Nerve Diabetic Neuropathy Research Articles

Using mHealth to Provide Mobile App Users With Visualization of Health Checkup Data and Educational Videos on Lifestyle-Related Diseases: Methodological Framework for Content Development.

BackgroundThe number of people with lifestyle-related diseases continues to increase worldwide. Improving lifestyle behavior with health literacy may be the key to address lifestyle-related diseases. The delivery of educational videos using mobile health (mHealth) services can replace the conventional way of educating individuals, and visualization can replace the provision of health checkup data.ObjectiveThis paper aimed to describe the development of educational content for MIRAMED, a mobile app aimed at improving users’ lifestyle behaviors and health literacy for lifestyle-related diseases.MethodsAll videos were based on a single unified framework to provide users with a consistent flow of information. The framework was later turned into a storyboard. The final video contents were created based on this storyboard and further discussions with leading experts and specialist physicians on effective communication with app users about lifestyle-related diseases.ResultsThe app uses visualization of personal health checkup data and educational videos on lifestyle-related diseases based on the current health guidelines, scientific evidence, and expert opinions of leading specialist physicians in the respective fields. A total of 8 videos were created for specific lifestyle-related diseases affecting 8 organs: (1) brain–cerebrovascular disorder, (2) eyes–diabetic retinopathy, (3) lungs–chronic obstructive pulmonary disease, (4) heart–ischemic heart disease, (5) liver–fatty liver, (6) kidneys–chronic kidney disease (diabetic kidney disease), (7) blood vessels–peripheral arterial disease, and (8) nerves–diabetic neuropathy.ConclusionsProviding enhanced mHealth education using novel digital technologies to visualize conventional health checkup data and lifestyle-related diseases is an innovative strategy. Future studies to evaluate the efficacy of the developed content are planned.

A Study of Nerve Conduction Test & Other Hematological Parameters in Diabetics

Background: Nerve conduction studies (NCS) are most sensitive, reliable and non-invasive investigation to detect diabetic neuropathy. Sensory nerves are more affected as compared to motor nerves in diabetic neuropathy. Understanding the Nerve conduction studies is useful for early detection polyneuropathy and prevention of its dreaded complications. Materials and Method: The present study was conducted among 30 subjects of type 2 Diabetic and 30 non diabetics subjects. Haematological parameters such as HbA1c, platelet count, prothrombin time, APTT, triglycerides, LDL and HDL levels were estimated. Motor nerve conduction velocity median , ulnar, common peroneal and posterior tibial nerve and sensory nerve conduction velocity median , ulnar and sural nerve were recorded. Result: Mean age of diabetic patients was 51±.4.8 year. Most of the subjects (86.7%) were male. Sensory nerve conduction of sural nerve was signiicantly reduced in diabetic patients as compared to non diabetic patients. SNCV of sural nerve showed deterioration with the duration of diabetes, poor glycemic control and patients with altered lipid profile. Conclusion: Nerve conduction velocity testing of sural nerve is useful for early detection of diabetic neuropathy and reduce the burden of complication and to improve the quality of life in diabetics.

The pattern of involvement of the lower limb nerves in diabetic neuropathy among children with type I diabetes mellitus

Background: Diabetic peripheral neuropathy (DPN) involves both sensory and motor nerves; from pathological point of view it can cause demyelinating neuropathy (evident by increase in latency and decrease in conduction-velocity [CV]) as well as axonal degeneration neuropathy (evident by decrease in amplitude) of compound action potential. However there is controversy on which is the most affected nerve and nerve conduction study (NCS) parameter in DPN.

Role of nitrosative and oxidative stress in neuropathy in patients with type 2 diabetes mellitus

