Improvement of Early Vascular Changes and Cardiovascular Risk Factors in Obese Children After a Six-Month Exercise Program

OBJECTIVE -Obese children have severe endothelial dysfunction as measured by flowmediated dilation (FMD). We have shown that folic acid normalizes endothelial function in children with type 1 diabetes who have a similar degree of endothelial dysfunction but lower total plasma homocyst(e)ine (tHcy) and higher folate status. Our aim was to evaluate, for the first time, the effect of folate supplementation on endothelial dysfunction in obese children. RESEARCH DESIGN AND METHODS-A total of 53 obese subjects (26 male, mean Ϯ SD age 13.3 Ϯ 2.2 years, and BMI Z score 2.29 Ϯ 0.25) participated in a randomized, double-blind, placebo-controlled, parallel trial of oral folic acid (5 mg/day) or placebo for 8 weeks. Before and after the intervention, we assessed endothelial function (FMD), smooth muscle function (glyceryl trinitrate-induced dilatation [GTN]), high-sensitivity C-reactive protein (hsCRP), tHcy, serum folate, red cell folate (RCF), and lipids.RESULTS -There were no group differences at baseline. FMD did not change with the intervention (folic acid group pre-and postintervention: 6.42 Ϯ 5.03 and 6.56 Ϯ 4.79%, respectively, vs. placebo group: 5.17 Ϯ 3.54 and 5.79 Ϯ 4.26%, respectively; P ϭ 0.6). Folate supplementation increased serum folate and RCF by 18.4 nmol/l (P Ͻ 0.001) and 240.1 nmol/l (P Ͻ 0.001), respectively, and decreased tHcy by 0.95 mol/l (P ϭ 0.008). The intervention did not change GTN, hsCRP, or lipids.CONCLUSIONS -Folic acid supplementation does not improve endothelial function in obese children without diabetes despite increasing folate status and reducing tHcy. This is in contrast to the response to folate in children with type 1 diabetes. Diabetes Care 30:2122-2127, 2007E ndothelium is a key regulator of vascular function. Endothelial dysfunction is an early and fundamental event in the development of atherosclerosis (1). Abnormal endothelial function can be measured by ultrasound, assessing artery responses to an increase in flowmediated dilatation (FMD) and to glyceryl trinitrate-induced dilatation (GTN).Abnormal FMD correlates with abnormal coronary angiography in adults (2).Childhood obesity is an independent risk factor for adult obesity and is associated with atherosclerosis independent of adult weight (3). Obese children have severe endothelial dysfunction (4,5). We have shown that endothelial dysfunction in obese children is comparable in severity with that in children with type 1 diabetes (5). Interventions that begin early in life to improve endothelial function in obese children, in addition to metabolic and weight control, may potentially prevent atherosclerosis.BMI, waist circumference, dyslipidemia, insulin resistance, and markers of the proinflammatory state such as highsensitivity C-reactive protein (hsCRP) and increased total plasma homocyst(e)ine (tHcy) contribute to endothelial dysfunction in obesity (4,5).Folic acid improves endothelial function in adults and children with upperquartile tHcy (6 -8) and improves endothelial dysfunction in adults independently of lowering homo...

show abstract

“…These changes were not significant in comparison with improvements with diet and exercise interventions (27,28).…”

Section: Statisticsmentioning

confidence: 65%

“…One limitation to our study was the participation rate, which is, however, comparable with previous trials in obese children (27,28) and did allow good retention of children during the 24-week study period.…”

Section: Statisticsmentioning

confidence: 72%

Folic Acid Does Not Improve Endothelial Function in Obese Children and Adolescents

et al. 2007

View full text Add to dashboard Cite

show abstract

“…27 Another study demonstrated that a 6 month regimen of diet alone or diet plus exercise training decreased carotid IMT in overweight children (BMI¼25 kg m À2 ±3; age between 9 and 12 years). 14 In this study, 1 year of intervention promoted a significant decrease in carotid IMT in obese adolescents (BMI¼36.50 kg m À2 ±4.99; age between 14 and 19 years).…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, this study recommends reducing fat intake and increasing physical activity as strategies to minimize the impact of obesity on inflammatory disorders. 27 A similar interdisciplinary intervention should be considered as a potential therapeutic strategy.…”

Section: Discussionmentioning

confidence: 99%

Improvement in HOMA-IR is an independent predictor of reduced carotid intima-media thickness in obese adolescents participating in an interdisciplinary weight-loss program

et al. 2010

View full text Add to dashboard Cite

The aim of this study was to verify whether a 1-year interdisciplinary weight-loss program improved common carotid artery intima-media thickness (IMT) and whether insulin resistance and/or inflammation (as measured by the markers plasminogen activator inhibitor type-1 and adiponectin) might underlie obesity in adolescents. A group of 29 post-pubescent obese adolescents were submitted to an interdisciplinary intervention over the course of 1 year. Common carotid artery IMT was determined ultrasonographically. Body composition, blood pressure (BP), glycemia, insulinemia, homeostasis model assessment of insulin resistance (HOMA-IR), lipid profile and adipokine concentrations were analyzed before and after the intervention. The interdisciplinary weight-loss program promoted a significant improvement in body composition, insulin concentration, HOMA-IR, lipid profile, BP and inflammatory state, in addition to significantly decreasing the common carotid artery IMT. Furthermore, this study demonstrated that the difference between baseline and final values of HOMA-IR (DHOMA-IR) was negatively correlated with concomitant changes in the adiponectin concentration (Dadiponectin; r¼À0.42; P¼0.02) and positively correlated with changes in common carotid artery IMT (Dcarotid IMT; r¼0.41; P¼0.03). Multiple regression analysis adjusted by age, cardiovascular risk factors and inflammatory markers showed that DHOMA-IR was an independent predictor of significant changes in common carotid artery IMT. This investigation demonstrated that an interdisciplinary weight-loss program promoted a reduction of the common carotid artery IMT in obese Brazilian adolescents, and the improvement of HOMA-IR was an independent predictor of carotid IMT changes in this population.

show abstract

“…12,13 A number of studies have reported higher IMT in obese compared with lean children and a reduction in IMT occurring with diet, physical activity and/or weight loss. [14][15][16] These factors, combined with the well-described tracking of obesity into adulthood, the greater clustering of cardiovascular risk factors with increasing levels of childhood obesity, including the presence of proinflammatory factors, [17][18][19] the presence of significant obesity-related morbidity in childhood, including fatty liver and psychosocial distress 20 and the important independent risk of adult obesity for cardiovascular disease, strongly argue for public health lifestyle interventions to target childhood overweight and obesity decades before the appearance of symptomatic cardiovascular disease.…”

mentioning

confidence: 99%

Placing the cardiovascular risk of childhood obesity in perspective

Ayer

Steinbeck

2010

Int J Obes

View full text Add to dashboard Cite

Improvement of Early Vascular Changes and Cardiovascular Risk Factors in Obese Children After a Six-Month Exercise Program

Cited by 377 publications

References 45 publications

Folic Acid Does Not Improve Endothelial Function in Obese Children and Adolescents

Folic Acid Does Not Improve Endothelial Function in Obese Children and Adolescents

Improvement in HOMA-IR is an independent predictor of reduced carotid intima-media thickness in obese adolescents participating in an interdisciplinary weight-loss program

Placing the cardiovascular risk of childhood obesity in perspective

Contact Info

Product

Resources

About