Activity of the antioxidant enzyme paraoxonase in Argentinean children living at high altitude.

BACKGROUND: Children living at high altitude in San Antonio de los Cobres (SAC), Argentina, were shown to have lower high-density lipoprotein cholesterol (HDL-C) levels than Buenos Aires (BA) children. HDL antioxidant capacity is mainly attributed to paraoxonase1 (PON1). OBJECTIVE: To compare PON1 activity in indigenous SAC vs. BA children. METHODS: A cross-sectional study compared 158 SAC vs. 97 BA children (6-16 years). Anthropometric data and lipoprotein profile were measured. PON1 was evaluated employing paraoxon (PON) and phenylacetate (ARE) activity. RESULTS: The prevalence of overweight/obesity was lower in SAC than in BA children (18.3 vs. 30.9%). Triglycerides (1.34 vs. 0.90 mmol/l), apo B (0.84 vs.0.72 g/l), apo A-I (1.33 vs. 1.27 g/l), and ARE activity (100 vs. 90 µmol/ml/min) were higher, while HDL-C (1.16 vs. 1.32 mmol/l) and PON activity (170 vs. 203 nmol/ml/min) were lower in SAC than in BA. Separate multiple linear regression analyses showed that SAC children had significantly higher triglyceride (Beta -0.38), apo B (Beta -0.34), and ARE (Beta -0.36) plus lower HDL-C (Beta 0.33) and PON (Beta 0.25) compared with BA; adjusted for age, gender, and BMI. CONCLUSION: SAC showed an unfavorable lipoprotein profile, lower PON and higher ARE activities compared with BA children, suggesting the presence of altered HDL metabolism and antioxidant capacity.

Cardiometabolic risk factors in native populations living at high altitudes.

BACKGROUND: It is generally accepted that metabolic changes that take place in individuals exposed to high elevation are because of ambient hypoxia, which occurs as a consequence of a low total atmospheric pressure. The discovery of hypoxia inducible factor 1 (HIF1), a transcription factor, has been a breakthrough in the understanding of adaption to high altitudes. OBJECTIVE: The purpose of the present review was to discuss specific epidemiological aspects of cardiovascular disease (CVD) risk factors and their mechanisms in vulnerable, understudied populations living at high altitudes. RESULTS: Obesity prevalence has been inversely associated with elevation. HIF1 has been related to plasma leptin--a hormone secreted by adipose tissue that produces negative feedback on appetite--and inversely associated with obesity. Diverse factors, such as genetics, chronic hypoxia, diet and lifestyle behaviours, could have an influence on the high dyslipidaemia rates of high-altitude natives. Hypoxia could mediate the effects of altitude on human physiology, including lipid metabolism. Genetic studies suggest that dyslipidaemia could be related to the HIF1. Hypoxia inhibits oxidative phosphorylation and stimulates the oxygen signalling pathway through the HIF1. Low fasting glycaemia in individuals at high altitudes has been shown. An increased GLUT4 protein content in skeletal muscle in response to hypoxia has been reported and could be associated with lower glucose levels. Given the high prevalence of dyslipidaemia and the low prevalence of obesity and diabetes in these impoverished high-altitude communities, changes in lifestyle including decreased physical activity and the consumption of a more westernised diet would likely increase the prevalence of CVD related mortality. CONCLUSIONS: Control over major CVD risk factors, when identified early, could be the key to reducing morbidity and mortality in patients with limited access to medical services such as Native populations.

Association between triglyceride to HDL-C ratio and insulin resistance in indigenous Argentinean children.