Objectives:Evidences of oxidative and/or nitrosative stress in type 2 diabetes mellitus were demonstrated in experimental and human studies. This study is aimed to assess the serum peroxynitrite and oxidized lipoproteins in patients with type 2 diabetes mellitus presented with clinical and laboratory evidences of peripheral neuropathy.Materials and Methods:Eighty four patients with type 2 diabetes mellitus (51 of them had neuropathy) and 31 apparent healthy subjects were studied in the unit of neurophysiology at the University Hospital of Medical College, Al-Nahrin University in Baghdad, Iraq. Neuropathy total symptom score (NTSS), neuropathy impairment score in the lower leg (NIS-LL), and nerve conduction velocity of sensory (ulnar and sural) and motor (ulnar and common peroneal) nerves were used to assess the neuropathy. Fasting venous blood was obtained from each participant for the determination of serum glucose and oxidized lipoproteins.Results:The electrophysiology study revealed significant decrease in conduction velocity of ulnar (sensory and motor components), sural, and common peroneal nerves in diabetic neuropathy compared to diabetics without neuropathy and healthy subjects. Significant high level of serum peroxynitrite was found in diabetic patients with or without neuropathy compared with non-diabetics. The changes in serum-oxidized lipoproteins in patients with diabetics with or without neuropathy were non-significantly differed from healthy subjects. Neither nitrosative stress nor oxidative stress indices correlated with the variables that are related to the neuropathy.Conclusion:It concludes that evidence of nitrosative and to less extent the oxidative stress is associated with neuropathy in type 2 diabetes mellitus and their indices not correlated with variables related to neuropathy.

Pathophysiology of Neuropathic Pain in Type 2 Diabetes

OBJECTIVENeuropathic pain due to small-fiber sensory neuropathy in type 2 diabetes can be diagnosed by skin biopsy with quantification of intra-epidermal nerve fiber (IENF) density. There is, however, a lack of noninvasive physiological assessment. Contact heat–evoked potential (CHEP) is a newly developed approach to record cerebral responses of Aδ fiber–mediated thermonociceptive stimuli. We investigated the diagnostic role of CHEP.RESEARCH DESIGN AND METHODSFrom 2006 to 2009, there were 32 type 2 diabetic patients (20 males and 12 females, aged 51.63 ± 10.93 years) with skin denervation and neuropathic pain. CHEPs were recorded with heat stimulations at the distal leg, where skin biopsy was performed.RESULTSCHEP amplitude was reduced in patients compared with age- and sex-matched control subjects (14.8 ± 15.6 vs. 33.7 ± 10.1 μV, P < 0.001). Abnormal CHEP patterns (reduced amplitude or prolonged latency) were noted in 81.3% of these patients. The CHEP amplitude was the most significant parameter correlated with IENF density (P = 0.003) and pain perception to contact heat stimuli (P = 0.019) on multiple linear regression models. An excitability index was derived by calculating the ratio of the CHEP amplitude over the IENF density. This excitability index was higher in diabetic patients than in control subjects (P = 0.023), indicating enhanced brain activities in neuropathic pain. Among different neuropathic pain symptoms, the subgroup with evoked pain had higher CHEP amplitudes than the subgroup without evoked pain (P = 0.011).CONCLUSIONSCHEP offers a noninvasive approach to evaluate the degeneration of thermonociceptive nerves in diabetic neuropathy by providing physiological correlates of skin denervation and neuropathic pain.

Concurrent targeting of nitrosative stress–PARP pathway corrects functional, behavioral and biochemical deficits in experimental diabetic neuropathy

Peroxynitrite mediated nitrosative stress, an indisputable initiator of DNA damage and overactivation of poly(ADP-ribose) polymerase (PARP), a nuclear enzyme activated after sensing DNA damage, are two crucial pathogenetic mechanisms in diabetic neuropathy. The intent of the present study was to investigate the effect of combination of a peroxynitrite decomposition catalyst (PDC), FeTMPyP and a PARP inhibitor, 4-ANI against diabetic peripheral neuropathy. The end points of evaluation of the study included motor nerve conduction velocity (MNCV) and nerve blood flow (NBF) for evaluating nerve functions; thermal hyperalgesia and mechanical allodynia for assessing nociceptive alterations, malondialdehyde and peroxynitrite levels to detect oxidative stress–nitrosative stress; NAD concentration in sciatic nerve to assess overactivation of PARP. Additionally immunohistochemical studies for nitrotyrosine and Poly(ADP-ribose) (PAR) was also performed. Treatment with the combination of FeTMPyP and 4-ANI led to significant improvement in nerve functions and pain parameters and also attenuated the oxidative–nitrosative stress markers. Further, the combination also reduced the overactivation of PARP as evident from increased NAD levels and decreased PAR immunopositivity in sciatic nerve microsections. Thus, it can be concluded that treatment with the combination of a PDC and PARP inhibitor attenuates alteration in peripheral nerves in diabetic neuropathy (DN).

