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Journal of Molecular Medicine (Berlin,... Aug 2023Multiple molecular pathways including the receptor for advanced glycation end-products-diaphanous related formin 1 (RAGE-Diaph1) signaling are known to play a role in...
Multiple molecular pathways including the receptor for advanced glycation end-products-diaphanous related formin 1 (RAGE-Diaph1) signaling are known to play a role in diabetic peripheral neuropathy (DPN). Evidence suggests that neuropathological alterations in type 1 diabetic spinal cord may occur at the same time as or following peripheral nerve abnormalities. We demonstrated that DPN was associated with perturbations of RAGE-Diaph1 signaling pathway in peripheral nerve accompanied by widespread spinal cord molecular changes. More than 500 differentially expressed genes (DEGs) belonging to multiple functional pathways were identified in diabetic spinal cord and of those the most enriched was RAGE-Diaph1 related PI3K-Akt pathway. Only seven of spinal cord DEGs overlapped with DEGs from type 1 diabetic sciatic nerve and only a single gene cathepsin E (CTSE) was common for both type 1 and type 2 diabetic mice. In silico analysis suggests that molecular changes in spinal cord may act synergistically with RAGE-Diaph1 signaling axis in the peripheral nerve. KEY MESSAGES: Molecular perturbations in spinal cord may be involved in the progression of diabetic peripheral neuropathy. Diabetic peripheral neuropathy was associated with perturbations of RAGE-Diaph1 signaling pathway in peripheral nerve accompanied by widespread spinal cord molecular changes. In silico analysis revealed that PI3K-Akt signaling axis related to RAGE-Diaph1 was the most enriched biological pathway in diabetic spinal cord. Cathepsin E may be the target molecular hub for intervention against diabetic peripheral neuropathy.
Topics: Animals; Mice; Receptor for Advanced Glycation End Products; Diabetic Neuropathies; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Cathepsin E; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Sciatic Nerve; Hyperglycemia
PubMed: 37462767
DOI: 10.1007/s00109-023-02347-y -
Current Pain and Headache Reports Sep 2023Almost half of people diagnosed with diabetes mellitus will develop painful diabetic neuropathy (PDN), a condition greatly impacting quality of life with complicated... (Review)
Review
PURPOSE OF REVIEW
Almost half of people diagnosed with diabetes mellitus will develop painful diabetic neuropathy (PDN), a condition greatly impacting quality of life with complicated pathology. While there are different FDA approved forms of treatment, many of the existing options are difficult to manage with comorbities and are associated with unwanted side effects. Here, we summarize the current and novel treatments for PDN.
RECENT FINDINGS
Current research is exploring alternative pain management treatments from the first line options of pregabalin, gabapentin, duloxetine, and amitriptyline which often have side effects. The use of FDA approved capsaicin and spinal cord stimulators (SCS) has been incredibly beneficial in addressing this. In addition, new treatments looking at different targets, such as NMDA receptor and the endocannabinoid system, show promising results. There are several treatment options that have been shown to be successful in helping treat PDN, but often require adjunct treatment or alterations due to side effects. While there is ample research for standard medications, treatments such as palmitoylethanolamide and endocannabinoid targets have extremely limited clinical trials. We also found that many studies did not evaluate additional variables other than pain relief, such as functional changes nor were there consistent measurement methods. Future research should continue trials comparing treatment efficacies along with more quality of life measures.
Topics: Humans; Diabetic Neuropathies; Quality of Life; Endocannabinoids; Gabapentin; Pregabalin; Diabetes Mellitus
PubMed: 37392335
DOI: 10.1007/s11916-023-01126-1 -
Metabolism: Clinical and Experimental May 2024Diabetic peripheral neuropathy (DPN) is a complication of diabetes with a high rate of disability. However, current clinical treatments for DPN are suboptimal.... (Review)
Review
Diabetic peripheral neuropathy (DPN) is a complication of diabetes with a high rate of disability. However, current clinical treatments for DPN are suboptimal. Non-coding RNAs (ncRNAs) are a type of RNAs that are not translated into proteins. NcRNAs perform functions that regulate epigenetic modifications, transcriptional or post-transcriptional regulators of proteins, and thus participate in the physiological and pathological processes of the body. NcRNAs play a role in the progress of DPN by affecting the processes of inflammation, oxidative stress, cellular autophagy or apoptosis. Therefore, ncRNAs treatment is regarded as a promising therapeutic approach for DPN. In addition, since some ncRNAs present stably in the blood of DPN patients, they are considered as potential biomarkers that contribute to early clinical diagnosis. In this paper, we review the studies on the role of ncRNAs in DPN in the last decade, and discuss the mechanisms of ncRNAs, aiming to provide a reference for the future research on the treatment and early diagnosis of DPN.
