ORCID Profile
0000-0003-2934-570X
Current Organisation
University of Wollongong
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: Elsevier BV
Date: 02-2016
DOI: 10.1016/J.CLINPH.2015.11.047
Abstract: Diabetic neuropathy is a debilitating complication of diabetes. Animal models of type 1 diabetes (T1DM) suggest that functional and structural changes, specifically axo-glial dysjunction, may contribute to neuropathy development. The present study sought to examine and characterise early sensory axonal function in T1DM patients in the absence of clinical neuropathy. Thirty patients with T1DM (15M:15F) without neuropathy underwent median nerve sensory and motor axonal excitability studies to examine axonal function. A verified mathematical model of human motor and sensory axons was used to elucidate the underlying causes of observed alterations. Compared to controls (NC), T1DM patients demonstrated significant axonal excitability abnormalities in sensory and motor axons. These included marked reductions in sensory and motor subexcitability during the recovery cycle (T1DM 7.9 ± 0.4:10.4 ± 0.6%, NC 10.4 ± 0.7:15.4 ± 1.2%, P<0.01) and during hyperpolarizing threshold electrotonus at 10-20 ms (T1DM -75.5 ± 0.8:-69.7 ± 0.8%, NC -78.4 ± 1:-72.7 ± 0.9%, P<0.01). Mathematical modelling demonstrated that these changes were due to reduced nodal Na(+) currents, nodal aranodal K(+) conductances and Na(+)/K(+) pump dysfunction, consistent with axo-glial dysjunction as outlined in animal models of T1DM. The study provided support for the occurrence of early changes in nodal and paranodal conductances in patients with T1DM. These data indicate that axonal excitability techniques may detect early changes in diabetic patients, providing a window of opportunity for prophylactic intervention in T1DM.
Publisher: Informa UK Limited
Date: 26-12-2019
DOI: 10.1080/02713683.2019.1705984
Abstract: To determine the utility of corneal confocal microscopy and tear neuromediator analysis in the diagnosis of diabetic peripheral neuropathy (DPN) as a result of type 1 and type 2 diabetes. Seventy in iduals with either type 1 diabetes or type 2 diabetes (T1D/T2D) underwent corneal confocal microscopy to assess the corneal nerve morphology. The concentration of substance P and calcitonin gene-related peptide (CGRP) in tears was measured by enzyme-linked immunosorbent assay. Motor excitability studies were conducted on the median nerve to assess axonal ion channel function. Based on total neuropathy score (TNS), participants were stratified into DPN (DPN+ve TNS ≥ 2 T1D, n = 19 T2D, n = 16) and without DPN (DPN-ve TNS ≤ 1 T1D, n = 19 T2D, n = 16). Areas under the receiver operating characteristic curves (AUCs) were calculated to obtain specificity and sensitivity of the measures to diagnose DPN. In T1D, the concentration of substance P and confocal microscopy measures were significantly reduced ( Corneal confocal microscopy parameters provide a better diagnostic ability to detect DPN in T1D and T2D than nerve excitability measures or concentrations of tear neuromediators. The concentration of substance P could also be useful in diagnosing DPN but for T1D only.
Publisher: American Diabetes Association
Date: 21-03-2017
DOI: 10.2337/DB16-0961
Abstract: Diabetes may impair the capacity for neuroplasticity such that patients experience a slower and poorer recovery after stroke. The current study investigated changes in cortical function in stroke patients with diabetes to determine how this comorbidity may affect poststroke cortical plasticity and thereby functional recovery. From a cohort of 57 participants, threshold-tracking transcranial magnetic stimulation was used to assess cortical function over the ipsilateral and contralesional hemispheres in 7 patients with diabetes after an acute stroke compared with 12 stroke patients without diabetes. Cortical function was also assessed in 8 patients with diabetes without stroke and 30 normal control subjects. After acute stroke, short-interval intracortical inhibition (SICI) was reduced over both motor cortices in stroke patients without diabetes compared with normal control patients, while in stroke patients with diabetes, SICI was only reduced over the contralesional but not the ipsilesional cortex compared with control patients with diabetes. In addition, SICI was significantly reduced in the control patients with diabetes compared with normal control patients. These results have demonstrated the absence of ipsilesional cortical excitability change after diabetic strokes, suggesting impaired capacity for neuroplasticity over this hemisphere as a consequence of a “double-hit” phenomenon because of preexisting alterations in cortical function in nonstroke patients with diabetes. The reliance on reorganization over the contralesional cortex after stroke will likely exert influence on poststroke recovery in patients with diabetes.
