ARTICLE | doi:10.20944/preprints202211.0274.v1
Subject: Medicine And Pharmacology, Ophthalmology Keywords: telemedicine; diabetic retinopathy; diabetic macular edema; epidemiology; COVID-19
Online: 15 November 2022 (04:40:58 CET)
(1) Background: Diabetic retinopathy (DR) is a complication of diabetes mellitus (DM) and the COVID-19 pandemic has affected screening programmes. The aim of present study was to determine the impact of the COVID-19 pandemic on the screening of diabetes patients in our Health Care Area (HCA); (2) Methods: A retrospective study of patients with DM who had attended the DR screening programme between January 2015 and June 2022. We studied attendance, DM metabolic control and DR incidence. (3) Results: Screening for DR decreased in the first months of the pandemic. Incidence of mild and moderate DR remained stable throughout the study, and we observed a little increase in severe-DR, proliferative-DR and neovascular glaucoma, during 2021 and 2022. (4) Conclusions: The COVID-19 pandemic caused a reduction in the number of patients screened for DM, although its effect on DR seems limited, with a similar number of patients with DR throughout 2015 to 2022, despite the number of patients with severe-DR and proliferative-DR increased in 2021 and 2022.
ARTICLE | doi:10.20944/preprints202302.0218.v1
Subject: Computer Science And Mathematics, Artificial Intelligence And Machine Learning Keywords: diabetic retinopathy; Vision loss; Deep learning; CLAHE; ESRGAN
Online: 13 February 2023 (14:33:05 CET)
Sometimes when diabetic retinopathy (DR) is found and treated quickly, vision loss can indeed be spared. This study deploys a deep learning (DL) model that can discover all 5 stages of DR more accurately than other methods. The proposed methodology shows two cases scenarios: case 1 with image enhancement using CLAHE and ESRGAN, and case 2 without image enhancement. Augmentation techniques are then employed to produce a balanced dataset with the identical criteria for both scenarios. The generated model using DenseNet-121 on the APTOS dataset outperformed other approaches for locating the 5 stages of DR, with an accuracy of 98.7 percent for case 1 and 81.2 percent for case 2. Using CLAHE and ESRGAN was shown to improve a model's performance and ability to learn.
ARTICLE | doi:10.20944/preprints202302.0097.v1
Subject: Computer Science And Mathematics, Computer Vision And Graphics Keywords: Vision loss; Diabetic retinopathy; Image enhancement; APTOS
Online: 6 February 2023 (09:50:58 CET)
Vision loss can be avoided if diabetic retinopathy (DR) is diagnosed and treated promptly. Following are the main 5 DR stages: none, moderate, mild, proliferate, and severe. In this study, a deep learning (DL) model is presented that diagnoses all 5 stages of DR with more accuracy than previous methods. The suggested method presents two scenarios: case 1 with image enhancement using contrast limited adaptive histogram equalization (CLAHE) filtering algorithm in conjunction with an Enhanced Super-resolution generative adversarial network (ESRGAN), and case 2 without image enhancement; augmentation techniques are then performed to generate a balanced dataset utilizing the same parameters for both cases. Using Inception-V3 applied to the Asia Pacific Tele-Ophthalmology Society (APTOS) datasets, the developed model achieved an accuracy of 98.7% for case 1 and 80.87% for case 2, which is greater than existing methods for detecting the five stages of DR. It was demonstrated that using CLAHE and ESRGAN improves a model's performance and learning ability.
ARTICLE | doi:10.20944/preprints202005.0493.v1
Subject: Computer Science And Mathematics, Computer Vision And Graphics Keywords: Convolutional Neural Networks; Dental Diagnosis; Image Recognition; Diabetic Retinopathy detection
Online: 31 May 2020 (18:55:43 CEST)
Retinopathy is a human eye disease that causes changes in retinal blood vessels that leads to bleed, leak fluid and vision impairment. Symptoms of retinopathy are blurred vision, changes in color perception, red spots, and eye pain. In this paper, a new methodology based on Convolutional Neural Networks (CNN) is developed and proposed to diagnose and give a decision about the presence of retinopathy. The CNN model is trained by different images of eyes that have retinopathy and those which do not have retinopathy. The performance of the proposed model is compared with the related methods of DREAM, KNN, GD-CNN and SVM. Experimental results show that the proposed CNN performs better.
