Angel Gil

Metformin for Obesity in Prepubertal and Pubertal Children: A Randomized Controlled Trial

The present study is an evaluation of metformin’s effect on BMI z score, insulin sensitivity, and inflammation and cardiovascular risk factors in prepubertal and pubertal children who are obese. OBJECTIVES: Metformin has shown its effectiveness in treating obesity in adults. However, little research has been conducted in children, with a lack of attention on pubertal status. The objectives were to determine whether oral metformin treatment reduces BMI z score, cardiovascular risk, and inflammation biomarkers in children who are obese depending on pubertal stage and sex. METHODS: This was a randomized, prospective, double-blind, placebo-controlled, multicenter trial, stratified according to pubertal stage and sex, conducted at 4 Spanish clinical hospitals. Eighty prepubertal and 80 pubertal nondiabetic children who were obese aged 7 to 14 years with a BMI >95th percentiles were recruited. The intervention included 1 g/d of metformin versus placebo for 6 months. The primary outcome was a reduction in BMI z score. Secondary outcomes comprised insulin resistance, cardiovascular risk, and inflammation biomarkers. RESULTS: A total of 140 children completed the study (72 boys). Metformin decreased the BMI z score versus placebo in the prepubertal group (−0.8 and −0.6, respectively; difference, 0.2; P = .04). Significant increments were observed in prepubertal children treated with metformin versus placebo recipients in the quantitative insulin sensitivity check index (0.010 and −0.007; difference, 0.017; P = .01) and the adiponectin–leptin ratio (0.96 and 0.15; difference, 0.81; P = .01) and declines in interferon-γ (−5.6 and 0; difference, 5.6; P = .02) and total plasminogen activator inhibitor-1 (−1.7 and 2.4; difference, 4.1; P = .04). No serious adverse effects were reported. CONCLUSIONS: Metformin decreased the BMI z score and improved inflammatory and cardiovascular-related obesity parameters in prepubertal children but not in pubertal children. Hence, the differential response according to puberty might be related to the dose of metformin per kilogram of weight. Further investigations are necessary.

Cardiovascular risk biomarkers and metabolically unhealthy status in prepubertal children: Comparison of definitions

BACKGROUND AND AIMS The early onset of cardio-metabolic abnormalities, known as metabolically unhealthy (MU) status, is highly associated with obesity and cardiovascular disease (CVD), as well as with increased morbidity and mortality later in life. Given the lack of a consensus MU classification for prepubertal children, we aimed to compare available MU definitions in terms of their association with CVD risk biomarkers. METHODS AND RESULTS A total of 930 prepubertal children (622 with overweight/obesity, 462 males) aged 5-10.9 years were recruited, anthropometric measures were taken and biomarkers were analyzed. Children were classified using eight MU definitions based on different cut-offs for blood pressure, triacylglycerides, high-density lipoprotein cholesterol, glucose and homeostasis model assessment for insulin resistance (HOMA-IR). MU prevalence in children with overweight/obesity ranged between 30% and 60% across definitions. Plasma concentrations of resistin, leptin, myeloperoxidase (MPO) and total plasminogen activator inhibitor 1 (tPAI-1) were higher, and those of adiponectin were lower, in MU compared to MH children with overweight/obesity. Linear regression analyses confirmed the contribution of MPO and tPAI-1 concentrations to MU status, with most significant results derived from definitions that use age and sex-specific criteria and that account for HOMA-IR. CONCLUSION Plasma concentrations of MPO and tPAI-1 are increased in prepubertal MU children irrespective of having normal-weight or overweight/obesity. Inclusion of age and sex-specific cut-offs for cardio-metabolic components as well as insulin resistance criteria increases the quality of MU definitions as seen by their stronger association with CVD biomarkers concentrations.

Additional file 1: of Evaluation of differential effects of metformin treatment in obese children according to pubertal stage and genetic variations: study protocol for a randomized controlled trial

SPIRIT 2013 Checklist (17.05.2016). File outlining how this study protocol meets the different guidelines from the SPIRIT 2013 Checklist. (PDF 48 kb)

The Contribution of Selected Urinary Solutes to the Determination of Urinary Osmolality in Guatemalan Preschool Children Consuming a Common Menu Offering

Background: Although water is the most abundant and most vital of all human nutrients, hydration is among the most ignored aspects of human nutrition. Many different solutes are eliminated by the kidneys in the urine flow, potentially contributing to the osmotic charge of this body fluid and acting as determinants of the urinary osmolality [Uosm]. Objectives: To measure urine osmolality concurrently with urea, uric acid, calcium, magnesium, potassium, sodium and inorganic phosphorus in a 24 h sample and to determine the patterns of their mutual interactions towards assessing the primary determinants of Uosm. Methods: Seventy-eight children from 2 to 7 years old, 40 girls and 38 boys, with median age of 57 mo underwent 24 h urine collections, with an aliquot separated for measuring urine osmolality by freezing-point-depression osmometry and solute concentrations by various analytical chemistry techniques. Spearman correlations and multiple regression models were run to assess interactions. Results: Backward-elimination multiple-regression models found that the urinary concentrations of inorganic phosphorus, urea, sodium, potassium and magnesium explained 95.1% of the variance in Uosm among the seven analytes quantified; calcium and uric acid made negligible contribution. Conclusion: The analyses allowed us to confirm the determinant roles of urea and the principal electrolytes, sodium and potassium, for urine osmolality and to appreciate coordination in the collateral collinear associations with other excreted solutes.