Understanding Diabetic Neuropathy-From Subclinical Nerve Lesions to Severe Nerve Fiber Deficits: A Cross-Sectional Study in Patients With Type 2 Diabetes and Healthy Control Subjects

Diabetes. 2020 Mar;69(3):436-447. doi: 10.2337/db19-0197. Epub 2019 Dec 11.


Studies on magnetic resonance neurography (MRN) in diabetic polyneuropathy (DPN) have found proximal sciatic nerve lesions. The aim of this study was to evaluate the functional relevance of sciatic nerve lesions in DPN, with the expectation of correlations with the impairment of large-fiber function. Sixty-one patients with type 2 diabetes (48 with and 13 without DPN) and 12 control subjects were enrolled and underwent MRN, quantitative sensory testing, and electrophysiological examinations. There were differences in mechanical detection (Aβ fibers) and mechanical pain (Aδ fibers) but not in thermal pain and thermal detection clusters (C fibers) among the groups. Lesion load correlated with lower Aα-, Aβ-, and Aδ-fiber but not with C-fiber function in all participants. Patients with lower function showed a higher load of nerve lesions than patients with elevated function or no measurable deficit despite apparent DPN. Longer diabetes duration was associated with higher lesion load in patients with DPN, suggesting that nerve lesions in DPN may accumulate over time and become clinically relevant once a critical amount of nerve fascicles is affected. Moreover, MRN is an objective method for determining lower function mainly in medium and large fibers in DPN.

Trial registration: ClinicalTrials.gov NCT03022721.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetic Neuropathies / diagnostic imaging*
  • Diabetic Neuropathies / etiology
  • Diabetic Neuropathies / physiopathology
  • Electrodiagnosis
  • Female
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Nerve Fibers, Myelinated / physiology
  • Nerve Fibers, Unmyelinated / physiology
  • Neural Conduction*
  • Nociception / physiology
  • Pain / physiopathology
  • Sciatic Nerve / diagnostic imaging*
  • Sciatic Nerve / physiopathology
  • Severity of Illness Index
  • Touch / physiology


  • Glycated Hemoglobin A
  • hemoglobin A1c protein, human

Associated data

  • ClinicalTrials.gov/NCT03022721