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EXCLI Journal 2023Hesperidin and hesperetin, two flavonoids with potential therapeutic value, have been extensively studied in the context of diabetes management. The main objective of... (Review)
Review
Hesperidin and hesperetin, two flavonoids with potential therapeutic value, have been extensively studied in the context of diabetes management. The main objective of this research is to ascertain their potential as therapeutic options for managing diabetes and its complications. The present study utilized a systematic review methodology and comprehensively explored relevant literature from databases, including PubMed, Scopus, and Web of Science, from inception until July 2023. The review summarized the outcomes related to the molecular, cellular, and metabolic effects of hesperidin and hesperetin in diabetes and its complications. Hesperetin exhibits a potential treatment for preventing diabetes and its associated complications through modulation of inflammatory cytokine release and expression via the pathway of signaling through Toll-like receptor/Myeloid differentiation factor 88/Nuclear factor-kappa B. Hesperidin shows promise as a biomolecule for treating diabetic neuropathy, primarily through activation of nuclear factor erythroid 2-related factor 2 (Nrf-2), as an antioxidant-response element signaling, leading to neuroprotective effects. Both compounds demonstrated the ability to normalize blood glucose levels and reduce serum and liver lipid levels, making them potential candidates for managing hypoglycemia and hypolipidemia in diabetes. Hesperidin also showed potential benefits against diabetic nephropathy by suppressing transforming growth factor-β1-integrin-linked kinase-Akt signaling and enhancing renal function. Furthermore, hesperidin's antioxidant, anti-inflammatory, and anti-depressant effects in diabetic conditions expanded its potential therapeutic applications. This systematic review provides substantial evidence supporting the consideration of hesperidin and hesperetin for diabetes and its complications. It offers exciting possibilities for developing novel, cost-effective treatment options to enhance diabetes management and patient outcomes.
PubMed: 38234970
DOI: 10.17179/excli2023-6577 -
The Cochrane Database of Systematic... Jan 2024Diabetic peripheral neuropathy (DPN) is a frequent complication in people living with type 1 or type 2 diabetes. There is currently no effective treatment for DPN.... (Review)
Review
BACKGROUND
Diabetic peripheral neuropathy (DPN) is a frequent complication in people living with type 1 or type 2 diabetes. There is currently no effective treatment for DPN. Although alpha-lipoic acid (ALA, also known as thioctic acid) is widely used, there is no consensus about its benefits and harms.
OBJECTIVES
To assess the effects of alpha-lipoic acid as a disease-modifying agent in people with diabetic peripheral neuropathy.
SEARCH METHODS
On 11 September 2022, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, and two clinical trials registers. We also searched the reference lists of the included studies and relevant review articles for additional references not identified by the electronic searches.
SELECTION CRITERIA
We included randomised clinical trials (RCTs) that compared ALA with placebo in adults (aged 18 years or older) and that applied the study interventions for at least six months. There were no language restrictions.
DATA COLLECTION AND ANALYSIS
We used standard methods expected by Cochrane. The primary outcome was change in neuropathy symptoms expressed as changes in the Total Symptom Score (TSS) at six months after randomisation. Secondary outcomes were change in neuropathy symptoms at six to 12 months and at 12 to 24 months, change in impairment, change in any validated quality of life total score, complications of DPN, and adverse events. We assessed the certainty of the evidence using GRADE.
MAIN RESULTS
Our analysis incorporated three trials involving 816 participants. Two studies included people with type 1 or type 2 diabetes, while one study included only people with type 2 diabetes. The duration of treatment was between six months and 48 months. We judged all studies at high risk of overall bias due to attrition. ALA compared with placebo probably has little or no effect on neuropathy symptoms measured by TSS (lower score is better) after six months (mean difference (MD) -0.16 points, 95% confidence interval (CI) -0.83 to 0.51; 1 study, 330 participants; moderate-certainty evidence). The CI of this effect estimate did not contain the minimal clinically important difference (MCID) of 0.97 points. ALA compared with placebo may have little or no effect on impairment measured by the Neuropathy Impairment Score-Lower Limbs (NIS-LL; lower score is better) after six months (MD -1.02 points, 95% CI -2.93 to 0.89; 1 study, 245 participants; low-certainty evidence). However, we cannot rule out a significant benefit, because the lower limit of the CI surpassed the MCID of 2 points. There is probably little or no difference between ALA and placebo in terms of adverse events leading to cessation of treatment within six months (risk ratio (RR) 1.48, 95% CI 0.50 to 4.35; 3 studies, 1090 participants; moderate-certainty evidence). No studies reported quality of life or complications associated with DPN.
