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Objectives: Evidence of the association between vitamin D and cardiovascular risk factors in the young is limited. We therefore assessed the relationships between circulating 25-hydroxyvitamin D3 (25(OH)D3) and metabolic syndrome (MetS), its components, and early atherosclerotic changes in 452 (304 overweight/obese and 148 healthy, normal weight) Caucasian children. Methods: We determined serum 25(OH)D3 concentrations in relation to MetS, its components (central obesity, hypertension, low high-density lipoprotein (HDL)-cholesterol, hypertriglyceridemia, glucose impairment, and/or insulin resistance (IR)), and impairment of flow-mediated vasodilatation (FMD) and increased carotid intima-media thickness (cIMT) - two markers of subclinical atherosclerosis. Results: Higher 25(OH)D3 was significantly associated with a reduced presence of MetS. Obesity, central obesity, hypertension, hypertriglyceridemia, low HDL-cholesterol, IR, and MetS were all associated with increased odds of having low 25(OH)D3 levels, after adjustment for age, sex, and Tanner stage. After additional adjustment for SDS-body mass index, elevated blood pressure (BP) and MetS remained significantly associated with low vitamin D status. The adjusted odds ratio (95% confidence interval) for those in the lowest (<17 ng/ml) compared with the highest tertile (>27 ng/ml) of 25(OH)D3 for hypertension was 1.72 (1.02-2.92), and for MetS, it was 2.30 (1.20-4.40). A similar pattern of association between 25(OH)D3, high BP, and MetS was observed when models were adjusted for waist circumference. No correlation was found between 25(OH)D3 concentrations and either FMD or cIMT. Conclusions: Low 25(OH)D3 levels in Caucasian children are inversely related to total adiposity, MetS, and hypertension. [ABSTRACT FROM AUTHOR]

Background: Ghrelin, a peptide mainly derived from the stomach, plays a pivotal role in the regulation of food intake, energy metabolism, and storage, as well as in insulin sensitivity. Ghrelin circulates in acylated (A-Ghr) and nonacylated (NA-Ghr) forms, and their potential differential associations with insulin resistance (IR) in childhood obesity remain undefined., Objective: We investigated the associations of ghrelin forms with IR in normal weight and obese children and the impact of metabolic syndrome (MS) on their plasma values., Design: A total of 210 children in four subgroups of normal weight/obese children with and without components of MS were studied. Fasting blood glucose, insulin, lipid profile, and acylated and total ghrelin were examined. IR was determined by a homeostasis model assessment (HOMA) of IR., Results: In the entire population, plasma insulin and HOMA-IR were associated negatively with T-Ghr and NA-Ghr, but positively with the ratio of A/NA-Ghr after adjustment for age, gender, and Tanner stage. Obese metabolically abnormal children had lower T-Ghr and NA-Ghr, but comparable A-Ghr and a higher A/NA-Ghr ratio than obese metabolically normal subjects. Compared with lean healthy children, lean metabolically abnormal subjects had higher A-Ghr and the A/NA-Ghr ratio, but comparable T-Ghr and NA-Ghr. A multiple regression analysis showed that A-Ghr and the A/NA-Ghr ratios were positively associated with HOMA-IR, independent of age, gender, Tanner stage, and body mass index (or waist circumference) and other components of MS., Conclusions: A-Ghr excess may negatively modulate insulin action in obese and nonobese children, and may contribute to the association of IR and MS.

