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International Journal of Molecular... Oct 2021The pathogenesis of diabetic neuropathy is complex, and various pathogenic pathways have been proposed. A better understanding of the pathophysiology is warranted for... (Review)
Review
The pathogenesis of diabetic neuropathy is complex, and various pathogenic pathways have been proposed. A better understanding of the pathophysiology is warranted for developing novel therapeutic strategies. Here, we summarize recent evidence from experiments using animal models of type 1 and type 2 diabetes showing that low-grade intraneural inflammation is a facet of diabetic neuropathy. Our experimental data suggest that these mild inflammatory processes are a likely common terminal pathway in diabetic neuropathy associated with the degeneration of intraepidermal nerve fibers. In contrast to earlier reports claiming toxic effects of high-iron content, we found the opposite, i.e., nutritional iron deficiency caused low-grade inflammation and fiber degeneration while in normal or high non-heme iron nutrition no or only extremely mild inflammatory signs were identified in nerve tissue. Obesity and dyslipidemia also appear to trigger mild inflammation of peripheral nerves, associated with neuropathy even in the absence of overt diabetes mellitus. Our finding may be the experimental analog of recent observations identifying systemic proinflammatory activity in human sensorimotor diabetic neuropathy. In a rat model of type 1 diabetes, a mild neuropathy with inflammatory components could be induced by insulin treatment causing an abrupt reduction in HbA1c. This is in line with observations in patients with severe diabetes developing a small fiber neuropathy upon treatment-induced rapid HbA1c reduction. If the inflammatory pathogenesis could be further substantiated by data from human tissues and intervention studies, anti-inflammatory compounds with different modes of action may become candidates for the treatment or prevention of diabetic neuropathy.
Topics: Animals; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Humans; Inflammation
PubMed: 34639176
DOI: 10.3390/ijms221910835 -
Medicine Dec 2021Diabetic peripheral neuropathy (DPN) is one of the most common complications of diabetes mellitus. The main clinical manifestations of DPN include pain, numbness,... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Diabetic peripheral neuropathy (DPN) is one of the most common complications of diabetes mellitus. The main clinical manifestations of DPN include pain, numbness, paraesthesia, and weakness of the lower limbs which often leads to diabetic foot ulceration, eventually resulting in amputation. Based on Traditional Chinese Medicine theory, moxibustion has a great effect on treating and preventing DPN. However, randomized clinical trials done to evaluate the efficacy of this treatment are still lacking. Hence, this study is carried out to evaluate the effectiveness and safety of moxibustion therapy on diabetic peripheral neuropathy.
METHODS
This study will be a pilot, interventional, randomized, 2-armed, parallel, singled-masked, controlled trial. A total of 40 diabetes mellitus patients with peripheral neuropathy will be recruited and assigned randomly into 2 groups (moxibustion group and waiting group) at a 1:1 ratio. This trial consists of an 8-week intervention period and a 4-week follow-up period. During the intervention period, the moxibustion group will take 3 moxibustion sessions per week, whereas no intervention will be done on the waiting group to act as the control group. The outcome will be assessed by an outcome assessor who is unaware of the group assignment. The primary outcome will be pain assessment measured with algometry, Leeds Assessment of Neuropathic Symptoms and Signs pain scale, visual analogue scale, and neuropathy pain scale. The secondary outcome will be an evaluation of functional performance capacity with 6 minutes walking test, evaluation of the Foot and Ankle Ability Measure, and serum HbA1c and albumin levels.
DISCUSSION
We hope that this trial will provide valuable insights on the efficacy of moxibustion in the management of diabetic peripheral neuropathy.
TRIAL REGISTRATION
ClinicalTrials.gov Registry No.: NCT04894461 (URL: https://clinicaltrials.gov/ct2/show/NCT04894461?term=NCT04894461&draw=2&rank=1) Registered on May 20, 2021.