REVIEW | doi:10.20944/preprints201704.0059.v1
Subject: Biology And Life Sciences, Endocrinology And Metabolism Keywords: Keywords: vitamin D deficiency; diabetic retinopathy; meta-analysis.
Online: 11 April 2017 (06:16:22 CEST)
Background: Diabetic retinopathy (DR) is one of the most prominent pathological microvascular complications in diabetes. A series of studies reported that vitamin D deficiency was associated with increased prevalence of retinopathy in diabetic patients but the results were inconsistent. In this study we focused on evaluating the relationship between vitamin D deficiency and DR by conducting a meta-analysis of observational studies. Methods: Systematic computerized searches were performed in PubMed, MEDLINE, and the Cochrane Library for relevant original articles till November 20, 2016. The pooled odds ratios (ORs) with corresponding confidence intervals (CIs) were calculated to assess the associated value of vitamin D deficiency to the risk of DR. 9 studies including 6332 participants were subjected to final analysis. Results: The results indicated that vitamin D deficiency increases the risk of DR (OR = 1.57, 95% CI 1.32-1.87) with a little heterogeneity (I2 = 23%). In addition, the subgroup analysis demonstrated that there were obvious heterogeneities in T2DM (I2 = 47.8%). Sensitivity analysis showed that the results were relatively stable and reliable. Conclusion: our meta-analysis demonstrated that vitamin D deficiency could increase the risk of DR.
ARTICLE | doi:10.20944/preprints202106.0268.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: diabetic retinopathy; mesenchymal stem cells; neural precursor cells; stem cell.
Online: 9 June 2021 (13:44:48 CEST)
This study aimed to evaluate cell therapy with human neural precursor cells (hNPCs) in diabetic retinopathy (DR) Wistar rats, induced to diabetes by intraperitoneal injection with streptozotocin. Wharton's Jelly Mesenchymal stem cells (WJ-MSCs) were isolated, expanded, and seeded onto a biopolymer substrate without growth factors to develop neurospheres to obtain the hNPCs, characterized by immunocytochemistry. The animals were divided into three groups; non-diabetic (ND) n = four; diabetic without treatment (DM) n = nine; and diabetic with cell therapy (DM + hNPCs) n = nine. After eight weeks of diabetes induction and verified DR, intravitreal injection of hNPCs (1 x 106 cel/µL) was performed in the DM + hNPCs group. Optical Coherence Tomography (OCT) and Electroretinography (ERG) evaluations were done before and after diabetes induction and after cell therapy. Eye enucleation occurred four weeks after treatment for the histopathological and immunohistochemistry analyses. In the treated group, there was the repair of the retinal structures and their arrangements. hNPCs increased the thickness of neuroretina layers, especially in the ganglion cell and photoreceptor layers. The results indicate that hNPCs reduced DR progression by a neuroprotective effect and promoted retinal repair, making them potential candidates for regeneration of the neuroretinal tissue.
ARTICLE | doi:10.20944/preprints202308.0206.v1
Subject: Medicine And Pharmacology, Ophthalmology Keywords: diabetic retinopathy; cataracts; gold nanoparticles; rutin; antioxidant; early; incipient
Online: 3 August 2023 (02:32:40 CEST)
Diabetic retinopathy (DR) and cataracts (CA) have an early onset in diabetes mellitus (DM) due to the redox imbalance and inflammation triggered by hyperglycemia. Plant-based therapies are characterized by low bioavailability in ocular tissues. The study aimed to investigate the effect of gold nanoparticles phytoreduced with Rutin (AuNPsR), as a possible solution. Insulin, Rutin, and AuNPsR, were administered to an early, six-week rat model of DR and CA. Oxidative stress (MDA, CAT, SOD) was assessed in serum and eye homogenates, and inflammatory cytokines (IL-1 beta, IL-6, TNF alpha) were quantified in ocular tissues. Fundus of retinal arterioles, retina histopathology and lens transmission electron microscopy (TEM), were also performed. DM was linked to constricted retinal arterioles, reduced endogen antioxidants, and eye inflammation. Histologically, retinal wall thickness decreased. TEM showed increased lens opacity and fiber disorganization. Rutin improved retinal arteriolar diameter, while reducing oxidative stress and inflammation. Retinas were moderately edematous. Lens structure was preserved on TEM. Insulin restored retinal arteriolar diameter, while increasing MDA, and amplifying TEM lens opacity. The best outcomes were obtained for AuNPsR, as it improved fundus appearance of retinal arterioles, decreased MDA formation and increased antioxidant capacity. Retinal edema and disorganization in lens fibers were still present.