Publisher: Public Library of Science (PLoS)
Date: 14-04-2016
Publisher: Elsevier BV
Date: 2017
DOI: 10.1016/J.CLINPH.2016.09.010
Abstract: We explored the nerve ultrasound (US) characteristics of 15 patients with end-stage kidney disease (ESKD) and correlated these findings with clinical severity and electrophysiological parameters of neuropathy. 15 ESKD patients on thrice-weekly high-flux haemodialysis and 15 healthy controls were enrolled. Sonographic and electrophysiologic studies were conducted before and after a single session of haemodialysis. Serial measurements of median nerve cross-sectional area (CSA) and hypoechoic fraction (HF) were performed at the same non-entrapment site in the mid-forearm. Neuropathy severity was quantified using the total neuropathy score (TNS). 86.7% of the ESKD cohort had neuropathy (TNS>1). ESKD patients had significantly higher baseline CSA (8.9±1.2mm This study shows that peripheral nerves in ESKD patients are larger and more hypoechoic and that these morphological abnormalities may be reversed by dialysis. US may be useful as an early marker of neuropathy in ESKD.
Publisher: Wiley
Date: 14-06-2017
DOI: 10.1002/MUS.25704
Abstract: We quantified intraneural blood flow (INBF) in 18 patients with end-stage kidney disease (ESKD) and examined its relationship with nerve size, neuropathy severity, and nerve excitability parameters. Sonographic measurements of the median nerve were performed at the same site before and after hemodialysis. INBF was quantified by analyzing power Doppler sonograms to obtain the vessel score (VSc) and maximum perfusion intensity (MPI). Corresponding median motor nerve excitability studies were performed. Neuropathy severity was assessed using Total Neuropathy Score. A total of 39% of ESKD patients had detectable INBF compared with none in the control group (P < 0.0001). Patients with detectable INBF had larger nerves and more severe neuropathy (P < 0.01). INBF parameters were significantly reduced after a session of dialysis (VSc: P < 0.01 MPI: P < 0.01). A significant relationship was found between interdialytic change in INBF and changes in nerve excitability. Increased INBF is a potential marker for neuropathy severity in ESKD patients. Muscle Nerve 57: 287-293, 2018.
Publisher: Informa UK Limited
Date: 15-01-2023
Publisher: Wiley
Date: 03-07-2018
DOI: 10.1002/DMRR.3028
Abstract: Clinical and experimental studies in patients with type 1 and type 2 diabetes have demonstrated changes in ion channel function and nerve structure. In this study, we investigated the relationship between axonal dysfunction and morphological change in diabetic polyneuropathy by using neuromuscular ultrasound and nerve excitability techniques. We also explored possible differences in this relationship between type 1 and type 2 diabetes. Nerve ultrasound and corresponding motor excitability studies were undertaken in 110 diabetes patients (50 type 1 60 type 2) and 60 age-matched controls (30 for each group). Neuropathy severity was assessed by using total neuropathy score. Median and tibial nerve cross-sectional areas were measured at nonentrapment sites by using high-resolution linear probe. Median and tibial nerve cross-sectional areas were significantly higher in diabetes patients compared with controls: type 1 (median = 7.6 ± 0.2 mm This study has identified correlation between markers of axonal membrane function and structural abnormalities in peripheral nerves of type 1 diabetes patients. The differential relationship in nerve function and structure between type 1 and type 2 diabetes provides clinical evidence that different pathophysiological mechanisms underlie the development of neuropathy in these patient groups.
