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Serum lipidomic determinants of human diabetic neuropathy in type 2 diabetes
Ann Clin Transl Neurol
2022 Aug 3;9(9):1392–1404. doi: 10.1002/acn3.51639
Author
Farsad Afshinnia , Evan L Reynolds , Thekkelnaycke M Rajendiran , Tanu Soni , Jaeman Byun , Masha G Savelieff , Helen C Looker , Robert G Nelson , George Michailidis , Brian C Callaghan , Subramaniam Pennathur , Eva L Feldman
Author Information
1 Department of Internal Medicine‐Nephrology, University of Michigan, Ann Arbor, Michigan, USA
2 NeuroNetwork for Emerging Therapies, University of Michigan, Ann Arbor, Michigan, USA
3Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA
4 University of Michigan, Michigan Regional Comprehensive Metabolomics Resource Core, Ann Arbor, Michigan, USA
5Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA
6 Chronic Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, Arizona, USA
7Department of Statistics and the Informatics Institute, University of Florida, Gainesville, Florida, USA
8 Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA
Correspondence , Eva L. Feldman, Russell N. DeJong Professor of Neurology, 5017 AAT‐BSRB, 109 Zina Pitcher Place, Ann Arbor, MI 48109, USA.
Tel: +1 (734) 763 7274;
Fax: +1 (734) 763 7275;
E‐mail: efeldman@umich.edu
Co‐first authors.
Article notes
Copyright and License information
© 2022 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.
This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
PMC Copyright notice
PMCID: PMC9463947 PMID: 35923113
Abstract
Objective
The serum lipidomic profile associated with neuropathy in type 2 diabetes is not well understood. Obesity and dyslipidemia are known neuropathy risk factors, suggesting lipid profiles early during type 2 diabetes may identify individuals who develop neuropathy later in the disease course. This retrospective cohort study examined lipidomic profiles 10 years prior to type 2 diabetic neuropathy assessment.
Methods
Participants comprised members of the Gila River Indian community with type 2 diabetes (n = 69) with available stored serum samples and neuropathy assessment 10 years later using the combined Michigan Neuropathy Screening Instrument (MNSI) examination and questionnaire scores. A combined MNSI index was calculated from examination and questionnaire scores. Serum lipids (435 species from 18 classes) were quantified by mass spectrometry.
Results
The cohort included 17 males and 52 females with a mean age of 45 years (SD = 9 years). Participants were stratified as with (high MNSI index score > 2.5407) versus without neuropathy (low MNSI index score ≤ 2.5407). Significantly decreased medium‐chain acylcarnitines and increased total free fatty acids, independent of chain length and saturation, in serum at baseline associated with incident peripheral neuropathy at follow‐up, that is, participants had high MNSI index scores, independent of covariates. Participants with neuropathy also had decreased phosphatidylcholines and increased lysophosphatidylcholines at baseline, independent of chain length and saturation. The abundance of other lipid classes did not differ significantly by neuropathy status.
Interpretation
Abundance differences in circulating acylcarnitines, free fatty acids, phosphatidylcholines, and lysophosphatidylcholines 10 years prior to neuropathy assessment are associated with neuropathy status in type 2 diabetes.