“Metformin decreased the BMI z score and improved inflammatory and cardiovascular-related obesity parameters only in prepubertal children, but a differential effect of metformin was not observed in prepubertal compared to pubertal children. Nevertheless, the doses per kilogram of weight administrated may have had an impact on the metformin effect. Further investigations are necessary.”

Inflammation biomarkers, endothelial dysfunction, and parameters associated with MetS are elevated in obese prepubertal children and correlate to uric acid levels.

At early ages, GH therapy appears to exert beneficial effects on the amount of aPAI-1. At the same time, it increases the state of insulin resistance (HOMA-IR index) without modifying the levels of fibrinogen, vWF, CRP, and IL6.

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BackgroundOverweight and obesity are considered to be serious public health problems. In pediatric populations, insulin resistance, dyslipidemia, and hypertension associated with obesity occur with increased frequencies. Metformin is an oral anti-hyperglycemic agent that has been demonstrated to be efficacious in the treatment of diabetic and non-diabetic obese adults. A considerable amount of pharmacogenetic research has demonstrated that genetic variation is one of the major factors affecting metformin response. Additionally, potential microbiota-mediated mechanisms of metformin effect have been recently described. However, scant work has been conducted in children, with no attention being paid to the potential effects of pubertal development. Thus, the main objective of the present study is to evaluate the effect of metformin treatment together with lifestyle recommendations in a randomized control trial (RCT) of obese children according to pubertal stage, genetic variants and signature of gut microbiota.Methods/designThis is a randomized, prospective, double-blind, placebo-controlled, multicenter trial, which is stratified by puberty and sex. Eighty pre-pubertal (40 boys and 40 girls) and 80 pubertal non-diabetic obese children (40 boys and 40 girls) are being recruited in four Spanish Clinical Hospitals. The inclusion criteria to participate in the RCT include a Body Mass Index (BMI) above the 95th percentile and age 7–14 years. The pubertal stage is determined based on the Tanner criteria. Participants are assigned to two groups in accordance with a randomization schedule and receive 1 g of metformin or placebo for six months in combination with healthy lifestyle recommendations in both groups. The primary outcomes include changes in the BMI Z score and the biomarkers associated with the early appearance of insulin resistance syndrome, inflammation, cardiovascular risk according of the presence of genetic determinants of metformin response, as well as possible modifications in microbiota.DiscussionThis study will assess the differential response of metformin treatment at six months in pre-pubertal and pubertal obese children.Trial registrationRegistered by European Clinical Trials Database (EudraCT, ID: 2010-023061-21) on 14 November 2011.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-016-1403-4) contains supplementary material, which is available to authorized users.

Background: Metabolic syndrome (MetS) can start in children with obesity at very young ages. Non-alcoholic fatty liver disease (NAFLD) is considered to be the hepatic component of metabolic syndrome. If left untreated, the clinical course of NAFLD can be progressive and can become chronic if not detected at an early stage.Objective: We aimed to quantify the differences in liver enzymes between prepubertal children with obesity and children with normal weight to determine any associations between them and parameters related to MetS, adipokines, or markers of endothelial dysfunction and inflammation.Methods: This cross-sectional study included 54 prepuberal children with obesity (aged 6–9 years) and 54 children with normal weight, matched by age and sex. Liver enzymes, C-reactive protein (CRP), interleukin-6, soluble intercellular adhesion molecule-1 (sICAM-1), adipokines, and parameters related to metabolic syndrome (MetS) were all measured.Results: Alanine aminotransferase (ALT) levels, serum butyryl cholinesterase (BChE), leptin, CRP, sICAM-1, triglycerides, blood pressure, and homeostasis model assessment for insulin resistance were significantly higher in children with obesity, while Apolipoprotein A-1, HDL-cholesterol, and adiponectin were significantly lower. In the children with obesity group, ALT and BChE levels correlated with anthropometric measurements, insulin resistance, and lipid parameters, leptin, interleukin-6, CRP, and sICAM-1 while BChE levels negatively correlated with adiponectin.Conclusions: Compared to children with normal weight, prepubertal children with obesity had elevated values for liver enzymes, leptin, markers of insulin resistance, inflammation, and endothelial dysfunction, and variables associated with MetS. There was also a correlation between these disorders and liver enzyme levels.

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