AUTHORS' CONCLUSIONS
Our analysis suggests that ALA probably has little or no effect on neuropathy symptoms or adverse events at six months, and may have little or no effect on impairment at six months. All the studies were at high risk of attrition bias. Therefore, future RCTs should ensure complete follow-up and transparent reporting of any participants missing from the analyses.
Topics: Adult; Humans; Thioctic Acid; Diabetic Neuropathies; Diabetes Mellitus, Type 2; Lower Extremity; MEDLINE
PubMed: 38205823
DOI: 10.1002/14651858.CD012967.pub2 -
Journal of Diabetes Science and... Mar 2024Diabetic microvascular complications significantly impact morbidity and mortality. This review focuses on machine learning/artificial intelligence (ML/AI) in predicting... (Review)
Review
IMPORTANCE AND AIMS
Diabetic microvascular complications significantly impact morbidity and mortality. This review focuses on machine learning/artificial intelligence (ML/AI) in predicting diabetic retinopathy (DR), diabetic kidney disease (DKD), and diabetic neuropathy (DN).
METHODS
A comprehensive PubMed search from 1990 to 2023 identified studies on ML/AI models for diabetic microvascular complications. The review analyzed study design, cohorts, predictors, ML techniques, prediction horizon, and performance metrics.
RESULTS
Among the 74 identified studies, 256 featured internally validated ML models and 124 had externally validated models, with about half being retrospective. Since 2010, there has been a rise in the use of ML for predicting microvascular complications, mainly driven by DKD research across 27 countries. A more modest increase in ML research on DR and DN was observed, with publications from fewer countries. For all microvascular complications, predictive models achieved a mean (standard deviation) c-statistic of 0.79 (0.09) on internal validation and 0.72 (0.12) on external validation. Diabetic kidney disease models had the highest discrimination, with c-statistics of 0.81 (0.09) on internal validation and 0.74 (0.13) on external validation, respectively. Few studies externally validated prediction of DN. The prediction horizon, outcome definitions, number and type of predictors, and ML technique significantly influenced model performance.
CONCLUSIONS AND RELEVANCE
There is growing global interest in using ML for predicting diabetic microvascular complications. Research on DKD is the most advanced in terms of publication volume and overall prediction performance. Both DR and DN require more research. External validation and adherence to recommended guidelines are crucial.
Topics: Humans; Artificial Intelligence; Diabetes Mellitus; Diabetic Nephropathies; Diabetic Neuropathies; Diabetic Retinopathy; Machine Learning; Retrospective Studies
PubMed: 38189280
DOI: 10.1177/19322968231223726 -
Cureus Dec 2023Diabetic peripheral neuropathy (DPN) is a prevalent and debilitating complication of diabetes mellitus, leading to sensory abnormalities, decreased balance, and... (Review)
Review
Diabetic peripheral neuropathy (DPN) is a prevalent and debilitating complication of diabetes mellitus, leading to sensory abnormalities, decreased balance, and increased risk of foot problems. Although tumor necrosis factor-alpha (TNF-α) has emerged as a potential factor in the pathogenesis of DPN, its role remains contested. This study intends to thoroughly analyze the association between TNF-α and DPN by combining data from various global studies. This systematic review and meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and included 23 articles investigating TNF-α levels in DPN patients for systematic review and 11 articles for meta-analysis. Data were extracted, and heterogeneity was examined. A random-effect model was chosen due to high heterogeneity. The major outcome measure across studies was serum TNF-α levels. The meta-analysis found a significant mean difference of 15.2464 (95% confidence interval = 4.4963; 25.9965) under the random-effect model due to the substantial heterogeneity (I = 98.1%) among included studies. The meta-analysis indicates a consistent elevation in TNF-α levels in individuals with DPN compared to those without neuropathy. This underlines the potential of TNF-α as a biomarker and contributor to diabetic neuropathy. Despite heterogeneity, the study's extensive scope and systematic approach enhance the trustworthiness and generalizability of the findings.
PubMed: 38179375
DOI: 10.7759/cureus.49926 -
Current Diabetes Reviews Jan 2024This article focuses on extracting a standard feature set for predicting the complications of diabetes mellitus by systematically reviewing the literature. It is...
