Improving Vascular Function in Childhood Obesity

According to the World Health Organization (2018), overweight and obese individuals are those with “excessive fat accumulation that may impair health,' and this occurs as a result of a positive energy balance i.e. energy intake is greater than energy expenditure. An individual is classed as overweight if they have a BMI (body mass index) of 25-29.9 kg/m2, and obese if they have a BMI of 30 kg/m2 or more. However, these values differ for children due to the rapid growth and development they experience during their childhood years. For children, BMI is calculated to produce a percentile value, which is then compared to children of the same age and sex in order to determine their level of obesity. A child is considered overweight if they are above the 85th percentile, and obese if they are in the 95th percentile (Lannelli, 2019). Although obesity may be caused by genetic factors, there are other modifiable risk factors such as diet, physical activity and sedentary behaviour (Sahoo, et al, 2015), with this essay focusing on the use of physical activity. According to the NHS (2016), 1 in 4 adults are obese which is a major problem as obesity can lead to the development of cardiovascular diseases, type 2 diabetes, some cancers, and many other conditions. However, childhood obesity is becoming more prevalent in the UK affecting 1 in 5 children (aged 10-11 years old). In addition to the conditions mentioned previously, childhood obesity can also cause other complications such as cholelithiasis, orthopaedic complications, early puberty, depression and a low self-esteem (Kuźbicka and Rachoń, 2013).

Obesity is linked to a decrease in vascular function. Specifically, it can cause endothelial dysfunction and reduced arterial compliance (Brook, 2006). The endothelium is imperative as it controls the blood vessel diameter by releasing vasoactive substances such as nitric oxide to allow vasodilation and endothelin to allow vasoconstriction. When there is an imbalance of vasodilators and vasoconstrictors, endothelial dysfunction occurs (Davignon, 2004) which can be evaluated by measuring flow-mediated dilation (FMD). Based on guidelines produced by Thijssen et al (2010), FMD is measured using ultrasound to assess blood vessel diameter (usually the brachial artery). A cuff is placed around the arm distally to the brachial artery and a resting measurement of the diameter is taken, followed by a 5 minute cuff occlusion period. Once the pressure in the cuff is released, there is an increase in blood flow and sheer stress along the brachial artery, leading to an increase in the diameter. The peak diameter is measured and FMD is calculated as the percent increase from baseline to the peak diameter. Being able to identify endothelial dysfunction at an early stage is important as this plays a key role in the development of atherosclerosis which in turn, leads to cardiovascular disease (a leading cause of death globally). Childhood obesity increases the risk of obesity throughout adulthood, which increases the risk of vascular dysfunction; for that reason it is important to treat or prevent obesity at an early age in order to improve vascular function and this can be achieved through physical activity/exercise. Regular physical activity that imposes sheer stress can lead to an increase in endothelial cell nitric oxide synthase (eNOS) gene expression which increases the production and bioavailability of nitric oxide (Kelly et al., 2004). This combined with vascular remodelling (increased vessel diameter) and a decrease in free radical degradation of nitric oxide improves endothelial function in obese/overweight individuals.

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There is a substantial amount of evidence to support the use of exercise interventions to improve vascular function by reversing endothelial dysfunction. However, these interventions differ in terms of the frequency and duration, and the type of exercise included in the program. Farpour-Lambert et al (2009), and Murphy et al (2009) both studied the effects of exercise on vascular function using interventions lasting 12 weeks in total. Murphy et al (2009) used a home-based aerobic exercise program using Dance Dance Revolution. Thirty-five overweight children aged 7-12 years old took part in the study, with 23 children allocated to the exercise group, and 12 children allocated to the control group. The exercise group were encouraged to use Dance Dance Revolution 5 times a week, starting off at 10 minutes for week 1 and progressing to 30 minutes for weeks 5-12. In order to determine vascular function, FMD was measured in the brachial artery. The results showed that the exercise group significantly increased FMD by 5.6% (which may be related to decreased low density lipoprotein and total cholesterol). This is quite a large increase when comparing to results of other studies; however, the ultrasound scans were performed by a trained vascular sonographer and repeated by a trained, blinded observer, therefore it can be assumed that this measurement is accurate. The control group showed an increase of 0.3% but this may be due to the fact they were instructed to continue their current levels of physical activity throughout the duration of the study. As this was a home-based program, all children wore a pedometer to record their activity levels, with those in the exercise group recording their steps and exercise duration in daily logs. Although self-reporting always raises questions in any study, the parents had to assist and sign off the child’s activity logs everyday which helps to eliminate any false or inaccurate reports from the children. The intervention was successful at improving vascular function using a home-based exercise program which is an advantage because this closely represents a real life environment, therefore continuation after the program should be easier. An additional long term follow up could have provided more information to see if those who normalized endothelial dysfunction were able to maintain the benefits.

