BACKGROUND: Diabetic neuropathy is one of the most common neuropathies. Although pathologic studies show both segmental demyelination and axonal loss in diabetic neuropathy, the relative importance of segmental demyelination is debated. Conduction block (CB) is a physiologic hallmark of segmental demyelination. If segmental demyelination were a main pathology of diabetic neuropathy, CB should be common. We undertook this study to determine the prevalence of CB in diabetic patients. METHODS: Fifty-two consecutive diabetic patients (M=30, F=22) were referred to EMG laboratory and underwent routine nerve conduction studies (NCS). CB was defined by two methods. One was > 20% drop in peak-to-peak amplitude and < 15% change in negative-peak duration between proximal and distal stimulation sites. The other was > 50% drop in the amplitude and area. Clinical findings, electrophysiological data, and effectiveness of immunomodulating therapy for some patients with CB were reviewed. RESULTS: A total 326 nerves were studied. The criteria for 20% and 50% CB were met in 35 nerves in 19 patients and 7 nerves in 6 patients, respectively (prevalence=10.7%, 2.1%, respectively). Some patients with CB were treated with IVIG or steroid and had a good response. CONCLUSIONS: CB in diabetic neuropathy is not a common finding. The rarity of CB in diabetic neuropathy suggests that segmental demyelination is not a prominent part of the underlying pathology. The presence of CB and good responsiveness to immunomodulating therapy in diabetic neuropathy also suggest alternative or additional causes for neuropathy, such as chronic inflammatory demyelinating polyneuropathy.
Axons ; Demyelinating Diseases* ; Diabetes Mellitus ; Diabetic Neuropathies* ; Humans ; Immunoglobulins, Intravenous ; Neural Conduction ; Pathology ; Polyneuropathies ; Prevalence

BACKGROUND: One of the most frequent problems caused by diabetes is the so called painful diabetic neuropathy. This condition can be treated through numerous types of therapy. The purpose of this study was to analyze, as a meta-analysis, different treatments used to alleviate painful diabetic neuropathy, with the aim of generating results that help making decisions when applying such treatments to tackle this pathology. METHODS: A search was conducted in the main databases for Health Sciences, such as PUBMED, Web of Science (WOS), and IME biomedicina (Spanish Medical Reports in Biomedicine), to gather randomized controlled trials about treatments used for painful diabetic neuropathy. The analyzed studies were required to meet the inclusion criteria selected, especially those results related to pain intensity. RESULTS: Nine randomized controlled trials were chosen. The meta-analysis shows significant positive effects for those treatments based on tapentadol [g: −1.333, 95% CI (−1.594; −1.072), P < 0.05], duloxetine [g: −1.622, 95 % CI (−1.650; −1.594), P < 0.05], pregabalin [g: −0.607, 95% CI (−0.980; −0.325), P < 0.05], and clonidine [g: −0.242, 95 % CI (−0.543; −0.058), P < 0.05]. CONCLUSIONS: This meta-analysis indicates the effectiveness of the treatments based on duloxetine, gabapentin and pregabalin, as well as other drugs, such as tapentadol and topic clonidine, whose use is better prescribed in more specific situations. The results provided can help increase the knowledge about the treatment of painful diabetic neuropathy and also in the making of clinical practice guidelines for healthcare professionals.
Chronic Pain ; Clonidine ; Delivery of Health Care ; Diabetes Complications ; Diabetic Neuropathies ; Duloxetine Hydrochloride ; Pain Management ; Pathology ; Pregabalin

Diabetic peripheral neuropathy(DPN) is a chronic complication resulted from peripheral nerve injury in the late stage of diabetes. It involves a variety of pathological changes such as oxidative stress, endoplasmic reticulum stress, neuroinflammation, and apoptosis of Schwann cells(SCs). DPN is the main factor leading to lower limb disability or amputation in diabetic patients, with high incidence, long disease course, and poor prognosis. The modern medicine treatment of DPN mainly focuses on controlling blood glucose and improving microcirculation and nerve nutrition, which can only mitigate the clinical symptoms and not fundamentally reverse the pathological changes of peripheral nerves. Autophagy is a self-clearing mechanism that maintains cellular homeostasis by removing excess metabolites. Traditional Chinese medicine(TCM), featuring the holistic concept and syndrome differentiation, can treat chronic diseases in a multi-target, multi-pathway, and wide-range manner. Modern studies have shown that the occurrence and development of DPN are related to a variety of pathological changes, and autophagy is a key mechanism associated with DPN. The environment with persistent high glucose can lead to the inhibition or over-activation of peripheral nerve cells, which causes irreversible damage of nerve cells and the occurrence and development of DPN. Therefore, restoring autophagy balance and reducing nerve damage is one of the key ways to treat DPN. The recent studies have confirmed that some active ingredients in traditional Chinese medicines and TCM compound prescriptions can inhibit the oxidative stress, endoplasmic reticulum stress, mitochondrial damage, inflammation, and apoptosis of SCs in DPN by regulating the autophagy pathway, thus playing a role in the prevention and treatment of DPN. However, the systematic induction in this field remains to be carried out. This paper reviewed the relevant literature, explained the mechanism of TCM in the prevention and treatment of DPN by regulating autophagy, and summarized the potential targets of TCM in the treatment of DPN, with a view to providing new ideas for clinical research and drug development.
Humans ; Autophagy ; Diabetes Mellitus ; Diabetic Neuropathies/complications* ; Medicine, Chinese Traditional ; Oxidative Stress ; Schwann Cells/pathology*

