Flavia Ferraro

Low 25(OH)D3 levels are associated with total adiposity, metabolic syndrome, and hypertension in Caucasian children and adolescents

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 D(3) (25(OH)D(3)) 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)D(3) 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)D(3) 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)D(3) 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)D(3) 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)D(3), high BP, and MetS was observed when models were adjusted for waist circumference. No correlation was found between 25(OH)D(3) concentrations and either FMD or cIMT. CONCLUSIONS Low 25(OH)D(3) levels in Caucasian children are inversely related to total adiposity, MetS, and hypertension.

Acylated and nonacylated ghrelin levels and their associations with insulin resistance in obese and normal weight children with metabolic syndrome

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.

Thyroid function in childhood obesity and metabolic comorbidity

Childhood obesity is a worldwide health problem and its prevalence is increasing steadily and dramatically all over the world. Obese subjects have a much greater likelihood than normal-weight children of acquiring dyslipidemia, elevated blood pressure, and impaired glucose metabolism, which significantly increase their risk of cardiovascular and metabolic diseases. Elevated TSH concentrations in association with normal or slightly elevated free T4 and/or free T3 levels have been consistently found in obese subjects, but the mechanisms underlying these thyroid hormonal changes are still unclear. Whether higher TSH in childhood obesity is adaptive, increasing metabolic rate in an attempt to reduce further weight gain, or indicates subclinical hypothyroidism or resistance and thereby contributes to lipid and/or glucose dysmetabolism, remains controversial. This review highlights current evidence on thyroid involvement in obese children and discusses the current controversy regarding the relationship between thyroid hormonal derangements and obesity-related metabolic changes (hypertension, dyslipidemia, hyperglycemia and insulin resistance, nonalcoholic fatty liver disease) in such population. Moreover, the possible mechanisms linking thyroid dysfunction and pediatric obesity are reviewed. Finally, the potential role of lifestyle intervention as well as of therapy with thyroid hormone in the treatment of thyroid abnormalities in childhood obesity is discussed.

Pediatric nonalcoholic fatty liver disease: A clinical and laboratory challenge

The true prevalence of pediatric nonalcoholic fatty liver disease (NAFLD) is unknown. Challenges in determining the population prevalence of NAFLD include the type of test (and the reference intervals used to define normal and abnormal), the type of population (general population, hospital series), the demographic characteristics of the population sampled, and the nature of the study design. The natural history of pediatric NAFLD remains uncertain. The issue of when to perform a liver biopsy in children with suspected NAFLD remains controversial. Children with NAFLD but normal alanine aminotransferase are rarely investigated. However, evidence of alterations in glucose metabolism parameters should prompt a better understanding of the natural history of pediatric NAFLD not only in terms of the progression of liver disease but also regarding its potential relationship with other health outcomes such as type 2 diabetes mellitus and cardiovascular disease. This evidence could make liver biopsy mandatory in the majority of cases at risk of progressive and severe hepatic and extrahepatic disease. This conclusion, however, raises the question of the feasibility of liver biopsy assessment in an extremely large at risk population, and of the cost/effectiveness of this policy. There is a considerable, continuous interest in reliable, noninvasive alternatives that will allow the prognosis of pediatric NAFLD to be followed in large community or population-based studies.

Adipokines and C-reactive protein in relation to bone mineralization in pediatric nonalcoholic fatty liver disease

AIM To investigate bone mineral density (BMD) in obese children with and without nonalcoholic fatty liver disease (NAFLD); and the association between BMD and serum adipokines, and high-sensitivity C-reactive protein (HSCRP). METHODS A case-control study was performed. Cases were 44 obese children with NAFLD. The diagnosis of NAFLD was based on magnetic resonance imaging (MRI) with high hepatic fat fraction (≥ 5%). Other causes of chronic liver disease were ruled out. Controls were selected from obese children with normal levels of aminotransferases, and without MRI evidence of fatty liver as well as of other causes of chronic liver diseases. Controls were matched (1- to 1-basis) with the cases on age, gender, pubertal stage and as closely as possible on body mass index-SD score. All participants underwent clinical examination, laboratory tests, and whole body (WB) and lumbar spine (LS) BMD by dual energy X-ray absorptiometry. BMD Z-scores were calculated using race and gender specific LMS curves. RESULTS Obese children with NAFLD had a significantly lower LS BMD Z-score than those without NAFLD [mean, 0.55 (95%CI: 0.23-0.86) vs 1.29 (95%CI: 0.95-1.63); P < 0.01]. WB BMD Z-score was also decreased in obese children with NAFLD compared to obese children with no NAFLD, though borderline significance was observed [1.55 (95%CI: 1.23-1.87) vs 1.95 (95%CI: 1.67-2.10); P = 0.06]. Children with NAFLD had significantly higher HSCRP, lower adiponectin, but similar leptin levels. Thirty five of the 44 children with MRI-diagnosed NAFLD underwent liver biopsy. Among the children with biopsy-proven NAFLD, 20 (57%) had nonalcoholic steatohepatitis (NASH), while 15 (43%) no NASH. Compared to children without NASH, those with NASH had a significantly lower LS BMD Z-score [mean, 0.27 (95%CI: -0.17-0.71) vs 0.75 (95%CI: 0.13-1.39); P < 0.05] as well as a significantly lower WB BMD Z-score [1.38 (95%CI: 0.89-1.17) vs 1.93 (95%CI: 1.32-2.36); P < 0.05]. In multiple regression analysis, NASH (standardized β coefficient, -0.272; P < 0.01) and HSCRP (standardized β coefficient, -0.192; P < 0.05) were significantly and independently associated with LS BMD Z-score. Similar results were obtained when NAFLD (instead of NASH) was included in the model. WB BMD Z-scores were significantly and independently associated with NASH (standardized β coefficient, -0.248; P < 0.05) and fat mass (standardized β coefficient, -0.224; P < 0.05). CONCLUSION This study reveals that NAFLD is associated with low BMD in obese children, and that systemic, low-grade inflammation may accelerate loss of bone mass in patients with NAFLD.

Procalcitonin in pediatrics.

Over the past two decades, the body of literature on the clinical usefulness of procalcitonin (PCT) in adults has grown rapidly. Although this approach has led to increased insight, it has also prompted debate regarding its potential use in diagnosis and management of severe infection. Clinicians, however, are less familiar with the use of PCT in pediatric populations. In this review, we examine PCT as a marker of severe clinical pediatric conditions including its role in systemic inflammation, infection, and sepsis.

Upper limit of normal for alanine aminotransferase: Quo vadis?

Several studies suggest that a substantial number of patients with normal serum alanine aminotransferase (ALT) levels, defined by current thresholds, have ongoing hepatic necro-inflammation and fibrosis, and are at risk of liver disease progression. A major problem lies in the definition of normality. The current upper limit of normal (ULN) for ALT was established in the 1980s when reference populations were likely to include many persons with hepatitis C virus infection and nonalcoholic fatty liver disease. Because ALT may be influenced, not only by liver disease, but also by other medical conditions, changing lifestyle factors and demographic determinants, the current ALT ULN threshold has recently been challenged. This review not only highlights current evidence on why and how ALT ULN should be redefined, but also discusses the current concerns about updating the ULN threshold for ALT.