title: The role of insulin resistance in the association between body fat and autonomic function.
abstract: OBJECTIVE
  Excess body fat is associated with altered autonomic function. We investigated whether this association is mediated by insulin resistance.
  
  
  RESULTS
  Cross-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.
  
  
  CONCLUSIONS
  In 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.
authors.affiliation: Department of Clinical Epidemiology, Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, The Netherlands. Electronic address: s.hillebrand@lumc.nl.
authors.forename: S
authors.initials: S
authors.lastname: Hillebrand
authors.affiliation: Department of Cardiology, Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, The Netherlands.
authors.forename: C A
authors.initials: CA
authors.lastname: Swenne
authors.affiliation: Department of Clinical Epidemiology, Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, The Netherlands; Department of Internal Medicine, Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, The Netherlands.
authors.forename: K B
authors.initials: KB
authors.lastname: Gast
authors.affiliation: Department of Cardiology, Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, The Netherlands.
authors.forename: A C
authors.initials: AC
authors.lastname: Maan
authors.affiliation: Department of Clinical Epidemiology, Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, The Netherlands; Department of Medical Statistics, Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, The Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: le Cessie
authors.affiliation: Department of Cardiology, Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, The Netherlands; Interuniversity Cardiology Institute of the Netherlands, PO Box 19258, 3501 DG Utrecht, The Netherlands.
authors.forename: J W
authors.initials: JW
authors.lastname: Jukema
authors.affiliation: Department of Clinical Epidemiology, Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, The Netherlands; Department of Thrombosis and Hemostasis, Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, The Netherlands.
authors.forename: F R
authors.initials: FR
authors.lastname: Rosendaal
authors.affiliation: Department of Clinical Epidemiology, Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, The Netherlands; Department of Internal Medicine, VU Medical Centre, PO Box 7057, 1007 MB Amsterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: den Heijer
authors.affiliation: Department of Clinical Epidemiology, Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: de Mutsert
mesh_terms: D000273:Adipose Tissue / Q000294:innervation / Q000378:metabolism*; D050154:Adiposity; D000368:Aged; D001341:Autonomic Nervous System / Q000378:metabolism* / Q000503:physiopathology; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000209:etiology*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D006339:Heart Rate; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D009765:Obesity / Q000378:metabolism* / Q000503:physiopathology; D050177:Overweight / Q000378:metabolism* / Q000503:physiopathology; D015995:Prevalence; D012306:Risk; D055105:Waist Circumference
keywords: Autonomic nervous system; Body composition; Epidemiology; Insulin resistance