BACKGROUND: Nearly half of patients with diabetes experience diabetic peripheral neuropathy (DPN), resulting in a mere 53% survival rate within 3 years. Aberrations in coagulation function have been implicated in the pathogenesis of microvascular complications, prompting the need for a thorough investigation into its role as a contributing factor in the development and progression of DPN.
METHODS: Data were gathered from 1211 type 2 diabetes patients admitted to five centers from September 2018 to October 2022 in China. DPN was evaluated by symptoms and electromyography. Motor and sensory nerve conduction velocity (NCV) was appraised and the NCV sum score was calculated for the median, ulnar, and peroneal motor or sensory nerves.
RESULTS: Patients with DPN exhibited alterations in coagulation function. (i) Specifically, they exhibited prolonged thrombin time (p = 0.012), elevated fibrinogen (p < 0.001), and shortened activated partial thromboplastin time (APTT; p = 0.026) when compared to the control group. (ii) After accounting for potential confounders in linear regression, fibrinogen, and D-dimer were negatively related to the motor NCV, motor amplitude values, and mean velocity and amplitude. Also, fibrinogen was associated with higher Michigan neuropathy screening instrument (MNSI) scores (β 0.140; p = 0.001). This result of fibrinogen can be validated in the validation cohort with 317 diabetic patients. (iii) Fibrinogen was independently associated with the risk of DPN (OR 1.172; p = 0.035). In the total age group, DPN occurred at a slower rate until the predicted fibrinogen level reached around 3.75 g/L, after which the risk sharply escalated.
CONCLUSIONS: Coagulation function is warranted to be concerned in patients with type 2 diabetes to predict and prevent the occurrence of DPN in clinical practice.

BACKGROUND: Diabetes peripheral neuropathy (DPN) is mainly treated with diabetes as a whole, and there is no targeted treatment. Some studies have reported that adjuvant hyperbaric oxygen therapy (HBOT) for DPN has achieved a good effect, our study aimed to evaluate the clinical efficacy and safety of HBOT for DPN and provide reference for the clinic by using a systematic review and meta-analysis.
METHODS: A comprehensive search was conducted across several databases, including PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Internet Database, Chinese BioMedical Database, China Scientific Journal Database, and Wanfang Database, for relevant randomized controlled trials published before July 2022. The population, intervention, comparison, outcomes, study design criteria were used to guide the selection of studies. Meta-analysis was performed using RevMan 5.4 and STATA 14.0, with odds ratios and mean differences along with 95% confidence intervals serving as measures of effect size.
RESULTS: Fourteen randomized controlled trials were included in the final analysis, comprising 675 patients in the HBOT group and 648 in the standard therapy (ST) group. The HBOT group demonstrated a significantly higher effective treatment rate compared to the ST group (P < .001). Additionally, the HBOT group showed significant improvements in motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNVC) across multiple nerves: median nerve (PMNCV < 0.001, PSNCV = 0.001), ulnar nerve (PMNCV = 0.02, PSNCV < 0.001), peroneal nerve (PMNCV < 0.001, PSNCV < 0.001), and tibial nerve (PMNCV = 0.001, PSNCV = 0.008). Six adverse events were reported in the HBOT group, while no adverse events occurred in the ST group, with no significant difference between the 2 groups. Publication bias was identified in some outcome variables through funnel plots, Begger test, and Egger test.
CONCLUSIONS: HBOT significantly enhances treatment efficacy and nerve conduction velocity in patients with DPN, with few adverse events, making it a safe and effective adjunctive therapy for DPN.

Chronic inflammation is associated with diabetes and contributes to the development and progression of micro- and macrovascular complications. Transcutaneous vagus nerve stimulation (tVNS) has been proposed to reduce levels of circulating inflammatory cytokines in non-diabetics by activating the cholinergic anti-inflammatory pathway. We investigated the anti-inflammatory potential of tVNS as a secondary endpoint of a randomized controlled trial in people with diabetes (NCT04143269). 131 people with diabetes (type 1: n = 63; type 2: n = 68), gastrointestinal symptoms and various degrees of autonomic neuropathy were included and randomly assigned to self-administer active (n = 63) or sham (n = 68) tVNS over two successive study periods: (1) Seven days with four daily administrations and, (2) 56 days with two daily administrations. Levels of systemic inflammatory cytokines (IL-6, IL-8, IL-10, TNF-α, IFN-γ) were quantified from blood samples by multiplex technology. Information regarding age, sex, diabetes type, and the presence of cardiac autonomic neuropathy (CAN) was included in the analysis as possible confounders. No differences in either cytokine were seen after study period 1 and 2 between active and sham tVNS (all p-values > 0.08). Age, sex, diabetes type, presence of CAN, and baseline levels of inflammatory cytokines were not associated with changes after treatment (all p-values > 0.07). A tendency towards slight reductions in TNF-α levels after active treatment was observed in those with no CAN compared to those with early or manifest CAN (p = 0.052). In conclusion, tVNS did not influence the level of systemic inflammation in people with diabetes.

