Plasma lipid metabolites associate with diabetic polyneuropathy in a cohort with type 2 diabetes

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

DOI

  • Amy E Rumora, University of Michigan
  • ,
  • Kai Guo, University of Michigan, University of North Dakota
  • ,
  • Fadhl M Alakwaa, University of Michigan
  • ,
  • Signe T Andersen
  • Evan L Reynolds, University of Michigan
  • ,
  • Marit E Jørgensen, Steno Diabetes Center, Copenhagen, Denmark., University of Southern Denmark
  • ,
  • Daniel R Witte
  • Hatice Tankisi
  • Morten Charles
  • Masha G Savelieff, University of Michigan
  • ,
  • Brian C Callaghan, University of Michigan
  • ,
  • Troels S Jensen
  • Eva L Feldman, University of Michigan

OBJECTIVE: The global rise in type 2 diabetes is associated with a concomitant increase in diabetic complications. Diabetic polyneuropathy is the most frequent type 2 diabetes complication and is associated with poor outcomes. The metabolic syndrome has emerged as a major risk factor for diabetic polyneuropathy; however, the metabolites associated with the metabolic syndrome that correlate with diabetic polyneuropathy are unknown.

METHODS: We conducted a global metabolomics analysis on plasma samples from a subcohort of participants from the Danish arm of Anglo-Danish-Dutch study of Intensive Treatment of Diabetes in Primary Care (ADDITION-Denmark) with and without diabetic polyneuropathy versus lean control participants.

RESULTS: Compared to lean controls, type 2 diabetes participants had significantly higher HbA1c (p = 0.0028), BMI (p = 0.0004), and waist circumference (p = 0.0001), but lower total cholesterol (p = 0.0001). Out of 991 total metabolites, we identified 15 plasma metabolites that differed in type 2 diabetes participants by diabetic polyneuropathy status, including metabolites belonging to energy, lipid, and xenobiotic pathways, among others. Additionally, these metabolites correlated with alterations in plasma lipid metabolites in type 2 diabetes participants based on neuropathy status. Further evaluating all plasma lipid metabolites identified a shift in abundance, chain length, and saturation of free fatty acids in type 2 diabetes participants. Importantly, the presence of diabetic polyneuropathy impacted the abundance of plasma complex lipids, including acylcarnitines and sphingolipids.

INTERPRETATION: Our explorative study suggests that diabetic polyneuropathy in type 2 diabetes is associated with novel alterations in plasma metabolites related to lipid metabolism.

Original languageEnglish
JournalAnnals of clinical and translational neurology
Volume8
Issue6
Pages (from-to)1292-1307
Number of pages16
ISSN2328-9503
DOIs
Publication statusPublished - Jun 2021

    Research areas

  • BETA-BLOCKER, METABOLOMICS, OUTCOMES, PEOPLE, PERIPHERAL NEUROPATHY, TRIAL

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