scholarly journals The Association between Serum Cytokines and Damage to Large and Small Nerve Fibers in Diabetic Peripheral Neuropathy

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Francesca Magrinelli ◽  
Chiara Briani ◽  
Marcello Romano ◽  
Susanna Ruggero ◽  
Elisabetta Toffanin ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Nerve Fiber ◽  
Diabetic Peripheral Neuropathy ◽  
Motor Nerve ◽  
Serum Levels ◽  
Nerve Fibers ◽  
Fiber Damage ◽  
Serum Cytokines ◽  
Small Nerve

Diabetic peripheral neuropathy (DPN) is a frequent complication of type 2 diabetes mellitus (DM) and may involve small and large peripheral nerve fibers. Recent evidence suggests a role of cytokines in DPN. The paper is aimed at exploring whether the serum concentration of cytokines is associated with small and large nerve fiber function and with neuropathic pain (NP). We recruited a group of 32 type 2 DM patients who underwent serum cytokines (TNF-α, IL-2, IL-4, IL-6, and IL-10) dosage as well as electrodiagnostic and quantitative sensory testing (QST) assessment to explore damage to large and small nerve fibers. Raised serum levels of IL-6 and IL-10 correlated with markers of large nerve fiber sensory and motor axonal damage. Raised IL-10 serum level was associated with signs of motor nerve demyelination. No differences were found in pain characteristics and electrodiagnostic and QST markers of small nerve fiber function in relation to cytokines serum levels. IL-6 and IL-10 serum levels were associated with large nerve fiber damage but not to small fibers function or NP. IL-6 and IL-10 cytokines might play a role in the pathogenesis of nerve fiber damage or represent a compensatory or neuroprotective mechanism.

scholarly journals Nerve and Vascular Biomarkers in Skin Biopsies Differentiate Painful From Painless Peripheral Neuropathy in Type 2 Diabetes

2021 ◽  
Vol 2 ◽  
Author(s):  
Pallai Shillo ◽  
Yiangos Yiangou ◽  
Philippe Donatien ◽  
Marni Greig ◽  
Dinesh Selvarajah ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Peripheral Neuropathy ◽  
Blood Vessels ◽  
Diabetic Peripheral Neuropathy ◽  
Nerve Fibers ◽  
Pain Mechanisms ◽  
Painful Diabetic Peripheral Neuropathy ◽  
Skin Biopsies ◽  
Vascular Biomarkers

Painful diabetic peripheral neuropathy can be intractable with a major impact, yet the underlying pain mechanisms remain uncertain. A range of neuronal and vascular biomarkers was investigated in painful diabetic peripheral neuropathy (painful-DPN) and painless-DPN and used to differentiate painful-DPN from painless-DPN. Skin biopsies were collected from 61 patients with type 2 diabetes (T2D), and 19 healthy volunteers (HV). All subjects underwent detailed clinical and neurophysiological assessments. Based on the neuropathy composite score of the lower limbs [NIS(LL)] plus seven tests, the T2D subjects were subsequently divided into three groups: painful-DPN (n = 23), painless-DPN (n = 19), and No-DPN (n = 19). All subjects underwent punch skin biopsy, and immunohistochemistry used to quantify total intraepidermal nerve fibers (IENF) with protein gene product 9.5 (PGP9.5), regenerating nerve fibers with growth-associated protein 43 (GAP43), peptidergic nerve fibers with calcitonin gene-related peptide (CGRP), and blood vessels with von Willebrand Factor (vWF). The results showed that IENF density was severely decreased (p < 0.001) in both DPN groups, with no differences for PGP9.5, GAP43, CGRP, or GAP43/PGP9.5 ratios. There was a significant increase in blood vessel (vWF) density in painless-DPN and No-DPN groups compared to the HV group, but this was markedly greater in the painful-DPN group, and significantly higher than in the painless-DPN group (p < 0.0001). The ratio of sub-epidermal nerve fiber (SENF) density of CGRP:vWF showed a significant decrease in painful-DPN vs. painless-DPN (p = 0.014). In patients with T2D with advanced DPN, increased dermal vasculature and its ratio to nociceptors may differentiate painful-DPN from painless-DPN. We hypothesized that hypoxia-induced increase of blood vessels, which secrete algogenic substances including nerve growth factor (NGF), may expose their associated nociceptor fibers to a relative excess of algogens, thus leading to painful-DPN.

scholarly journals Insulin Treatment Attenuates Small Nerve Fiber Damage in Rat Model of Type 2 Diabetes

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Laura J. Andreasen ◽  
Rikke K. Kirk ◽  
Christian Fledelius ◽  
Mark A. Yorek ◽  
Jens Lykkesfeldt ◽  
...  
Keyword(s):  
Glycemic Control ◽  
Nerve Fiber ◽  
Rat Model ◽  
Low Dose ◽  
Insulin Treatment ◽  
High Dose ◽  
High Fat ◽  
Fiber Damage ◽  
Small Nerve