Topics: Acupuncture Therapy; Diabetes Mellitus, Type 2; Diabetic Foot; Diabetic Neuropathies; Humans; Moxibustion; Outcome Assessment, Health Care; Pain; Pain Measurement; Treatment Outcome
PubMed: 34889293
DOI: 10.1097/MD.0000000000028173 -
Experimental and Clinical Endocrinology... Feb 2023
Topics: Humans; Diabetic Neuropathies; Diabetes Mellitus
PubMed: 36720239
DOI: 10.1055/a-1946-3813 -
The Journal of International Medical... May 2018Objective To examine the effect of α-lipoic acid on neuropathic symptoms in patients with diabetic neuropathy (DN). Methods Patients with painful DN were treated with... (Clinical Trial)
Clinical Trial
Objective To examine the effect of α-lipoic acid on neuropathic symptoms in patients with diabetic neuropathy (DN). Methods Patients with painful DN were treated with 600 mg/day α-lipoic acid, orally, for 40 days. Neuropathy Symptom Score (NSS), Subjective Peripheral Neuropathy Screen Questionnaire (SPNSQ) and douleur neuropathique (DN)4 questionnaire scores were assessed at baseline and day 40. Quality-of-life treatment effects were assessed by Brief Pain Inventory (BPI), Neuropathic Pain Symptom Inventory (NPSI) and Sheehan Disability Scale (SDS). Changes in body weight, arterial blood pressure, fasting serum glucose and lipids were also assessed. Results Out of 72 patients included, significant reductions in neuropathic symptoms were shown by reduced NSS, SPNSQ and DN4 scores at day 40 versus baseline. BPI, NPSI, and SDS in terms of work disability, social life disability, and family life disability scores were also significantly reduced. Moreover, 50% of patients rated their health condition as 'very much better' or 'much better' following α-lipoic acid administration. Fasting triglyceride levels were reduced, but no difference was found in body weight, blood pressure, fasting glucose, or other lipids at day 40 versus baseline. Conclusions A-lipoic acid administration was associated with reduced neuropathic symptoms and triglycerides, and improved quality of life.
Topics: Adult; Aged; Demography; Diabetic Neuropathies; Disability Evaluation; Female; Humans; Male; Neuralgia; Quality of Life; Surveys and Questionnaires; Thioctic Acid
PubMed: 29517942
DOI: 10.1177/0300060518756540 -
Continuum (Minneapolis, Minn.) Oct 2014This article provides an overview for understanding the diagnosis, pathogenesis, and management of diabetic neuropathy. (Review)
Review
PURPOSE OF REVIEW
This article provides an overview for understanding the diagnosis, pathogenesis, and management of diabetic neuropathy.
RECENT FINDINGS
New information about the pathogenesis of diabetic neuropathy continues to emerge, which will lead to identifying new drug targets. It is clear that the natural history of diabetic neuropathy is changing and the rate of progression is slowing. This is likely because of a combination of earlier diagnosis, improved glycemic management, and improved control of related complications such as hyperlipidemia and hypertension. Early diagnosis is critical, and small fiber neuropathy or subclinical diabetic neuropathy may be reversed or significantly improved with appropriate intervention. The American Academy of Neurology recently published guidelines for the treatment of painful diabetic neuropathy.
SUMMARY
Diabetic neuropathy is common and can present with varied clinical presentations discussed in this article. Although treatment currently focuses on pain management, attention should be paid to potential risk factors for neuropathy. For example, glycemic control, hyperlipidemia, and hypertension should be managed with diet, exercise, and medications. Class I or II clinical studies indicate that pregabalin, duloxetine, amitriptyline, gabapentin, and opioids are effective in the management of diabetic neuropathic pain.