BACKGROUND
This article focuses on extracting a standard feature set for predicting the complications of diabetes mellitus by systematically reviewing the literature. It is conducted and reported by following the guidelines of PRISMA, a well-known systematic review and meta-analysis method. The research articles included in this study are extracted using the search engine "Web of Science" over eight years. The most common complications of diabetes, diabetic neuropathy, retinopathy, nephropathy, and cardiovascular diseases are considered in the study.
METHOD
The features used to predict the complications are identified and categorised by scrutinising the standards of electronic health records.
RESULT
Overall, 102 research articles have been reviewed, resulting in 59 frequent features being identified. Nineteen attributes are recognised as a standard in all four considered complications, which are age, gender, ethnicity, weight, height, BMI, smoking history, HbA1c, SBP, eGFR, DBP, HDL, LDL, total cholesterol, triglyceride, use of insulin, duration of diabetes, family history of CVD, and diabetes. The existence of a well-accepted and updated feature set for health analytics models to predict the complications of diabetes mellitus is a vital and contemporary requirement. A widely accepted feature set is beneficial for benchmarking the risk factors of complications of diabetes.
CONCLUSION
This study is a thorough literature review to provide a clear state of the art for academicians, clinicians, and other stakeholders regarding the risk factors and their importance.
PubMed: 38178670
DOI: 10.2174/0115733998271863231116062601 -
BMC Microbiology Jan 2024Staphylococcus aureus isolates are the leading cause of diabetic foot infections (DFIs). Identification of specific virulence factors of S. aureus involved in the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Staphylococcus aureus isolates are the leading cause of diabetic foot infections (DFIs). Identification of specific virulence factors of S. aureus involved in the pathogenesis of DFIs may help control the infection more effectively. Since the most prevalent virulence factor genes are probably related to the DFI pathogenesis, the aim of this study is to evaluate the proportion of virulence factor genes of S. aureus isolates from DFIs.
MATERIALS AND METHODS
We conducted a systematic search of PubMed, Embase, Web of Science, and Scopus to identify all articles reporting the proportion of different types of virulence factors of S. aureus isolates from DFI samples.
RESULTS
Seventeen studies were eligible, in which 1062 S. aureus isolates were obtained from 1948 patients and 2131 DFI samples. Among the toxin virulence factors, hld 100.0% (95% CI: 97.0, 100.0%), hlg 88.0% (95% CI: 58.0, 100.0%), hla 80.0% (95% CI: 31.0, 100.0%), hlgv 79.0% (95% CI: 35.0, 100.0%) and luk-ED 72.0% (95% CI: 42.0, 95.0%) had the highest proportion respectively. Among the genes associated with biofilm formation, both icaA and icaD had the highest proportion 100.0% (95% CI: 95.6, 100.0%).
CONCLUSION
The results of the present study showed that among the toxin virulence factors, hemolysins (hld, hlg, hla, hlgv) and luk-ED and among the non-toxin virulence factors, icaA and icaD have the greatest proportion in S. aureus isolates from DFIs. These prevalent genes may have the potential to evaluate as virulence factors involved in DFI pathogenesis. Finding these probable virulence factor genes can help control diabetic foot infection more effectively via anti-virulence therapy or preparation of multi-epitope vaccines.
Topics: Humans; Staphylococcus aureus; Virulence Factors; Diabetic Foot; Staphylococcal Infections; Virulence; Diabetes Mellitus
PubMed: 38172669
DOI: 10.1186/s12866-023-03142-y -
Frontiers in Endocrinology 2023With the increasing incidence of diabetes, diabetic foot ulcer(DFU) has become one of the most common and serious complications in people with diabetes. DFU is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
With the increasing incidence of diabetes, diabetic foot ulcer(DFU) has become one of the most common and serious complications in people with diabetes. DFU is associated with significant morbidity and mortality, and can also result in significant economic, social and public health burdens. Due to peripheral neuropathy, peripheral vascular disease, hyperglycemic environment, inflammatory disorders and other factors, the healing of DFU is impaired or delayed, resulting in the formation of diabetic chronic refractory ulcer. Because of these pathological abnormalities in DFU, it may be difficult to promote wound healing with conventional therapies or antibiotics, whereas platelet-rich plasma(PRP) can promote wound healing by releasing various bioactive molecules stored in platelets, making it more promising than traditional antibiotics. Therefore, the purpose of this systematic review is to summarize and analyze the efficacy of PRP in the treatment of DFU.
