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Diabetes Research and Clinical Practice Jul 2023Diabetic neuropathy is associated with increased risk of morbidity and all-cause mortality. It is unclear whether these outcomes differ in patients with diabetic...
Morbidity and mortality of patients with diabetic neuropathy treated with pathogenetically oriented alpha-lipoic acid versus symptomatic pharmacotherapies - A nationwide database analysis from Hungary.
AIMS
Diabetic neuropathy is associated with increased risk of morbidity and all-cause mortality. It is unclear whether these outcomes differ in patients with diabetic neuropathy treated with pathogenetically oriented vs symptomatic pharmacotherapies.
METHODS
We performed a retrospective (2009-2019) database analysis of patients treated with pathogenetically oriented alpha-lipoic acid (ALA) or symptomatic pharmacotherapies for diabetic neuropathy. We investigated clinical outcomes in propensity score matched patients in Hungary. Changes in hazard ratios and annualized event rates were assessed and sensitivity analyses performed.
RESULTS
Hazard ratios favored treatment with ALA vs symptomatic pharmacotherapies regarding acute myocardial infarction (HR 0.73, 95% CI: 0.60-0.89, p = 0.0016), stroke (HR 0.71, 95% CI: 0.62-0.82, p < 0.0001), hospitalization for heart failure (HR 0.72, 95% CI: 0.66-0.78, p < 0.0001), cancer events (HR 0.83, 95% CI: 0.76-0.92, p = 0.0002) and all-cause mortality (HR 0.55, 95% CI: 0.49-0.61, p < 0.0001), but not for lower limb amputation (HR 1.05, 95% CI: 0.89-1.25, p = 0.5455). This association was supported by results of evaluating annual event rates and sensitivity analyses.
CONCLUSIONS
This retrospective database analysis revealed a lower occurrence of cardio- and cerebrovascular morbidity, cancer events and all-cause mortality in patients with diabetic neuropathy treated with pathogenetically oriented ALA vs symptomatic pharmacotherapies. This hypothesis-generating result requires further investigations.
Topics: Humans; Thioctic Acid; Diabetic Neuropathies; Retrospective Studies; Hungary; Antioxidants; Diabetes Mellitus
PubMed: 37257759
DOI: 10.1016/j.diabres.2023.110734 -
BMC Medical Informatics and Decision... Aug 2023Diabetic peripheral neuropathy (DPN) is a common complication of diabetes. Predicting the risk of developing DPN is important for clinical decision-making and designing...
BACKGROUND
Diabetic peripheral neuropathy (DPN) is a common complication of diabetes. Predicting the risk of developing DPN is important for clinical decision-making and designing clinical trials.
METHODS
We retrospectively reviewed the data of 1278 patients with diabetes treated in two central hospitals from 2020 to 2022. The data included medical history, physical examination, and biochemical index test results. After feature selection and data balancing, the cohort was divided into training and internal validation datasets at a 7:3 ratio. Training was made in logistic regression, k-nearest neighbor, decision tree, naive bayes, random forest, and extreme gradient boosting (XGBoost) based on machine learning. The k-fold cross-validation was used for model assessment, and the accuracy, precision, recall, F1-score, and the area under the receiver operating characteristic curve (AUC) were adopted to validate the models' discrimination and clinical practicality. The SHapley Additive exPlanation (SHAP) was used to interpret the best-performing model.
RESULTS
The XGBoost model outperformed other models, which had an accuracy of 0·746, precision of 0·765, recall of 0·711, F1-score of 0·736, and AUC of 0·813. The SHAP results indicated that age, disease duration, glycated hemoglobin, insulin resistance index, 24-h urine protein quantification, and urine protein concentration were risk factors for DPN, while the ratio between 2-h postprandial C-peptide and fasting C-peptide(C2/C0), total cholesterol, activated partial thromboplastin time, and creatinine were protective factors.
CONCLUSIONS
The machine learning approach helped established a DPN risk prediction model with good performance. The model identified the factors most closely related to DPN.
Topics: Humans; Bayes Theorem; C-Peptide; Diabetic Neuropathies; Retrospective Studies; Risk Factors; Machine Learning; Diabetes Mellitus
PubMed: 37533059
DOI: 10.1186/s12911-023-02232-1 -
PeerJ 2023The current treatments for diabetic foot ulcers have disadvantages of slow action and numerous complications. Tibial cortex transverse transport (TTT) surgery is an...