Publisher: Wiley
Date: 17-05-2020
DOI: 10.1111/DME.14306
Publisher: Wiley
Date: 21-03-2021
DOI: 10.1111/ENE.14805
Publisher: Elsevier BV
Date: 11-2019
DOI: 10.1016/J.CLINPH.2019.08.005
Abstract: Chronic kidney disease (CKD) caused by diabetes is known as diabetic kidney disease (DKD). The present study aimed to examine the underlying mechanisms of axonal dysfunction and features of neuropathy in DKD compared to CKD and type 2 diabetes (T2DM) alone. Patients with DKD (n = 30), CKD (n = 28) or T2DM (n = 40) and healthy controls (n = 41) underwent nerve excitability assessments to examine axonal function. Neuropathy was assessed using the Total Neuropathy Score. A validated mathematical model of human axons was utilised to provide an indication of the underlying causes of nerve pathophysiology. Total neuropathy score was significantly higher in patients with DKD compared to those with either CKD or T2DM (p < 0.05). In DKD, nerve excitability measures (S2 accommodation and superexcitability, p < 0.05) were more severely affected compared to both CKD and T2DM and worsened with increasing serum K Patients with DKD manifested a more severe neuropathy phenotype and shared features of nerve dysfunction to that of CKD. The CKD, and not diabetes component, appears to underlie axonal pathophysiology in DKD.
Publisher: Wiley
Date: 06-04-2019
DOI: 10.1111/DME.13952
Abstract: To investigate changes in corneal nerve morphology in Type 2 diabetes and to establish relationships between in vivo corneal confocal microscopy and markers of peripheral nerve structure and function. We recruited 57 participants with Type 2 diabetes and 26 healthy controls of similar age and sex distribution. We also recruited a disease control group of 54 participants with Type 1 diabetes. All participants were assessed for distal symmetrical polyneuropathy using the Total Neuropathy Score. In vivo corneal confocal microscopy was used to assess corneal nerve fibre length, corneal nerve fibre density, corneal nerve branch density and inferior whorl length. Peripheral nerve structure was assessed using median nerve ultrasonography. Large fibre function was assessed according to median nerve axonal excitability. Small fibre function was assessed using Sudoscan Corneal nerve fibre length, fibre density and branch density and inferior whorl length were significantly lower in in iduals with Type 2 diabetes compared to controls (P<0.001 for all). In the Type 2 diabetes cohort, correlations were observed between neuropathy severity and corneal nerve fibre density (P=0.004), corneal nerve branch density (P=0.003), corneal nerve fibre length (P=0.002) and inferior whorl length (P=0.01). Significant correlations were observed between corneal confocal outcomes and axonal excitability measurements. No association was found between corneal confocal microscopy and median nerve cross-sectional area, Sudoscan measurements or the Survey of Autonomic Symptoms. This study demonstrated significant changes in corneal nerves in in iduals with Type 2 diabetes. Reductions in corneal nerve measures correlated with increasing neuropathy severity. Associations were found between corneal confocal microscopy and markers of voltage-gated potassium channel function.
Publisher: American Diabetes Association
Date: 13-04-2013
DOI: 10.2337/DC12-1310
Abstract: Pharmacological agents for diabetic peripheral neuropathy (DN) target a number of mechanisms, including sodium channel function and γ-aminobutyric acid–minergic processes. At present, prescription is undertaken on a trial-and-error basis, leading to prolonged medication trials and greater healthcare costs. Nerve-excitability techniques are a novel method of assessing axonal ion channel function in the clinical setting. The aim of this study was to determine the effects of axonal ion channel dysfunction on neuropathy-specific quality-of-life (QoL) measures in DN. Fifty-four patients with type 2 diabetes mellitus underwent comprehensive neurologic assessment, nerve-conduction studies, and nerve-excitability assessment. Neuropathy severity was assessed using the Total Neuropathy Score. Neuropathy-specific QoL was assessed using a DN-specific QoL questionnaire (Neuropathy-Specific Quality of Life Questionnaire [NeuroQoL]). Glycosylated hemoglobin and BMI were recorded in all patients. NeuroQoL scores indicated significant QoL impairment (mean 9.08 ± 5.93). Strength-duration time constant (SDTC), an excitability parameter reflecting sodium channel function, was strongly correlated with QoL scores (r = 0.545 P & 0.005). SDTC was prolonged in 48.6% of patients who experienced neuropathic symptoms. A significant correlation was also noted between SDTC and neuropathy severity (r = 0.29 P & 0.05). This relationship was strengthened when looking specifically at patients with clinically graded neuropathy (r = 0.366 P & 0.05). The current study has demonstrated an association between markers of sodium channel function and QoL in DN. The study demonstrates that excitability techniques may identify patients in whom altered sodium channel function may be the dominant abnormality. The findings suggest that excitability techniques may have a role in clinical decision making regarding neuropathic treatment prescription.
