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Diabetologia. 2019 Jun 7. doi: 10.1007/s00125-019-4897-y. [Epub ahead of print]

Early nerve fibre regeneration in individuals with type 1 diabetes after simultaneous pancreas and kidney transplantation.

Author information

1
Institute of Cardiovascular Sciences, University of Manchester and Central Manchester NHS Foundation Trust, Core Technology Facility, Grafton Street, Manchester, M13 9NT, UK.
2
Department of Medicine, Weill Cornell Medicine-Qatar, Education City, Qatar Foundation, Doha, Qatar.
3
Department of Clinical Neurophysiology, Central Manchester NHS Foundation Trust, Manchester, UK.
4
Department of Eye and Vision Science, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK.
5
Araim Pharmaceuticals, Tarrytown, NY, USA.
6
Department of Transplant and Endocrine Surgery, Central Manchester University Hospital NHS Foundation Trust, Manchester, UK.
7
Institute of Cardiovascular Sciences, University of Manchester and Central Manchester NHS Foundation Trust, Core Technology Facility, Grafton Street, Manchester, M13 9NT, UK. rayaz.a.malik@manchester.ac.uk.
8
Department of Medicine, Weill Cornell Medicine-Qatar, Education City, Qatar Foundation, Doha, Qatar. rayaz.a.malik@manchester.ac.uk.

Abstract

AIMS/HYPOTHESIS:

The study aimed to assess the impact on neuropathy of simultaneous pancreas and kidney transplantation (SPK) in individuals with type 1 diabetes.

METHODS:

This longitudinal observational study examined neuropathic symptoms, deficits, quantitative sensory testing, neurophysiology, corneal confocal microscopy and skin biopsy results in 32 healthy (non-diabetic) control participants, 29 individuals with type 1 diabetes and severe diabetic peripheral neuropathy [DPN] and 36 individuals with type 1 diabetes after SPK.

RESULTS:

Following SPK, HbA1c, eGFR, triacylglycerols and HDL improved significantly (all p < 0.05). Compared with the DPN group, which remained unchanged over the 36 month study period, corneal confocal microscopy assessments improved over 36 months following SPK, with increasing corneal nerve fibre density of 5/mm2 (95% CI 1.8, 8.2; p = 0.003) and corneal nerve fibre length of 3.2 mm/mm2 (95% CI 0.9, 5.5; p = 0.006). The Neuropathy Symptom Profile and peroneal nerve conduction velocity also improved significantly by 36 months compared with DPN (2.5; 95% CI 0.7, 4.3; p = 0.008 and 4.7 m/s; 95% CI 2.2, 7.4; p = 0.0004, respectively), but with a temporal delay compared with the corneal confocal microscopy assessments. Intraepidermal nerve fibre density did not change following SPK; however, mean dendritic length improved significantly at 12 (p = 0.020) and 36 (p = 0.019) months. In contrast, there were no changes in the Neuropathy Disability Score, quantitative sensory testing or cardiac autonomic function assessments. Except for a small decrease in corneal nerve fibre density in the healthy control group, there were no changes in any other neuropathy measure in the healthy control or DPN groups over 36 months.

CONCLUSIONS/INTERPRETATION:

SPK is associated with early and maintained small nerve fibre regeneration in the cornea and skin, followed by an improvement in neuropathic symptoms and peroneal nerve conduction velocity.

KEYWORDS:

Corneal confocal microscopy; Diabetic neuropathy; Pancreas and kidney transplantation; Skin biopsy

PMID:
31175373
DOI:
10.1007/s00125-019-4897-y

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