Dysfunction of autonomic nervous system in childhood obesity: a cross-sectional study

Abstract

Objective: To assess the distribution of autonomic nervous system (ANS) dysfunction in overweight and obese children.

Methods: Parasympathetic and sympathetic ANS function was assessed in children and adolescents with no evidence of impaired glucose metabolism by analysis of heart rate variability (low frequency power ln(LF), high frequency power, ln(HF); ln(LF/HF) ratio, ratio of longest RR interval during expiration to shortest interval during inspiration (E/I ratio), root mean square of successive differences (RMSSD); sympathetic skin response (SSR); and quantitative pupillography (pupil diameter in darkness, light reflex amplitude, latency, constriction velocity, re-dilation velocity). The relationship of each ANS variable to the standard deviation score of body mass index (BMI-SDS) was assessed in a linear model considering age, gender and pubertal stage as co-variates and employing an F-statistic to compare the fit of nested models. Group comparisons between normal weight and obese children as well as an analysis of dependence on insulin resistance (as indexed by the Homeostasis Model Assessment of Insulin Resistance, HOMA-IR) were performed for parameters shown to correlate with BMI-SDS. Statistical significance was set at 5%.

Results: Measurements were performed in 149 individuals (mean age 12.0 y; 90 obese 45 boys; 59 normal weight, 34 boys). E/I ratio (p = 0.003), ln(HF) (p = 0.03), pupil diameter in darkness (p = 0.01) were negatively correlated with BMI-SDS, whereas ln(LF/HF) was positively correlated (p = 0.05). Early re-dilation velocity was in trend negatively correlated to BMI-SDS (p = 0.08). None of the parameters that depended significantly on BMI-SDS was found to be significantly correlated with HOMA-IR.

Conclusion: These findings demonstrate extended ANS dysfunction in obese children and adolescents, affecting several organ systems. Both parasympathetic activity and sympathetic activity are reduced. The conspicuous pattern of ANS dysfunction raises the possibility that obesity may give rise to dysfunction of the peripheral autonomic nerves resembling that observed in normal-weight diabetic children and adolescents.

Figure 1. Correlation between E/I ratio (index of parasympathetic nervous system) and BMI-SDS in 149 normal-weight and obese children.

The solid regression line is found using all the data points, whereas the dashed line is found upon eliminating the outliers marked as triangles. For all the data points, Pearson’s correlation coefficient = −0.24 (p = 0.003) and without the outliers, it is −0.41 (p = 3×10⁻⁷).

Figure 2. Correlation between ln(HF) (index of parasympathetic nervous system) and BMI-SDS in 149 normal-weight and obese children.

Pearson’s correlation coefficient = −0.19, 95% CI = [−0.34, −0.03], (p = 0.03).

Figure 3. Correlation between pupil diameter (index of sympathetic nervous system) and BMI-SDS in 149 normal-weight and obese children.

Pearson’s correlation coefficient = −0.21, 95% CI = [−0.36, −0.05], (p = 0.01).

Figure 4. Correlation between early re-dilation (index of sympathetic nervous system) and BMI-SDS in 149 normal-weight and obese children.

Pearson’s correlation coefficient = −0.15, 95% CI = [−0.30, 0.02], (p = 0.08). Note that only boys have values above 2.2 mm/s (dashed line). The average age of these boys was 11.1 and only one of them was older than 13. This helps explain the strong interaction between age and gender, i.e. that the age dependence for boys is significantly different than that for girls. The regression line showing the downward trend for increasing BMI-SDS is also shown (solid line).