Publisher: Elsevier BV
Date: 10-2021
Publisher: Elsevier BV
Date: 2020
DOI: 10.1016/J.JTOS.2019.11.010
Abstract: Patients with chronic kidney disease (CKD) in type 2 diabetes typically manifest with severe peripheral neuropathy. Corneal confocal microscopy is a novel technique that may serve as a marker of nerve injury in peripheral neuropathy. This study examines the changes that occur in corneal nerve morphology as a result of peripheral neuropathy due to renal dysfunction in people with type 2 diabetes. Sixty-two participants (mean age, 62 ± 12 years) with type 2 diabetes and 25 age-matched healthy controls underwent a comprehensive assessment of neuropathy using the total neuropathy score (TNS). The corneal sub-basal nerve plexus was imaged using corneal confocal microscopy. Corneal nerve fiber length, fiber density, branch density, total branch density, nerve fractal dimension, inferior whorl length and inferior whorl nerve fractal dimension were quantified. Based on the eGFR, participants were classified into those with diabetic CKD (eGFR < 60 n = 22) and those without CKD (eGFR ≥ 60 n = 40). Participants with diabetic CKD had significantly lower corneal nerve fiber density (P = 0.037), length (P = 0.036) and nerve fractal dimension (P = 0.036) compared to those without CKD. Multiple linear regression analysis revealed that reduced corneal nerve fiber density (ß coefficient = 0.098, P = 0.017), length (ß coefficient = 0.006, P = 0.008) and nerve fractal dimension (ß coefficient = 0.001, P = 0.007) was associated with low eGFR levels when adjusted for age, duration of diabetes and severity of neuropathy. Corneal confocal microscopy detects corneal nerve loss in patients with diabetic CKD and reduction in corneal nerve parameters is associated with the decline of kidney function.
Publisher: Informa UK Limited
Date: 18-09-2019
Publisher: Wiley
Date: 13-12-2019
DOI: 10.1002/DMRR.3260
Abstract: The present study was undertaken to investigate mechanisms of peripheral nerve dysfunction in latent autoimmune diabetes in adults (LADA). Participants with LADA (n = 15) underwent median nerve ultrasonography and nerve excitability to examine axonal structure and function, in comparison to cohorts of type 1 diabetes (n = 15), type 2 diabetes (n = 23) and healthy controls (n = 26). The LADA group was matched for diabetes duration, glycaemic control, and neuropathy severity with the type 1 and type 2 diabetes groups. A validated mathematical model of the human axon was utilized to investigate the pathophysiological basis of nerve dysfunction. The most severe changes in nerve structure and function were noted in the LADA group. The LADA cohort demonstrated a significant increase in nerve cross-sectional area compared to type 1 participants and controls. Compared to type 1 and 2 diabetes, measures of threshold electrotonus, which assesses nodal and internodal conductances, were significantly worse in LADA in response to both depolarising currents and hyperpolarising currents. In the recovery cycle, participants with LADA had a significant increase in the relative refractory period. Mathematical modelling of excitability recordings indicated the basis of nerve dysfunction in LADA was different to type 1 and 2 diabetes. Participants with LADA exhibited more severe changes in nerve function and different underlying pathophysiological mechanisms compared to participants with type 1 or 2 diabetes. Intensive management of risk factors to delay the progression of neuropathy in LADA may be required.