REVIEW | doi:10.20944/preprints202108.0030.v1
Subject: Medicine And Pharmacology, Ophthalmology Keywords: Artificial Intelligence; Neural Networks; Deep Learning; Diabetic Retinopathy; Diabetes Mellitus
Online: 2 August 2021 (12:26:52 CEST)
Diabetic retinopathy is the most common microvascular complication of diabetes mellitus and one of the leading causes of blindness globally. Due to the progressive nature of the disease, earlier detection and timely treatment can lead to substantial reductions in the incidence of irreversible vision-loss. Artificial intelligence (AI) screening systems have offered clinically acceptable and quicker results in detecting diabetic retinopathy from retinal fundus and optical coherence tomography (OCT) images. Thus, this systematic review and meta-analysis of relevant investigations was performed to document the performance of AI screening systems that were applied to fundus and OCT images of patients from diverse geographic locations including North America, Europe, Africa, Asia, and Australia. A systematic literature search on Medline, Global Health, and PubMed was performed and studies published between October 2015 and January 2020 were included. The search strategy was based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines, and AI-based investigations were mandatory for studies inclusion. The abstracts, titles, and full-texts of potentially eligible studies were screened against inclusion and exclusion criteria. Twenty-one studies were included in this systematic review; 18 met inclusion criteria for the meta-analysis. The pooled sensitivity of the evaluated AI screening systems in detecting diabetic retinopathy was 0.93 (95% CI: 0.92-0.94) and the specificity was 0.88 (95% CI: 0.86-0.89). The included studies detailed training and external validation datasets, criteria for diabetic retinopathy case ascertainment, imaging modalities, DR-grading scales, and compared AI results to those of human graders (e.g., ophthalmologists, retinal specialists, trained nurses, and other healthcare providers) as a reference standard. The findings of this study showed that the majority AI screening systems demonstrated clinically acceptable levels of sensitivity and specificity for detecting referable diabetic retinopathy from retinal fundus and OCT photographs. Further improvement depends on the continual development of novel algorithms with large and gradable sets of images for training and validation. If cost-effectiveness ratios can be optimized, AI can become a financially sustainable and clinically effective intervention that can be incorporated into the healthcare systems of low-to-middle income countries (LMICs) and geographically remote locations. Combining screening technologies with treatment interventions such as anti-VEGF therapy, acellular capillary laser treatment, and vitreoretinal surgery can lead to substantial reductions in the incidence of irreversible vision-loss due to proliferative diabetic retinopathy.
ARTICLE | doi:10.20944/preprints202307.0691.v1
Subject: Medicine And Pharmacology, Ophthalmology Keywords: diabetic retinopathy, adaptive optics, rtx-1 technology, cone morphology, retinal microcirculation
Online: 11 July 2023 (08:11:09 CEST)
Background: With the increasing global incidence of diabetes mellitus (DM), diabetic retinopathy (DR) has become one of the leading causes of blindness in developed countries. DR leads to changes in retinal neurons and microcirculation. Rtx1TM (Imagine Eyes, France) is a microscope that allows histological visualisations of cones and retinal microcirculation throughout the DM duration. Objective: This study aimed to analyse the cones and retinal microvascular changes in 50 diabetic individuals and 18 healthy volunteers. The patients participated in the initial visit and two fol-low-up appointments: one and two years after the study, beginning with rtx1 image acquisition, visual acuity assessment, macular OCT scans and blood measurements. Results: The study revealed significant differences in the cone density, mosaic arrangement and vascular morphology between healthy and diabetic patients. The final measurements have shown decreased photoreceptor and microvascular parameters in the DR group compared to the control group. Furthermore, in the 2-year follow-up, both groups' rtx1-acquired morphological changes were statistically significant. Conclusions: Rtx-1 technology was successfully used as a non-invasive method of photoreceptors and retinal vasculature assessment over time in patients with diabetic retinopathy. The study has revealed a trend toward more vascular morphological changes occurring over time in diabetic patients.
