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Frontiers in Public Health 2023The anticipation of diabetes-related complications remains a challenge for numerous T2DM patients, as there is presently no effective method for early prediction of...
BACKGROUND
The anticipation of diabetes-related complications remains a challenge for numerous T2DM patients, as there is presently no effective method for early prediction of these complications. This study aims to investigate the association between renal function-related indicators and the occurrence of peripheral neuropathy and retinopathy in individuals diagnosed with type 2 diabetes mellitus (T2DM) who currently have normal renal function.
METHODS
Patients with T2DM who met the criteria were selected from the MMC database and divided into diabetic peripheral neuropathy (DPN) and diabetic retinopathy (DR) groups, with a total of 859 and 487 patients included, respectively. Multivariate logistic regression was used to analyze the relationship between blood urea nitrogen (BUN), creatinine (Cr), uric acid (UA), urine albumin(ALB), albumin-to-creatinine ratio (ACR), estimated glomerular filtration rate (eGFR), and diabetic peripheral neuropathy and retinopathy. Spearman correlation analysis was used to determine the correlation between these indicators and peripheral neuropathy and retinopathy in diabetes.
RESULTS
In a total of 221 patients diagnosed with DPN, we found positive correlation between the prevalence of DPN and eGFR (18.2, 23.3, 35.7%, < 0.05). Specifically, as BUN (T1: references; T2:OR:0.598, 95%CI: 0.403, 0.886; T3:OR:1.017, 95%CI: 0.702, 1.473; < 0.05) and eGFR (T1: references; T2:OR:1.294, 95%CI: 0.857, 1.953; T3:OR:2.142, 95%CI: 1.425, 3.222; < 0.05) increased, the odds ratio of DPN also increased. Conversely, with an increase in Cr(T1: references; T2:OR:0.86, 95%CI: 0.56, 1.33; T3:OR:0.57, 95%CI: 0.36, 0.91; < 0.05), the odds ratio of DPN decreased. Furthermore, when considering sensitivity and specificity, eGFR exhibited a sensitivity of 65.2% and specificity of 54.4%, with a 95% confidence interval of 0.568-0.656.
CONCLUSION
In this experimental sample, we found a clear positive correlation between eGFR and DPN prevalence.
Topics: Humans; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Risk Factors; Diabetic Neuropathies; Creatinine; Correlation of Data; Retinal Diseases; Kidney; Albumins
PubMed: 38174078
DOI: 10.3389/fpubh.2023.1302615 -
CNS Neuroscience & Therapeutics Apr 2024Painful diabetic neuropathy (PDN) is a common complication of diabetes. Previous studies have implicated that mitochondrial dysfunction plays a role in the development...
INTRODUCTION
Painful diabetic neuropathy (PDN) is a common complication of diabetes. Previous studies have implicated that mitochondrial dysfunction plays a role in the development of PDN, but its pathogenesis and mechanism have not been fully investigated.
METHODS
In this study, we used high-fat diet/low-dose streptozotocin-induced rats as a model of type 2 diabetes mellitus. Behavioral testing, whole-cell patch-clamp recordings of dorsal root ganglion (DRG) neurons, and complex sensory nerve conduction velocity studies were used to assess peripheral neuropathy. Mitochondrial membrane potential (MMP), ATP, tissue reactive oxygen species, and transmission electron microscopy were used to evaluate the function and morphology of mitochondria in DRG. Real-time PCR, western blot, and immunofluorescence were performed to investigate the mechanism.
RESULTS
We found that damaged mitochondria were accumulated and mitophagy was inhibited in PDN rats. The expression of sirtuin 3 (SIRT3), which is an NAD-dependent deacetylase in mitochondria, was inhibited. Overexpression of SIRT3 in DRG neurons by intrathecally administered LV-SIRT3 lentivirus ameliorated neurological and mitochondrial dysfunctions. This was evidenced by the reversal of allodynia and nociceptor hyperexcitability, as well as the restoration of MMP and ATP levels. Overexpression of SIRT3 restored the inhibited mitophagy by activating the FoxO3a-PINK1-Parkin signaling pathway. The effects of SIRT3 overexpression, including the reversal of allodynia and nociceptor hyperexcitability, the improvement of impaired mitochondria and mitophagy, and the restoration of PINK1 and Parkin expression, were counteracted when FoxO3a siRNA was intrathecally injected.
