With this review, we aim to focus the attention on some established as well as new concepts for the metabolic syndrome (MetS) in children and adolescents spanning from definition to recommendations for the diagnostic approach. Even though there is no international commonly used definition of the metabolic syndrome in children and adolescents, all definitions include obesity as precondition for the development of MetS even in children. Obesity is one of the major cardiometabolic risk factors and it is strongly linked to other metabolic diseases like hyperlipidemia, hyperinsulinemia as well as hypertension. The metabolic syndrome is commonly known as a constellation of the mentioned morbidities. Pediatricians and researchers agree that early diagnosis and early interventions of the MetS are important to improve the prevention of cardiovascular disease and type 2 diabetes in adulthood. However, this requires appropriate screening tools for children and adolescents at risk for the MetS and its comorbidities. Due to controversies regarding the definition of MetS and the lack of consensus thresholds for the single components in children and adolescents, there is no internationally accepted diagnostic pathway for MetS available. However, several consensus statements and national guidelines for the assessment of obesity and its comorbidities in children and adolescents are available. Obesity seems to be the driving factor for the development of the other risk factors of MetS. In order to avoid conflicts concerning the definition of overweight and obesity, we recommend using the WHO definition of overweight (one standard deviation body mass index for age and sex and obesity; two standard deviations body mass index for age and sex) in children and adolescents.
Adipokines were shown to affect glucose homeostasis and β-cell function in patients with pancreatic dysfunction which is associated with changes in the adipose tissue secretory profile. However, information about adipokines associated with β-cell dysfunction is lacking in pediatric patients with type 1 diabetes.
(1) We compared serum concentrations of nicotinamide phosphoribosyltransferase (NAMPT), omentin-1 and caspase-cleaved cytokeratin 18 fragment M30 (CK-18) in pediatric type 1 diabetes patients (n=245) and healthy age, sex and body mass index standard deviation score (BMI-SDS) matched controls (n=243). (2) We investigated the influence of insulin treatment on serum concentrations of NAMPT, omentin-1 and CK-18 in groups of patients with type 1 diabetes stratified according to the duration of their disease: at onset (n=50), ≥6 months and <5 years (n=185), ≥5 and <10 years (n=98), and ≥10 years (n=52).
Patients at onset compared with healthy controls demonstrated no significant differences in NAMPT levels (p=0.129), whereas omentin-1 levels were elevated (p<0.001) and CK-18 levels were lowered (p=0.034). In contrast, NAMPT and omentin-1 were elevated and CK-18 serum levels were lower in longstanding patients compared to healthy controls (p<0.001). NAMPT serum levels did not change significantly during the duration of type 1 diabetes (p=0.546). At onset, omentin-1 and CK-18 levels were higher than in any group of longstanding type 1 diabetes (p<0.025).
Altered serum levels of NAMPT, omentin-1 and CK-18 in pediatric type 1 diabetes patients indicate metabolic changes caused by adipose tissue dysregulation which do not normalize during insulin therapy.
The objective of the study was to investigate the association of neck circumference (NC) to parameters of glucose homeostasis compared to classical anthropometric parameters of lean and obese children.
Three dimensional (3D)-body scanning quantified anthropometric (height, weight, NC, hip/waist circumference, BMI) and metabolic parameters (fasting plasma glucose [FPG], insulin, HbA1c, oGTT, HOMA-IR) were determined cross-sectionally in 1542 participants (5–18 years).
NC was positively correlated with all metabolic parameters, except for FPG. For HbA1c there was only a modestly positive correlation. The associations between NC and glucose parameters were rather weak, while the correlation to insulin parameters were stronger. Overall the strongest association to glucose metabolism parameters was found for waist circumference (WC), except for FPG and 2h-postload glucose. In multiple linear regression analyses, NC provided additional benefit beyond classical anthropometric indices to describe impairment of glucose homeostasis.
We suggest that NC is comparable or additive to established anthropometric parameters but might not be superior to them. However NC is simple to measure, reproducible and may be considered in clinical practice as an additional measurement tool.
