Abstract Details

Title Plasma Deoxydihydroceramides are Elevated in People with Diabetic Neuropathy and Correlate with Neuropathy Severity

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) S56 - Neuromuscular Therapeutics (5:18 PM-5:30 PM)

Poster/Presentation
Number 010

Background DN is a debilitating condition that affects up to 50% of people with diabetes. Altered sphingolipid metabolism in diabetes may lead to an accumulation of atypical, neurotoxic dSLs associated with neuropathy. dSLs can arise from reduced availability of the amino acid L-serine and/or excessive levels of L-alanine. Studies have not investigated which dSL molecules are relevant to DN.

Objective Evaluate deoxysphingolipid (dSL) profiles in people with obesity, Type 2 Diabetes (T2D) and diabetic neuropathy (DN).

Design/Methods We examined dSL species using LC/MS/MS in plasma samples from a university based weight management program from age and HbA1C matched subjects with obesity (O, n=19), obesity with T2D (OD, n=18), obesity with T2D and DN (ODN, n=19), and lean controls (LC n=19).

Results Sample means for the majority of deoxydihydroceramides (1-deoxyDHCer) for the four groups followed the same order from lowest to highest: LC, O, OD, ODN. Adjusting for pair-wise comparisons, mean levels of most 1-deoxyDHCer species were higher in the ODN as compared to the LC groups (0.527 vs. 0.226 pmol/100 µl for C16 1-deoxyDHCer, p=0.0021; 1.129 vs. 0.385 pmol/100 µl for C18 1-deoxyDHCer, p=0.0002; 1.136 vs. 0.492 pmol/100 µl for C20 1-deoxyDHCer, p<0.0001; 2.461 vs 1.585 for C22 1-deoxyDHCer, p=0.0496; 0.181 vs. 0.932 pmol/100 µl for C24:1 1-deoxyDHCer, p=0.0073). No significant difference was observed between OD and OND groups. Further analysis demonstrated that L-alanine was higher and L-serine lower in ODN versus LC (326.2 vs. 248.0, p=0.0086 and 70.2 vs. 89.8, p=0.0110), consistent with a causal contribution to the observed dSL profiles. 1-deoxyDHCer correlated inversely with nerve fiber density across all groups.

Conclusions These novel findings indicate that 1-deoxyDHCer are elevated in individuals with obesity, T2D and DN and may be important biomarkers and/or mediators of DN.

Authors/Disclosures
Vera Fridman, MD (University of Colorado School of Medicine) PRESENTER	Dr. Fridman has nothing to disclose.
	No disclosure on file
Stefan Sillau	Stefan Sillau has nothing to disclose.
	No disclosure on file
	No disclosure on file
Eva Feldman, MD, PhD, FAAN (University of Michigan)	The institution of Dr. Feldman has received research support from National Institutes of Health. The institution of Dr. Feldman has received research support from Centers for Disease Control and Prevention / Agency for Toxic Substances and Disease Registry. The institution of Dr. Feldman has received research support from Juvenile Diabetes Research Foundation. Dr. Feldman has received intellectual property interests from a discovery or technology relating to health care. Dr. Feldman has a non-compensated relationship as a Editorial Board Member with Journal of the Peripheral Nervous System, Experimental Neurology, Nature Neurology Reviews, Neurobiology of Disease, NeuroRx, Journal of Neurology Neurosurgery and Psychiatry, Scientific Reports, Lancet Neurology, Med (Cell Press Journal) that is relevant to AAN interests or activities. Dr. Feldman has a non-compensated relationship as a Editor-in-Chief with Oxford University Press Contemporary Neurology Series that is relevant to AAN interests or activities. Dr. Feldman has a non-compensated relationship as a Membership Committee Member, Strategic Planning Committee Member, and Chair of Section 07 with National Academy of Medicine that is relevant to AAN interests or activities. Dr. Feldman has a non-compensated relationship as a Associate Editor with Annals of Neurology that is relevant to AAN interests or activities. Dr. Feldman has a non-compensated relationship as a Governance Committee Chair with American Neurological Association that is relevant to AAN interests or activities. Dr. Feldman has a non-compensated relationship as a Membership Committee Member, Strategic Planning Committee Member, Chair of Section 07, Neuroscience Forum, Council Member with National Academy of Medicine that is relevant to AAN interests or activities. Dr. Feldman has a non-compensated relationship as a Committee on Making ALS a Livable Disease Member with National Academy of Sciences, Engineering, and Medicine that is relevant to AAN interests or activities. Dr. Feldman has a non-compensated relationship as a Member, Blueprint Neurotherapeutics Network for Biologics (BPN-Biologics) External Oversight Committee with National Institutes of Health that is relevant to AAN interests or activities.
Brian Callaghan, MD, MS, FAAN (University of Michigan Health System)	Dr. Callaghan has received personal compensation for serving as an employee of University of Michigan. Dr. Callaghan has received personal compensation for serving as an employee of Ann Arbor Veterans Affairs. Dr. Callaghan has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Dynamed. Dr. Callaghan has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for 好色先生. Dr. Callaghan has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Medico-legal work. Dr. Callaghan has received personal compensation in the range of $50,000-$99,999 for serving as an Expert Witness for Vaccine Injury Compensation Program. The institution of Dr. Callaghan has received research support from 好色先生. The institution of Dr. Callaghan has received research support from JDRF. The institution of Dr. Callaghan has received research support from NIA. Dr. Callaghan has received personal compensation in the range of $500-$4,999 for serving as a Grant Reviewer with NIH.
	No disclosure on file