Introduction. Current clinical guidelines for management of diabetic peripheral neuropathy (DPN) emphasize good glycemic control. However, this has limited effect on prevention of DPN in type 2 diabetic (T2D) patients. This study investigates the effect of insulin treatment on development of DPN in a rat model of T2D to assess the underlying causes leading to DPN. Methods. Twelve-week-old male Sprague-Dawley rats were allocated to a normal chow diet or a 45% kcal high-fat diet. After eight weeks, the high-fat fed animals received a mild dose of streptozotocin to induce hyperglycemia. Four weeks after diabetes induction, the diabetic animals were allocated into three treatment groups receiving either no insulin or insulin-releasing implants in a high or low dose. During the 12-week treatment period, blood glucose and body weight were monitored weekly, whereas Hargreaves’ test was performed four, eight, and 12 weeks after treatment initiation. At study termination, several blood parameters, body composition, and neuropathy endpoints were assessed. Results. Insulin treatment lowered blood glucose in a dose-dependent manner. In addition, both doses of insulin lowered lipids and increased body fat percentage. High-dose insulin treatment attenuated small nerve fiber damage assessed by Hargreaves’ test and intraepidermal nerve fiber density compared to untreated diabetes and low-dose insulin; however, neuropathy was not completely prevented by tight glycemic control. Linear regression analysis revealed that glycemic status, circulating lipids, and sciatic nerve sorbitol level were all negatively associated with the small nerve fiber damage observed. Conclusion. In summary, our data suggest that high-dose insulin treatment attenuates small nerve fiber damage. Furthermore, data also indicate that both poor glycemic control and dyslipidemia are associated with disease progression. Consequently, this rat model of T2D seems to fit well with progression of DPN in humans and could be a relevant preclinical model to use in relation to research investigating treatment opportunities for DPN.

scholarly journals Phenotyping animal models of diabetic peripheral neuropathy in rats: advantages and limitations

2018 ◽  
Vol 64 (3) ◽  
pp. 188-193
Author(s):  
Zera N. Abdulvapova ◽  
Ekaterina V. Artemova ◽  
Anna M. Gorbacheva ◽  
Gagik R. Galstyan ◽  
Alla Yu. Tokmakova ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Animal Models ◽  
Diabetic Peripheral Neuropathy ◽  
Diabetic Polyneuropathy ◽  
Late Complications ◽  
Nerve Fibers ◽  
New Drugs ◽  
Diagnostic Features ◽  
Local Immunity ◽  
Fiber Damage

Diabetic polyneuropathy is one of the most common late complications of diabetes mellitus, as well as the main cause of ulcerative foot defects. The prevalence of neuropathy among people with diabetes varies from 28 to 65%, depending on the disease duration and diagnostic features. Initial signs of damage are detected as early as in prediabetes. To date, there is a fairly limited knowledge of the mechanisms of nerve fiber damage in diabetes. Also, it is unclear which type of nerve fibers is involved in damage first and how the nervous system regulates repair of tissues and local immunity. Animal models of diabetic peripheral neuropathy enable studying new aspects of the pathogenesis of this common diabetes complication and open prospects for the search and development of new drugs.

scholarly journals Small Nerve Fiber Damage and Langerhans Cells in Type 1 and Type 2 Diabetes and LADA Measured by Corneal Confocal Microscopy

2021 ◽  
Vol 62 (6) ◽  
pp. 5
Author(s):  
Luca D'Onofrio ◽  
Alise Kalteniece ◽  
Maryam Ferdousi ◽  
Shazli Azmi ◽  
Ioannis N. Petropoulos ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Confocal Microscopy ◽  
Nerve Fiber ◽  
Langerhans Cells ◽  
Fiber Damage ◽  
Corneal Confocal Microscopy ◽  
Small Nerve

scholarly journals Early Detection of Diabetic Peripheral Neuropathy: A Focus on Small Nerve Fibres

Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 165
Author(s):  
Jamie Burgess ◽  
Bernhard Frank ◽  
Andrew Marshall ◽  
Rashaad S. Khalil ◽  
Georgios Ponirakis ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Nerve Fibre ◽  
Diabetic Peripheral Neuropathy ◽  
Point Of Care ◽  
Unmet Need ◽  
Screening Tools ◽  
Nerve Fibres ◽  
Diagnostic Laboratory ◽  
Corneal Confocal Microscopy ◽  
Small Nerve

Diabetic peripheral neuropathy (DPN) is the most common complication of both type 1 and 2 diabetes. As a result, neuropathic pain, diabetic foot ulcers and lower-limb amputations impact drastically on quality of life, contributing to the individual, societal, financial and healthcare burden of diabetes. DPN is diagnosed at a late, often pre-ulcerative stage due to a lack of early systematic screening and the endorsement of monofilament testing which identifies advanced neuropathy only. Compared to the success of the diabetic eye and kidney screening programmes there is clearly an unmet need for an objective reliable biomarker for the detection of early DPN. This article critically appraises research and clinical methods for the diagnosis or screening of early DPN. In brief, functional measures are subjective and are difficult to implement due to technical complexity. Moreover, skin biopsy is invasive, expensive and lacks diagnostic laboratory capacity. Indeed, point-of-care nerve conduction tests are convenient and easy to implement however questions are raised regarding their suitability for use in screening due to the lack of small nerve fibre evaluation. Corneal confocal microscopy (CCM) is a rapid, non-invasive, and reproducible technique to quantify small nerve fibre damage and repair which can be conducted alongside retinopathy screening. CCM identifies early sub-clinical DPN, predicts the development and allows staging of DPN severity. Automated quantification of CCM with AI has enabled enhanced unbiased quantification of small nerve fibres and potentially early diagnosis of DPN. Improved screening tools will prevent and reduce the burden of foot ulceration and amputations with the primary aim of reducing the prevalence of this common microvascular complication.