Publisher: Wiley
Date: 26-05-2017
DOI: 10.1002/MUS.25677
Abstract: Axonal excitability measures give insight into the biophysical properties of peripheral nerve axons. In this study we applied these techniques to the study of facial palsy. Thirty patients with established facial palsy due to unresolved Bell's palsy or herpes zoster (>6 months duration), tumor invasion of the facial nerve, or traumatic facial nerve injury were assessed using facial nerve excitability techniques. Full recordings were obtained in 23 patients (15 unrecovered Bell's palsy or herpes zoster, 5 trauma, 3 tumor-related). Compared with normal controls, the facial palsy group demonstrated changes in stimulus response properties, threshold electrotonus, refractoriness, superexcitability, and I/V slope. Depolarizing threshold electrotonus distinguished between viral and non-viral etiologies on subgroup analysis. In this cross-sectional study, established facial palsy demonstrated findings similar to those seen in studies of regenerated axons. The improved understanding of underlying axonal characteristics offered by the technique may guide future treatment. Muscle Nerve 57: 268-272, 2018.
Publisher: Wiley
Date: 02-08-2019
DOI: 10.1111/DME.14085
Abstract: To undertake sonographic assessment of nerve blood flow in people with Type 2 diabetes and correlate the findings with neuropathy severity scores and electrophysiological measurements. Median and tibial nerve ultrasound scans were undertaken in 75 people with diabetes and 30 aged-matched controls without diabetes, using a high-resolution linear probe at non-entrapment sites. Nerve blood flow was quantified using power Doppler techniques to obtain the vessel score and the maximum perfusion intensity. Neuropathy severity was assessed using a total neuropathy score. Diabetic nerves had higher rates of nerve blood flow detection (28%) compared to the control group (P < 0.0001). Significant correlations were found between nerve blood flow measurements and nerve size (P <0.001), reported sensory symptoms (P < 0.05) and neuropathy severity scores (P < 0.001). The cohort with diabetes had significantly larger median (8.5 ± 0.3 mm Peripheral nerve hypervascularity is detectable by ultrasonography in moderate to severe diabetic neuropathy with prominent sensory dysfunction.
Publisher: Wiley
Date: 17-08-2201
DOI: 10.1002/MUS.25274
Abstract: Glycemic variability (GV) may be a novel factor in the pathogenesis of diabetic complications. However, the effect of GV on peripheral nerve function has not been explored systematically. The relationship between GV and acute glucose levels on motor and sensory nerve function in 17 patients with type 1 diabetes mellitus (T1DM) was assessed using continuous glucose monitoring and nerve excitability techniques to provide insight into the behavior of axonal voltage-gated ion channels. The mean litude of glycemic excursions (MAGE) was calculated to quantify GV. MAGE strongly correlated with excitability markers of altered motor and sensory axonal function, including superexcitability (r = 0.54), S2 accommodation (r = -0.76), minimum current threshold (I/V) slope (r = 0.71), strength duration time constant (r = 0.66), and latency (r = 0.65 P < 0.05). Acute glucose levels did not correlate with markers of axonal function. These findings suggest that GV may be an important mediator of axonal dysfunction in T1DM and a contributing factor in development of diabetic neuropathy. Muscle Nerve, 2016 Muscle Nerve 54: 967-969, 2016.
Publisher: Elsevier BV
Date: 11-2013
DOI: 10.1016/J.CLINPH.2013.04.012
Abstract: The global burden imposed by metabolic diseases and associated complications continue to escalate. Neurological complications, most commonly peripheral neuropathy, represent a significant cause of morbidity and disability in patients with diabetes and chronic kidney disease. Furthermore, health care costs are substantially increased by the presence of complications making investigation into treatment a matter of high priority. Over the last decade nerve excitability techniques have entered the clinical realm and enabled in vivo assessment of biophysical properties and function of peripheral nerves in health and disease. Studies of excitability in diabetic neuropathy have demonstrated alteration in biophysical properties, including changes in Na(+) conductances and Na(+)/K(+) pump function, which may contribute to the development of neuropathic symptoms. Interventional studies have demonstrated that these changes are responsive to pharmacological agents. Excitability studies in patients with chronic kidney disease have demonstrated prominent changes that may contribute to the development of uraemic neuropathy. In particular, these studies have demonstrated strong correlation between hyperkalaemia and the development of nerve dysfunction. These studies have provided a basis for future work assessing the benefits of potassium restriction as a therapeutic strategy in this condition.