Topics: Humans; Diabetic Neuropathies; RNA, Untranslated; RNA; Biomarkers; Diabetes Mellitus
PubMed: 38462040
DOI: 10.1016/j.metabol.2024.155833 -
Endocrine Practice : Official Journal... Aug 2023One of the most frequently occurring complications of diabetes mellitus is peripheral neuropathy. Despite the painful symptoms associated with diabetic peripheral... (Review)
Review
OBJECTIVE
One of the most frequently occurring complications of diabetes mellitus is peripheral neuropathy. Despite the painful symptoms associated with diabetic peripheral neuropathy (DPN), the current treatment landscape focuses on managing symptoms without addressing the underlying causes of DPN. This narrative review describes the mechanistic effects and clinical trial data supporting the use of L-methylfolate calcium (LMF), the bioactive form of folate, which is available in the United States as a prescription medical food that also contains other B vitamins for the dietary management of DPN.
METHODS
Preclinical and clinical trial data evaluating the impact of LMF on DPN were identified using PubMed searches for articles published between 2010 and 2023. Search terms included: folate, LMF, diabetes, neuropathy, and neuropathic pain. Additionally, a literature search was conducted to identify studies related to LMF, genetic polymorphisms, and DPN pathophysiology.
RESULTS
Several studies show that the C677T variant of the methylenetetrahydrofolate reductase gene is linked to greater risk of DPN than other methylenetetrahydrofolate reductase variants due to its inhibitory effects on several folic acid metabolic pathways. One double-blind, randomized controlled trial, 5 open-label studies, and 1 retrospective study found that LMF has a significant beneficial effect on DPN that extends beyond symptomatic relief to include modulating the underlying pathophysiology that leads to the progression and symptoms of DPN. LMF also significantly improves patient quality of life, with minimal adverse effects.
CONCLUSION
Preclinical and clinical studies have found that LMF can be used to treat the underlying causes of DPN and provide long-lasting symptomatic relief.
Topics: Humans; Diabetic Neuropathies; Diabetes Mellitus, Type 2; Methylenetetrahydrofolate Reductase (NADPH2); Quality of Life; Retrospective Studies; Folic Acid; Randomized Controlled Trials as Topic
PubMed: 37088147
DOI: 10.1016/j.eprac.2023.04.005 -
Frontiers in Endocrinology 2023Nepal is a developing country where diabetes is becoming a major health challenge due to its high prevalence of 8.5% affecting around 2 million people. Due to limited...
INTRODUCTION
Nepal is a developing country where diabetes is becoming a major health challenge due to its high prevalence of 8.5% affecting around 2 million people. Due to limited resources, there are many barriers to providing affordable and convenient diabetes care or regular screening for complications. There is no reliable data on incidence, prevalence, and complications of diabetic foot problems in Nepal.
METHODS
We conducted an online survey amongst senior physicians, who were members of 'Diabetes & Endocrine Association of Nepal' to assess their perception of diabetic foot problems in Nepal.
RESULTS
Thirty-Eight physicians responded to the survey who saw a total of 17597 patients in the preceding month. They recalled seeing 647 with 'Diabetic Foot Ulcers', giving a crude Diabetic Foot Ulcer prevalence rate of 3.7%. They recalled seeing 2522 patients with painful neuropathy that required medical treatment, giving a crude painful neuropathy prevalence rate of 14.3%. A history of foot ulcer was present in an additional 578 patients. Previous minor amputation had been performed in 215 patients (1.2%) and major amputation in 135 patients (0.8%).
DISCUSSION
Despite having expertise in various fields there is no dedicated multi-disciplinary diabetic foot clinic in Nepal. This survey shows that diabetic foot problems are abundant in Nepal and there is a need for structured multi-disciplinary approach for screening and treatment.
Topics: Humans; Diabetic Foot; Nepal; Amputation, Surgical; Pain; Diabetes Mellitus
PubMed: 38027189
DOI: 10.3389/fendo.2023.1277940 -
The International Journal of Lower... Mar 2024Diabetic foot ulcer represents the primary cause of hospital admissions, amputations, and mortality in diabetic patients. The development of diabetic foot ulcers is...
Diabetic foot ulcer represents the primary cause of hospital admissions, amputations, and mortality in diabetic patients. The development of diabetic foot ulcers is influenced by peripheral neuropathy, infection, and ischemia, with diabetes contributing to peripheral artery disease. Free tissue transfer combined with revascularisation of the lower extremity provides the potential opportunity for limb salvage in individuals with lower extremity defects due to critical limb ischemia and diabetic foot.
Topics: Humans; Diabetic Foot; Vascular Surgical Procedures; Lower Extremity; Limb Salvage; Peripheral Arterial Disease; Ischemia; Treatment Outcome
PubMed: 37946321
DOI: 10.1177/15347346231210144 -
Current Problems in Cardiology Aug 2023Microvascular complications of diabetes seem to be clustered and put patients at higher risk of developing cardiovascular disease (CVD). This was a questionnaire-based... (Review)
Review
Microvascular complications of diabetes seem to be clustered and put patients at higher risk of developing cardiovascular disease (CVD). This was a questionnaire-based study designed to screen for the presence of diabetic peripheral neuropathy (DPN), defined as the score in the Michigan Neuropathy Screening Instrument (MNSI) above 2, and to evaluate its association with other complication of diabetes, including CVD. There were 184 patients included into the study. The prevalence of DPN in the study group was 37.5%. The regression model analysis revealed that the presence of DPN was significantly associated with the presence of diabetic kidney disease (DKD) (P = 0.0034;) and patient's age (P < 0.0001). Thirty-four patients (49.3%) with MNSI score >2 were diagnosed with CVD in comparison to 24 (20.1%) subjects with MNSI score ≤ 2 (P = 0.00006). In case of having one diabetes complication diagnosed, it is important to screen for others, including macrovascular ones.