BACKGROUND: Proprioceptive disorders may occur when thick fibers are affected in diabetic neuropathy. This can lead to impaired joint stabilization and increased risk of falls and fractures. We evaluated joint position sense (JPS) in diabetic patients to detect those at risk for neuropathy earlier.
METHODS: Sixty diabetic patients and 30 healthy individuals aged 30 to 60 years were included in the study and divided into three groups: 30 diabetic patients with peripheral neuropathy, 30 diabetic patients without peripheral neuropathy, and 30 nondiabetic control patients. Presence of neuropathy was determined electrophysiologically. Passive ankle JPS was evaluated by an isokinetic system in all three groups. Both 10° and 30° plantarflexion and 10° dorsiflexion were determined as target angles. The mean absolute angular error (MAAE) values for three trials with each angle were assessed by Kruskal-Wallis and Mann-Whitney U tests.
RESULTS: The MAAEs with all of the angles were significantly higher in diabetic patients with peripheral neuropathy compared with diabetic patients without peripheral neuropathy and the control group (P < .001 for all of the comparisons). The MAAEs with right ankle 10° plantarflexion (P = .004) and 10° dorsiflexion (P = .007) and left ankle 10° plantarflexion (P = .008) were significantly higher in diabetic patients without peripheral neuropathy than in the control group.
CONCLUSIONS: According to these results, ankle JPS may be deteriorated before determination of neuropathy electrophysiologically.Therefore, we believe that prophylactic programs in terms of the risk of falls and fractures by evaluating JPS need to be developed in the early stages of diabetes.

OBJECTIVE: Diabetic polyneuropathy is a long-standing microvascular complication of diabetes that affects the postural control and functional mobility of patients. There are other microvascular complications, including pulmonary complications that reduce lung function. Multifactorial Inspiratory Muscle Training (IMT) can act as a home-based technique targeted to affect both these complications. This study aims to determine the effects of IMT on respiratory and functional parameters in diabetic polyneuropathy patients.
METHODS: This is a Pre-Test Post-Test Randomized Controlled Trial (NCT#04947163) with 62 diabetic polyneuropathy patients. Each was randomly assigned to the IMT or sham-IMT group. Both the groups performed OTAGO exercises , with the sham-IMT group performing IMT at 15% of baseline maximal inspiratory pressure (MIP), whereas IMT were trained at 50% of baseline MIP as an initial intensity, which was increased as per the tolerance of patients. Both groups performed training for 12 weeks. The study investigated diaphragmatic strength, pulmonary function, functional capacity through 6MWT, 30s sit to stand test and anterior trunk muscle endurance tested through sit up test as outcome variables. Data was analysed on SPSS v26 at the significance level of 0.0.5.
RESULTS: The IMT group significantly improved diaphragmatic strength, pulmonary function, 6MWT and anterior trunk muscle endurance when compared to the sham-IMT group.
CONCLUSIONS: The study concluded that home-based IMT can improve pulmonary parameters including diaphragmatic strength and lung function as well as functional parameters including functional capacity in patients with diabetic polyneuropathy. The study was registered at ClinicalTrials.gov, NCT#04947163.

Mitophagy, the cellular process of selectively eliminating damaged mitochondria, plays a crucial role in maintaining metabolic balance and preventing insulin resistance, both key factors in type 2 diabetes mellitus (T2DM) development. When mitophagy malfunctions in diabetic neuropathy, it triggers a cascade of metabolic disruptions, including reduced energy production, increased oxidative stress, and cell death, ultimately leading to various complications. Thus, targeting mitophagy to enhance the process may have emerged as a promising therapeutic strategy for T2DM and its complications. Notably, plant-derived compounds with β-cell protective and mitophagy-stimulating properties offer potential as novel therapeutic agents. This review highlights the intricate mechanisms linking mitophagy dysfunction to T2DM and its complications, particularly neuropathy, elucidating potential therapeutic interventions for this debilitating disease.