METHODS
A literature search was undertaken in PubMed, CNKI, EMB-ASE, the Cochrane Library, the WanFang Database and the WeiPu Database by computer. Included controlled studies evaluating the efficacy of PRP in the treatment of diabetic foot ulcers. The data extraction and assessment are on the basis of PRISMA.
RESULTS
Twenty studies were evaluated, and nineteen measures for the evaluation of the efficacy of PRP in DFU treatment were introduced by eliminating relevant duplicate measures. The efficacy measures that were repeated in various studies mainly included the rate of complete ulcer healing, the percentage of ulcer area reduction, the time required for ulcer healing, wound complications (including infection rate, amputation rate, and degree of amputation), the rate of ulcer recurrence, and the cost and duration of hospitalization for DFU, as well as subsequent survival and quality of life scores. One of the most important indicators were healing rate, ulcer area reduction and healing time. The meta-analysis found that PRP was significantly improve the healing rate(OR = 4.37, 95% CI 3.02-6.33, P < 0.001) and shorten the healing time(MD = -3.21, 95% CI -3.83 to -2.59,P < 0.001)of patients with DFU when compared to the conventional treatment, but there was no significant difference in reducing the of ulcer area(MD = 5.67, 95% CI -0.77 to 12.11,P =0.08>0.05 ).
CONCLUSION
The application of PRP to DFU can improve ulcer healing rate and shorten ulcer healing time, but more clinical data are needed to clarify some efficacy measures. At the same time, a standardized preparation process for PRP is essential.
Topics: Humans; Diabetic Foot; Quality of Life; Anti-Bacterial Agents; Platelet-Rich Plasma; Wound Healing; Diabetes Mellitus
PubMed: 38169990
DOI: 10.3389/fendo.2023.1256081 -
BMC Endocrine Disorders Jan 2024The current systematic review aimed to elucidate the effects of lipid variability on microvascular complication risk in diabetic patients. The lipid components studied... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
The current systematic review aimed to elucidate the effects of lipid variability on microvascular complication risk in diabetic patients. The lipid components studied were as follows: High-density lipoprotein (HDL), High-density lipoprotein (LDL), Triglyceride (TG), Total Cholesterol (TC), and Remnant Cholesterol (RC).
METHOD
We carried out a systematic search in multiple databases, including PubMed, Web of Science, and SCOPUS, up to October 2nd, 2023. After omitting the duplicates, we screened the title and abstract of the studies. Next, we retrieved and reviewed the full text of the remaining articles and included the ones that met our inclusion criteria in the study.
RESULT
In this research, we examined seven studies, comprising six cohort studies and one cross-sectional study. This research was conducted in Hong Kong, China, Japan, Taiwan, Finland, and Italy. The publication years of these articles ranged from 2012 to 2022, and the duration of each study ranged from 5 to 14.3 years. The study group consisted of patients with type 2 diabetes aged between 45 and 84 years, with a diabetes history of 7 to 12 years. These studies have demonstrated that higher levels of LDL, HDL, and TG variability can have adverse effects on microvascular complications, especially nephropathy and neuropathic complications. TG and LDL variability were associated with the development of albuminuria and GFR decline. Additionally, reducing HDL levels showed a protective effect against microalbuminuria. However, other studies did not reveal an apparent relationship between lipid variations and microvascular complications, such as retinopathy. Current research lacks geographic and demographic diversity. Increased HDL, TG, and RC variability have been associated with several microvascular difficulties. Still, the pathogenic mechanism is not entirely known, and understanding how lipid variability affects microvascular disorders may lead to novel treatments. Furthermore, the current body of this research is restricted in its coverage. This field's lack of thorough investigations required a more extensive study and comprehensive effort.
CONCLUSION
The relationship between lipid variation (LDL, HDL, and TG) (adverse effects) on microvascular complications, especially nephropathy and neuropathic (and maybe not retinopathy), is proven. Physicians and health policymakers should be highly vigilant to lipid variation in a general population.
