Comparison of Different Definitions of Pediatric Metabolic Syndrome: Relation to Abdominal Adiposity, Insulin Resistance, Adiponectin, and Inflammatory Biomarkers

Division of Weight Management & Wellness, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
The Journal of pediatrics (Impact Factor: 3.79). 03/2008; 152(2):177-84. DOI: 10.1016/j.jpeds.2007.07.053
Source: PubMed


To examine the prevalence of the metabolic syndrome using different pediatric definitions reported in the literature and its relationship to abdominal adipose tissue (AT), in vivo insulin resistance, and inflammatory biomarkers in children and adolescents, as well as the utility of fasting insulin and adiponectin as predictors of the metabolic syndrome.
Cross-sectional measurements were obtained from 122 African Americans and 129 Caucasians age 8 to 19 years. Insulin sensitivity (IS) was measured by a 3-h hyperinsulinemic-euglycemic clamp. Blood pressure, fasting lipids, adiponectin, interleukin (IL)-6, adhesion molecules (intercellular adhesion molecule [ICAM]-1, vascular cell adhesion molecule [VCAM]-1, and E-selectin), and abdominal AT were measured.
Regardless of the metabolic syndrome criteria used, the prevalence of the metabolic syndrome was higher in overweight (24% approximately 51%) compared with non-overweight youths (1% approximately 3%) in both African Americans and Caucasians (P <.01). Youths with the metabolic syndrome had higher visceral AT and fasting insulin and lower IS and adiponetin independent of race (P < .01). In Caucasians, youths with the metabolic syndrome had higher levels of inflammatory biomarkers (IL-6, ICAM-1, and E-selectin). The area under the receiver operating curve (AUC) for insulin was 0.86 approximately 0.89 in African Americans and 0.86 approximately 0.89 in Caucasians, depending on the metabolic syndrome criteria used. For adiponetin, the AUC was 0.73 approximately 0.78 in African Americans and 0.81 approximately 0.86 in Caucasians.
The prevalence of metabolic syndrome varies depending on the definition used in the literature. Thus, there is a need for a unified definition of this syndrome in children and adolescents to streamline the research in this area. Independent of race, visceral obesity, insulin resistance, hyperinsulinemia, and hypoadiponectinemia are the common characteristics of youths with the metabolic syndrome. In Caucasians but not in African Americans, the metabolic syndrome is associated with increased inflammatory markers; however, the translation of such findings remains to be determined based on long-term longitudinal outcome studies in different racial groups.