On the other hand, Farpour-Lambert et al (2009) also used a 12 week exercise intervention but showed conflicting results to Murphy et al (2009). Forty-four obese children (BMI over 97th percentile) were recruited for the study, with 22 assigned to the exercise group and 22 assigned to a control group. There were also twenty-two lean children recruited for baseline comparison. The intervention group took part in exercise 3 times a week for 60 minutes; 30 minutes of aerobic exercise (e.g. ball games, swimming), 20 minutes of strength training, and 10 minutes of stretching. When comparing obese and lean children at baseline, the obese children have a significantly lower FMD, indicating endothelial dysfunction at baseline. After 12 weeks, the group of obese children showed a decrease in FMD by 0.59% whereas the control group showed an increase of 0.13%, but these changes were non-significant. However, this study did not mention any restrictions placed on subjects prior to FMD measurements. There are a number of factors that can affect FMD such as exercise, diet, and drugs (Corretti et al, 2002) therefore these should be controlled in any study measuring FMD. This was evident in the study by Murphy et al (2009) mentioned above in which subjects were instructed to fast for 12 hours, and had to abstain from caffeine and exercise 24 hours prior to FMD measurements. Another weakness of the study by Farpour-Lambert et al (2009) was the unequal ratio of males to females, therefore gender may have played a role in the decrease in FMD after 12 weeks. Although Farpour-Lambert et al (2009) looks at pre-pubertal children, a balanced male to female ratio becomes more significant when looking at vascular function in obese adolescents as this specific group usually experience puberty throughout this time. As a result of this, the effects of estrogen on FMD should be considered. Estrogen can increase the bioavailability of nitric oxide (Moreau et al, 2013) and therefore improve endothelial dependent dilation. In females, estrogen levels fluctuate throughout the menstrual cycle, therefore; not only is the male to female ratio important, but the stage of the menstrual cycle in females is another important factor to consider.

Watts et al (2004) supported the findings by Murphy et al (2009) with a shorter exercise intervention of 8 weeks. Fourteen obese children were recruited for the study and 7 lean children were recruited for comparison. Both groups were assigned to an exercise program consisting of 3 one hour sessions of whole body exercise including soccer, tag, and other continuous activities. As shown by Murphy et al (2009), this study also shows impaired FMD at baseline for obese children compared with the lean children. With exercise, FMD significantly increased from 6.00% to 7.35% for the obese group, however, their resting brachial artery diameter remained unaltered. Although the study showed an increase in FMD, the sample size is quite small, therefore another study should be conducted with a larger sample size to ensure that it truly represents the population, and to ensure the increase of 1.35% is accurate as this may be over or under exaggerated.

Another 8 week intervention was conducted by Kelly et al (2004) to investigate the effects of exercise on inflammation, insulin and endothelial function in overweight children and adolescents. Twenty overweight subjects were randomly assigned to an exercise group or a control group. The exercise group consisted of stationary cycling 4 times per week, starting at 50-60% of VO₂ peak for 30 minutes and gradually increasing the intensity and duration of exercise each week. This study differed from the previous studies mentioned as endothelial function was determined by FMD AUC (area under curve) rather than FMD peak percentage which is interesting. Kelly and colleagues established this was the best method as it enabled changes in the brachial artery diameter to be seen over a period of time rather than one specific time point which is more appropriate for children due to their changes in FMD over the time course. The results showed that FMD AUC significantly increased as expected from 746%•s to 919%•s, hence an improvement in vascular function. A strength of this study was that it also measured endothelium-independent dilation using nitro-glycerine unlike the other studies mentioned. This is important as it helps to distinguish if changes in FMD are due to endothelial dependent dilation or increased smooth muscle sensitivity.

Nitro-glycerine was also used in a study by Woo et al (2004) to investigate epithelium independent dilation in addition to endothelium dependent dilation. This included 2 groups; a diet plus exercise group, and a diet only group. FMD improved after a 6 week exercise intervention, but these changes were greater in the combined group. Also, there was a significant decrease in arterial wall thickening and an increase in vascular function in those who continued to train for 12 months after the intervention. Although Woo et al (2004) produced the smallest increase in FMD (0.56%) when compared to each study mentioned so far, this result may be the most representative as it includes a much larger sample size, a balanced number of males to females, and a 12 month follow up. Results from the follow up showed that overweight/obese children who continued to train were able to maintain their vascular benefits, whereas these benefits were lost in those who decided to discontinue exercise. After reading this study, it would be interesting to include an exercise only group and a non intervention group in future research to provide more information.

Overall, it is clear that Murphy et al (2009) produced the greatest improvements in endothelial function using Dance Dance Revolution which was performed 5 days per week, therefore proves to be an excellent intervention in improving vascular function. However, with each study using different exercise interventions, it leads into the question of the frequency, mode, and duration of exercise when seeking to improve vascular function in this specific population, and serves to be a potential topic for further research. FMD proves to be a sufficient method to assess endothelial function, but only when the guidelines regarding restrictions (diet, exercise, caffeine intake and drugs) are followed to ensure FMD measurements are valid and reliable. Based on the studies mentioned, exercise interventions are successful at improving vascular function in obese/overweight children, however, according to Woo et al (2004), it is important to continue to exercise in order to maintain the benefits associated with vascular function.

References

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