OBJECTIVE: Isorhamnetin, a naturally occurring flavonoid compound, holds paramount importance as a primary constituent within several medicinal plants, exhibiting profound pharmacological significance. The aim of this study is to investigate the pain-relieving attributes of isorhamnetin in murine models through both formalin-induced pain and diabetic neuropathy scenarios.
METHODS: To achieve our objective, isorhamnetin was orally administered to mice at varying dosage levels (10 to 100 mg/kg). Pain-related behaviors were assessed using the formalin test during its secondary phase. Additionally, the potential pain-alleviating effect of isorhamnetin was evaluated in a diabetic neuropathy model induced by streptozotocin. Additionally, we carried out advanced interventions using naloxone, which is a well-known antagonist of opioid receptors, yohimbine, which blocks α2-adrenergic receptors, and methysergide, which inhibits serotonergic receptors, during the formalin test.
RESULTS: The oral intake of isorhamnetin showed a decrease in behaviors associated with pain that was proportional to the dose observed during the second phase of the formalin test when induced by formalin. In the diabetic neuropathy model, isorhamnetin administration effectively reversed the reduced pain threshold observed. Notably, naloxone, the opioid receptor antagonist, effectively counteracted the pain-relieving effect produced by isorhamnetin in the formalin test, whereas yohimbine and methysergide did not yield similar outcomes. Isorhamnetin also led to a reduction in elevated spinal cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) levels triggered by formalin, with this effect reversed by pre-treatment with naloxone. The compound also suppressed heightened spinal phosphorylated CREB (p-CREB) levels caused by diabetic neuropathy.
CONCLUSIONS: This research determined that isorhamnetin has notable abilities to relieve pain in models of formalin-induced pain and diabetic neuropathy. The pain-relieving mechanism of isorhamnetin in the formalin-induced pain model seems to be connected to the activation of spinal opioid receptors and the adjustment of CREB protein amounts. This insight improves our knowledge of how isorhamnetin could be used therapeutically to treat pain conditions stemming from formalin-induced pain and diabetic neuropathy.

UNASSIGNED: The aim of this study is to assess the effectiveness of foot skin protection technology in elderly patients with diabetic peripheral neuropathy.
UNASSIGNED: The foot skin protection technology was developed based on a comprehensive literature review and preliminary research conducted by our research team. Subsequently, 88 elderly patients with diabetic peripheral neuropathy and experiencing foot skin problems were recruited from two community health service centers in Shanghai. Using a random number table, the participants were randomly assigned to either the control group or the experimental group. Patients in the experimental group received foot skin protection technology interventions, while those in the control group received standard community nursing guidance for a duration of 3 months. The incidence, severity, and discomfort associated with foot skin problems were evaluated before and after the intervention period in both groups.
UNASSIGNED: The incidence, severity, and discomfort of foot skin problems notably reduced in the experimental group (all P< 0.05).
UNASSIGNED: The foot skin protection technology demonstrates significant potential in enhancing foot skin condition.

OBJECTIVE: To explore the lifestyle-related characteristics of people having type 2 diabetes mellitus with peripheral neuropathy.
METHODS: The phenomenological study was conducted from July 5 to September 18, 2021, at Sadabuan Health Centre, Batunadua Health Centre and Wek 3 Health Centre, Padangsidimpuan, Indonesia, and comprised diabetic neuropathy patients who had cognitive impairment, anxiety and depression. Data was collected using in-depth interviews. Data was analysed using Collaizi\'s method.
RESULTS: There were 8 subjects with mean age 48.38±13,606 years (range: 27-65 years), and mean duration of diabetes was 6±3.207 years. The majority of participants in this study were women 6 (75%). There were 7 themes that emerged from the collected data: level of physical activity, diet, sleep pattern, habit of consuming sweet drinks, smoking habit, social interaction, and self-care.
CONCLUSIONS: Diabetes mellitus patient with peripheral neuropathy had not been able to completely switch to a healthier lifestyle.

UNASSIGNED: Plai or Zingiber cassumunar Roxb. was registered into the Thai Traditional Medicine list since 2011. However, there is limited evidence regarding Plai as a treatment in painful diabetic neuropathy (PDN). Therefore, this study aimed to evaluate the efficacy of topical Zingiber cassumunar.
UNASSIGNED: A RCT was conducted in patients with PDN during February to March 2019. All participants received oral gabapentin 300 mg before bed as a standard regimen. The intervention group (n=16) received Plai balm 15%w/w 0.5 gram to apply on their feet three times a day and the control group (n=15) received placebo balm to similarly apply. Pain score at baseline, 2 nd and 4 th weeks were assessed and compared. Patients\' quality of life, and adverse events, were collected. Mean pain scores before and after treatment in each group and between groups were also analyzed.
UNASSIGNED: At the end of week two and week four, the Plai group showed statistically significant lesser mean pain scores than the placebo group by -1.47 (95%CI: -1.96 to -1.30, p-value < 0.001), and by -1.51 (95%CI: -1.92 to -0.13, p-value = 0.027), respectively. Moreover, the Plai group had more cases number/ percentages with at least 50% pain score reduction than the placebo group [12/16 (75%) vs 3/15 (20%), p-value = 0.004]. However, there was no statistically significant difference in quality of life between the two groups (overall p-value = 0.366). Adverse event was not found in any groups.
UNASSIGNED: Zingiber cassumunar balm (Plai) was efficacious for pain reduction in painful diabetic neuropathy.
UNASSIGNED: Registered with the Thai Clinical Trials Registry; TCTR20200221001.