CONCLUSION
These results showed that SIRT3 overexpression ameliorates PDN via activation of FoxO3a-PINK1-Parkin-mediated mitophagy, suggesting that SIRT3 may become an encouraging therapeutic strategy for PDN.
Topics: Animals; Rats; Adenosine Triphosphate; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Hyperalgesia; Mitophagy; Protein Kinases; Signal Transduction; Sirtuin 3; Ubiquitin-Protein Ligases
PubMed: 38572816
DOI: 10.1111/cns.14703 -
Current Opinion in Neurology Oct 2023The purpose if this review is to provide an overview of the available data on the use of nerve ultrasound for the diagnosis and follow-up of peripheral neuropathies. (Review)
Review
PURPOSE OF REVIEW
The purpose if this review is to provide an overview of the available data on the use of nerve ultrasound for the diagnosis and follow-up of peripheral neuropathies.
RECENT FINDINGS
During the last decade, nerve ultrasound has been established as a complementary tool for the evaluation of morphological changes mostly for immune-mediated polyneuropathies. Through the development of ultrasound protocols for evaluation of disease-specific sites, nerve ultrasound has proven to be a practical, widely available, reproducible diagnostic tool with no relevant contraindications.
SUMMARY
Cross-sectional area, echogenicity, morphology of the individual nerve fascicles, thickness of the epineurium, vascularization and mobility of the nerve are the main parameters evaluated with nerve ultrasound in polyneuropathies. Patients with typical chronic inflammatory demyelinating polyneuropathy show multifocal nerve enlargements easily visible on the upper extremities and the brachial plexus, whereas its variants show focal nerve enlargements. On the other hand, axonal neuropathies including diabetic neuropathy present with isolated nerve enlargement mostly in compression sites.
Topics: Humans; Follow-Up Studies; Polyneuropathies; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Ultrasonography; Diabetic Neuropathies; Peripheral Nerves
PubMed: 37382111
DOI: 10.1097/WCO.0000000000001183 -
British Journal of Community Nursing Jun 2024The escalating prevalence of diabetes mellitus presents concern due to its widespread organ damage, including the heart, kidneys, eyes, and nerves, leading to severe... (Review)
Review
The escalating prevalence of diabetes mellitus presents concern due to its widespread organ damage, including the heart, kidneys, eyes, and nerves, leading to severe complications such as heart attacks, strokes, blindness, and diabetes-related foot ulcers (DFUs). Management in the community setting should be focused on prevention, assessment and patient-centred care. By understanding the complex aetiology, risk factors, and classification of DFUs, along with utilising evidence-based interventions like the Wound, Infection and Ischemia (WIfI) system, we can streamline care. Neuropathy, peripheral arterial disease and infection are major contributors to DFU development, highlighting the importance of early detection and intervention. Comprehensive care addressing vascular health, infection control, pressure offloading, wound management, metabolic control, and patient education is essential for successful DFU management. Ultimately, proactive prevention strategies and interdisciplinary collaboration are necessary in the management of DFUs and improving patient outcomes.