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    • "It is the most abundant adipokine in serum and interestingly, studies in adults have demonstrated an inverse correlation between hormone secretion and adipose tissue hypertrophy as the serum adiponectin concentration decreases with increasing fat tissue [2] [3]. Recently, adiponectin has gained increasing attention in pediatrics as a serum biomarker due to its correlation to various metabolic risk factors such as insulin resistance, dyslipidemia, metabolic syndrome, and also cardiovascular disease [4] [5] [6] [7]. "
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    ABSTRACT: Adiponectin is an abundant adipocyte-secreted hormone that modulates a number of metabolic processes and is correlated to various metabolic disorders. Pediatric reference levels are needed for the risk stratification and interpretation of individual serum adiponectin levels. A total of 1193 healthy, non-obese Danish schoolchildren (730 girls, 463 boys) aged 6-18 years (median 11.9) were examined by trained medical staff. Total serum adiponectin concentrations in venous fasting blood samples were quantitated by a DuoSet® ELISA human Adiponectin/Acrp30 (R&D Systems) following optimization. In a generalized linear model adjusted for BMI SDS, total serum adiponectin concentrations were correlated to age in girls (p<0.0001) and boys (p=<0.0001) and for both sexes combined (p<0.0001). No significant difference between sexes was found. Reference intervals were calculated using age as a continuous variable. The best fitted reference curve for both sexes was: 50th percentile: Y=-0.1478X+6.046; 2.5th percentile: Y=-0.06256*X+2.34; 97.5th percentile: Y=-0.4086*X+22.39, where y= adiponectin in μg/mL and x= years of age (from 6-18 yr). We developed a pediatric reference levels for total serum adiponection in a sample of 1193 Danish children and adolescents aged 6-18 years. A correlation with age was demonstrated in children, but no significant difference was seen between the sexes. Copyright © 2015. Published by Elsevier B.V.
    Clinica chimica acta; international journal of clinical chemistry 07/2015; 450. DOI:10.1016/j.cca.2015.07.012 · 2.82 Impact Factor
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    • "These factors include central obesity, hypertension, hypertriglyceridemia, low HDL-cholesterol, and elevated fasting glucose [12] and show in increase in prevalence with age [13]. MetS appears to be associated with insulin resistance in adolescents in that increasing degrees of insulin resistance as determined by homeostasis model [14,15] and hyperinsulinemic clamp [16] are significantly associated with risk of MetS and/or its individual components. While the pathophysiology of T2DM consists of multiple overlying factors, including insulin resistance, excess hepatic glucose release and defects in adequate insulin production [17,18], the potential utility for MetS to identify risk in adolescents for future T2DM was demonstrated in that adolescents with MetS (compared to those without MetS) have an odds ratio (OR) of 10 for developing T2DM by age 32 [19]. "
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    ABSTRACT: The presence of impaired glucose tolerance (IGT) and metabolic syndrome (MetS) are two risk factors for Type 2 diabetes. The inter-relatedness of these factors among adolescents is unclear. We evaluated the sensitivity and specificity of MetS for identifying IGT in an unselected group of adolescents undergoing oral glucose tolerance tests (OGTT) in the National Health and Nutrition Evaluation Survey 1999-2010. We characterized IGT as a 2-hour glucose >=140 mg/dL and MetS using ATP-III-based criteria and a continuous sex- and race/ethnicity-specific MetS Z-score at cut-offs of +1.0 and +0.75 standard deviations (SD) above the mean. Among 1513 adolescents, IGT was present in 4.8 %, while ATP-III-MetS was present in 7.9 %. MetS performed poorly in identifying adolescents with IGT with a sensitivity/specificity of 23.7 %/92.9 % for ATP-III-MetS, 23.6 %/90.8 % for the MetS Z-score at +1.0 SD and 35.8 %/85.0 for the MetS Z-score at +0.75 SD. Sensitivity was higher (and specificity lower) but was still overall poor among overweight/obese adolescents: 44.7 %/83.0 % for ATP-III-MetS, 43.1 %/77.1 % for the MetS Z-score at +1.0 SD and 64.3 %/64.3 % for MetS Z-score at +0.75 SD. This lack of overlap between MetS and IGT may indicate that assessment of MetS is not likely to be a good indicator of which adolescents to screen using OGTT. These data further underscore the importance of other potential contributors to IGT, including Type 1 diabetes and genetic causes of poor beta-cell function. Practitioners should keep these potential causes of IGT in mind, even when evaluating obese adolescents with IGT.
    Cardiovascular Diabetology 04/2014; 13(1):83. DOI:10.1186/1475-2840-13-83 · 4.02 Impact Factor
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    • "We decided to use the OGTT instead of IVGTT because OGTT describes the post-meal dynamics which is of interest for the GH physiology being GH a hormone that principally acts in the post-absorptive phase [1]. Moreover, we chose the OGTT-derived indices of insulin sensitivity and secretion because they correlate well with clamp measures in children [44], [45], are easily calculated in epidemiological or intervention studies, and DI calculated by the OGTT has been demonstrated to predict diabetes development in adults [24]. Furthermore, the OGTT is the test that is classically performed in the clinical practice during rhGH treatment being simpler and cheaper than IVGTT. "
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    ABSTRACT: Growth hormone deficiency (GHD) is associated with insulin resistance and diabetes, in particular after treatment in children and adults with pre-existing metabolic risk factors. Our aims were. i) to evaluate the effect on glucose metabolism of rhGH treatment and withdrawal in not confirmed GHD adolescents at the achievement of adult height; ii) to investigate the impact of GH receptor gene genomic deletion of exon 3 (d3GHR). We performed a longitudinal study (1 year) in a tertiary care center. 23 GHD adolescent were followed in the last year of rhGH treatment (T0), 6 (T6) and 12 (T12) months after rhGH withdrawal with fasting and post-OGTT evaluations. 40 healthy adolescents were used as controls. HOMA-IR, HOMA%β, insulinogenic (INS) and disposition (DI) indexes were calculated. GHR genotypes were determined by multiplex PCR. In the group as a whole, fasting insulin (p<0.05), HOMA-IR (p<0.05), insulin and glucose levels during OGTT (p<0.01) progressively decreased from T0 to T12 becoming similar to controls. During rhGH, a compensatory insulin secretion with a stable DI was recorded, and, then, HOMAβ and INS decreased at T6 and T12 (p<0.05). By evaluating the GHR genotype, nDel GHD showed a decrease from T0 to T12 in HOMA-IR, HOMAβ, INS (p<0.05) and DI. Del GHD showed a gradual increase in DI (p<0.05) and INS with a stable HOMA-IR and higher HDL-cholesterol (p<0.01). In not confirmed GHD adolescents the fasting deterioration in glucose homeostasis during rhGH is efficaciously coupled with a compensatory insulin secretion and activity at OGTT. The presence of at least one d3GHR allele is associated with lower glucose levels and higher HOMA-β and DI after rhGH withdrawal. Screening for the d3GHR in the pediatric age may help physicians to follow and phenotype GHD patients also by a metabolic point of view.
    PLoS ONE 01/2014; 9(1):e87157. DOI:10.1371/journal.pone.0087157 · 3.23 Impact Factor
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