BACKGROUND: Insulin resistance is considered one of the major risk factors for the development of type 2 diabetes mellitus (T2DM). Thus, early identification, preferably by using simple and inexpensive diagnostic tools, is essential for preventing T2DM. Triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) ratio (TG/HDL-C) has been proposed as an inexpensive tool to identify individuals at high risk of T2DM. The objective of this study was to determine the relationship between insulin resistance and TG/HDL-C in indigenous Argentinean children. METHODS: A cross-sectional study of 501 (243 boys) indigenous school children aged 10.0 ± 2.4 yr were assessed for anthropometry, lipids, glucose, and insulin levels from November 2011 to November 2013. Insulin resistance was defined as the upper third quartile of homeostasis model assessment (HOMA-IR). RESULTS: The prevalence of overweight/obesity was 11.4% per Centers for Disease Control. Mean levels of various characteristics were: body mass index (BMI) 17.2 ± 2.6, HDL-C 39 ± 9 mg/dL, TGs 121 ± 58 mg/dL, TG/HDL-C 2.9 ± 1.8, glucose 77 ± 8 mg/dL, HOMA-IR 1.0 ± 0.8, and insulin 44 ± 9 mUI/L. Children in the higher quartiles of TG/HDL-C had significantly higher HOMA-IR values than children in the lower quartiles. Multiple linear regression analysis showed that TG/HDL-C was significantly associated with HOMA-IR (r² = 0.19) adjusted for age, gender, and BMI. Furthermore, for a 1-unit increase in log TG/HDL-C, the odds of being insulin resistant (HOMA-IR>III quartile) increased by 2.58 times [odds ratio (OR), 2.58 (1.63-4.05); p < 0.01], adjusted for age, gender, and BMI. CONCLUSION: This study suggests that TG/HDL-C may be a good marker to identify insulin resistant indigenous Argentinean children.

Adiposity in children and adolescents: correlates and clinical consequences of fat stored in specific body depots.

The 2011 Pennington Biomedical Research Center's Scientific Symposium focused on adiposity in children and adolescents. The symposium was attended by 15 speakers and other invited experts. The specific objectives of the symposium were to (i) integrate the latest published and unpublished findings on the laboratory and clinical assessment of depot-specific adiposity in children and adolescents, (ii) understand the variation in depot-specific adiposity and related health outcomes associated with age, sex, maturation, ethnicity and other factors and (iii) identify opportunities for incorporating new markers of abdominal obesity into clinical practice guidelines for obesity in children and adolescents. This symposium provided an overview of important new advances in the field and identified directions for future research. The long-term goal of the symposium is to aid in the early identification of children and adolescents who are at increased health risk because of obesity and obesity-related conditions.

Measurement of fasting salivary insulin and its relationship with serum insulin in children.

BACKGROUND: Saliva is a useful sample as a source of hormones for the diagnosis of different diseases, particularly in pediatric patients and aged individuals, because saliva offers a noninvasive and stress-free alternative to serum collection. The aim of this study was to validate a salivary insulin method and to check its clinical application in pediatric patients. METHODS: Saliva samples were collected from 130 boys and 147 girls aged 6-14 years. Salivary and serum insulin levels were measured with the chemiluminescent automated method Access (Beckman Coulter, Brea, CA, USA). Serum blood glucose levels were measured with the glucose oxidase method in an autoanalyzer. RESULTS: The precision profile of the method was determined for six aliquots of different concentrations from pools of saliva, and the coefficients of variation (CV) were 2.4% for 1 µUI/ml, 4% for 0.5, 8.9% for 0.25, 19% for 0.12, 28% for 0.06, and 38% for 0.03 µUI/ml, being the functional sensibility (concentration corresponding to a 20% CV) 0.12 µUI/ml. Insulin recovery was 100.13%. Salivary insulin levels diminished 29.8% in samples stored during 7 days at 2-8 °C. Differences in insulin values were not observed when samples were stored at -20 °C during 7 days. The methods used to measure salivary and serum insulin correlated significantly (r=0.92, P<0.001). However, at levels of serum insulin >20 µUI/ml, this correlation declined (r=0.57, P=0.083). CONCLUSION: The proposed method for salivary insulin measurement showed convenient analytical characteristics.

Comparison of various maternal anthropometric indices of obesity for identifying metabolic syndrome in offspring.

