Reduced vitamin D levels in painful diabetic peripheral neuropathy.

AIM: Recent studies have reported an association between low vitamin D levels and diabetic peripheral neuropathy. However, many of these did not differentiate between people with painful diabetic peripheral neuropathy and those with painless diabetic peripheral neuropathy, or assess major confounding factors including sunlight exposure and daily activity. Our study addressed these limitations and evaluated vitamin D levels in people with carefully phenotyped diabetic peripheral neuropathy and controls. METHODS: Forty-five white Europeans with Type 2 diabetes and 14 healthy volunteers underwent clinical and neurophysiological assessments. People with Type 2 diabetes were then divided into three groups (17 with painful diabetic peripheral neuropathy, 14 with painless diabetic peripheral neuropathy and 14 with no diabetic peripheral neuropathy). All had seasonal sunlight exposure and daily activity measured, underwent a lower limb skin biopsy and had 25-hydroxyvitamin D measured during the summer months, July to September. RESULTS: After adjusting for age, BMI, activity score and sunlight exposure, 25-hydroxyvitamin D levels (nmol/l) (se) were significantly lower in people with painful diabetic peripheral neuropathy [painful diabetic peripheral neuropathy 34.9 (5.8), healthy volunteers 62.05 (6.7), no diabetic peripheral neuropathy 49.6 (6.1), painless diabetic peripheral neuropathy 53.1 (6.2); ANCOVAP = 0.03]. Direct logistic regression was used to assess the impact of seven independent variables on painful diabetic peripheral neuropathy. Vitamin D was the only independent variable to make a statistically significant contribution to the model with an inverted odds ratio of 1.11. Lower 25-hydroxyvitamin D levels also correlated with lower cold detection thresholds (r = 0.39, P = 0.02) and subepidermal nerve fibre densities (r = 0.42, P = 0.01). CONCLUSIONS: We have demonstrated a significant difference in 25-hydroxyvitamin D levels in well-characterized people with painful diabetic peripheral neuropathy, while accounting for the main confounding factors. This suggests a possible role for vitamin D in the pathogenesis of painful diabetic peripheral neuropathy. Further prospective and intervention trials are required to prove causality between low vitamin D levels and painful diabetic peripheral neuropathy.

One-stop microvascular screening service: an effective model for the early detection of diabetic peripheral neuropathy and the high-risk foot.

AIMS: To evaluate the feasibility of a one-stop microvascular screening service for the early diagnosis of diabetic distal symmetrical polyneuropathy, painful distal symmetrical polyneuropathy and the at-risk diabetic foot. METHODS: People with diabetes attending retinal screening in hospital and community settings had their feet examined by a podiatrist. Assessment included: Toronto Clinical Neuropathy Score evaluation; a 10-g monofilament test; and two validated, objective and quick measures of neuropathy obtained using the point-of-care devices 'DPN-Check', a hand-held device that measures sural nerve conduction velocity and amplitude, and 'Sudoscan', a device that measures sudomotor function. The diagnostic utility of these devices was assessed against the Toronto Clinical Neuropathy Score as the 'gold standard'. RESULTS: A total of 236 consecutive people attending the retinal screening service, 18.9% of whom had never previously had their feet examined, were evaluated. The prevalence of distal symmetrical polyneuropathy, assessed using the Toronto Clinical Neuropathy Score, was 30.9%, and was underestimated by 10-g monofilament test (14.4%). The prevalence of distal symmetrical polyneuropathy using DPN-check was 51.5% (84.3% sensitivity, 68.3% specificity), 38.2% using Sudoscan foot electrochemical skin conductance (77.4% sensitivity, 68.3% specificity), and 61.9% using abnormality in either of the results (93.2% sensitivity, 52.8% specificity). The results of both devices correlated with Toronto Clinical Neuropathy Score (P<0.001). A new diagnosis of painful distal symmetrical polyneuropathy was made in 59 participants (25%), and 56.6% had moderate- or high-risk foot. Participants rated the service very highly. CONCLUSIONS: Combined, eye, foot and renal screening is feasible, has a high uptake, reduces clinic visits, and identifies painful distal symmetrical polyneuropathy and the at-risk foot. Combined large- and small-nerve-fibre assessment using non-invasive, quantitative and quick point-of-care devices may be an effective model for the early diagnosis of distal symmetrical polyneuropathy.

Understanding and treating painful diabetic neuropathy: time for a paradigm shift.

