The prevalence of diabetes mellitus (DM) and obstructive sleep apnea (OSA) are increasing rapidly with the current epidemic of obesity in the United States. Both DM and OSA are associated with autonomic dysfunction, increasing the risk of sudden death and cardiovascular disease in these disorders. Additional links between these disorders exist as well, as OSA is associated with a significantly higher prevalence of impaired glucose regulation (undiagnosed diabetes, impaired glucose tolerance, or impaired fasting glucose collectively called IGR for the purpose of this study). The current model is that OSA causes increased sympathetic activity secondary to intermittent hypoxia. Controversy exists, however, as to whether OSA causes autonomic dysfunction via hyperglycemia, or whether damage to the autonomic nervous system through hyperglycemia causes sleep apnea. My hypothesis is that IGR resulting from OSA is an independent cause of autonomic dysfunction in these patients. The goals of this proposal are to answer the questions: 1) Does autonomic dysfunction occur in OSA independently of IGR and 2) What is the effect of continuous positive airway pressure (CPAP) therapy on glucose regulation and autonomic function.
My specific aims are 1) Define whether autonomic dysfunction in patients with OSA is directly associated with OSA or is secondary to IGR;2) Determine if there is associated peripheral nerve dysfunction in OSA subjects with IGR;and 3) Evaluate the effect of CPAP on glucose and autonomic function in a six-month longitudinal study. The training component of my proposal will consist of learning new methodology in assessment of autonomic and peripheral nerve physiology, and in designing and implementing a longitudinal study. As part of my training, I will learn techniques such as spectral analysis of heart rate variability and evaluation of intraepidermal nerve fiber density in skin biopsies. My progress will be followed by my mentors, Drs. Beth Malow and Stephen Davis, and by consultants Drs. Eva Feldman and David Robertson. This career development award will allow me to achieve my long-term goal of becoming a clinician-scientist specializing in neuromuscular disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23NS056009-05
Application #
8040907
Study Section
NST-2 Subcommittee (NST)
Program Officer
Mitler, Merrill
Project Start
2007-04-01
Project End
2012-06-30
Budget Start
2011-04-01
Budget End
2012-06-30
Support Year
5
Fiscal Year
2011
Total Cost
$165,629
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Neurology
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
Peltier, Amanda C; Myers, M Iliza; Artibee, Kay J et al. (2013) Evaluation of dermal myelinated nerve fibers in diabetes mellitus. J Peripher Nerv Syst 18:162-7
Myers, M Iliza; Peltier, Amanda C (2013) Uses of skin biopsy for sensory and autonomic nerve assessment. Curr Neurol Neurosci Rep 13:323
Myers, M Iliza; Peltier, Amanda C; Li, Jun (2013) Evaluating dermal myelinated nerve fibers in skin biopsy. Muscle Nerve 47:1-11
Peltier, Amanda C; Bagai, Kanika; Artibee, Kay et al. (2012) Effect of mild hyperglycemia on autonomic function in obstructive sleep apnea. Clin Auton Res 22:1-8
Peltier, Amanda C; Donofrio, Peter D (2012) Chronic inflammatory demyelinating polyradiculoneuropathy: from bench to bedside. Semin Neurol 32:187-95
Boger, M S; Hulgan, T; Haas, D W et al. (2012) Measures of small-fiber neuropathy in HIV infection. Auton Neurosci 169:56-61
Zilliox, L; Peltier, A C; Wren, P A et al. (2011) Assessing autonomic dysfunction in early diabetic neuropathy: the Survey of Autonomic Symptoms. Neurology 76:1099-105
Peltier, Amanda C; Black, Bonnie K; Raj, Satish R et al. (2010) Coexistent autoimmune autonomic ganglionopathy and myasthenia gravis associated with non-small-cell lung cancer. Muscle Nerve 41:416-9
Peltier, Amanda Catherine; Garland, Emily; Raj, Satish R et al. (2010) Distal sudomotor findings in postural tachycardia syndrome. Clin Auton Res 20:93-9