Alzheimer Disease ; Diabetic Neuropathies ; pathology ; Glaucoma ; pathology ; Humans ; Multiple Sclerosis ; pathology ; Nerve Fibers ; pathology ; Ophthalmoscopy ; Optic Nerve ; pathology ; Parkinson Disease ; pathology ; Retinal Neurons ; pathology ; Tomography, Optical Coherence

OBJECTIVES: Rodenticide Vacor causes a severe peripheral neuropathy in humans. Electrophysiologic studies on a peripheral motor nerve-skeletal system of Vacor-treated rat showed decreased amplitude of muscle action potential without conduction velocity abnormalities. The ultrastructural studies of the neuromuscular junction were performed to clarify the anatomic site of the Vacor-induced peripheral neuropathy in male Wistar rats. METHODS: After oral administration of a single dose of Vacor, 80 mg/kg of body weight, to the experimental animals, neuromuscular junctions within the interosseous muscles of the hind foot were observed in time. RESULTS: No axon terminal change was noted until 24 hours after the administration of Vacor. Remarkable loss of presynaptic vesicles and swollen endoplasmic reticulum in the axon terminal were developed at 3 days after Vacor treatment. Progressive degenerative changes consisting of marked loss of presynaptic vesicles, focal disruption of membrane in the axon terminal with disappearance of the number of the damaged axon terminal appeared, and flattening of postsynaptic folds was also seen. CONCLUSIONS: These results suggest that degenerative changes in axon terminal at neuromuscular junction may contribute to the peripheral neuropathy developed in the early phase of Vacor poisoning.
Animal ; Diabetic Neuropathies/physiopathology ; Diabetic Neuropathies/pathology* ; Diabetic Neuropathies/chemically induced* ; Human ; Male ; Microscopy, Electron ; Neuromuscular Junction/ultrastructure ; Neuromuscular Junction/physiopathology ; Neuromuscular Junction/drug effects ; Peripheral Nervous System Diseases/physiopathology ; Peripheral Nervous System Diseases/pathology ; Peripheral Nervous System Diseases/chemically induced ; Phenylurea Compounds/toxicity* ; Rats ; Rats, Wistar ; Rodenticides/toxicity*

OBJECTIVES: This study examined the effect of cilostazol, a potent phosphodiesterase inhibitor, on the progression of neuropathies associated with streptozotocin-induced diabetes mellitus in Sprague-Dawley rats. METHODS: Eight weeks after streptozotocin treatment, a pelleted diet containing 0.03% cilostazol (15 mg/kg body weight) was given for four weeks. Body weight, blood glucose level, motor nerve conduction velocity (MNCV), myelinated fiber density and size distribution of sciatic nerves were compared between age-matched normal rats (Group 1), control diabetic rats (Group 2) and cilostazol-treated diabetic rats (Group 3). RESULTS: Body weight was significantly reduced and blood glucose level was significantly increased in diabetic rats (Group 2 and 3) compared to normal rats. MNCV and cAMP content of sciatic nerves were significantly reduced in diabetic rats 12 weeks after streptozotocin treatment. Myelinated fiber size and density were also significantly reduced, and thickening of the capillary walls and duplication of the basement membranes of the endoneural vessels were observed in the diabetic rats. Whereas both body weight and blood glucose level of Group 3 did not differ significantly from those of Group 2, cilostazol treatment significantly increased MNCV and cAMP content of sciatic nerves in Group 3 but not to the levels observed in Group 1. MNCV positively correlated with cAMP content of sciatic nerves (r = 0.86; p < 0.001). Cilostazol treatment not only restored myelinated fiber density and size distribution but reversed some of the vascular abnormalities. CONCLUSION: These findings suggest that a reduced cAMP content in motor nerves may be involved in the development of diabetic neuropathy, and that cilostazol may prevent the progression of diabetic neuropathy by restoring functional impairment and morphological changes of peripheral nerves.
Animal ; Cyclic AMP/metabolism ; Diabetes Mellitus, Experimental/physiopathology ; Diabetes Mellitus, Experimental/drug therapy ; Diabetic Neuropathies/prevention & control* ; Diabetic Neuropathies/physiopathology ; Diabetic Neuropathies/pathology ; Male ; Neural Conduction/drug effects ; Phosphodiesterase Inhibitors/pharmacology* ; Rats ; Rats, Sprague-Dawley ; Sciatic Nerve/physiopathology ; Sciatic Nerve/pathology ; Sciatic Nerve/drug effects ; Tetrazoles/pharmacology*