ARTICLE | doi:10.20944/preprints201901.0245.v1
Subject: Biology And Life Sciences, Endocrinology And Metabolism Keywords: Osteomeles Schwerinae; diabetic retinopathy (DR); spontaneously diabetic Torii (SDT) rat; human retinal microvascular endothelial cells (HRMECs); advanced glycation end products (AGEs); retinal apoptosis; oxidative stress; mitochondrial function; adjunctive effect; combination therapy
Online: 24 January 2019 (08:37:29 CET)
Retinal apoptosis plays a critical role in the progression of diabetic retinopathy (DR), a common diabetic complication. Currently, the tight control of blood glucose levels is the standard approach to prevent or delay the progression of DR. However, prevalence of DR among diabetic patients remains high. Focusing on natural nutrients or herbal medicines that can prevent or delay the onset of diabetic complications, we administered an ethanol extract of the aerial portion of Osteomeles Schwerinae (OSSCE), a Chinese herbal medicine, over a period of 17 weeks to spontaneously diabetic Torii (SDT) rats. OSSCE was found to ameliorate retinal apoptosis through the regulation of advanced glycation end products (AGEs) accumulation, oxidative stress, and mitochondrial function via inhibition of NF-κB activity, in turn through the downregulation of PKCδ, P47phox, and ERK1/2. We further demonstrated in 25 mM glucose-treated human retinal microvascular endothelial cells (HRMECs) that hyperoside (3-O-galactoside-quercetin), quercitrin (3-O-rhamnoside-quercetin), and 2''-O-acetylvitexin (8-C-(2''-O-acetyl-glucoside)-apigenin) were the active components of OSSCE that mediated its pharmacological action. Our results provide evidence that OSSCE is a powerful agent that may directly mediate a delay in development or disease improvement in patients of DR.
ARTICLE | doi:10.20944/preprints202206.0129.v1
Subject: Biology And Life Sciences, Endocrinology And Metabolism Keywords: Diabetic retinopathy; Oxidative stress; Advanced glycation end products (AGEs); Antioxidant enzymes; Vascular endothelial growth factor; B-vitamins; Vitamin-C; Vitamin- E
Online: 8 June 2022 (12:40:07 CEST)
Excessive intracellular glucose in insulin independent tissues including nerve, nephron, lens and retina invites mishandling of metabolism of glucose resulting in a background of increased oxidative stress, advanced glycation end products (AGE) formation, lipid peroxidation and failure of antioxidant defense systems in type 2 diabetes mellitus (T2DM). All these detrimental biochemical anomalies ultimately attack biological membranes and especially capillary beds of retina and glomerulus of kidney, resulting in break-down of inner blood-retinal i.e. initiation of diabetic retinopathy (DR). If these disarrays are corrected to a large extent, development of DR can be avoided or delayed. In this prospective clinical trial, 185 patients with T2DM who received B-vitamins, vitamin-C, and E along with anti-diabetic medication for five years, demonstrated a slower rate of the development of DR and reduced abnormal biochemical mediators like reactive oxygen species (ROS), malondialdehyde (MDA), AGE, and vascular endothelial growth factor (VEGF) compared to 175 T2DM individuals who were treated with only anti-hyperglycemic drugs.
ARTICLE | doi:10.20944/preprints202106.0144.v1
Subject: Medicine And Pharmacology, Endocrinology And Metabolism Keywords: Diabetic; Diabetic Mellitus; Diabetic Prediction; PIMA diabetic dataset; Female diabetic Patients; Machine Learning
Online: 4 June 2021 (15:25:16 CEST)
Diabetics or Diabetic Mellitus is a metabolic disorder of blood sugar levels in the human body. It is a major non-communicable disease and involved many serious health risk issues. This disease is rapidly increasing in India. It is a chronic condition and it occurs when a body doesn't produce enough insulin hormone to control the blood sugar level. In this study, different variables have been analyzed that cause the diabetics, and different machine learning algorithms are used to predict whether an unknown sample is diabetes or not. For this purpose, PIMA diabetic detection for Female patients was used. Here 10 different classification model is used for prediction. Finally, the detailed performance analysis of the different variables of the PIMA dataset and also the classification model are discussed.
