS study (Identification and prevention of dietary- and lifestyle-induced health effects in children and infants) investigated the aetiology of diet- and lifestyle-related diseases and disorders with a strong focus on overweight and obesity in a large population-based cohort of 16,228 European children aged 2–9 years who were recruited from eight European countries. Details of the general design, instruments and survey characteristics can be found elsewhere [24]. The baseline survey

Results

The characteristics of the study subjects are shown in Table 1. All the factors included in the definition of the MetS were significantly different between OW/Ob boys and girls and their Non-OW counterparts, the OW/Ob showing higher WC, BP, glucose, insulin, HOMA-IR, TRG levels and lower HDL-C. Serum leptin concentration and L/A ratio were significantly higher, and serum adiponectin concentration was significantly lower in OW/Ob as compared to Non-OW. Hs-CRP concentration was also significantly

Discussion

The primary goal of the present study was to characterize the association of leptin, adiponectin, and L/A ratio with MetS in European children participating in the IDEFICS study. A unique feature of this study is the adoption of the novel definition of metabolic syndrome developed in the framework of the IDEFICS project, using the sex- and age-specific cut-offs based on the distribution of all MetS components in the healthy children of the IDEFICS cohort [6]. In our definition, we considered

Sources of funding

This work was done as part of the IDEFICS study (www.idefics.eu). We gratefully acknowledge the financial support of the European Commission within the Sixth RTD Framework Programme Contract No. 016181 (FOOD).

Conflict of interest

None.

Acknowledgments

We thank the IDEFICS children for their participation in this extensive examination and all the centres that provided data.

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