scholarly journals Sensory-Motor Mechanisms Increasing Falls Risk in Diabetic Peripheral Neuropathy

Medicina ◽  
2021 ◽  
Vol 57 (5) ◽  
pp. 457
Author(s):  
Neil D. Reeves ◽  
Giorgio Orlando ◽  
Steven J. Brown
Keyword(s):  
Peripheral Neuropathy ◽  
Diabetic Peripheral Neuropathy ◽  
Motor Nerve ◽  
Step Length ◽  
Falls Prevention ◽  
Motor Deficits ◽  
Falls Risk ◽  
Walking Gait ◽  
Risk Of Falls ◽  
Diabetes Patients

Diabetic peripheral neuropathy (DPN) is associated with peripheral sensory and motor nerve damage that affects up to half of diabetes patients and is an independent risk factor for falls. Clinical implications of DPN-related falls include injury, psychological distress and physical activity curtailment. This review describes how the sensory and motor deficits associated with DPN underpin biomechanical alterations to the pattern of walking (gait), which contribute to balance impairments underpinning falls. Changes to gait with diabetes occur even before the onset of measurable DPN, but changes become much more marked with DPN. Gait impairments with diabetes and DPN include alterations to walking speed, step length, step width and joint ranges of motion. These alterations also impact the rotational forces around joints known as joint moments, which are reduced as part of a natural strategy to lower the muscular demands of gait to compensate for lower strength capacities due to diabetes and DPN. Muscle weakness and atrophy are most striking in patients with DPN, but also present in non-neuropathic diabetes patients, affecting not only distal muscles of the foot and ankle, but also proximal thigh muscles. Insensate feet with DPN cause a delayed neuromuscular response immediately following foot–ground contact during gait and this is a major factor contributing to increased falls risk. Pronounced balance impairments measured in the gait laboratory are only seen in DPN patients and not non-neuropathic diabetes patients. Self-perception of unsteadiness matches gait laboratory measures and can distinguish between patients with and without DPN. Diabetic foot ulcers and their associated risk factors including insensate feet with DPN and offloading devices further increase falls risk. Falls prevention strategies based on sensory and motor mechanisms should target those most at risk of falls with DPN, with further research needed to optimise interventions.

Vitamin D Status in a Bulgarian Population With Type 2 Diabetes and Diabetic Foot Ulcers

2020 ◽  
pp. 153473462096582
Author(s):  
Ani S. Todorova ◽  
Edward B. Jude ◽  
Rumyana B. Dimova ◽  
Nevena Y. Chakarova ◽  
Mina S. Serdarova ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Vitamin D ◽  
Peripheral Neuropathy ◽  
Diabetic Foot ◽  
Diabetic Peripheral Neuropathy ◽  
Foot Ulcers ◽  
Diabetic Foot Ulcers ◽  
Vitamin D Status ◽  
Active Infection

The aim of this study was to assess vitamin D status in patients with type 2 diabetes and diabetic foot ulcers (DFU). A total of 242 participants with type 2 diabetes, mean age 59.1 ± 10 years, mean body mass index 31.4 ± 6.3 kg/m2, and estimated glomerular filtration rate ≥45 mL/min/1.73m2, were divided into 2 groups: 73 with DFU (35 with and 38 without active infection) and 169 without DFU (106 with diabetic peripheral neuropathy, 63 without complications). Neuropathy was assessed by 10 g monofilament, Rydel-Seiffer 128 Hz tuning fork, and temperature discrimination. Serum 25(OH)D (25-hydroxy vitamin D) was assessed by ECLIA (electro-chemiluminescence immunoassay) method. Median 25(OH)D level was 12.6 ng/mL (IQR [interquartile range] 9.3-17.6 ng/mL) in the studied cohort. The DFU group presented with lower 25(OH)D level as compared with diabetic patients without foot ulcers (non-DFU group): 11.6 ng/mL (IQR 8.5-15.8 ng/mL) versus 13.5 ng/mL (IQR 9.6-18.6 ng/mL), P = .001; the diabetic peripheral neuropathy subgroup demonstrated lower 25(OH)D level in comparison with participants without complications: 12.5 ng/mL (IQR 9-17.2 ng/mL) versus 15.9 ng/mL (IQR 10.4-20.8 ng/mL), P = .031. This remained significantly different even after correction for age and duration of diabetes. There was no difference in 25(OH)D level between the subgroups according to the presence of active infection. In conclusion, vitamin D deficiency may play a role in the development of diabetes complications.

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