Topics: Diabetic Neuropathies; Humans
PubMed: 25299279
DOI: 10.1212/01.CON.0000455884.29545.d2 -
Nutrients Oct 2020To investigate the efficacy of Superoxide Dismutase, Alpha Lipoic Acid, Acetyl L-Carnitine, and Vitamin B12 (B12) in one tablet in Diabetic Neuropathy (DN). (Randomized Controlled Trial)
Randomized Controlled Trial
AIM
To investigate the efficacy of Superoxide Dismutase, Alpha Lipoic Acid, Acetyl L-Carnitine, and Vitamin B12 (B12) in one tablet in Diabetic Neuropathy (DN).
PATIENTS-METHODS
In this prospective, double-blind, placebo-controlled study, 85 patients with Diabetes Mellitus Type 2 (DMT2) were randomly assigned, either to receive the combination of four elements (active group, = 43), or placebo ( = 42) for 12 months. We used the Michigan Neuropathy Screening Instrument Questionnaire and Examination (MNSIQ and MNSIE), measured the vibration perception threshold (BIO), and Cardiovascular Autonomic Reflex Tests (CARTs). Nerve function was assessed by DPN Check [sural nerve conduction velocity (SNCV) and amplitude (SNAP)]. Pain (PS) and quality of life (QL) questionnaires were administered.
RESULTS
At follow-up, BIO, MNSIQ, QL, PAIN, and SNCV, SNAP, and B12 levels had significantly improved inactive group ( <0.001, <0.001, <0.001, <0.001, = 0.027, = 0.031, and <0.001 respectively), whereas the inplacebo group MCR (mean circular resultant) and PAIN deteriorated ( <0.001, <0.001). The changes in MNSIQ, QL, SNCV, BIO, and PAIN differed significantly between groups ( <0.001, <0.001, = 0.031, <0.001, and <0.001 respectively).
CONCLUSIONS
The combination of the four elements in one tablet for 12 months in patients with DMT2 improved all indices of peripheral neuropathy, including SNAP and SNCV, pain, and Quality of Life perception, except CARTs and MNSIE.
Topics: Aged; Carnitine; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Double-Blind Method; Drug Combinations; Female; Humans; Male; Middle Aged; Neural Conduction; Pain Measurement; Prospective Studies; Quality of Life; Reflex; Superoxide Dismutase; Thioctic Acid; Treatment Outcome; Vitamin B 12
PubMed: 33114210
DOI: 10.3390/nu12113254 -
Agri : Agri (Algoloji) Dernegi'nin... Oct 2018Diabetic peripheral neuropathy (DPN) is the most common and troublesome complication of diabetes leading to great morbidity and resulting in a huge economic burden for... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
Diabetic peripheral neuropathy (DPN) is the most common and troublesome complication of diabetes leading to great morbidity and resulting in a huge economic burden for diabetes care. Over half of people with diabetes develop neuropathy. Also, DPN is a major cause of reduced quality of life due to pain, sensory loss, gait instability, fall-related injury, and foot ulceration and amputation. The aim of this study was evaluating the effects of lifestyle interventions on diabetic neuropathy severity in diabetes type 2 outpatients.
METHODS
This clinical trial conducted on 74 patients with DPN that divided with random allocation into intervention or control group. The lifestyle interventions applied in the intervention group beginning four educational sessions on lifestyle that emphasize strategies for lowering blood sugar, increasing physical activity, promoting weight loss, prudent diet, and foot caring. Each session was lasted for1.5 hour. Then patients followed for 12 weeks. During this period, they received counseling on mentioned lifestyle interventions. DPN severity in both groups measured using modified Toronto Clinical Neuropathy Score (mTCNS) at the beginning of study and at the end of counseling for 12 weeks.
RESULTS
Comparing differences of mean of DNP severity before and after lifestyle intervention between two groups of study, there was a significant difference (p<0.001). DNP severity in control group had not any change or it increased in some participants, but DNP decreased in intervention group, after applying lifestyle intervention.
CONCLUSION
Lifestyle interventions can contribute to reducing DPN severity, and consequently decreasing neuropathic pain.