Phrenic nerve diabetic neuropathy in rats: unmyelinated fibers morphometry

We have demonstrated that phrenic nerves' large myelinated fibers in streptozotocin (STZ)-induced diabetic rats show axonal atrophy, which is reversed by insulin treatment. However, studies on structural abnormalities of the small myelinated and the unmyelinated fibers in the STZ-model of neuropathy are limited. Also, structural changes in the endoneural vasculature are not clearly described in this model and require detailed study. We have undertaken morphometric studies of the phrenic nerve in insulin-treated and untreated STZ-diabetic rats and non-diabetic control animals over a 12-week period. The presence of neuropathy was assessed by means of transmission electron microscopy, and morphometry of the unmyelinated fibers was performed. The most striking finding was the morphological evidence of small myelinated fiber neuropathy due to the STZ injection, which was not protected or reversed by conventional insulin treatment. This neuropathy was clearly associated with severe damage of the endoneural vessels present on both STZ groups, besides the insulin treatment. The STZ-diabetes model is widely used to investigate experimental diabetic neuropathies, but few studies have performed a detailed assessment of either unmyelinated fibers or capillary morphology in this animal model. The present study adds useful information for further investigations on the ultrastructural basis of nerve function in diabetes.

Comparison of the Effects of Various Decompression Patterns of Peripheral Nerves in Diabetic Neuropathy

The presence of compressive neuropathy overlying an existing diabetic neuropathy in symptomatic patients and surgical decompression of these compressed nerves in selected patients in a number of series have demonstrated that diabetic patients with neuropathy, but still having positive Tinel signs, can benefit from the releasing procedures. These include the decompression of the peripheral nerves in specific sites by releasing the external limiting bands and adding only epineurolysis, if necessary. In a previous experimental study, the authors determined that these procedures could not insure adequate decompression to the nerves, and they underwent perineurolysis to augment the effects.

Recent advances in the diagnosis and management of diabetic neuropathy

The World Health Organisation estimated that in the year 2000, 150 million people had diabetes mellitus, and it is predicted that this number will rise to 366 million by the year 2030.[1][1] Neuropathy is a common complication of diabetes and is characterised by a progressive loss of peripheral

Changing the Natural History of Diabetic Neuropathy: Incidence of Ulcer/Amputation in the Contralateral Limb of Patients With a Unilateral Nerve Decompression Procedure

The natural history of diabetes neuropathy is progressive and irreversible loss of sensibility in the feet, leading to ulceration and/or amputation in 15% of patients. The prevalence of neuropathy is more than 50% in those who have been diabetic for 20 years. Decompression of the tibial and peroneal nerves in those with diabetic neuropathy improves sensation in 70% of patients. The impact of this surgery on the development of ulcers and amputations in both the operated and the contralateral, nonoperated limb was evaluated in a retrospective analysis of 50 patients with diabetes a mean of 4.5 years (range, 2-7 years) from the date of surgery. No ulcers or amputations occurred in the index limb of these patients. In contrast, there were 12 ulcers and 3 amputations in 15 different patients in contralateral limbs. This difference was significant at P < 0.001. It is concluded that decompression of lower extremity nerves in diabetic neuropathy changes the natural history of this disease, representing a paradigm shift in health care costs.

Enhanced activation of axonally transported stress-activated protein kinases in peripheral nerve in diabetic neuropathy is prevented by neurotrophin-3.

