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Paed Obesity – Improved biochemical markers

Evidence Summary
Obesity is associated with a low-grade inflammation, with release of inflammatory cytokines/adipokines such as tumour necrosis factor, C-reactive protein (CRP) & interleukin-6 (IL-6). Some evidence suggests that physical activity (even without additional dietary or lifestyle changes) reduces levels of these cytokines and, in addition, increases anti-inflammatory cytokines such as interleukin 10 and adiponectin1. Adipokines are implicated in insulin resistance, diabetes and development of atherosclerosis and, therefore, modification of adipokine level may be associated with prevention of long-term morbidity associated with obesity.

Physical activity in overweight children (BMI >95th percentile for age & sex) has been associated with an improved inflammatory state, with reduced leptin (standardised mean difference -1.13, 95%CI -1.89 to -0.37) & interleukin-6 (standardised mean difference -0.84, 95%CI -1.45 to 0.23), and increased adiponectin (standardised mean difference 0.69, 95%CI 0.02 to 1.35) compared with controls (7 trials, 250 participants)2. Another meta-analysis (14 RCTs, 347 participants) confirmed an increase in adiponectin (weighted mean difference 0.882 micrograms/ml, 95%CI 0.271 to 1.493) with exercise interventions3. They report no significant change in leptin or resistin level. However, when non-RCT data was included in their analysis, the reduction in leptin levels in response to exercise became significant, especially with longer exercise sessions and longer duration of the intervention overall. When compared with aerobic interventions alone, combined aerobic & resistance training (especially interventions lasting >24 weeks) were associated with greater increase in adiponectin (mean difference 2.59 micrograms/ml)4. A non-significant trend toward reduction in CRP (weighted mean difference -0.72mg/l; 95%CI -1.52 to 0.08; p=0.077) has also been reported with exercise interventions, compared with controls (9 RCTs, 427 participants)5.

Childhood obesity is linked with dyslipidaemia, and this has been linked to persistent dyslipidaemia into adulthood. There is increasing evidence in childhood obesity for the modification of serum lipids with physical activity and dietary interventions. Compared with aerobic exercise alone, combined aerobic and resistance training (especially interventions lasting >24 weeks) were associated with greater reduction in low-density lipoprotein (LDL) cholesterol (mean difference -10.20mg/dl)6. This is also found in obesity prevention, with diet and physical activity interventions associated with a significant reduction in LDL cholesterol (mean reduction -6.06mg/dl) and significant increase in high-density lipoprotein (HDL) cholesterol (mean increase 1.87mg/dl), and is especially marked in studies where there was also an improvement in adiposity measures7.

Non-alcoholic fatty liver disease (NAFLD) is increasing in overweight and obese paediatric populations. In all age groups, the first line treatment for this condition is lifestyle modification and weight loss, and there is strong evidence that physical activity reduces the severity of NAFLD in adults8. Supervised exercise interventions in 6-18y olds (14 trials, 1231 participants) are associated with a reduction of visceral fat (standardised mean difference (SMD) –0.661, 95%CI -0.976 to -0.346; p<0.001), intrahepatic fat (SMD -0.802, 95%CI -1.124 to -0.480; p<0.001), and the liver enzyme gamma-glutamyl transferase, GGT (SMD –0.726, 95%CI -1.203 to -0.249; p<0.001)9. The greatest improvement in visceral fat percentage occurred with aerobic exercise interventions, with activity at least 3 times per week. Both aerobic and resistance exercise, of moderate or vigorous intensity, and of at least 60 minutes/session, 3 times a week or more, are beneficial for hepatic fat content10.

Many interventions offer a combined dietary and physical activity programme. These combined exercise (usually aerobic) and dietary lifestyle interventions are associated with a significant reduction in hepatic steatosis, with a reduced risk of 61%, and reduced serum aminotransferase levels (meta-analysis of 19 studies, 923 individuals, aged 6-18y)11. Diet and exercise interventions of >3 months duration (meta-analysis of 9 studies, 392 individuals, mostly teenagers) were associated with reduced hepatic fat content (SMD -0.54, 95%CI -0.69 to -0.38; p<0.0001)12.

Quality of Evidence
Grade C – There is evidence from randomised controlled trials regarding fatty liver disease, but these have limitations including inconsistencies in intervention and risk of bias. Low quality evidence regarding other biochemical markers

Strength of Recommendation
Grade 2 – Apparent positive balance of risk/benefit – on the basis of the existing evidence, opinion is that most patients will be best served by following this.

Conclusion
Physical activity, especially combined aerobic and resistance interventions, is associated with an improved inflammatory state (reduced leptin, interleukin-6, and increased adiponectin) and reduced LDL cholesterol.
Physical activity interventions, especially those with an aerobic component, are associated with reduced hepatic steatosis and liver enzymes.

References

  1. Physical activity: benefits for prevention and treatment of childhood obesity
    Pinto RM, Silva JVP et al
    J Child Obes. 2018;3 No.S2:003
  2. Effects of physical exercise on adiponectin, leptin and inflammatory markers in childhood obesity: systematic review and meta-analysis
    Siricio F, Bianco A et al
    Child Obes. 2018 May/Jun;14(4):207-217
  3. Exercise, adipokines and pediatric obesity: a meta-analysis of randomised controlled trials
    Garcia-Hermoso A, Ceballos-Ceballos RJM et al
    Int J Obes (Lond). 2017 Apr;41(4):475-482
  4. Concurrent aerobic plus resistance exercise versus aerobic exercise alone to improve health outcomes in paediatric obesity: a systematic review and meta-analysis
    Garcia-Hermoso A, Ramirez-Velez R et al
    Br J Sports Med 2018;52(3):161-166
  5. Exercise-based interventions and C-reactive protein in overweight and obese youths: a meta-analysis of randomised controlled trials
    Garcia-Hermoso A, Sanchez-Lopez M et al
    Pediatr Res. 2016 Apr;79(4):522-7
  6. Concurrent aerobic plus resistance exercise versus aerobic exercise alone to improve health outcomes in paediatric obesity: a systematic review and meta-analysis
    Garcia-Hermoso A, Ramirez-Velez R et al
    Br J Sports Med. 2018 Feb;52(3):161-166
  7. The effect of childhood obesity prevention programs on blood lipids: a systematic review and meta-analysis
    Cai L, Yang W et al
    Obes Rev. 2014 December;15(12):933-944
  8. Exercise and non-alcoholic fatty liver disease: a systematic review and meta-analysis
    Keating SE, Hackett DA et al
    J Hepatol 2012;578:157-66
  9. The effects of exercise on abdominal fat and liver enzymes in pediatric obesity: a systematic review and meta-analysis
    Gonzalez-Ruiz K, Ramirez-Velez R et al
    Child Obes. 2017 Aug;13(4):272-282
  10. Evidence-based exercise recommendations to reduce hepatic fat content in youth – a systematic review and meta-analysis
    Medrano M, Cadenas-Sanchez C et al
    Prog Cardiovascular Dis. 2018 July-Aug;61(2):222-231
  11. Non-alcoholic fatty liver disease in children and adolescents: Lifestyle change – a systematic review and meta-analysis
    Utz-Melere M, Targa-Ferreira C et al
    Ann Hepatol. 2018 May-June;17(3):345-354
  12. The effect of diet or exercise on ectopic adiposity in children and adolescents with obesity: a systematic review and meta-analysis
    Hens W, Vissers D et al
    Obes Rev. 2017 Nov;18(11):1310-1322

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