How is painful diabetic sensorimotor polyneuropathy associated to axonal swelling in T2D?

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

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

The investigators performed nerve conduction studies on bilateral sural nerves and unilateral median, peroneal and tibial nerves to compare them with laboratory controls. Skin biopsies were also obtained and analyzed according to the guidelines of the European Federation of Neurological Societies and the Peripheral Nerve Society on the use of skin biopsy in the diagnosis of peripheral neuropathies. DSP was diagnosed using the Toronto Diabetic Neuropathy Expert Group criteria.

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

The researchers identified a difference between the groups in terms of IENFC and swelling ratios. The IENFD was decreased in people with DSP + compared to DSP and healthy control group participants, and no difference was seen between painful and painless DSP + participants (P = 0.08). The mean IENFD was 6.7 fibers / mm for healthy control group participants, 6.2 fibers / mm for the DSP group, 1.3 fibers / mm for the painless DSP + group and 0.84 fibers / mm for the painful DSP + Group.

A total of 86 participants had an IENFD of 1 fiber / mm or less; When these participants were excluded, the mean swelling ratio for the painless and painful DSP + groups increased from 0.0 to 0.3 and 0.13 fibers / mm, respectively, with the axonal swelling ratio in subjects with type 2 diabetes being independent of the Presence of DSP was higher.

After excluding participants with an IENFD of 1 or less, the researchers also found a weak correlation between HbA1c and axonal swelling ratio (r = 0.16; P = 0.04), but no correlation with the Toronto Clinical Scoring System, the Body Mass Index or Type 2 Diabetes Duration.

The limitations of the study include its retrospective design, the use of participants from two study sites, and the uneven distribution between the subgroups.

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

Disclosure: Several authors of the study have stated that they are part of the pharmaceutical industry. For a full list of the authors’ information, see the original reference.


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

This article originally appeared on Clinical Pain Advisor

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