title: Residual sympathetic tone is associated with reduced insulin sensitivity in patients with autonomic failure.
abstract: OBJECTIVE
  Parkinson disease, an α-synucleinopathy, is associated with reduced insulin sensitivity, impaired glucose tolerance, and diabetes mellitus. Importantly, these metabolic alterations have been shown to contribute to disease progression. The purpose of this study was to determine if reduced insulin sensitivity is also present in other α-synucleinopathies associated with autonomic failure.
  
  
  METHODS
  We studied 19 patients with multiple system atrophy and 26 patients with pure autonomic failure. For comparison, we studied 8 healthy controls matched for body mass index. Insulin sensitivity and beta cell function were calculated using fasting glucose and insulin levels according to the homeostatic model assessment 2. A multiple linear regression model was performed to determine factors that predict insulin sensitivity in autonomic failure.
  
  
  RESULTS
  There was a significant difference in insulin sensitivity among groups (P = 0.048). This difference was due to lower insulin sensitivity in multiple system atrophy patients: 64% [interquartile range (IQR), 43 to 117] compared to healthy controls 139% (IQR, 83 to 212), P = 0.032. The main factor that contributed to the reduced insulin sensitivity was the presence of supine hypertension and residual sympathetic tone.
  
  
  CONCLUSIONS
  Multiple system atrophy patients have reduced insulin sensitivity that is associated with residual sympathetic activation and supine hypertension. These patients may therefore be at high risk for development of impaired glucose tolerance and diabetes mellitus.
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, The Autonomic Dysfunction Center, Vanderbilt University School of Medicine, 562 Preston Research Building, Nashville, TN, 37232, USA.
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Celedonio
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, The Autonomic Dysfunction Center, Vanderbilt University School of Medicine, 562 Preston Research Building, Nashville, TN, 37232, USA.
authors.forename: Amy C
authors.initials: AC
authors.lastname: Arnold
authors.affiliation: Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, USA.
authors.forename: William D
authors.initials: WD
authors.lastname: Dupont
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, The Autonomic Dysfunction Center, Vanderbilt University School of Medicine, 562 Preston Research Building, Nashville, TN, 37232, USA.
authors.forename: Claudia E
authors.initials: CE
authors.lastname: Ramirez
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, The Autonomic Dysfunction Center, Vanderbilt University School of Medicine, 562 Preston Research Building, Nashville, TN, 37232, USA.
authors.forename: André
authors.initials: A
authors.lastname: Diedrich
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, The Autonomic Dysfunction Center, Vanderbilt University School of Medicine, 562 Preston Research Building, Nashville, TN, 37232, USA.
authors.forename: Luis E
authors.initials: LE
authors.lastname: Okamoto
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, The Autonomic Dysfunction Center, Vanderbilt University School of Medicine, 562 Preston Research Building, Nashville, TN, 37232, USA.
authors.forename: Satish R
authors.initials: SR
authors.lastname: Raj
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, The Autonomic Dysfunction Center, Vanderbilt University School of Medicine, 562 Preston Research Building, Nashville, TN, 37232, USA.
authors.forename: David
authors.initials: D
authors.lastname: Robertson
authors.affiliation: Department of Neurology, The Autonomic Dysfunction Center, Vanderbilt University School of Medicine, Nashville, USA.
authors.forename: Amanda C
authors.initials: AC
authors.lastname: Peltier
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, The Autonomic Dysfunction Center, Vanderbilt University School of Medicine, 562 Preston Research Building, Nashville, TN, 37232, USA.
authors.forename: Italo
authors.initials: I
authors.lastname: Biaggioni
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, The Autonomic Dysfunction Center, Vanderbilt University School of Medicine, 562 Preston Research Building, Nashville, TN, 37232, USA. cyndya.shibao@vanderbilt.edu.
authors.forename: Cyndya A
authors.initials: CA
authors.lastname: Shibao
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology; D015331:Cohort Studies; D005260:Female; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D019578:Multiple System Atrophy / Q000097:blood* / Q000175:diagnosis* / Q000453:epidemiology; D054970:Pure Autonomic Failure / Q000097:blood* / Q000175:diagnosis* / Q000453:epidemiology; D013564:Sympathetic Nervous System / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D007328:Insulin
keywords: Autonomic failure; Hypertension; Insulin sensitivity; Sympathetic activity