The pathogenesis of diabetic neuropathy (DN) continues to be unclear and as a result, progress in developing effective therapies has been disappointing. In particular, there is only limited understanding of why some patients suffer severe chronic pain, whilst others have painless symptoms. Assessment of the peripheral nerves frequently shows no differences between painful and painless DN. There is growing evidence that the nerve damage in DN is more generalized, including the central nervous system, and these central changes are key to the development and persistence of pain in DN. The advent of new radiological techniques provides us with non-invasive modalities to study central pathophysiological processes in greater detail. These insights are increasingly leading to the recognition that painful DN is a complex and heterogeneous disorder, which requires a multimodal approach to treatment.

User involvement throughout development of technology to support diabetes foot care: a case illustration of the devices for dignity PPIE model.

The successful development and implementation of any healthcare technology requires input from multiple stakeholders including clinical leads, trust information technology directorates as well as project management and procurement. In this process however, a key stakeholder that is often overlooked is the patient.This paper illustrates the crucial importance of patient involvement to avoid poor design and poor uptake of technology and subsequently poor health outcomes.To highlight this, we share a case example evidencing involvement of people with lived experience of foot ulcers resulting from Diabetic foot neuropathy throughout identification of unmet technology needs, design requirements for the device and iterative device development and evaluation.

Alterations of tibialis anterior muscle activation pattern in subjects with type 2 diabetes and diabetic peripheral neuropathy.

Diabetic peripheral neuropathy (DPN) is associated with loss of motor units (MUs), which can cause changes in the activation pattern of muscle fibres. This study investigated the pattern of muscle activation using high-density surface electromyography (HD-sEMG) signals from subjects with type 2 diabetes mellitus (T2DM) and DPN. Thirty-five adults participated in the study: 12 healthy subjects (HV), 12 patients with T2DM without DPN (No-DPN) and 11 patients with T2DM with DPN (DPN). HD-sEMG signals were recorded in the tibialis anterior muscle during an isometric contraction of ankle dorsiflexion at 50% of the maximum voluntary isometric contraction (MVIC) during 30-s. The calculated HD-sEMG signals parameters were the normalised root mean square (RMS), normalised median frequency (MDF), coefficient of variation (CoV) and modified entropy (ME). The RMS increased significantly (p = 0.001) with time only for the DPN group, while the MDF decreased significantly (p < 0.01) with time for the three groups. Moreover, the ME was significantly lower (p = 0.005), and CoV was significantly higher (p = 0.003) for the DPN group than the HV group. Using HD-sEMG, we have demonstrated a reduction in the number of MU recruited by individuals with DPN. This study provides proof of concept for the clinical utility of this technique for identifying neuromuscular impairment caused by DPN.

Thalamic neuronal dysfunction and chronic sensorimotor distal symmetrical polyneuropathy in patients with type 1 diabetes mellitus.

AIMS/HYPOTHESIS: Although clear peripheral nerve pathological abnormalities have been demonstrated in diabetic peripheral neuropathy (DPN), there is little information with regard to brain involvement. Our aim was to use in vivo proton magnetic resonance specroscopy (H-MRS) in patients with DPN in order to assess the neuro-chemical status of the thalamus, which acts as the gateway to the brain for somatosensory information. METHODS: Participants included 18 type 1 diabetic men (eight without DPN, ten with DPN) and six non-diabetic healthy volunteers, who all underwent detailed clinical and neurophysiological assessments yielding a Neuropathy Composite Score (NCS) derived from Neuropathy Impairment Score of the Lower Limbs plus seven tests of nerve function prior to investigation via a single-voxel H-MRS technique, which was used to sample ventral posterior thalamic parenchyma. Spectroscopic resonances including those due to N-acetyl aspartate (NAA) were assessed at both short and long echo-time, providing putative indicators of neuronal function and integrity, respectively. RESULTS: At long echo-time we observed significantly lower NAA:creatine (p = 0.04) and NAA:choline (p = 0.02) ratios in DPN patients than in the other groups. No group differences were detected at short echo-time. We found a significant positive association between both sural amplitude (rho = 0.61, p = 0.004) and nerve conduction velocity (r = 0.58, p = 0.006) and NAA:creatine signal among participants with diabetes. Vibration detection threshold (rho = -0.70, p = 0.004) was significantly related to NAA:choline ratio. Heart rate variability with deep breathing (rho = -0.46, p = 0.05) and NCS (rho = -0.53, p = 0.03) were significantly related to NAA:creatine ratio. CONCLUSIONS/INTERPRETATION: The significantly lower NAA:creatine ratio in DPN is suggestive of thalamic neuronal dysfunction, while the lack of difference in short echo-time between the groups does not suggest neuronal loss. Taken together with the observed correlations between NAA and neurophysiological assessments, these findings provide evidence for thalamic neuronal involvement in DPN.