BACKGROUND
The current treatments for diabetic foot ulcers have disadvantages of slow action and numerous complications. Tibial cortex transverse transport (TTT) surgery is an extension of the Ilizarov technique used to treat diabetic foot ulcers, and can shorten the repair time of diabetic foot ulcers. This study assessed the TTT technique for its effectiveness in healing diabetic foot ulcer skin lesions and its related molecular mechanisms.
METHODS
Diabetic rat models were established by injecting healthy Sprague-Dawley rats with streptozotocin (STZ). The effects of TTT surgery on the model rats were assessed by recording changes in body weight, analyzing skin wound pictures, and performing H&E staining to assess the recovery of wounded skin. The numbers of endothelial progenitor cells (EPCs) in peripheral blood were analyzed by flow cytometry, and levels of CXCR4 and SDF-1 expression were qualitatively analyzed by immunofluorescence, immunohistochemistry, qRT-PCR, and western blotting.
RESULTS
Both the histological results and foot wound pictures indicated that TTT promoted diabetic wound healing. Flow cytometry results showed that TTT increased the numbers of EPCs in peripheral blood as determined by CD34 and CD133 expression. In addition, activation of the SDF-1/CXCR4 signaling pathway and an accumulation of EPCs were observed in skin ulcers sites after TTT surgery. Finally, the levels of SDF-1 and CXCR4 mRNA and protein expression in the TTT group were higher than those in a blank or fixator group.
CONCLUSION
TTT promoted skin wound healing in diabetic foot ulcers possibly by activating the SDF-1/CXCR4 signaling pathway.
Topics: Animals; Rats; Rats, Sprague-Dawley; Diabetic Foot; Antigens, CD34; Blotting, Western; Wound Healing; Diabetes Mellitus
PubMed: 37727693
DOI: 10.7717/peerj.15894 -
Nature Communications Feb 2024Chronic diabetic wounds are at lifelong risk of developing diabetic foot ulcers owing to severe hypoxia, excessive reactive oxygen species (ROS), a complex inflammatory...
Chronic diabetic wounds are at lifelong risk of developing diabetic foot ulcers owing to severe hypoxia, excessive reactive oxygen species (ROS), a complex inflammatory microenvironment, and the potential for bacterial infection. Here we develop a programmed treatment strategy employing live Haematococcus (HEA). By modulating light intensity, HEA can be programmed to perform a variety of functions, such as antibacterial activity, oxygen supply, ROS scavenging, and immune regulation, suggesting its potential for use in programmed therapy. Under high light intensity (658 nm, 0.5 W/cm), green HEA (GHEA) with efficient photothermal conversion mediate wound surface disinfection. By decreasing the light intensity (658 nm, 0.1 W/cm), the photosynthetic system of GHEA can continuously produce oxygen, effectively resolving the problems of hypoxia and promoting vascular regeneration. Continuous light irradiation induces astaxanthin (AST) accumulation in HEA cells, resulting in a gradual transformation from a green to red hue (RHEA). RHEA effectively scavenges excess ROS, enhances the expression of intracellular antioxidant enzymes, and directs polarization to M2 macrophages by secreting AST vesicles via exosomes. The living HEA hydrogel can sterilize and enhance cell proliferation and migration and promote neoangiogenesis, which could improve infected diabetic wound healing in female mice.