Objective: The association between hyperuricemia, metabolic syndrome (MS), and atherosclerotic vascular disease has been reported in adults, but very little is known about this association in children. The aims of our study were to ascertain the correlates of uric acid (UA) in a sample of obese children, and to investigate whether UA is associated with carotid intima-media thickness (IMT) independently from classical risk factors including MS., Methods: We analyzed carotid IMT along with serum triglycerides, total and high-density lipoprotein cholesterol, glucose, insulin, insulin resistance index (as homeostasis model assessment of insulin resistance), alanine aminotransferase, gamma-glutamyltransferase, creatinine, and UA in 120 obese children and 50 healthy control children., Results: UA concentrations were significantly higher in obese children compared with controls; moreover, they correlated with the most established cardiovascular risk factors. In the group of obese children, after adjustment for age, sex, pubertal stage, and creatinine, an independent association between UA levels and the presence of MS syndrome was observed (unstandardized coefficient, 0.044 (95% confidence intervals (CI) 0.015-0.072); P<0.01). Carotid IMT significantly increased in the fourth quartile of UA compared with that in the first, second, and third quartile (0.49 (0.46-0.53), 0.53 (0.49-0.56), and 0.55 (0.52-0.59) vs 0.61 (95% CI, 0.58-0.64); P<0.01). When multivariate analysis was performed after adjusting for age, gender, pubertal stage, creatinine, and MS (considered as a single clinical entity), or the individual components of MS simultaneously included, the association between UA and carotid IMT was significant (P<0.01)., Conclusions: In obese children and adolescents, increased UA levels are associated with carotid atherosclerosis.

Background: Helicobacter pylori, and the chronic gastric inflammation that it causes, may compromise the function and survival of ghrelin-producing cells, resulting in a decrease of circulating ghrelin levels. This finding raises the possibility that the infection might affect growth in children by reducing the ghrelin production., Aims: To determine baseline circulating levels of ghrelin and leptin in prepubertal children with and without H. pylori infection and to evaluate the long-term effects of H. pylori eradication on circulating levels of ghrelin and leptin as well as on body composition., Patients: Thirty children with H. pylori-associated gastritis, 35 children with H. pylori-negative gastric mucosa, and 20 healthy controls were studied., Results: At baseline, while leptin levels were significantly lower in H. pylori-positive patients, ghrelin concentrations did not differ among the three study groups. However, a significant inverse correlation between ghrelin concentrations and histological severity of gastritis was found. Eradication of the organism was associated with a progressive decrease in ghrelin concentrations over baseline at both 6- and 12-month follow-ups. SDS-body mass index (BMI), lean and fat mass, as well as leptin concentrations, significantly increased over baseline at both follow-ups., Conclusions: In prepubertal children, serum ghrelin concentrations are inversely related to the severity of H. pylori-associated gastritis. In these youngsters, long-term eradication of H. pylori infection is associated with a significant increase in BMI, lean and fat mass along with a significant decrease in circulating ghrelin levels and an increase in leptin levels.

Objective: Leptin, an adipocyte-secreted hormone, has emerged as a potential candidate for the link between obesity and the proinflammatory state. Specifically, leptin modulates T-helper (Th) cells toward a Th1 phenotype, with the secretion of proinflammatory cytokines. The aim of this study was to evaluate the Th1/Th2 balance in obese children and its relation with hormonal and metabolic features., Study Design: In 50 obese children and 20 control children, we measured the CD4-positive Th cells that secrete interferon (IFN)-gamma or interleukin (IL)-2 (taken as an index of Th1 cells), and IL-4 (taken as an index of Th2 cells) as well as serum glucose, insulin, insulin resistance (IR) index (as homeostasis model assessment model (HOMA)), lipid profile, aminotransferases, leptin and ghrelin. Obese children also underwent dual energy X-ray absorptiometry scan measurements, and liver ultrasound scanning., Results: Geometric mean percentages of IL-2- and IL-4-CD4 secreting cells in obese children were not significantly different from those found in control children. However, the geometric mean percentage of CD4-positive T cells secreting IFN-gamma was significantly higher in the obese than in the control (P < 0.0001, t-test) group. Within the entire group of study children, the percentage of IFN-gamma-positive cells was positively associated with leptin (P = 0.002), insulin (P < 0.00 005), and HOMA-IR values (P < 0.00 005). However, when these associations were restricted to the group of obese subjects, insulin and HOMA-IR values, but not leptin, retained statistical significance. Yet, in the obese group, the percentage of IFN-gamma-positive cells was associated with nonalcoholic steatohepatitis (NASH) (P = 0.001), but not with body mass index-standard deviation score and total body fat mass., Conclusions: In obese children, a shift to Th1-cytokine profile dominated by the production of IFN-gamma is related to insulin resistance as well as to NASH independently of anthropometric features and other metabolic characteristics. The prevalent Th1 pattern of secreted cytokines may be regarded as a mechanism contributing to inflammation in obesity.