Diabetic Neuropathy: a Critical, Narrative Review of Published Data from 2019

Nagpal, Ameet S.; Leet, Jennifer; Egan, Kaitlyn E.; Garza, Rudy

doi:10.1007/s11916-020-00928-x

Cited by 6 publications

(4 citation statements)

References 67 publications

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“…Both pre-existing, pre-clinical, and emerging clinical data raise the potential of using omega-3 PU-FAS as a primary or complementary treatment of several human chronic and traumatic conditions. The lack of toxicity and the ready availability of omega-3 PUFAs suggest an exciting avenue for therapy conditions associated with both acute and chronic pain [11,15,[46][47][48]. To date, most studies with omega-3 PUFAs have been largely descriptive.…”

Section: Discussionmentioning

confidence: 99%

Dietary Omega-3 Polyunsaturated Fatty-Acid Supplementation Upregulates Protective Cellular Pathways in Patients with Type 2 Diabetes Exhibiting Improvement in Painful Diabetic Neuropathy

et al. 2022

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Background: Omega-3 polyunsaturated fatty acids (PUFAs) have been proposed to improve chronic neuroinflammatory diseases in peripheral and central nervous systems. For instance, docosahexaenoic acid (DHA) protects nerve cells from noxious stimuli in vitro and in vivo. Recent reports link PUFA supplementation to improving painful diabetic neuropathy (pDN) symptoms, but cellular mechanisms responsible for this therapeutic effect are not well understood. The objective of this study is to identify distinct cellular pathways elicited by dietary omega-3 PUFA supplementation in patients with type 2 diabetes mellitus (T2DM) affected by pDN. Methods: Forty volunteers diagnosed with type 2 diabetes were enrolled in the “En Balance-PLUS” diabetes education study. The volunteers participated in weekly lifestyle/nutrition education and daily supplementation with 1000 mg DHA and 200 mg eicosapentaenoic acid. The Short-Form McGill Pain Questionnaire validated clinical determination of baseline and post-intervention pain complaints. Laboratory and untargeted metabolomics analyses were conducted using blood plasma collected at baseline and after three months of participation in the dietary regimen. The metabolomics data were analyzed using random forest, hierarchical clustering, ingenuity pathway analysis, and metabolic pathway mapping. Results: The data show that metabolites involved in oxidative stress and glutathione production shifted significantly to a more anti-inflammatory state post supplementation. Example of these metabolites include cystathionine (+90%), S-methylmethionine (+9%), glycine cysteine-glutathione disulfide (+157%) cysteinylglycine (+19%), glutamate (−11%), glycine (+11%), and arginine (+13.4%). In addition, the levels of phospholipids associated with improved membrane fluidity such as linoleoyl-docosahexaenoyl-glycerol (18:2/22:6) (+253%) were significantly increased. Ingenuity pathway analysis suggested several key bio functions associated with omega-3 PUFA supplementation such as formation of reactive oxygen species (p = 4.38 × 10−4, z-score = −1.96), peroxidation of lipids (p = 2.24 × 10−5, z-score = −1.944), Ca2+ transport (p = 1.55 × 10−4, z-score = −1.969), excitation of neurons (p = 1.07 ×10−4, z-score = −1.091), and concentration of glutathione (p = 3.06 × 10−4, z-score = 1.974). Conclusion: The reduction of pro-inflammatory and oxidative stress pathways following dietary omega-3 PUFA supplementation is consistent with the promising role of these fatty acids in reducing adverse symptoms associated with neuroinflammatory diseases and painful neuropathy.

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Section: Discussionmentioning

confidence: 99%

Dietary Omega-3 Polyunsaturated Fatty-Acid Supplementation Upregulates Protective Cellular Pathways in Patients with Type 2 Diabetes Exhibiting Improvement in Painful Diabetic Neuropathy

et al. 2022

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“…The articles describe the use of the Michigan Diabetic Neuropathy (MDN) questionnaire, medical diagnoses, sensitivity tests and blood parameters (HbA1c and blood glycaemia). Nagpal et al [54] observed that the predictive models for diagnosing diabetic neuropathy were ambiguous; electrodiagnostic studies do not enable detecting lesions in fibres of small diameter (which are the most damaged in this type of patient); imaging tests present different limitations and their usefulness has not yet been demonstrated in this type of clinical picture; and biomarkers need further studies [55]. Consequently, no agreement has been reached as to which criterion or criteria should be taken into account in diagnosing diabetic neuropathy.…”