Topics: Humans; Diabetic Neuropathies; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Cardiovascular Diseases
PubMed: 36967071
DOI: 10.1016/j.cpcardiol.2023.101726 -
Wound Repair and Regeneration :... 2023Cutaneous manifestations affect most patients with diabetes mellitus, clinically presenting with numerous dermatologic diseases from xerosis to diabetic foot ulcers... (Review)
Review
Cutaneous manifestations affect most patients with diabetes mellitus, clinically presenting with numerous dermatologic diseases from xerosis to diabetic foot ulcers (DFUs). Skin conditions not only impose a significantly impaired quality of life on individuals with diabetes but also predispose patients to further complications. Knowledge of cutaneous biology and the wound healing process under diabetic conditions is largely limited to animal models, and studies focusing on biology of the human condition of DFUs remain limited. In this review, we discuss the critical molecular, cellular, and structural changes to the skin in the hyperglycaemic and insulin-resistant environment of diabetes with a focus specifically on human-derived data. Elucidating the breadth of the cutaneous manifestations coupled with effective diabetes management is important for improving patient quality of life and averting future complications including wound healing disorders.
Topics: Animals; Humans; Wound Healing; Quality of Life; Diabetic Foot; Skin; Diabetes Mellitus
PubMed: 37365017
DOI: 10.1111/wrr.13108 -
Biomedicine & Pharmacotherapy =... Apr 2024Painful diabetic neuropathy (PDN) is a common chronic complication of diabetes that causes neuropathic pain and negatively affects the quality of life. The management of... (Review)
Review
Painful diabetic neuropathy (PDN) is a common chronic complication of diabetes that causes neuropathic pain and negatively affects the quality of life. The management of PDN is far from satisfactory. At present, interventions are primarily focused on symptomatic treatment. Ion channel disorders are a major cause of PDN, and a complete understanding of their roles and mechanisms may provide better options for the clinical treatment of PDN. Therefore, this review summarizes the important role of ion channels in PDN and the current drug development targeting these ion channels.
Topics: Humans; Diabetic Neuropathies; Quality of Life; Neuralgia; Drug Development; Diabetes Mellitus
PubMed: 38490158
DOI: 10.1016/j.biopha.2024.116417 -
Journal of Diabetes and Its... May 2024We investigated associations between gastrointestinal symptoms - evaluated as a combined weighted symptom score (CWSS) - Diabetic autonomic neuropathy (DAN), and distal...
OBJECTIVE
We investigated associations between gastrointestinal symptoms - evaluated as a combined weighted symptom score (CWSS) - Diabetic autonomic neuropathy (DAN), and distal symmetrical polyneuropathy (DSPN) in type 1 and type 2 diabetes.
RESEARCH DESIGN AND METHODS
Cross-sectional study in a tertiary outpatient clinic. CWSS was calculated based on questionnaires: gastroparesis composite symptom index (GCSI) and gastrointestinal symptom rating score (GSRS). DAN and DSPN were addressed using the composite autonomic symptom score 31 (COMPASS-31) questionnaire, cardiac autonomic reflex tests (CARTs), electrochemical skin conductance (ESC), vibration perception threshold (VPT), Michigan Neuropathy Screening Instrument (MNSI), pain- and thermal sensation. Analyses were adjusted for age, sex, diabetes duration, smoking, LDL-cholesterol, HbA and systolic blood pressure. Type 1 and type 2 diabetes were evaluated separately.
RESULTS
We included 566 with type 1 diabetes and 377 with type 2 diabetes. Mean ± SD age was 58 ± 15 years and 565 (59.9 %) were women. A high CWSS was present in 143 (25 %) with type 1 and 142 (38 %) with type 2 diabetes. The odds of DAN by COMPASS-31 (p < 0.001) were higher in the high score group. For type 1 diabetes, odds of cardiac autonomic neuropathy were higher in the high CWSS group. The odds of DSPN by VPT and MNSI in type 1 diabetes, and by ESC, VPT and pain sensation in type 2 diabetes were higher in the high CWSS group.
CONCLUSIONS
A high symptom score was associated with neuropathy by COMPASS-31 and vibration perception. Gastrointestinal symptom burden associated inconsistently with other neuropathy tests between diabetes types.
Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Autonomic Nervous System Diseases; Cohort Studies; Cost of Illness; Cross-Sectional Studies; Denmark; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Gastrointestinal Diseases; Scandinavians and Nordic People; Severity of Illness Index; Surveys and Questionnaires; Symptom Burden
PubMed: 38615421
DOI: 10.1016/j.jdiacomp.2024.108745