Publisher: American Diabetes Association
Date: 14-05-2012
DOI: 10.2337/DB11-1509
Abstract: To evaluate the development of diabetic neuropathy, the current study examined changes in peripheral axonal function. Nerve excitability techniques were undertaken in 108 type 2 diabetic patients with nerve conduction studies (NCS), HbA1c levels, and total neuropathy score (TNS). Patients were categorized into two cohorts: patients with diabetes without neuropathy (DWN group [n = 56]) and patients with diabetes with neuropathy (DN group [n = 52]) and further into severity grade 0 (TNS 0–1 [n = 35]), grade 1 (TNS 2–8 [n = 42]), and grade 2/3 (TNS 9–24 [n = 31]). Results revealed that the DWN group had a significantly increased threshold, prolonged latency, and changes in excitability parameters compared with age-matched control subjects. Patients with neuropathy demonstrated significant alteration in recovery cycle parameters and depolarizing threshold electrotonus. Within the DWN cohort, there were significant correlations between HbA1c level and latency and subexcitability, whereas the estimated glomerular filtration rate correlated with superexcitability in patients with neuropathy. Furthermore, excitability parameters became progressively more abnormal with increasing clinical severity. These results suggest a spectrum of excitability abnormalities in patients with diabetes and that early axonal dysfunction may be detected prior to the development of neuropathy. As progressive changes in excitability parameters correlated to neuropathy severity, excitability testing may provide a biomarker of the early development and severity of diabetic neuropathy, providing insights into the pathophysiological mechanisms producing axonal dysfunction.
Publisher: Elsevier BV
Date: 10-2019
DOI: 10.1016/J.JTOS.2019.08.010
Abstract: To explore the changes that occur in the concentrations of substance P (SP) and calcitonin gene-related peptide (CGRP) in tears as a result of corneal denervation and its association with diabetic peripheral neuropathy (DPN). Sixty-three in iduals with type 1 diabetes/type 2 diabetes (T1D/T2D) and 34 age-matched healthy controls underwent a detailed assessment of neuropathy using the Total Neuropathy Score (TNS). The concentration of SP and CGRP in tears was measured by enzyme-linked immunosorbent assay. The corneal sub-basal nerve plexus was imaged using corneal confocal microscopy. Corneal nerve fibre length, fibre density, branch density, total branch density, nerve fractal dimension and inferior whorl length were quantified. In T1D, the median [IQR] concentration of SP in tears was significantly reduced in those with DPN, (130 [61-692]pg/mL) compared to both control subjects (763 [405-1555]pg/mL, P < 0.01) and in those without DPN (914 [339-1832]pg/mL, P = 0.01) the concentration of CGRP was not changed. In T2D, there was no difference in neuropeptides between participants with diabetes and controls, regardless of neuropathic status. In T1D and T2D, corneal nerve parameters were significantly different between those with DPN or without DPN and controls. A significant correlation was noted between the concentration of tear film SP and TNS in T1D (r = -0.49 P < 0.001) and corneal nerve fibre density (r = 0.45 P < 0.001). The concentration of tear film CGRP was correlated significantly with the reduction of corneal nerve fibre density (r = 0.41 P = 0.01) in T1D. Tear film SP may provide a potential non-invasive biomarker for assessing neuropathy in T1D.
Publisher: Wiley
Date: 02-08-2020
DOI: 10.1002/MUS.27010
Publisher: Elsevier BV
Date: 2020
DOI: 10.1016/J.CLINPH.2019.09.029
Abstract: Corneal confocal microscopy (CCM) has been identified as a non-invasive technique to assess corneal nerve fiber morphology. It is not known how corneal nerve changes relate to measures of peripheral nerve function in diabetic peripheral neuropathy (DPN). The present study investigates the relationship between nerve structure and function in DPN. Fifty participants with type 1 diabetes (T1DM) and 29 healthy controls underwent CCM to assess corneal nerve fiber density (CNFD), branch density (CNBD), fiber length (CNFL), total branch density (CTBD), nerve fractal dimension (CNFrD) and inferior whorl length (IWL). The severity of DPN was assessed as Total Neuropathy Score (TNS). Motor nerve axonal excitability tests were conducted to assess axonal function. Significant correlations were noted between CNFD (rho = -0.783 P < 0.01) or superexcitability (rho = 0.435 P < 0.01) and TNS. CNFrD was significantly correlated with peak response to stimulus (r = 0.414 P < 0.01) and superexcitability (r = -0.467 P < 0.01) measurements. Corneal nerve loss demonstrates a significant association with axonal ion channel dysfunction in T1DM. Detection of altered corneal nerve morphology may lead to the earlier diagnosis of DPN.