Topics: Humans; Diabetic Foot; Risk Factors
PubMed: 38814845
DOI: 10.12968/bjcn.2024.29.Sup6.S30 -
Brain and Nerve = Shinkei Kenkyu No... May 2024Diabetes stands as the predominant cause of peripheral neuropathy, and diabetic neuropathy (DN) is an early-onset and most frequent complication of diabetes. Distal... (Review)
Review
Diabetes stands as the predominant cause of peripheral neuropathy, and diabetic neuropathy (DN) is an early-onset and most frequent complication of diabetes. Distal symmetric polyneuropathy is the major form of DN; however, various patterns of nerve injury can manifest. Growing evidence suggests that hyperglycemia-related metabolic disorders in neurons, Schwann cells, and vascular endothelial cells play a major role in the development and progression of DN; however, its pathogenesis and development of disease-modifying therapies warrant further investigation. Herein, recent studies regarding the possible pathogenic factors of DN (polyol and other collateral glycolysis pathways, glycation, oxidative stress, Rho/Rho kinase signaling pathways, etc.) and therapeutic strategies targeting these factors are introduced.
Topics: Humans; Diabetic Neuropathies; Oxidative Stress; Animals; Signal Transduction
PubMed: 38741511
DOI: 10.11477/mf.1416202658 -
Clinical Drug Investigation Dec 2023Painful peripheral neuropathy is a common and challenging complication of diabetes mellitus. Combination therapy is used widely by clinicians, although strong evidence... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVE
Painful peripheral neuropathy is a common and challenging complication of diabetes mellitus. Combination therapy is used widely by clinicians, although strong evidence for efficacy and safety is lacking. The goal of this study is to compare the efficacy and safety of combination versus monotherapy of first-line medications for peripheral diabetic neuropathy.
METHODS
PubMed, Embase, Cochrane Central, and clinicaltrials.gov databases were searched on December 5, 2022, for randomized clinical trials comparing combined therapy with gabapentinoids and either tricyclic antidepressants (TCAs) or serotonin and norepinephrine reuptake inhibitors (SNRIs) versus monotherapy with any of these drugs. Pooled mean differences (MD) with a 95% confidence interval (CI) were computed for pain outcomes, measured on an 11-point numeric rating scale averaging pain scores in the last 7 days. Risk ratios (RRs) were computed for binary endpoints. Risk assessment was performed using the Risk of Bias 2 tool.
RESULTS
A total of five randomized studies and 916 patients were included. Follow-up ranged from 6 to 12 weeks. Mean pain reduction was greater for combination therapy than monotherapy (MD - 0.39; 95% CI - 0.67 to - 0.12; p = 0.005). Similarly, there was an improvement in ≥ 30% reduction in average pain (RR 1.16; 95% CI 1.07-1.26; p < 0.01) with combination therapy. In contrast, there was no significant difference between groups in ≥ 50% reduction in average pain (RR 1.21; 95% CI 0.99-1.49; p = 0.06). When comparing combination therapy versus gabapentinoid monotherapy, there was also a significant reduction in average pain (MD - 0.61; 95% CI - 0.85 to - 0.37; p < 0.01) with combination therapy.
CONCLUSION
In patients with painful diabetic peripheral neuropathy, the combination of gabapentinoids with TCAs or SNRIs is associated with a greater reduction in pain as compared with monotherapy, although this difference may not translate into a clinically important difference.
Topics: Humans; Diabetic Neuropathies; Serotonin and Noradrenaline Reuptake Inhibitors; Selective Serotonin Reuptake Inhibitors; Pain; Diabetes Mellitus; Randomized Controlled Trials as Topic
PubMed: 37940831
DOI: 10.1007/s40261-023-01318-y -
BMC Endocrine Disorders Oct 2023Peripheral neuropathy is not only the most prevalent consequence of diabetes but also the main reason for foot ulceration, disability, and amputation. Therefore, the... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Peripheral neuropathy is not only the most prevalent consequence of diabetes but also the main reason for foot ulceration, disability, and amputation. Therefore, the current study aims to determine the effectiveness of oral clonidine and gabapentin on peripheral neuropathy in diabetic patients.
METHODS
This 12-week, randomized, and parallel-group trial was conducted to compare the efficacy of oral clonidine and gabapentin with gabapentin alone in diabetic patients in southwest Iran during the first half of 2021. Thirty patients with type 2 diabetes with peripheral neuropathy as assessed by a visual analog scale (VAS) and divided into two groups of 15 patients, treated for up to three months. The data were analyzed using SPSS-21 software. In order to report the results, descriptive indices, independent t-test, one-way analysis of covariance (ANCOVA) and analysis of variance with repeated measures were used.
