204 Severe lower limb epidermal nerve fiber loss in diabetic neuropathy is not reversed by long-term normoglycemia following simultaneous pancreas and kidney transplantation
Monday November 16, 2015 from 07:00 to 08:00
Room 110

Frantisek Saudek, Czech Republic


Diabetes Center

Institute for Clinical and Experimental Medicine


Severe lower limb epidermal nerve fiber loss in diabetic neuropathy is not reversed by long-term normoglycemia following simultaneous pancreas and kidney transplantation

Petr Boucek1, Tereza Havrdova1, Ludek Voska1, Alena Lodererova1, Helena Vondrova2, Nurcan Uceyler3, Frantisek Saudek1, Kvetoslav Lipar1, Claudia Sommer3.

1Diabetes Center, Institute for Clinical and Experimental Medicine, Prague, Czech Republic; 2Department of Neurology, Thomayer Hospital, Prague, Czech Republic; 3University of Wurzburg, Wurzburg, Germany

Background: Very advanced forms of diabetic peripheral neuropathy with nerve fiber loss which are important risk factors for diabetic foot disease are generally present in diabetic patients who are pancreas/kidney transplant candidates. We present long-term follow-up data on the effect of normoglycemia after simultaneous pancreas/kidney transplantation (SPK) on epidermal nerve fiber (ENF) density and neurological function in type 1 diabetic (DM) recipients.
Methods: Lower thigh 3-mm skin biopsies with ENF counts (indirect immunofluorescence method), autonomic function (AFT) and quantitative sensory testing (QST) and electrophysiological examinations were performed at time of and at 8 years post-SPK in 12 Type 1 DM patients (M/F 4/8; mean ± SD age 44 ± 10; pre-transplant DM duration 28 ± 9 years). A modified Ewing battery of cardiovascular autonomic reflex tests included heart rate variation with deep breathing (mean inspiration-expiration heart rates), Valsalva maneuver ratio (VR) and heart rate (30th:15th R-R interval) and systolic blood pressure (Δ sBP) responses to standing. Vibration perception thresholds at the big toe dorsum (VPT; biothesiometer) were used for quantitative sensory testing. Electrophysiology data analyzed were sensory (median and sural) and motor (median, tibial and peroneal) nerve conduction velocities (NCV) and peak action potential amplitudes. ENF counts, AFT and QST were also performed in 14 sex- and age-matched healthy controls(C). The Mann-Whitney U test and Wilcoxon test were used for statistical analysis.
Results: At follow-up, SPK recipients were still insulin-independent with excellent glycemic control (HbA1c 37 ± 3 mmol/mol, 5.5 ± 0.3 %; NGSP) and kidney graft function (S-creatinine 102 ± 2 μmol/L; eGFR 61 ± 17 ml/min). However, the severe ENF depletion present at baseline (SPK vs. C: 0.8 ± 1.3 vs. 11.4 ± 4.2 ENF/mm skin surface; p < 0.001) was not improved at follow-up (1.4 ± 4.7 ENF/mm; p > 0.05 vs. baseline) with total ENF absence in 11 biopsies. Similarly, no improvement was seen in the AFT and VPT results. Although some amelioration was present at follow-up in several electrophysiological parameters, statistical significance for the SPK group as a whole was achieved in median motor NCV only (median; interquartile range, pre- vs. post-SPK: 47.5; 43.0 to 50.0 vs. 51.4; 50.9 to 55.3 m/s; p = 0.004).
Conclusion: Lower limb epidermal nerve fiber depletion and neurological function tests - except for median motor nerve conduction velocity - were not significantly improved following establishment of long-term normoglycemia in pancreas/kidney transplant recipients. These results confirm the poor reversibility of structural and functional changes in advanced diabetic peripheral neuropathy present in type 1 diabetic patients with end-stage renal disease.

Supported by a New Horizons Collaborative Research Initiative 2012 grant of the European Foundation.

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