This review summarizes current data on influences of childhood obesity on the 12-lead electrocardiogram (ECG). Studies on obese adults showed a higher risk of cardiovascular complications and also, partly pathological, ECG alterations. Data on ECG alterations in obese children is rare. In current studies, no pathological findings were found. All alterations, which mimic the later pathological phenomena in obese adults, were within normal ranges. Studies reported significantly longer P-wave time and P-wave dispersion (Pd) in obese children [Üner A, Doğan M, Epcacan Z, Epçaçan S. The effect of childhood obesity on cardiac functions. J Pediatr Endocr Met 2014;27:261–71.], no correlation of heart rate, P-wave, or QT dispersions (QTd) [Akyüz A, Alpsoy S, Akkoyun DC, Nalbantoǧlu B, Tülübaș F, et al. Effect of overweight on P-wave and QT dispersions in childhood. Turk Kardiyol Dern Ars 2013;41:515–21.], significantly higher QTd in obese children [Yildirim S, Binnetoglu FK, Battal F, Aylanc H, Nazan Kaymaz N, et al. Relation between QT variables and left ventricular geometry in athletes and obese children. Acta Med Port 2016;29:95–100.], no significant association between obesity and QTc interval (QTc), but longer PR intervals, wider QRS duration and left axis shifting of frontal P-wave, QRS and T-wave axes [Sun G, Li Y, Zho X, Guuo X, Zhang X, et al. Association between obesity and ECG variables in children and adolescents: a cross-sectional study. Exp Ther Med 2013;6:1455–62.], significant prolongation of QTc, T peak-to-end, and QTd in the obese children [Paech C, Liebold A, Gebauer RA, Wagner F, Vogel M, et al. Relative QT interval prolongation and electrical inhomogeneity of cardiac repolarization in childhood obesity. Prog Pediatr Cardiol 2017;47:64–7.], slight shift to the left in the QRS axis (with no changes in the P axis), increased amplitudes of the left-sided leads in obese children, and no correlation of the heart rate with the weight [Paech C, Anhalt M, Gebauer RA, Wagner F, Vogel M, et al. New normal limits for pediatric ECG in childhood obesity? Influence of childhood obesity on the ECG. Prog Pediatr Cardiol 2018;48:119–23.]. Altogether, the study results are inconsistent. Clearly, pathological phenomena in the ECG of obese children were not reported: only preliminary stages like QTc prolongation within the norm were found. The pathological alterations seen in adult obese patients are not (yet) seen in childhood. The slight changes reported in childhood obesity are likely to manifest later and to develop into pathological phenomena in obese adults and, therefore, might increase the risk of cardiovascular events like arrhythmia and sudden cardiac death in adulthood.
Adipokines have been implicated in obesity, insulin resistance and sleep regulation. However, the role of chemerin and progranulin, two recently described adipokines, in the context of sleep remains unclear. The aim of this study was to compare nocturnal serum chemerin and progranulin levels between overweight/obese and normal-weight adolescents and to assess variations by sex, across different sleep stages and in relation to glucose metabolism.
The study sample included 34 overweight/obese and 32 normal-weight adolescents from secondary schools and the Leipzig Research Center for Civilization Diseases (LIFE) Child study cohort. We obtained longitudinal serum adipokine levels during in-laboratory polysomnography followed by an oral glucose tolerance test.
Overweight/obese adolescents had significantly higher mean nocturnal serum chemerin area under the curve (AUC) levels (348.2±133.3 vs. 241.7±67.7 vs. ng/mL×h, p<0.001) compared to normal-weight controls. In detail, higher chemerin AUC levels in obese/overweight subjects were exclusively due to increased levels in females. No overall difference for serum progranulin AUC was found between the groups. However, when assessing sex-specific levels, serum progranulin AUC levels were ~30% higher in overweight/obese males compared to overweight/obese females. Of note, nocturnal serum chemerin and progranulin AUC did not exhibit a correlation with markers of glucose metabolism or sleep stages.
Collectively, we report a sexual dimorphism in nocturnal progranulin and chemerin levels, which may help explain underlying differences in energy balance and body composition between males and females in the context of obesity.