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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, HbA 1c , 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/mm 2  (95% CI 1.8, 8.2;  p  = 0.003) and corneal nerve fibre length of 3.2 mm/mm 2  (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.    Electronic supplementary material  The online version of this article (10.1007/s00125-019-4897-y) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

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