The objective was to determine whether stress-activated protein kinases (SAPKs) mediated the transfer of diabetes-induced stress signals from the periphery to somata of sensory neurons. Thus, we characterized axonal transport of SAPKs in peripheral nerve, studied any alteration in streptozotocin (STZ)-diabetic rats and examined effects of neurotrophin-3 (NT-3) on diabetes-induced events. We demonstrate that c-jun N-terminal kinase (JNK) and p38 are bidirectionally axonally transported at fast rates in sciatic nerve. In STZ-diabetic rats the relative levels of retrograde axonal transport of phosphorylated (activated) JNK and p38 were raised compared with age-matched controls (all data are in arbitrary units and expressed as fold increase over control: JNK 54-56 kDa isoforms, control 1.0 +/- 0.19, diabetic 2.5 +/- 0.26; p38, control 1.0 +/- 0.09, diabetic 2.9 +/- 0.52; both P < 0.05). Transport of total enzyme levels of JNK and p38 and phosphorylated extracellular signal-regulated kinase (ERK) was not significantly altered and anterograde axonal transport of phosphorylated JNK and p38 was unaffected by diabetes. The transcription factor ATF-2, which is phosphorylated and activated by JNK and p38, also exhibited elevated retrograde axonal transport in STZ-diabetic animals (control 1.0 +/- 0.07, diabetic 3.0 +/- 0.41; P < 0.05). Treatment of STZ-diabetic animals with 5 mg/kg human recombinant NT-3 prevented activation of JNK and p38 in sciatic nerve (phosphorylated JNK, control 1.0 +/- 0.09, diabetic 1.95 +/- 0.35, diabetic + NT-3 1.09 +/- 0.12; P < 0.05 diabetic versus others; phosphorylated p38, control 1.0 +/- 0.16, diabetic 4.7 +/- 0.9, diabetic + NT-3 1.19 +/- 0.18; P < 0.05 diabetic versus others). The results show that JNK and p38 are transported axonally and may mediate the transfer of diabetes-related stress signals, possibly triggered by loss of neurotrophic support, from the periphery to the neuronal soma.

Quantitation of epidermal nerves in diabetic neuropathy.

We describe methods to quantify epidermal nerve fibers (ENFs) in skin biopsy specimens from diabetic candidates for pancreas transplantation and control subjects. ENFs and the dermal-epidermal basement membrane were stained by immunohistochemical methods, imaged with a confocal microscope, and quantified using a neuron tracing system. The number of ENFs per surface of epidermis was diminished in diabetic subjects. ENF number and summed length of all ENFs per volume of epidermis examined were also decreased. Length and number of branch points of single surviving ENFs were similar in skin of control and diabetic subjects. The methods and results constitute a basis for continued study of the effects of the euglycemia that attends successful pancreas transplantation and the effects of therapy in patients with various types of polyneuropathy.

Structure-function relationships within peripheral nerves in diabetic neuropathy: the hydration hypothesis

Structure-function relationships within peripheral nerves in diabetic neuropathy: the hydration hypothesis

SS-11-4 Effect of a prostacyclin derivative on cutaneous nerves in diabetic neuropathy

Chronic constriction injury (CCI) to peripheral nerve causes a painful neuropathy in association with a process of axonal degeneration and endoneural remodeling that involves macrophage recruitment and local increase in extracellular proteases and tumor necrosis factor alpha (TNF-α). Cell surface activation of TNF-α from its transmembrane precursor, as well as sequestration of TNF-α receptors II and I, is performed by the zinc-dependent endopeptidase family of matrix metalloproteinases (MMPs). Among TNF-α-converting MMPs, basal lamina degrading gelatinases are thought to play a role in sciatic nerve injury. In the present study, we determined the forms of TNF-α involved in the development of CCI neuropathy in rats, using Western blot analysis, and the temporal correlation of TNF-α and TNFRI protein profiles with gelatinases activity at the site of peripheral nerve injury. We observed two peaks in TNF-α protein during the first week of CCI that correspond to previously reported peaks in painful behavior. We propose that the first peak at 6 h post-CCI is due to the local expression of the cytotoxic transmembrane 26 kDa TNF-α protein released by resident Schwann cells, mast cells and macrophages. This peak in TNF-α protein expression corresponds to an increase in gelatinase B (MMP-9) activity, which is greatly upregulated as early as 3 h following CCI to rat sciatic nerve. The second peak occurs at 5 days post-CCI, and may represent TNF-α protein released by hematogenously recruited macrophages. This peak is marked by the increase in active soluble 17 kDa TNF-α and by gelatinase A (MMP-2) upregulation. These observations suggest that there is a pathogenic role for the TNF-α-converting function of MMP-2 in painful CCI neuropathy. We conclude that severe nerve injury induces MMPs, TNF-α and TNFRI, which interactively control the privileged endoneurial environment and the pathogenesis of the painful neuropathies associated with the macrophage-dependent processes of Wallerian degeneration.