Topics: Humans; Middle Aged; Aged; Aged, 80 and over; Diabetes Mellitus, Type 2; Cross-Sectional Studies; Cholesterol, HDL; Triglycerides; Cholesterol; Lipoproteins, HDL
PubMed: 38167035
DOI: 10.1186/s12902-023-01526-9 -
International Wound Journal Apr 2024The assessment for safety and effectiveness of surgical interventions in the management of diabetic foot ulcers (DFUs) in comparison to non-surgical approaches was... (Meta-Analysis)
Meta-Analysis Review
The assessment for safety and effectiveness of surgical interventions in the management of diabetic foot ulcers (DFUs) in comparison to non-surgical approaches was performed. A comprehensive search was performed across PubMed, MEDLINE, Cochrane Library and EMBASE in order to identify case-control studies, randomized controlled trials (RCTs), observational studies, cohort studies and observational studies pertaining to DFU treatments. Studies conducted in English language and focusing on wound healing rates, recurrence rates, time to healing and complication management met the inclusion criteria. There were six studies included in this meta-analysis. Surgical procedures, such as debridement, revascularization and skin transplantation, demonstrated significantly superior efficacy in promoting wound healing (84%) and shorter duration of healing (6 weeks) in comparison to non-surgical approaches, including off-loading, wound dressings and pharmacological therapies. Surgical interventions for DFUs resulted in a wound recovery rate of 84%, a significantly higher mean rate than non-surgical approaches (60%) that was observed. In addition, it was observed that the surgical group experienced considerably reduced average healing period of 9 weeks, in contrast to the non-surgical group's mean healing period of 12 weeks. Nevertheless, it is imperative to acknowledge that surgical procedures were notably correlated with a heightened occurrence of complications, such as amputations, which transpired in 19% of instances. Surgical interventions for DFUs may provide superior short-term results with regard to healing rates and recovery time, as indicated by this meta-analysis. However, they are additionally correlated with the heightened likelihood of complications. Although non-surgical techniques offered comparatively secure option, they were also less reliable. Individualized treatment modalities should be chosen in consideration of patient-specific factors and comparative advantages and disadvantages.
Topics: Humans; Diabetic Foot; Wound Healing; Bandages; Amputation, Surgical; Case-Control Studies; Diabetes Mellitus
PubMed: 38158715
DOI: 10.1111/iwj.14601 -
Journal of Foot and Ankle Research Dec 2023Diabetes-related foot disease (DFD) is a common, costly, and severe complication of diabetes mellitus. DFD is associated with high rates of morbidity and mortality and... (Review)
Review
BACKGROUND
Diabetes-related foot disease (DFD) is a common, costly, and severe complication of diabetes mellitus. DFD is associated with high rates of morbidity and mortality and poses a significant burden on patients, healthcare systems and society. While the detrimental impact of DFD is widely recognised, the precise financial implications of its management in Australia remain unclear due to inconsistent and inconclusive contemporary data. Therefore, the aim of this review was to identify, summarise and synthesise existing evidence to estimate the costs associated with DFD management in Australia.
METHODS
Searches were conducted in MEDLINE, Embase, AMED, CINAHL, Joanna Briggs Institute EBP, and the Cochrane Library from November 2011 to July 2023. Australian studies investigating costs associated with DFD management were eligible for inclusion. Two independent reviewers performed the study selection, data extraction and quality assessment steps. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS 2022) checklist was used to assess study quality. A descriptive analysis was performed due to limited existing evidence and large heterogeneity between study populations to conduct meta-analyses.
RESULTS
Three economic evaluations were included in the review. One study was rated as 'poor', one as 'very good' and one as 'excellent' when assessed against the CHEERS checklist. The estimated cost of DFD management varied between studies and comparisons were not possible due to the different methodological approaches and data sources. The studies were unable to provide an overall cost of DFD with respect to all aspects of care as they did not capture the multi-faceted level of care throughout the entire patient journey between sectors and over time.
CONCLUSION
There is limited contemporary evidence for the costs associated with DFD management within Australia, particularly related to direct costs and resource utilisation. Further research into the economic impact of DFD management is needed to inform optimisation of national service delivery and improve health outcomes for individuals with DFD in Australia. Integrating real-world data on impact of clinical interventions with parallel economic evaluation could be a valuable approach for future research, which would offer a more comprehensive understanding of the clinical and economic outcomes beyond solely model-based evaluations.
TRIAL REGISTRATION
PROSPERO Registration No. CRD42022290910.
Topics: Humans; Financial Stress; Australia; Diabetic Foot; Delivery of Health Care; Foot Diseases; Diabetes Mellitus
PubMed: 38151723
DOI: 10.1186/s13047-023-00688-y