RESULTS
The mean and standard deviation of the age of the participants in the clonidine + gabapentin group was equal to 50.20 ± 7.44, and in the gabapentin group was equal to 50.47 ± 7.57 (t = 0.10, P-value = 0.923). This research showed a significant difference between the clonidine + gabapentin group and with gabapentin group in terms of neuropathic pain and the severity of neuropathic pain (P < 0.001).
CONCLUSIONS
According to this research results, clonidine + gabapentin can reduce neuropathic pain and the severity of neuropathic pain in diabetic patients. Therefore, it is recommended that healthcare professionals with diabetes expertise prescribe these medications to reduce neuropathic pain and its severity.
TRIAL REGISTRATION
This study was registered in the Iranian Clinical Trials System with the ID (IRCT20211106052983N1) on 14/01/2022.
Topics: Humans; Gabapentin; Iran; Clonidine; Analgesics; Diabetes Mellitus, Type 2; gamma-Aminobutyric Acid; Diabetic Neuropathies; Amines; Cyclohexanecarboxylic Acids; Neuralgia
PubMed: 37845651
DOI: 10.1186/s12902-023-01486-0 -
Pain Jan 2024This preregistered (CRD42021223379) systematic review and meta-analysis aimed to characterize the placebo and nocebo responses in placebo-controlled randomized clinical... (Meta-Analysis)
Meta-Analysis
This preregistered (CRD42021223379) systematic review and meta-analysis aimed to characterize the placebo and nocebo responses in placebo-controlled randomized clinical trials (RCTs) on painful diabetic neuropathy (PDN), updating the previous literature by a decade. Four databases were searched for PDN trials published in the past 20 years, testing oral medications, adopting a parallel-group design. Magnitude of placebo or nocebo responses, Cochrane risk of bias, heterogeneity, and moderators were evaluated. Searches identified 21 studies (2425 placebo-treated patients). The overall mean pooled placebo response was -1.54 change in the pain intensity from baseline [95% confidence interval (CI): -1.52, -1.56, I 2 = 72], with a moderate effect size (Cohen d = 0.72). The pooled placebo 50% response rate was 25% [95% CI: 22, 29, I 2 = 50%]. The overall percentage of patients with adverse events (AEs) in the placebo arms was 53.3% [95% CI: 50.9, 55.7], with 5.1% [95% CI: 4.2, 6] of patients dropping out due to AEs. The year of study initiation was the only significant moderator of placebo response (regression coefficient = -0.06, [95% CI: -0.10, -0.02, P = 0.007]). More recent RCTs tended to be longer, bigger, and to include older patients (N = 21, rs = 0.455, P = 0.038, rs = 0.600, P = 0.004, rs = 0.472, P = 0.031, respectively). Our findings confirm the magnitude of placebo and nocebo responses, identify the year of study initiation as the only significant moderator of placebo response, draw attention to contextual factors such as confidence in PDN treatments, patients' previous negative experiences, intervention duration, and information provided to patients before enrollment.
Topics: Humans; Nocebo Effect; Diabetic Neuropathies; Placebo Effect; Pain Measurement; Diabetes Mellitus
PubMed: 37530658
DOI: 10.1097/j.pain.0000000000003000 -
CNS Neuroscience & Therapeutics Oct 2023Oxidative stress mediates the pathophysiology of diabetic neuropathy (DN) with activation of apoptotic pathway and reduction of autophagy. Arctigenin (ARC) is a natural...
BACKGROUND
Oxidative stress mediates the pathophysiology of diabetic neuropathy (DN) with activation of apoptotic pathway and reduction of autophagy. Arctigenin (ARC) is a natural lignan isolated from some plants of the Asteraceae family that shows antioxidant property. The present study aimed to explore the mechanistic neuroprotective effect of ARC on animal model for DN.
