How Is Painful Diabetic Sensorimotor Polyneuropathy Related to Axonal Swelling in T2D?

neuropathy foot pain
neuropathy foot pain
The researchers investigated how axonal swellings in cutaneous nerve fibers are related to T2D mellitus and distal diabetic sensorimotor polyneuropathy in patents with T2D.

Axonal swelling ratio is not associated with the presence of painful diabetic sensorimotor polyneuropathy (DSP) in people with type 2 diabetes and intraepidermal nerve fiber density (IENFD) greater than 1.0 fiber/mm, according to research published in Diabetologia.

Using data from the Pain in Neuropathy Study (PiNS) and the International Diabetic Neuropathy Consortium (IDNC), researchers investigated whether the axonal swelling ratio is related to DSP, neuropathic pain, and clinical variables in a “comprehensively phenotyped” cohort of people with type 2 diabetes.

Study investigators performed nerve conduction studies of bilateral sural nerves and unilateral median, peroneal, and tibial nerves to compare with laboratory controls. Skin biopsies were also taken and analyzed following guidelines from the European Federation of Neurological Societies and the Peripheral Nerve Society Guidelines on the use of skin biopsy in peripheral neuropathy diagnosis. DSP was diagnosed via the Toronto Diabetic Neuropathy Expert Group criteria.

The total cohort included 249 participants, divided into 4 groups: healthy control participants (n=45), DSP negative (DSP-; n=31), and DSP positive (DSP+), subdivided into painful DSP+ (n=99) and painless DSP+ (n=74). Participants in the painful DSP+ group demonstrated the highest TCSS scores, highest HbA1c levels, highest body mass index, and the longest duration of diabetes.

Investigators identified a between-group difference in IENFC and swelling ratios; IENFD was decreased in people with DSP+ compared with DSP- and healthy control group participants, and no difference was noted between painful and painless DSP+ participants (P =.08). Median IENFD was 6.7 fiber/mm for healthy control group participants, 6.2 fiber/mm for the DSP- group, 1.3 fiber/mm for the painless DSP+ group, and 0.84 fiber/mm for the painful DSP+ group.

A total of 86 participants had IENFD of 1 fiber/mm or less; when those participants were excluded, median swelling ratio for the painless and painful DSP+ groups increased from 0.0 to 0.3 and 0.13 fiber/mm, respectively, with a higher axonal swelling ratio in study participants with type 2 diabetes regardless of the presence of DSP.

After excluding participants with IENFD of 1 or less, investigators also found a weak correlation between HbA1c and axonal swelling ratio (r=0.16; P =.04), but no correlation with the Toronto Clinical Scoring System, body mass index, or type 2 diabetes duration.

Study limitations include the retrospective design, the use of participants from 2 study sites, and unequal distribution among subgroups.

“We have shown in a large cohort of well-characterized participants that skin biopsies from participants with type 2 diabetes have higher axonal swelling ratio compared with skin biopsies from healthy study participants, independent of DSP, if IENFD >1 fiber/mm,” the researchers concluded.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Karlsson P, Gylfadottir SS, Kristensen AG, et al. Axonal swellings are related to type 2 diabetes, but not to distal diabetic sensorimotor polyneuropathy. Diabetologia. Published online January 23, 2021. doi:10.1007/s00125-020-05352-9