ARTICLE | doi:10.20944/preprints202111.0303.v1
Subject: Computer Science And Mathematics, Artificial Intelligence And Machine Learning Keywords: Microvascular complications; Cardiac autonomic neuropathy; Diabetic peripheral neuropathy; Diabetic nephropathy; Diabetic retinopathy; patient profiles; machine learning
Online: 17 November 2021 (11:54:23 CET)
Microvascular complications are one of the key causes of mortality among type-2 diabetic patients. This study was sought to investigate the use of a novel machine learning approach for predicting these complications from patient demographic, clinical, and laboratory profiles only. A total of 96 Bangladeshi participants having type-2 diabetes were recruited during their routine hospital visits. All patient profiles were assessed by using a Chi-squared (2) test to statistically determine the most important markers in predicting four microvascular complications; namely cardiac autonomic neuropathy (CAN), diabetic peripheral neuropathy (DPN), diabetic nephropathy (NEP), and diabetic retinopathy (RET). A machine learning approach based on random forest (RF) and support vector machine (SVM) was then developed to ensure automated clinical testing for microvascular complication in diabetic patients. The highest prediction accuracies were obtained by RF using diastolic blood pressure, Albumin-Creatinine ratio, and gender for CAN testing (98.67%), Microalbuminuria, smoking history, and hemoglobin A1C for DPN testing (67.78%), Albumin-Creatinine ratio for NEP testing (100%), and hemoglobin A1C, Microalbuminuria, and smoking history for RET testing (84.38%). This study suggests machine learning as a promising automated tool for predicting microvascular complications in diabetic patients using their profiles, which could help prvent those patients from further microvascular complications leading to early death.
ARTICLE | doi:10.20944/preprints201908.0285.v1
Subject: Medicine And Pharmacology, Dentistry And Oral Surgery Keywords: oral health , pre-diabetic, diabetic, oral systemic, screening, H1A1c, Findrisk , periodontal
Online: 27 August 2019 (11:58:44 CEST)
Pre-diabetes is a serious health condition where blood sugar levels are higher than normal, but not high enough yet to be diagnosed as type 2 diabetes. Pre-diabetes puts one at an increased risk of developing type 2 diabetes and heart disease Methodology: A cross-sectional study was carried out on 384 patients aged 20-70 years old, attending the dental clinics to assess the risk for diabetes, using the FINDRISC questionnaire, HbA1c blood test and a periodontal examination. Results: The mean age of participants was 38.90±10.74. 32.3% were categorized as no risk, 46.6% low risk, while 19% and 2.1% moderate and high risk of developing diabetes respectively. Tests for serum HbA1c Level showed 46.1 % had normal HbA1c followed by 18.0% and 3.6 % were pre-diabetic and diabetic respectively. 19.3% of participants had periodontal pockets measuring more than 4mm and 15.9% measuring more than 6mm. Conclusion: The study has proven to be useful in identifying patients at high-risk of developing diabetes. Controlling and managing periodontal disease could be a new aspect to include in the standards for diabetes care. Dental settings could be a successful platform to carry out the screening and risk stratification of pre-diabetic patients.
ARTICLE | doi:10.20944/preprints202305.1240.v1
Subject: Biology And Life Sciences, Endocrinology And Metabolism Keywords: DNP; PNS; Diabetic neuropathic pain; Peripheral pain; Distal symmetric polyneuropathy; diabetic neuropathy; diabetes mellitus; DM; T1D; T2D; DPN; DPNP; Diabetic peripheral neuropathic pain; Diabetic peripheral neuropathy
Online: 17 May 2023 (10:55:11 CEST)
Diabetes mellitus is the global epidemic of the 21st century affecting millions worldwide. Usually, patients with long-standing type one diabetes (T1D) or type two diabetes (T2D) tend to develop complications. A common complication is the degenerative of the nerves in the peripheral nervous system (PNS). This complication is known as distal symmetric polyneuropathy or just diabetic neuropathy. A variety of symptoms can be experienced with this complication, including pain and numbness. One characterization of this complication is the sensory loss that begins in the lower extremities and spreads substantially to the fingers and hand. There is no clear mechanism for how this happens in diabetic patients. Studies have shown that nerve damage from this complication can be due to oxidative stress, sorbitol accumulation, and advanced glycation end products (AGEs). Some of the most common medications being provided for diabetic neuropathic pain (DNP) include amitriptyline and desipramine. Other medications also include gabapentin and duloxetine. There are noninvasive options, such as acupuncture, that could provide beneficial data if rigorous studies are conducted. A number of new studies are being completed to identify more effective treatments for this condition.