BACKGROUND: Several maternal anthropometric markers have been associated with the metabolic syndrome (MS) in offspring. The objectives of this study were (1) to determine the association between children's MS and maternal anthropometric markers such as body mass index (BMI), waist circumference (WC), WC/height, weight/sitting height squared, and WC/sitting height and (2) to compare the abilities of these five indices to identify children with MS. METHODS: Data were collected cross-sectionally from five elementary schools between April 2007 and March 2008. BMI, WC, WC/height, weight/sitting height squared, and WC/sitting height were acquired in mothers and their children. Tanner stage, blood pressure, glucose, lipids, and insulin were measured in children. Criteria analogous to Adult Treatment Panel III for MS were used for children. RESULTS: Of 624 children (307 boys) 8.96 +/- 1.86 years old, with their mothers being 36.25 +/- 7.14 years old, examined, 107 (17.1%) of children were obese (BMI >95th percentile per Centers for Disease Control and Prevention norms), and 95 (15.2%) were overweight (OW) (85th percentile < or =BMI < 95th percentile). Of the mothers, 109 (30.4%) were obese (BMI > 30 kg/m(2)), and 206 (33.0%) were OW (25 kg/m(2) < BMI < 30 kg/m(2)). Approximately 68% of the children were prepubertal. The prevalence of MS was 3.5% overall: 6.7% in OW and 13.9% in obese children. To determine which marker was a better predictor for MS, a receiver operating characteristics (ROC) curve was generated for the five maternal anthropometric measures, with children's MS as the dichotomous variable. The areas under the ROC curves were 0.697 +/- 0.07 for BMI, 0.698 +/- 0.07 for WC, 0.717 +/- 0.07 for WC/height, 0.725 +/- 0.07 for WC/sitting height, and 0.704 +/- 0.07 for weight/sitting height squared. There was no significant difference between the areas of the five maternal anthropometric markers as predictors of children's MS. CONCLUSIONS: Measurement of maternal sitting height had no advantages over total height in the prediction of children's MS. All maternal anthropometric measures identified the MS in their children consistent with known familial associations of obesity and type 2 diabetes.

Glucokinase gene mutation screening in Argentinean clinically characterized MODY patients.

INTRODUCTION: Mutations in the glucokinase gene (GCK) produce a subtype of Maturity onset diabetes in the young (MODY), named MODY 2. To date over than 190 different mutations have been identified, distributed over the coding regions and the exon-intron boundaries of the gene. The aim of this work was to study the nature and frequency of mutations in the GCK gene, in a MODY clinically characterized Argentinean population. MATERIAL AND METHODS: Seventy unrelated individuals were selected based on MODY clinical features. The study methodology consisted in PCR amplification of the coding regions of the GCK gene, SSCP electrophoresis analysis of the amplified fragments and direct sequencing of the fragments with abnormal electrophoresis pattern. RESULTS: We identified a total of six patients with mutations in the GCK gene. This included two novel mutations: g.1831C>A, g.3792T>A, one already reported by our group, g.168fsdelC (same mutation in two non-related patients) and two already reported: p.Gln138Pro and p.Gly261Glu. With that data, we could establish the prevalence of MODY 2 among the patients in study reaching to 8.6%. DISCUSSION: The main contribution of this study is to inform about two novel mutations not described to date and to make an approach to the establishment of the prevalence of MODY 2 in the population under study. These findings contribute to confirm the allelic heterogeneity of GCK gene mutations and may provide an insight into the structure-function relationship of the GCK.

Are girls more insulin-resistant than boys?

OBJECTIVE: The objective was to determine whether girls were more insulin-resistant than boys. DESIGN AND METHODS: Data from 1009 children (508 males) in 10 elementary schools, between April and September, 2007 were collected. BMI, waist circumference (WC), blood pressure, Tanner stage, lipids, insulin, and glucose were obtained. RESULTS: One hundred and sixty five (16.4%) of the children were obese (>95%ile), and 166 (16.5%) were overweight (85-95%ile). Mean HOMA-IR and insulin were higher among 10.0-13.9-year-old girls than boys. Multiple logistic regression using the 3rd quartile of HOMA-IR as the dependent variable showed that only BMI OR=1.18 (95% CI 1.12-1.24; p<0.001), Tanner OR=1.39 (95% CI 1.12-1.73; p=0.003) and triglycerides 1.005 (95% CI 1.00-1.01; p=0.04) were significantly associated with insulin resistance while sex and HDL-C were not. CONCLUSIONS: This study showed that no significant sex-related differences were found, and HOMA-IR was associated with adiposity and pubertal stage suggesting that the higher values of HOMA-IR in girls than in boys could be due to their earlier pubertal development.