CMAP variation over a length of nerve in diabetic neuropathy

CMAP variation over a length of nerve in diabetic neuropathy

Cutaneous nerves in diabetic neuropathy: an immunohistochemical study

AbstractBackground Diabetic neuropathy is usually investigated using the invasive sural nerve biopsy technique; while little is known about dermal nerve alteration in diabetic neuropathy.Patients and Methods Skin biopsies from the lower leg of five diabetics (mean age, 55 years)with autonomic and sensorimotor peripheral neuropathy were compared to biopsies from five non‐diabetic controls (mean age, 47 years). Immunohistochemical methods were employed using the anti‐neurofilament monoclonal antibodies 127.11 and UJ 13A. The dermal nerve profile areas were counted with a Quantimet image analyser.Results he diabetic biopsies gave significantly lower readings than the controls (P &lt; 0.05, Mann‐Whitney U‐test).Conclusion Skin biopsy is a simple and reliable method for evaluating distal nerves in diabetes.

Endoneurial blood flow and oxygen tension in the sciatic nerves of rats with experimental diabetic neuropathy.

Endoneurial hypoxia has been postulated to be important in the pathogenesis of diabetic peripheral neuropathy and may be due to reduced nerve blood flow. Neither blood flow nor oxygen tension have previously been measured in peripheral nerve in diabetic neuropathy. We have therefore measured both nerve blood flow and endoneurial oxygen tension in the sciatic nerves of 8 rats with streptozotocin-induced diabetes for four months, and in 8 age-matched controls. In 7 of the diabetic animals mean nerve blood flow was 8.7 +/- 1.3 ml X min-1 X 100 g-1 which is significantly less than mean nerve blood flow in the controls (13.08 +/- 0.8 ml X min-1 X 100 g-1; P less than 0.01). In one diabetic animal, nerve blood flow was too low to be accurately measured. The reduction in nerve blood flow in diabetic neuropathy is due to an increase in resistance to flow which may be due to microangiopathy and to blood hyperviscosity. Endoneurial oxygen tension was also significantly reduced in experimental diabetic neuropathy in which 60 per cent of the oxygen measurements were less than 25 mmHg, compared with 19 per cent in the controls. Nerve blood flow was also measured in rats with experimental galactose neuropathy in which there is more marked sugar-alcohol accumulation, endoneurial oedema and elevation of endoneurial fluid pressure than in experimental diabetic neuropathy. The results obtained in this neuropathy suggest that the reduction in nerve blood flow which occurs in experimental diabetic neuropathy is due largely to factors other than sugar-alcohol accumulation in nerve. We postulate that endoneurial hypoxia may produce many of the observed morphological and biochemical changes in experimental diabetic neuropathy.

Morphometric analysis of sural nerve in elderly diabetes mellitus.

Biopsy specimens of the sural nerve obtained from 28 middle-aged and elderly diabetics suffering from neuropathy were studied morphometrically. Myelinated nerve fiber density, especially large fibers, was decreased, and the bimodal distribution of myelinated fiber diameter shifted to unimodal distribution containing only a small fiber peak and the mean diameter of myelinated fiber was decreased. An insulin-treated group and a group with severe retinopathy showed a prominent decrease of myelinated fiber density; the severity and duration of diabetes may be a factor in this decrease. Large unmyelinated nerve fibers were also decreased and the mean diameter of unmyelinated fibers was reduced. Three patients with prominent autonomic nervous system symptoms showed a significant reduction of total unmyelinated fibers. The linear correlation between the square root of the transverse axis cylinder area and the number of myelin lamellae was obscured, and the plots were towards two directions, axonal atrophy and remyelination in diabetes. The latter process tended to be dominant in the middle-aged patients, but the importance of these two processes was reversed with age. To discuss the morphological changes of the sural nerve in diabetic neuropathy, the influence of aging as well as the duration, severity and clinical symptoms should be considered.

Proteins of peripheral nerve myelin in diabetic neuropathy

The proteins of human peripheral nerve myelin are similar to those of other mammalian peripheral nerves and different from those of the central nervous system. The most notable characteristics of the peripheral myelin are the lack of the encephalitogenic basic protein and the presence of the main protein between the major membrane protein and the group of basic proteins. The sedimentation properties of the diabetic peripheral myelin are different from those of normal myelin suggesting serious structural disintegration. The amount of the main protein is decreased and the basic proteins are also weaker. The intensity of the major membrane protein is increased. It is concluded that demyelination of the peripheral nerve in diabetic neuropathy is at least partly based on the inability of the Schwann cell to produce proteins for the formation of myelin.