Increased Plasma Levels of Select Deoxy-ceramide and Ceramide Species are
Associated with Increased Odds of Diabetic Neuropathy in Type 1 Diabetes: A
Pilot Study.
Authors Hammad SM, Baker NL, El Abiad JM, Spassieva SD, Pierce JS, Rembiesa B, Bielawski
J, Lopes-Virella MF, Klein RL,
Submitted By Richard Klein on 8/1/2016
Status Published
Journal Neuromolecular medicine
Year 2016
Date Published 7/1/2016
Volume : Pages Not Specified : Not Specified
PubMed Reference 27388466
Abstract Plasma deoxy-sphingoid bases are elevated in type 2 diabetes patients and
correlate with the stage of diabetic distal sensorimotor polyneuropathy;
however, associations between deoxy-sphingolipids (DSL) and neuropathy in type 1
diabetes have not been examined. The primary aim of this exploratory pilot study
was to assess the associations between multiple sphingolipid species including
DSL and free amino acids and the presence of symptomatic neuropathy in a
DCCT/EDIC type 1 diabetes subcohort. Using mass spectroscopy, plasma levels of
DSL and free amino acids in DCCT/EDIC type 1 diabetes participants (n = 80),
with and without symptoms of neuropathy, were investigated. Patient-determined
neuropathy was based on 15-item self-administered questionnaire (Michigan
Neuropathy Screening Instrument) developed to assess distal symmetrical
peripheral neuropathy in diabetes. Patients who scored =4, or reported inability
to sense their feet during walking or to distinguish hot from cold water while
bathing were considered neuropathic. Plasma levels of ceramide, sphingomyelin,
hexosyl- and lactosylceramide species, and amino acids were measured and
analyzed relative to neuropathy status in the patient. Deoxy-C24-ceramide, C24-
and C26-ceramide were higher in patients with neuropathy than those without
neuropathy. Cysteine was higher in patients with neuropathy. No differences in
other sphingolipids or amino acids were detected. The covariate-adjusted Odds
Ratios of positive patient-reported neuropathy was associated with increased
levels of deoxy-C24-, and deoxy-C24:1-ceramide; C22-, C24-, and C26-ceramide;
and cysteine. Plasma deoxy-ceramide and ceramide species may have potential
diagnostic and prognostic significance in diabetic neuropathy.

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