Topics: Diabetes Mellitus, Type 2; Diabetic Neuropathies; Female; Humans; Life Style; Male; Middle Aged; Pain Measurement; Severity of Illness Index; Treatment Outcome
PubMed: 30403270
DOI: 10.5505/agri.2018.45477 -
BMC Endocrine Disorders Feb 2021Advanced glycation end-products (AGEs) are heterogeneous molecules produced by the non-enzymatic glycation of proteins, lipids, or nucleic acids during hyperglycaemia.... (Review)
Review
Advanced glycation end-products (AGEs) are heterogeneous molecules produced by the non-enzymatic glycation of proteins, lipids, or nucleic acids during hyperglycaemia. Accumulation of AGEs in the peripheral nerves has recently been proposed as an additional risk factor for the development of diabetic neuropathy (DN). The gold standard for measurement of tissue-bound AGEs is tissue biopsy. However, their assessment with the newer, fast and simple method of skin autofluorescence (sAF) has recently gained special interest by virtue of its non-invasive, highly reproducible nature and its acceptable correlation with the reference method of skin biopsy. Accumulation of tissue AGEs evaluated by sAF has been shown to independently correlate with DN. Importantly, increasing evidence underscores their potential value as early biomarkers of the latter. Further important associations include diabetic nephropathy, diabetic retinopathy and cardiovascular autonomic neuropathy. However, the value of the implementation of screening with skin AGEs for DN remains unclear. The aim of the present review is to critically summarise current evidence on the association between skin AGEs and diabetic microvascular complications, with a particular emphasis on diabetic neuropathy, and to note the most important limitations of existing knowledge. Longer follow-up studies are also highly anticipated to clarify its role and provide data on patient selection and cost-effectiveness.
Topics: Diabetic Angiopathies; Diabetic Neuropathies; Glycation End Products, Advanced; Humans; Optical Imaging; Skin
PubMed: 33622304
DOI: 10.1186/s12902-021-00697-7 -
Diabetes Research and Clinical Practice Dec 2023Diabetic peripheral neuropathy (DPN) is found in around one third of people with diabetes, but remains inadequately diagnosed and treated. Its management includes three... (Review)
Review
Diabetic peripheral neuropathy (DPN) is found in around one third of people with diabetes, but remains inadequately diagnosed and treated. Its management includes three cornerstones: 1) causal treatment with lifestyle modification, intensive diabetes therapy aimed at near-normoglycemia, and multifactorial cardiovascular risk intervention, 2) pathogenesis-oriented pharmacotherapy, and 3) symptomatic pain relief. Since symptomatic analgesic monotherapy only relieves the pain without targeting the underlying neuropathy and both has limited efficacy and is associated with adverse events, there is an unmet need for additional approaches derived from the pathogenetic concepts of DPN. Preclinical studies have suggested that diabetic neuropathy can be prevented or improved through the use of various agents that interfere with the pathophysiology of the underlying condition. Some of these encouraging findings could be translated successfully into the clinical setting. Efficacy and excellent safety were demonstrated in several meta-analyses (α-lipoic acid) and randomized clinical trials (benfotiamine, actovegin, epalrestat) in the treatment of symptomatic DPN. The NATHAN 1 trial demonstrated an improvement of neuropathic signs (deficits, impairments) after four years in asymptomatic DPN. These compounds are currently authorized for treatment of DPN in several countries. Long-term pivotal clinical trials should further establish their value as mono- and combination therapies in DPN.
Topics: Humans; Combined Modality Therapy; Diabetes Mellitus; Diabetic Neuropathies; Pain; Thioctic Acid
PubMed: 38245327
DOI: 10.1016/j.diabres.2023.110764 -
Journal of Diabetes Research 2017
Topics: Diabetic Neuropathies; Humans; Hypoglycemic Agents; Prevalence
PubMed: 28770231
DOI: 10.1155/2017/5825971