title: Autonomic function is not associated with the incidence of type 2 diabetes in a high-risk population: the Hoorn study.
abstract: OBJECTIVE
  Impaired autonomic function is a complication of type 2 diabetes mellitus (DM2), but may also be involved in its development. For this reason, this study looked at the association of autonomic function with the incidence of DM2 in a homogeneous Caucasian population.
  
  
  METHODS
  This Hoorn study was a prospective population-based study of individuals aged 50-75 years. For the 631 participants, the standard deviation of all normal-to-normal intervals (SDNN) and eight other parameters of autonomic function were calculated at baseline. Fasting and 2-h glucose were measured during follow-up by oral glucose tolerance test (OGTT). DM2 at baseline and follow-up was ascertained by questionnaire and OGTT. After excluding participants with DM2 at baseline, the association of parameters of autonomic function with incident diabetes was examined using logistic-regression analysis while adjusting for possible confounders.
  
  
  RESULTS
  After excluding those with known (n=67) or newly diagnosed (n=126) DM2 at baseline and those missing follow-up data (n=140), 298 participants were eligible for the study (182 with normal glucose tolerance, 19 with impaired fasting glucose and 97 with impaired glucose tolerance). During a median follow-up of 9.2 (range 4.5-11.1) years, 94 incident cases of DM2 were observed. After adjusting for confounding variables, the DM2 odds ratio was 1.12 (95% CI: 0.77, 1.64) per SDNN increase. Results for other parameters of autonomic function were similar.
  
  
  CONCLUSIONS
  The present study found no evidence of an association between autonomic function and DM2 incidence in a population at high risk of diabetes. This implies that previously observed associations between autonomic function and glucose metabolism in cross-sectional settings may reflect reverse causation.
authors.affiliation: Leiden University Medical Centre, Department of Clinical Epidemiology, C7-112, Albinusdreef 2, 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: Leiden University Medical Centre, Department of Clinical Epidemiology, C7-112, Albinusdreef 2, PO Box 9600, 2300 RC Leiden, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: de Mutsert
authors.affiliation: Leiden University Medical Centre, Department of Clinical Epidemiology, C7-112, Albinusdreef 2, PO Box 9600, 2300 RC Leiden, The Netherlands; Department of Endocrinology, VU University Medical Centre, PO Box 7057, 1007 MB, Amsterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: den Heijer
authors.affiliation: Leiden University Medical Centre, Department of Clinical Epidemiology, C7-112, Albinusdreef 2, PO Box 9600, 2300 RC Leiden, The Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: le Cessie
authors.affiliation: Department of Internal Medicine, Endocrinology, Maastricht University Medical Centre, PO Box 5800, 6202 AZ Maastricht, The Netherlands.
authors.forename: C D A
authors.initials: CD
authors.lastname: Stehouwer
authors.affiliation: Department of General Practice, EMGO Institute VU University Medical Centre, PO Box 7057, 1007 MB, Amsterdam, The Netherlands.
authors.forename: G
authors.initials: G
authors.lastname: Nijpels
authors.affiliation: Department of Epidemiology and Biostatistics, EMGO Institute VU University Medical Centre, PO Box 7057, 1007 MB, Amsterdam, The Netherlands.
authors.forename: J M
authors.initials: JM
authors.lastname: Dekker
mesh_terms: D000368:Aged; D001342:Autonomic Nervous System Diseases / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D001786:Blood Glucose / Q000378:metabolism*; D048909:Diabetes Complications / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D005215:Fasting; D005260:Female; D005500:Follow-Up Studies; D018149:Glucose Intolerance / Q000503:physiopathology; D005951:Glucose Tolerance Test; D006339:Heart Rate; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011446:Prospective Studies; D012307:Risk Factors; D011795:Surveys and Questionnaires
chemical_list: D001786:Blood Glucose
keywords: Autonomic nervous system; Diabetes mellitus; Population-based; Prospective cohort study; Type 2