REVIEW | doi:10.20944/preprints202304.1198.v1
Subject: Medicine And Pharmacology, Endocrinology And Metabolism Keywords: Diabetic foot ulcer; ulcer remission; ulcer recurrence; ulcer relapse; diabetic complications; metabolic memory
Online: 29 April 2023 (03:39:18 CEST)
An impaired healing response underlies diabetic foot wounds chronicity, frequently translating in amputation, disability, and early mortality. In addition, diabetics frequently suffer of the underappreciated episode of post-epithelization ulcer recurrence. Recurrence epidemiological data are alarmingly high; so that the ulcer is considered in “remission” and not healed for the time it remains epithelialized. Recurrence may result from the conspiracy of behavioral and biological factors. Although the damaging role of behavioral, clinical predisposing factors is undebatable, the role of endogenous biological signalers that prime the residual scar tissue to recurrence has remained elusive. We propose that ulcer recurrence is deeply impinged by chronic hyperglycemia and its downstream biological effectors, which originate epigenetic drivers that enforce abnormal pathologic phenotypes to dermal fibroblasts, and keratinocytes as memory cells. Hyperglycemia-derived cytotoxic reactants accumulate and modify dermal proteins, reduce scar tissue mechanical tolerance, and disrupt fibroblasts-secretory activity. Accordingly, the combination of epigenetic and local and systemic cytotoxic signalers, induce the onset of “at-risk phenotypes” as premature skin cells aging, dysmetabolism, inflammatory, pro-degradative, and oxidative programs that may ultimately converge to scar cells demise. Unfortunately, post epithelialization recurrence rates data are missing in clinical studies of accepted ulcer healing therapies during follow-up periods. Intra-ulcer infiltration of epidermal growth factor exhibits the most consistent remission data with the lowest recurrences during 12-month follow-up. Recurrence data should be regarded as a valuable clinical endpoint during the investigational period for each emergent healing candidate.
ARTICLE | doi:10.20944/preprints201809.0153.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: diabetic nephropathy; exosomes; autophagy; mTOR
Online: 10 September 2018 (06:26:55 CEST)
Background: diabetic nephropathy (DN) is a serious complication of diabetes mellitus and a common cause for end stage renal disease. Autophagy has a defensive role against kidney damage caused by hyperglycemia. The mesenchymal stem cells (MSCs) derived exosomes are currently considered as a new promising therapy in chronic renal injury. However, the renal protective mechanism of exosomes on DN has not been completely understood. We examined the potential role of MSCs derived exosomes in enhancement of autophagy activity and its effect on DN. In our study we used five groups of rats; control, DN, DN treated with exosomes, DN treated with 3-methyladenine (3-MA) and chloroquine (inhibitors of autophagy) and DN treated with 3-methyladenine (3-MA) and chloroquine and exosomes groups. We assessed renal functions, morphology and fibrosis. Moreover, autophagy markers; mTOR, Beclin-1, light chain-3 (LC3-II), and LC3-II/LC3-I ratio were detected. Additionally, electron microscopy was used for detection of autophagosomes. Results: Exosomes markedly improved the renal functions and showed histological restoration of renal tissues with significant increase in LC3 and Beclin-1 besides the significant decrease in mTOR and fibrotic markers expression in renal tissue. All previous effects were partially abolished by the autophagy inhibitor, chloroquine and 3-MA. Conclusions: we conclude that autophagy induction by exosomes could attenuate DN in a rat model of streptozotocin-induced diabetes mellitus.
REVIEW | doi:10.20944/preprints202308.1042.v1
Subject: Biology And Life Sciences, Other Keywords: Sphingolipid, Diabetes, Obesity, Insulin Resistance, Metabolic Syndrome, Diabetic Kidney Disease, Cardiovascular Disease, Diabetic Complications
Online: 14 August 2023 (11:14:44 CEST)
Sphingolipids play an important role in the development of diabetes both type 1 and type 2 diabetes as well as in the development of both micro- and macro-vascular complications. Several reviews have been published concerning the role of sphingolipids in diabetes but most of the emphasis has been on the possible mechanisms by which sphingolipids, mainly ceramides, contribute to the development of diabetes. Research on circulating levels of the different classes of sphingolipids in serum and in lipoproteins and their importance as biomarkers to predict not only the development of diabetes but also of its complications has only recently emerged and it is still in its infancy. This review summarizes the previously published literature concerning sphingolipid-mediated mechanisms involved in the development of diabetes and its complications focusing on how circulating plasma sphingolipid levels and the relative content carried by the different lipoproteins may impact their role as possible biomarkers both in the development of diabetes and mainly in the development of diabetic complications. