Leandro Soriano-Guillén

High-sensitivity C-reactive protein is a good marker of cardiovascular risk in obese children and adolescents.

OBJECTIVE We intend to assess the utility of the high-sensitivity C-reactive protein (hs-CRP) as a marker of cardiovascular risk in obese children and adolescents. METHODS The study included children and adolescents between 6 and 18 years of age with a body mass index (BMI) higher than 2 SDS. All the patients had their blood pressure taken and hs-CRP, hepatic function, lipid profile and uric acid were determined after 12 h of fasting. Likewise, an oral glucose tolerance test was performed, determining basal glucose and insulin levels, and after stimulus. We considered the presence of metabolic syndrome when the obese children and teenagers showed at least two of the following conditions: decreased high density lipoprotein (HDL)-cholesterol, hypertriglyceridemia, hypertension or alteration in glucose metabolism. RESULTS Out of the 115 obese children studied, 24% showed signs of metabolic syndrome. Those with metabolic syndrome presented higher levels of hs-CRP (mean: 3.8 mg/l; 95% CI: 2.8-4.8) in comparison with the obese patients who did not show signs of metabolic syndrome (mean: 2 mg/l; 95% CI: 1.5-2.5). After a multivariate analysis, the variables that appear to influence the changes in hs-CRP were BMI, triglycerides and HDL-cholesterol levels. CONCLUSION The hs-CRP is a useful tool for early diagnosis of cardiovascular risk in obese children and teenagers.

Central Precocious Puberty in Children Living in Spain: Incidence, Prevalence, and Influence of Adoption and Immigration

CONTEXT No epidemiological data are available on central precocious puberty (CPP) in the general population or in adopted or immigrant children in Spain. OBJECTIVE We aimed to study the incidence and prevalence of CPP, assess the risk of developing this disorder among adopted and immigrant children, and analyze the predictive variables of CPP associated with intracranial pathology. DESIGN, SETTINGS, AND PATIENTS An observational study of children diagnosed with CPP in Spain was carried out between January 2008 and January 2010. A computer program was designed to process clinical and biological data and information on 250 patients treated in 34 pediatric endocrinology units throughout the country. RESULTS Of the patients registered, 226 were girls and 24 were boys. The global incidence rate of CPP was 5.66 cases per million person-years at risk, with an annual incidence ranging between 0.02 and 1.07 new cases per 100,000. The relative risk of CPP in domestic and internationally adopted children compared with those born in Spain was 27.82 (19.99-38.77), whereas the relative risk among immigrants was 1.55 (0.97-2.38). A logistic regression model developed for the study showed that the combined effect of four variables had a significant influence over the presence of organic disease: being male, having been adopted, age at diagnosis, and estimation of adult height. CONCLUSIONS CPP is a rare disease whose risk markedly increases with both national and international adoption but is not influenced by immigration. These results suggest a psychological influence on CPP.

Response of Circulating Ghrelin Levels to Insulin Therapy in Children with Newly Diagnosed Type 1 Diabetes Mellitus

Ghrelin is secreted primarily by the stomach, although other tissues such as the pancreas synthesize a minor proportion. The discovery of a new cell type that produces ghrelin in the human pancreas and that this organ expresses GHS-R opens new perspectives in the understanding of the control of glucose metabolism. We have studied 22 children with newly diagnosed type 1 diabetes mellitus at four different points: at diagnosis before insulin therapy, after 48–60 h of insulin therapy, and after 1 and 4 mo of insulin treatment. At each point circulating levels of ghrelin, leptin, IGF-I, IGF binding protein (IGFBP)-1, IGFBP-2, IGFBP-3, and glucose were determined. Ghrelin levels were significantly decreased at diagnosis (573 ± 68 pg/mL, p < 0.01) compared with controls (867 ± 38 pg/mL) and remained decreased after insulin therapy (d 2: 595 ± 68 pg/mL; 1 mo: 590 ± 61 pg/mL; 4 mo: 538 ± 67 pg/mL) with no differences before or after insulin treatment. There was a negative correlation between ghrelin levels and body mass index at all of the study points, whereas a negative correlation between ghrelin and glucose concentrations was only observed after insulin therapy. No correlation between ghrelin and HbA1c was found at any point. A positive correlation between ghrelin and IGFBP-1 was found after insulin therapy, but no correlation with other members of the IGF system or leptin was found. In conclusion, these data could indicate a possible link between glucose concentrations and ghrelin; hence, the persisting low ghrelin levels in diabetic children may suggest a defensive mechanism against hyperglycemia.

Circulating kisspeptin levels exhibit sexual dimorphism in adults, are increased in obese prepubertal girls and do not suffer modifications in girls with idiopathic central precocious puberty.

The system KISS1-KISS1R is one of the main regulators of the hypothalamic-pituitary-gonadal axis and constitutes a link between metabolism and reproduction through its interaction with leptin. The aim of this study was to clarify the possible utility of kisspeptin as a pubertal marker and/or the possible influence of nutritional status in kisspeptin levels. To this end, we have studied kisspeptin plasma levels throughout sexual development and in prepubertal obese girls and girls affected by idiopathic central precocious puberty (CPP). Plasma kisspeptin concentrations were analyzed by RIA. An increase in kisspeptin levels was observed in adult females compared to healthy prepubertal and pubertal girls (p<0.001) and to adult males (p<0.001). Additionally, kisspeptin was increased in prepubertal obese girls compared to healthy prepubertal girls (p<0.01) and girls with idiopathic CPP (p<0.05). As revealed by the regression analysis, in prepubertal healthy and obese girls and girls with idiopathic CCP, the parameters that influenced kisspeptin levels were BMI (R(2)=0.10, p<0.05) and leptin levels (R(2)=0.14, p<0.01). In conclusion, kisspeptin levels do not seem to be a good pubertal marker. The results obtained in prepubertal and idiopathic CCP girls point to a relationship between leptin, BMI and kisspeptin at least in this group, and suggest a possible role for adipose tissue in the modulation kisspeptin synthesis.

The insulin sensitizing effects of PPAR-γ agonist are associated to changes in adiponectin index and adiponectin receptors in Zucker fatty rats.

The adiponectin high molecular weight isoform (HMW-adp) and its relation with the other adiponectin isoforms (adiponectin index, S(A)), have been identified as essential for the adiponectin insulin sensitizing effects. The objective of this study is to gain further insight on the effect of the insulin sensitizing agents, PPAR-γ agonists, on the distribution of the adiponectin isoforms and the adiponectin receptors, adipoR1 and adipoR2 in an animal model of obesity and insulin resistance. To achieve the objective, Zucker fatty rats were treated with pioglitazone, rosiglitazone or placebo for six weeks. At the end of the treatment, total adiponectin, adiponectin isoforms and adiponectin receptors expression were measured. In order to see the possible relation with insulin sensitivity parameters, HOMA-IR, muscle insulin-stimulated glucose transport, muscle GLUT4 and plasma free fatty acids were also measured. The two glitazones improved insulin sensitivity and both muscle insulin-stimulated glucose transport and GLUT4 total content. Total plasma adiponectin and visceral fat HMW-adp were increased only by pioglitazone. On the other hand, both glitazones changed the distribution of adiponectin isoforms in plasma, leading to an increase in the S(A) of 21% by pioglitazone and 31% by rosiglitazone. Muscle adipoR1 expression was increased by both glitazones whereas liver adipoR2 expression was increased by rosiglitazone and tended to increase in the pioglitazone group. The insulin sensitizing action of glitazones is mediated, at least in part, by their effect on muscle insulin-stimulated glucose transport and by their direct influence on the adiponectin index and the adiponectin receptors expression.

Elevada prevalencia de déficit de vitamina D entre los niños y adolescentes obesos españoles

INTRODUCTION Vitamin D deficiency has been associated with extra-skeletal outcomes such as, insulin resistance, type 2 diabetes, and cardiovascular disease. The aim of this study is to determine the prevalence of vitamin D deficiency among obese children and adolescents in Spain and to analyze the relationship between 25-OH-vitamin D (25-OH-D) levels and markers of abnormal glucose metabolism. PATIENTS AND METHODS A cross-sectional study was conducted in which the clinical and biochemical data were recorded for 120 obese and 50 non-overweight children in Pediatric Clinics from January 2011 to January 2013. RESULTS The mean 25-OH-D levels among obese children was 19.5 ng/ml and among non-overweight children was 31.6 ng/ml. 58,3% of obese subjects, and 10% of non-overweight subjects had vitamin D deficiency. Serum 25-OH-D levels were lower in winter. Higher HOMA-SDS (3.8 versus 2.4), and triglycerides (97 versus 81 mg/dl) were found in vitamin D deficient obese children compared to obese children without vitamin D deficiency. A negative correlation was found between 25-OH-D levels and HOMA in absolute values (r=-0.2; P=.04) that was not maintained when HOMA-SDS was analyzed. CONCLUSIONS There is a high prevalence of vitamin D deficiency among obese children with a multifactorial etiology. A lower 25-OH-D level could be a risk factor for developing insulin resistance and type 2 diabetes in obese population.

Resistin levels are related to fat mass, but not to body mass index in children.

The relationship of resistin levels with obesity remains unclear. The aim of this study was to determine resistin levels in prepubertal children and adolescents and evaluate their association with anthropometric parameters and body composition. The study population included 420 randomly selected 6-8-year-old children and 712 children aged 12-16 years. Anthropometric data were measured and body mass index (BMI) and waist-to-hip and waist-to-height ratios were calculated. Body composition was assessed using an impedance body composition analyzer. Serum resistin levels were determined using a multiplexed bead immunoassay. Resistin levels were not significantly different between sexes. No significant differences in serum resistin concentrations were found between obese, overweight, and normal weight children at any age, and no significant correlations were observed between resistin concentrations and weight or BMI. However, resistin levels showed a significant positive correlation with fat mass in 12-16-year-old children, particularly in girls. In addition to describing serum resistin levels in prepubertal children and adolescents, our study suggests that resistin is related to body fat rather than to BMI in adolescents.

Pubertad precoz central: aspectos epidemiológicos, etiológicos y diagnóstico-terapéuticos

Central precocious puberty (CPP) is a rare disease with female predominance and a higher incidence among adopted children. Of idiopathic aetiology in most cases, in the past few years the first mutations in patients with CPP have been described. The prevalence of organic disease is notably lower among girls with CPP. However, no predictors have been described to select which kind of girls should undergo an imaging tests. Although the sensitivity of the determination of basal LH as a marker of CPP has improved with the new techniques, to date, the LH peak after LHRH stimulation test remains the gold standard for the diagnosis of CPP. Finally, the use of GnRH analogues has shown to be particularly effective in the treatment of CPP patients less than 6 years-old.

The influence of puberty on vitamin D status in obese children and the possible relation between vitamin D deficiency and insulin resistance

Abstract Background: Puberty can affect vitamin D levels. Objectives: The goal of this study was to analyze the relation between vitamin D deficiency and puberty in obese Spanish children, along with the possible interrelation between vitamin D status and degree of insulin resistance. Methods: A cross-sectional study was carried out, in which clinical and biochemical data were gathered from 120 obese and 50 normal weight children between January 2011 and January 2013. Results: Mean vitamin D levels were 19.5 and 31.6 ng/mL in obese pubertal and obese prepubertal children, respectively. About 75% of the obese pubertal subjects and 46% of the obese prepubertal subjects had vitamin D deficiency. Vitamin D levels were significantly lower in pubescent subjects compared with pre-pubescent subjects in summer, fall, and winter. There was no apparent relation between vitamin D levels and homeostasis model assessment index for insulin resistence (expressed in standard deviation score for sex and Tanner stage) in either puberty or pre-puberty. Conclusion: Puberty may be a risk factor for the vitamin D deficiency commonly found in the obese child population. This deficiency is not associated with higher insulin resistance in obese pubertal children compared with obese prepubertal children.

Earlier menarcheal age in Spanish girls is related with an increase in body mass index between pre-pubertal school age and adolescence.

Higher body mass index (BMI) has been associated with earlier pubertal development.