Topics: Female; Animals; Mice; Microalgae; Reactive Oxygen Species; Diabetes Mellitus; Diabetic Foot; Anti-Bacterial Agents; Hypoxia; Oxygen; Wound Healing; Hydrogels
PubMed: 38310127
DOI: 10.1038/s41467-024-45101-9 -
Journal of Diabetes Science and... Jan 2024Spinal cord stimulation (SCS) technology has been recently approved by the US Food and Drug Administration (FDA) for painful diabetic neuropathy (PDN). The treatment... (Review)
Review
Spinal cord stimulation (SCS) technology has been recently approved by the US Food and Drug Administration (FDA) for painful diabetic neuropathy (PDN). The treatment involves surgical implantation of electrodes and a power source that delivers electrical current to the spinal cord. This treatment decreases the perception of pain in many chronic pain conditions, such as PDN. The number of patients with PDN treated with SCS and the amount of data describing their outcomes is expected to increase given four factors: (1) the large number of patients with this diagnosis, (2) the poor results that have been obtained for pain relief with pharmacotherapy and noninvasive non-pharmacotherapy, (3) the results to date with investigational SCS technology, and (4) the recent FDA approval of systems that deliver this treatment. Whereas traditional SCS replaces pain with paresthesias, a new form of SCS, called high-frequency 10-kHz SCS, first used for pain in 2015, can relieve PDN pain without causing paresthesias, although not all patients experience pain relief by SCS. This article describes (1) an overview of SCS technology, (2) the use of SCS for diseases other than diabetes, (3) the use of SCS for PDN, (4) a comparison of high-frequency 10-kHz and traditional SCS for PDN, (5) other SCS technology for PDN, (6) deployment of SCS systems, (7) barriers to the use of SCS for PDN, (8) risks of SCS technology, (9) current recommendations for using SCS for PDN, and (10) future developments in SCS.
Topics: Humans; Diabetic Neuropathies; Spinal Cord Stimulation; Paresthesia; Pain Measurement; Pain; Diabetes Mellitus
PubMed: 36384312
DOI: 10.1177/19322968221133795 -
International Wound Journal Oct 2023A meta-analysis investigation to measure the relationship between vitamin D deficiency (VDD) and diabetic foot ulcer (DFU). A comprehensive literature inspection till... (Meta-Analysis)
Meta-Analysis
A meta-analysis investigation to measure the relationship between vitamin D deficiency (VDD) and diabetic foot ulcer (DFU). A comprehensive literature inspection till February 2023 was applied and 1765 interrelated investigations were reviewed. The 15 chosen investigations enclosed 2648 individuals with diabetes mellitus in the chosen investigations' starting point, 1413 of them were with DFUs, and 1235 were without DFUs. Odds ratio (OR) in addition to 95% confidence intervals (CIs) were used to compute the value of the relationship between VDD and DFU by the dichotomous and continuous approaches and a fixed or random model. Individuals with DFUs had significantly lower vitamin D levels (VDL) (MD, -7.14; 95% CI, -8.83 to -5.44, P < 0.001) compared to those without DFU individuals. Individuals with DFUs had a significantly higher number of VDD individuals (OR, 2.27; 95% CI, 1.63-3.16, P < 0.001) compared to those without DFU individuals. Individuals with DFU had significantly lower VDL and a significantly higher number of VDD individuals compared to those without DFU individuals. However, caused of the small sample sizes of several chosen investigations for this meta-analysis, care must be exercised when dealing with its values.
Topics: Humans; Diabetic Foot; Diabetes Mellitus; Vitamin D Deficiency; Foot Ulcer
PubMed: 37194326
DOI: 10.1111/iwj.14177 -
Journal of the Mechanical Behavior of... Feb 2024Diabetic foot ulceration is linked to high amputation and mortality rates, with the substantial associated annual spend on the at-risk diabetic foot reflecting the...
Diabetic foot ulceration is linked to high amputation and mortality rates, with the substantial associated annual spend on the at-risk diabetic foot reflecting the intensive time and labour involved in treatment. Assessing plantar interactions and developing improved understanding of the formation pathways of diabetic ulceration is important to orthotic interventions and patient outcomes. Plantar skin surrogates which emulate the mechanical and tribological characteristics can help improve physical models of ulceration, reduce reliance on cadaveric use and inform more complex computational modelling approaches. The information available from existing studies to characterise plantar skin is limited, typically featuring ex-vivo representations of skin and subcutaneous tissue combined and given focus to shear studies with time dependency. The aim of this study is to improve understanding of plantar tissue mechanics by assessing the mechanical characteristics of plantar skin in two groups; (1) non-diabetic and (2) diabetic donors without the subcutaneous tissue attachment of previous work in this field. Digital image correlation was used to assess inherent skin pre-tension of the plantar rearfoot prior to dissection. Young's modulus, storage and loss moduli were tested for using tensile stress-strain failure analysis and tensile and compressive dynamic mechanical analysis, which was conducted on excised plantar rearfoot donor specimens for both disease state cohorts at frequencies reflecting those achieved in activities of daily living. Plantar skin thickness for donor specimens were comparable to values obtained using ultrasound acquired in vivo values. Median tensile storage and loss moduli, along with Young's modulus, was higher in the diabetic cohort. With a mean Young's modulus of 0.83 ± 0.49 MPa and 1.33 ± 0.43 MPa for non-diabetic and diabetic specimens respectively. Compressive studies showed consistency between cohorts for median storage and loss moduli. The outcomes from this study show mechanical characteristics of plantar skin without the involvement of subcuteanous tissues under reflective daily achieved loading regimes, showing differences in the non-diabetic and diabetic specimens trialled to support improved understanding of plantar tissue response under tribological interactions.
