Diabetes mellitus is associated with elevated urinary pyrrole markers of i 3-diketones known to cause axonal neuropathy

Xiao Chen, Wei Liu, Lu Wang, Dafeng Lin, Lulin Nie, Kaiwu He, Zhiwei Guo, Feiqi Zhu, Wenting Feng, Weimin Liu, Jing Yuan, Xifei Yang, Peter Spencer, Jianjun Liu

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction Progressive distal symmetrical axonal neuropathy, a complication of diabetes mellitus (DM), has an unknown cause. Normal physiological metabolism and diabetic dysmetabolism are associated with the generation of i 3-diketones. i 3-Diketones form pyrroles with protein amines, notably with axonal proteins required for the maintenance of nerve fiber integrity, especially elongate, large-diameter peripheral nerve fibers innervating the extremities. We tested the hypothesis that neuropathy-associated i 3-diketone pyrroles are elevated in DM. Research design and methods We measured the urinary concentration of i 3-diketone pyrroles in age-matched and gender-matched elderly (60-84 years) persons with (n=267) or without (n=267) indicators of DM based in a community population (9411 community older adults aged ≥60 years) in Shenzhen city, Guangdong, China. We used statistical methods, including a generalized linear model, multivariate logistic regression analysis and restricted cubic splines, to assess linear and nonlinear relationships between urinary i 3-diketone pyrroles and indicators of DM. Results Compared with healthy controls, those with DM had significantly higher levels of fasting blood glucose, glycated hemoglobin A1c, urinary ketone bodies and urinary i 3-diketone pyrroles. The median concentration of urinary i 3-diketone pyrrole adducts was significantly higher (p<0.0001) in individuals with DM (7.5 (5.4) μM) compared with healthy controls (5.9 (4.3) μM). Both linear and non-linear relations were found between urinary i 3-diketone pyrroles and indicators of DM. Conclusions Diabetic dysmetabolism includes increased generation and excretion of neuropathy-associated i 3-diketone pyrroles. These findings form the foundation for studies to test whether i 3-diketone pyrrole concentration correlates with quantitative sensory (vibration and temperature) and electrodiagnostic testing.

Original languageEnglish (US)
Article numbere001575
JournalBMJ Open Diabetes Research and Care
Volume8
Issue number1
DOIs
StatePublished - Sep 10 2020

Keywords

  • diabetic ketoacidosis
  • diabetic neuropathies
  • metabolism

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

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