Section: Discussionmentioning

confidence: 99%

Exercise and Manual Therapy for Diabetic Peripheral Neuropathy: A Systematic Review

et al. 2021

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(1) Background: Diabetic peripheral neuropathy (DPN) is one of the most common complications of diabetes mellitus (DM). Control of hyperglycaemia as well as surgical decompression are effective treatments for these patients. However, surgery is not indicated for all candidates. Manual therapy and physical exercise have been shown to be effective for peripheral neuropathies, and exercise for DM. The aim is to review the effectiveness of manual therapy and/or exercise in patients with DPN. (2) Methods: Randomised controlled clinical trials comparing the effects of manual therapy and/or exercise on pain, function and/or balance were selected. The search strategy was performed in PubMed, PEDro, Scopus, Cochrane and Web of Science databases. The PRISMA statement was followed. (3) Results: A total of 656 articles were registered, and 29 were selected. There was little consensus on DPN criteria selection. Aerobic, strength and balance exercises are beneficial for DPN. Sessions of 30–60 min, three times per week for 8 weeks seems to be the most used dose. Manual therapy is effective in the short term. A combination of both modalities was more beneficial than alone in one study. (4) Conclusions: Exercise and manual therapy are beneficial for patients with DPN. More studies should be carried out for analysing the potential effect of combining manual therapy and exercise.

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“…Both pre-existing pre-clinical and emerging clinical data raise the potential of using omega-3 PUFAS as a primary or complementary treatment of several human chronic and traumatic conditions. The lack of toxicity and the ready availability of omega 3-PUFAs suggest an exciting avenue for therapy conditions associate with both acute and chronic pain [11,15,[41][42][43]. To date most studies with omega 3 PUFAS has been largely descriptive.…”

Section: Discussionmentioning

confidence: 99%

Dietary Omega-3 Polyunsaturated Fatty-Acid Supplementation Upregulates Protective Cellular Pathways in Patients with Type 2 Diabetes that reduces Painful Diabetic Neuropathy

Durán¹,

Beeson²,

Firek³

et al. 2021

Preprint

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Background: Omega-3 polyunsaturated fatty acids (PUFAs) are increasingly reported to improve chronic neuroinflammatory diseases in peripheral and central nervous systems. Specifically, docosahexaenoic acid (DHA) protects nerve cells from noxious stimuli in vitro and in vivo. Recent reports link PUFA supplementation to improving painful diabetic neuropathy (pDN) symptoms. However, the molecular mechanism behind omega-3 PUFAs ameliorating pDN symptoms is lacking. Therefore, we sought to determine the distinct cellular pathways that omega-3 PUFAs dietary supplementation promotes in reducing painful neuropathy in type 2 diabetes mellitus (DM2) patients. Methods: Forty volunteers diagnosed with type 2 diabetes were enrolled in the "En Balance-PLUS" diabetes education study. The volunteers participated in weekly lifestyle/nutrition education and daily supplementation with 1,000 mg DHA and 200 mg eicosapentaenoic acid. The Short-Form McGill Pain Questionnaire validated clinical determination of baseline and post-intervention pain complaints. Laboratory and untargeted metabolomics analyses were conducted using blood plasma collected at baseline and after three months of participation in the dietary regimen. The metabolomics data was analyzed using random forest, hierarchical cluster, ingenuity pathway analysis, and metabolic pathway mapping. Results: We found that metabolites involved in oxidative stress and glutathione production shifted significantly to a more anti-inflammatory state post supplementation. Example of these metabolites include cystathionine (+90%), S-methylmethionine (+9%), glycine cysteine-glutathione disulfide (+157%) cysteinylglycine (+19%), glutamate (-11%), glycine (+11%) and arginine (+13.4%). In addition, the levels of phospholipids associated with improved membrane fluidity such as linoleoyl-docosahexaenoyl-glycerol (18:2/22:6) (+253 %) were significantly increased. Ingenuity pathway analysis suggested several key bio functions associated with omega-3 PUFA supplementation such as formation of reactive oxygen species (p = 4.38 × 10-4, z-score = -1.96), peroxidation of lipids (p = 2.24 × 10-5, z-score = -1.944), Ca2+ transport (p = 1.55 × 10-4, z-score = -1.969), excitation of neurons (p = 1.07 ×10-4, z-score = -1.091), and concentration of glutathione (p = 3.06 × 10-4, z-score = 1.974). Conclusion: The reduction of pro-inflammatory and oxidative stress pathways following omega-3 PUFAS supplementation is consistent with using omega-3 PUFAs as a complementary dietary strategy as part of the overall treatment of painful diabetic neuropathy.

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Diabetic Neuropathy: a Critical, Narrative Review of Published Data from 2019

Cited by 6 publications

References 67 publications

Dietary Omega-3 Polyunsaturated Fatty-Acid Supplementation Upregulates Protective Cellular Pathways in Patients with Type 2 Diabetes Exhibiting Improvement in Painful Diabetic Neuropathy

Dietary Omega-3 Polyunsaturated Fatty-Acid Supplementation Upregulates Protective Cellular Pathways in Patients with Type 2 Diabetes Exhibiting Improvement in Painful Diabetic Neuropathy

Exercise and Manual Therapy for Diabetic Peripheral Neuropathy: A Systematic Review

Dietary Omega-3 Polyunsaturated Fatty-Acid Supplementation Upregulates Protective Cellular Pathways in Patients with Type 2 Diabetes that reduces Painful Diabetic Neuropathy

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