METHODS
DN was induced using streptozotocin (STZ) at a dose of 45 mg/kg, i.p, for five consecutive days and ARC was administered orally (25 or 50 mg) for 3 weeks. The mechanical sensitivity and thermal latency were determined using von Frey and hotplate, respectively. Beclin, p62, and LC3 were detected as markers for autophagy by western blot. Levels of reduced glutathione, lipid peroxides, and activities of catalase and superoxide dismutase were detected as readout for oxidative stress. Apoptotic parameters and histopathological changes were revealed in all experimental groups.
RESULTS
The present study showed deterioration of the function and structure of neurons as a result of hyperglycemia. Oxidative stress and impaired autophagy were observed in diabetic neurons as well as the activation of apoptotic pathway. ARC improved the behavioral and histopathological changes of diabetic mice. ARC combated oxidative stress through diminishing lipid peroxidation and improving the activity of antioxidant enzymes. This was concomitant by reducing the biomarkers of apoptosis. ARC augmented the expression of Beclin and LC3 while it lessened the expression of p62 indicating the activation of autophagy. These findings suggest that ARC can ameliorate DN by combating apoptosis and oxidative stress and improving autophagy.
Topics: Mice; Animals; Antioxidants; Streptozocin; Diabetes Mellitus, Experimental; Oxidative Stress; Lignans; Apoptosis; Diabetic Neuropathies; Autophagy
PubMed: 37170684
DOI: 10.1111/cns.14249 -
Middle East African Journal of... 2022The purpose of the study was to evaluate the corneal sensitivity and its quadrature variability in patients with diabetic neuropathy (DN) diagnosed with electromyography...
PURPOSE
The purpose of the study was to evaluate the corneal sensitivity and its quadrature variability in patients with diabetic neuropathy (DN) diagnosed with electromyography and to compare these results with age- and sex-matched healthy individuals.
METHODS
The left eyes of 32 patients who applied for refraction or fundus examination and had a diagnosis of DN by electromyography in their medical history were included in this study. Corneal sensitivity was evaluated using the Cochet-Bonnet esthesiometer (Luneau, Paris) in five zones: central, nasal, superior, temporal, and inferior. The measurements of the patients were compared with the measurements of 32 age- and sex-matched healthy volunteers. Furthermore, the measurements of five corneal zones were compared with each other, and the level of correlation was investigated in each group.
RESULTS
The central corneal sensitivity values were measured as 4.12 ± 1.04 (mm) and 5.92 ± 0.14 (mm) ( < 0.001). While the sensitivity values at the superior, inferior, nasal, and temporal quadrants were detected as 5.85 ± 0.21, 5.85 ± 0.26, 5.94 ± 0.13, 5.93 ± 0.13, and 5.92 ± 0.14 (mm) in the control group, it was measured as 3.67 ± 0.66, 3.67 ± 0.62, 3.67 ± 0.62, and 3.89 ± 0.73 (mm) in the DN group, respectively. The corneal sensitivity values were all found to be significantly lower in the DN group ( < 0.001 for all parameters) at all quadrants as well as the central cornea. Furthermore, a moderate positive correlation between all five zones in the control group and a very strong positive correlation in the DN group were found in terms of the corneal quadrature sensitivity.
CONCLUSION
The current study revealed a significant reduction in corneal sensitivity in patients with DN. In both the control group and DN group, all corneal zones showed positive correlations which show the consistency of the measurement in different quadratures. Evaluating corneal sensitivity with a Cochet-Bonnet esthesiometer might serve as a useful screening tool in detecting neuropathy development. By taking the necessary precautions, further damage can be prevented.
Topics: Humans; Cornea; Diabetes Mellitus; Diabetic Neuropathies; Microscopy, Confocal; Refraction, Ocular; Vision Tests
PubMed: 38162562
DOI: 10.4103/meajo.meajo_111_23