The role of insulin resistance in the association between body fat and autonomic function

• We studied insulin resistance as an underlying mechanism in the association between body fat and autonomic function.
• We performed a mediation analysis according to the method of Baron and Kenny.
• Body fat was associated with autonomic function measured as heart rate variability.
• This association seemed to be mediated for 29–81% by insulin resistance.
• Altered autonomic function in obesity may be preceded by insulin resistance.

Background and aimExcess body fat is associated with altered autonomic function. We investigated whether this association is mediated by insulin resistance.Methods and resultsCross-sectional analysis of a subgroup of the Netherlands Epidemiology of Obesity study with measurements of autonomic function (heart rate variability calculated as mean interbeat interval, standard deviation of all normal intervals (SDNN), low frequency (LF) power and high frequency (HF) power). We measured BMI(kg/m²), total body fat(%) and waist circumference(cm), and calculated the HOMA-index of insulin resistance (HOMA-IR). We examined the association between body fat and heart rate variability with multivariate linear regression analysis. To investigate whether the association was mediated by insulin resistance, we additionally adjusted for HOMA-IR.After exclusion of participants with glucose lowering medication (n = 19), 466 participants were included. Per SD of BMI, the difference in SDNN was −2.7% (95%CI: −5.5, 0.1) in the multivariate model. Additional adjustment for HOMA-IR attenuated this association to −1.2% (95%CI: −4.2, 1.7), suggesting that 55% of the association between BMI and SDNN was mediated by HOMA-IR. All measures of body fat were associated with mean interbeat interval, SDNN and LF power. Depending on the parameter of body fat or heart rate variability, 29–81% of the association was mediated by HOMA-IR.ConclusionIn this cross-sectional study, body fat was associated with heart rate variability. This association may at least partially be mediated by insulin resistance. Future studies should investigate whether a reduction in obesity and insulin resistance may prevent the adverse cardiovascular consequences of altered autonomic function.