Topics: Humans; Diabetic Foot; Activities of Daily Living; Skin; Subcutaneous Tissue; Elastic Modulus; Diabetes Mellitus
PubMed: 38007990
DOI: 10.1016/j.jmbbm.2023.106279 -
Biosensors Aug 2023Some chronic diseases, including Parkinson's disease (PD), diabetic foot, flat foot, stroke, elderly falling, and knee osteoarthritis (KOA), are related to orthopedic... (Review)
Review
Some chronic diseases, including Parkinson's disease (PD), diabetic foot, flat foot, stroke, elderly falling, and knee osteoarthritis (KOA), are related to orthopedic organs, nerves, and muscles. The interaction of these three parts will generate a comprehensive result: gait. Furthermore, the lesions in these regions can produce abnormal gait features. Therefore, monitoring the gait features can assist medical professionals in the diagnosis and analysis of these diseases. Nowadays, various insole systems based on different sensing techniques have been developed to monitor gait and aid in medical research. Hence, a detailed review of insole systems and their applications in disease management can greatly benefit researchers working in the field of medical engineering. This essay is composed of the following sections: the essay firstly provides an overview of the sensing mechanisms and parameters of typical insole systems based on different sensing techniques. Then this essay respectively discusses the three stages of gait parameters pre-processing, respectively: pressure reconstruction, feature extraction, and data normalization. Then, the relationship between gait features and pathogenic mechanisms is discussed, along with the introduction of insole systems that aid in medical research; Finally, the current challenges and future trends in the development of insole systems are discussed.
Topics: Aged; Humans; Medicine; Biomedical Research; Diabetic Foot; Gait; Muscles
PubMed: 37622919
DOI: 10.3390/bios13080833 -
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 -
Frontiers in Endocrinology 2024We explore the effect of suboptimal glycemic control on the incidence of diabetic peripheral neuropathy (DPN) in both non-elderly and elderly patients with type 2...
BACKGROUND
We explore the effect of suboptimal glycemic control on the incidence of diabetic peripheral neuropathy (DPN) in both non-elderly and elderly patients with type 2 diabetes mellitus (T2DM).
METHODS
A 6-year follow-up study (2013-2019) enrolled T2DM patients aged >20 without DPN. Participants were classified into two groups: those below 65 years (non-elderly) and those 65 years or older (elderly). Biochemical measurements, including glycated hemoglobin (HbA1C), were recorded regularly. DPN was diagnosed using the Michigan Neuropathy Screening Instrument examination. The outcome was DPN occurrence in 2019.
RESULTS
In 552 enrollments (69% non-elderly), DPN occurred in 8.4% non-elderly and 24.0% elderly patients. A higher initial HbA1C level was significantly linked with a higher risk of future DPN in the non-elderly group (adjusted odds ratio [AOR] 1.46, 95% CI 1.13-1.89, p=0.004). In comparison, HbA1c at the end of the study period was not associated with DPN in the non-elderly group (AOR 1.17, 95% CI 0.72-1.90, p=0.526). In the elderly group, no statistical relationship was found between HbA1C levels and DPN, either in 2013 or in 2019.
CONCLUSION
Suboptimal glycemic control at baseline, rather than at the end of the study period, predicts an increased risk of future DPN in individuals with T2DM under age 65. This correlation is not seen in elderly patients. Therefore, we recommend implementing enhanced glycemic control early in middle-aged T2DM patients and propose individualized therapeutic strategies for diabetes in different age groups.
Topics: Humans; Diabetic Neuropathies; Male; Female; Diabetes Mellitus, Type 2; Middle Aged; Aged; Glycemic Control; Glycated Hemoglobin; Follow-Up Studies; Age Factors; Blood Glucose; Adult; Incidence; Risk Factors
PubMed: 38694945
DOI: 10.3389/fendo.2024.1377923