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes mellitus. The prevalence of neuropathic pain is estimated to occur in about 30-50% of all diabetic patients. Clinical symptoms vary depending on the nerves affected, and may include both positive and negative symptoms. Many patients with DPN experience pain or discomfort, anxiety, depression, and limitations in activity, which can significantly impact their physical, emotional, and social well-being. Early diagnosis is essential for the successful management of DPN. Routine management consists of glucose and risk factor control, and symptomatic relief, along with therapies designed to target the underlying disease pathology. Pharmacological treatment of DPN includes tricyclic compounds, serotonin noradrenalin reuptake inhibitors, the antioxidant alpha-lipoic acid, anticonvulsants, opiates, membrane stabilizers, topical capsaicin, and other drugs. Management of DPN must be tailored to each individual, and depends on a variety of factors, including disease severity and response to treatment.
Anticonvulsants ; Anxiety ; Capsaicin ; Depression ; Diabetes Mellitus ; Diabetic Neuropathies ; Early Diagnosis ; Glucose ; Humans ; Membranes ; Neuralgia ; Pathology ; Peripheral Nervous System Diseases* ; Prevalence ; Risk Factors ; Serotonin ; Thioctic Acid

Diabetic peripheral neuropathy (DPN) is a progressive neurodegenerative disease of peripheral nervous system with high energy requirement. The adenosine monophosphate-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor- γ coactivator 1 α (PGC-1 α) axis plays a key role in regulating mitochondrial energy metabolism. Increasing preclinical evidences have shown that inhibition of AMPK/PGC-1 α pathway leading to mitochondrial dysfunction in neurons or Schwann cells contributes to neuron apoptosis, distal axonopathy and nerve demyelination in DPN. Some Chinese medicine formulae or extracts from herbs may have potential neuroprotective effects on DPN via activating AMPK/PGC-1 α pathway and improving mitochondrial function.
AMP-Activated Protein Kinases ; metabolism ; Diabetic Neuropathies ; drug therapy ; pathology ; Humans ; Medicine, Chinese Traditional ; Mitochondria ; metabolism ; pathology ; Neuroprotective Agents ; therapeutic use ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; metabolism ; Signal Transduction

The pathogenesis of diabetic peripheral neuropathy (DPN) is not illustrated clearly nowadays, and there are several hypotheses. Oxidative stress response is penetrated in several different hypotheses as the formation of advanced glycosylation end products, polyhydric alcohol metabolic pathway, protein kinase C activation and microvascular lesion, etc. The influence of oxidative stress on DPN and the current status of anti-oxidation therapy by using integrative traditional and Western medicine were reviewed in this paper.
Antioxidants ; therapeutic use ; Diabetic Neuropathies ; drug therapy ; physiopathology ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Oxidative Stress ; drug effects ; physiology ; Peripheral Nerves ; drug effects ; pathology ; physiopathology ; Phytotherapy

OBJECTIVE: To evaluate the effect of hepatic insulin gene therapy on diabetic enteric neuropathy. METHODS: Mice were randomly allocated into 3 groups: a normal control group, a diabetic group, and a diabetic gene therapy group. Diabetes were induced by penial vein injection of streptozocin (STZ). The gene therapy group received hepatic insulin gene therapy while the other 2 groups only received an empty virus expressing green fluorescent protein. Random blood glucose, body weight growth, gastric emptying, total bowel length, absolute and relative bowel transit, electric field stimulation of colon smooth muscle, colon nuclei staining and counting were measured. RESULTS: We successully established a mouse model of diabetic enteric neuropathy which manifests as: 8 weeks of continuous hyperglycemia,increased total bowel length, decreased relative bowel transit, impaired colon smooth muscle relaxation and loss of inhibitory neurons in colon. Through gene therapy, the above indexes were normalized or ameliorated, suggesting hepatic insulin gene therapy is capable of preventing diabetic enteric neuropathy. CONCLUSION Hepatic insulin gene therapy can prevent STZ induced diabetic enteric neuropathy.
Adenoviridae ; Animals ; Diabetes Mellitus, Experimental ; complications ; therapy ; Diabetic Neuropathies ; therapy ; Enteric Nervous System ; metabolism ; pathology ; Gastrointestinal Diseases ; etiology ; therapy ; Gene Transfer Techniques ; Genetic Therapy ; Genetic Vectors ; Hepatocytes ; metabolism ; Insulin ; genetics ; metabolism ; Mice ; Proinsulin ; genetics