Publisher: Wiley
Date: 2013
DOI: 10.1002/DMRR.2360
Abstract: The present study was undertaken to determine whether there were changes evident in axonal membrane function prior to the onset of neuropathy in patients with type 1 and type 2 diabetes. From a cohort of 110 consecutive referrals, nerve excitability was investigated in 40 diabetic patients without clinical evidence of neuropathy (20 type 1 diabetic patients and 20 type 2 diabetic patients). Groups were matched for gender, disease duration and HbA(1c). Studies were also undertaken in two control groups, younger controls and older controls, matched for age and gender with the diabetic cohorts. Subjects with type 1 diabetes demonstrated significant nerve excitability abnormalities when compared with younger normal controls. Specifically, type 1 subjects showed a significant reduction at multiple time points in both depolarising and hyperpolarising threshold electrotonus. Additionally, the relative refractory period was prolonged (type 1, 3.19 ms younger normal controls, 3.0 ms p < 0.05) and superexcitability was reduced (type 1, -23.12% younger normal controls, -26.37% p < 0.05), consistent with axonal membrane depolarisation. Correlations were identified in type 1 patients between disease duration and nerve excitability parameters, including the relative refractory period (r = -0.533, p < 0.05). In contrast, only minor non-specific changes were noted in the type 2 group. This study provides clear evidence of altered axonal function in patients with type 1 diabetes in the absence of clinical neuropathy. These findings suggest that altered axonal membrane potential may precede neuropathy onset in type 1 diabetes and as such may indicate a window of opportunity to intervene and potentially reverse axonal membrane dysfunction before the development of irreversible neuropathy.
Publisher: Wiley
Date: 15-09-2014
DOI: 10.1002/DMRR.2583
Abstract: Diabetic peripheral neuropathy is a common and debilitating complication of diabetes mellitus. Although strict glycaemic control may reduce the risk of developing diabetic peripheral neuropathy, the neurological benefits of different insulin regimens remain relatively unknown. In the present study, 55 consecutive patients with type 1 diabetes mellitus underwent clinical neurological assessment. Subsequently, 41 non-neuropathic patients, 24 of whom were receiving multiple daily insulin injections (MDII) and 17 receiving continuous subcutaneous insulin infusion (CSII), underwent nerve excitability testing, a technique that assesses axonal ion channel function and membrane potential in human nerves. Treatment groups were matched for glycaemic control, body mass index, disease duration and gender. Neurophysiological parameters were compared between treatment groups and those taken from age and sex-matched normal controls. Prominent differences in axonal function were noted between MDII-treated and CSII-treated patients. Specifically, MDII patients manifested prominent abnormalities when compared with normal controls in threshold electrotonus (TE) parameters including depolarizing TE(10-20ms), undershoot and hyperpolarizing TE (90-100 ms) (P < 0.05). Additionally, recovery cycle parameters superexcitability and subexcitability were also abnormal (P < 0.05). In contrast, axonal function in CSII-treated patients was within normal limits when compared with age-matched controls. The differences between the groups were noted in cross-sectional analysis and remained at longitudinal follow-up. Axonal function in type 1 diabetes is maintained within normal limits in patients treated with continuous subcutaneous insulin infusion and not with multiple daily insulin injections. This raises the possibility that CSII therapy may have neuroprotective potential in patients with type 1 diabetes.
Publisher: Elsevier BV
Date: 03-2020
No related grants have been discovered for Natalie Kwai.