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Residual sympathetic tone is associated with reduced insulin sensitivity in patients with autonomic failure

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Abstract

Purpose

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.

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Author information

Authors and Affiliations

  1. Division of Clinical Pharmacology, Department of Medicine, The Autonomic Dysfunction Center, Vanderbilt University School of Medicine, 562 Preston Research Building, Nashville, TN, 37232, USA

    Jorge E. Celedonio, Amy C. Arnold, Claudia E. Ramirez, André Diedrich, Luis E. Okamoto, Satish R. Raj, David Robertson, Italo Biaggioni & Cyndya A. Shibao

  2. Department of Neurology, The Autonomic Dysfunction Center, Vanderbilt University School of Medicine, Nashville, USA

    Amanda C. Peltier

  3. Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, USA

    William D. Dupont

Authors
  1. Jorge E. Celedonio
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  2. Amy C. Arnold
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  3. William D. Dupont
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  4. Claudia E. Ramirez
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  5. André Diedrich
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  6. Luis E. Okamoto
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  7. Satish R. Raj
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  8. David Robertson
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  9. Amanda C. Peltier
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  10. Italo Biaggioni
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  11. Cyndya A. Shibao
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Corresponding author

Correspondence to Cyndya A. Shibao.

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Conflict of interest

CAS and IB are consultants for Lundbeck Pharmaceuticals.

Sources of funding

This work was supported in part by grant P01 HL056693, R01 HL102387, Autonomic Rare Diseases Clinical Research Consortium Grant U54 NS065736, the Vanderbilt Clinical and Translational Science Award Grant UL1 RR024975 from the National Center for Research Resources, and the National Institutes of Health. Cyndya A. Shibao is supported by Grant K23 HL103976 from the National Institutes of Health, PhRMA Foundation Career Development Award, Doris Duke Clinical Scientist Career Development Award.

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Celedonio, J.E., Arnold, A.C., Dupont, W.D. et al. Residual sympathetic tone is associated with reduced insulin sensitivity in patients with autonomic failure. Clin Auton Res 25, 309–315 (2015). https://doi.org/10.1007/s10286-015-0307-9

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  • DOI: https://doi.org/10.1007/s10286-015-0307-9

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