Axonal swellings are related to type 2 diabetes, but not to distal diabetic sensorimotor polyneuropathy

Aims/hypothesis Distal diabetic sensorimotor polyneuropathy (DSP) is a common complication of diabetes with many patients showing a reduction of intraepidermal nerve fibre density (IENFD) from skin biopsy, a validated and sensitive diagnostic tool for the assessment of DSP. Axonal swelling ratio is...

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Published in:Diabetologia 2021-04, Vol.64 (4), p.923-931
Main Authors: Karlsson, Pall, Gylfadottir, Sandra S., Kristensen, Alexander G., Ramirez, Juan D., Cruz, Pedro, Le, Nhu, Shillo, Pallai R., Tesfaye, Solomon, Rice, Andrew S. C., Tankisi, Hatice, Finnerup, Nanna B., Nyengaard, Jens R., Jensen, Troels S., Bennett, David L. H., Themistocleous, Andreas C.
Format: Article
Language:English
Subjects:
Aged
Axons - pathology
Biopsy
Diabetes
Diabetes mellitus (non-insulin dependent)
Diabetes Mellitus, Type 2 - pathology
Diabetic Neuropathies - pathology
Diabetic neuropathy
Early Diagnosis
Female
Fibers
Human Physiology
Humans
Internal Medicine
Male
Medicine
Medicine & Public Health
Metabolic Diseases
Middle Aged
Nerve conduction
Neurologic Examination
Pain Measurement
Polyneuropathy
Predictive Value of Tests
Retrospective Studies
Sensorimotor system
Sensory neurons
Skin - innervation
Skin tests
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Summary:Aims/hypothesis Distal diabetic sensorimotor polyneuropathy (DSP) is a common complication of diabetes with many patients showing a reduction of intraepidermal nerve fibre density (IENFD) from skin biopsy, a validated and sensitive diagnostic tool for the assessment of DSP. Axonal swelling ratio is a morphological quantification altered in DSP. It is, however, unclear if axonal swellings are related to diabetes or DSP. The aim of this study was to investigate how axonal swellings in cutaneous nerve fibres are related to type 2 diabetes mellitus, DSP and neuropathic pain in a well-defined cohort of patients diagnosed with type 2 diabetes. Methods A total of 249 participants, from the Pain in Neuropathy Study (UK) and the International Diabetic Neuropathy Consortium (Denmark), underwent a structured neurological examination, nerve conduction studies, quantitative sensory testing and skin biopsy. The study included four groups: healthy control study participants without diabetes ( n  = 45); participants with type 2 diabetes without DSP (DSP−; n  = 31); and participants with evidence of DSP (DSP+; n  = 173); the last were further separated into painless DSP+ ( n  = 74) and painful DSP+ ( n  = 99). Axonal swellings were defined as enlargements on epidermal-penetrating fibres exceeding 1.5 μm in diameter. Axonal swelling ratio is calculated by dividing the number of axonal swellings by the number of intraepidermal nerve fibres. Results Median (IQR) IENFD (fibres/mm) was: 6.7 (5.2–9.2) for healthy control participants; 6.2 (4.4–7.3) for DSP−; 1.3 (0.5–2.2) for painless DSP+; and 0.84 (0.4–1.6) for painful DSP+. Swelling ratios were calculated for all participants and those with IENFD > 1.0 fibre/mm. When only those participants with IENFD > 1.0 fibre/mm were included, the axonal swelling ratio was higher in participants with type 2 diabetes when compared with healthy control participants ( p  1.0 fibre/mm, axonal swelling ratio is related to type 2 diabetes but is not related to DSP or painful DSP. Axonal swellings may be an early mar
ISSN:0012-186X
1432-0428
DOI:10.1007/s00125-020-05352-9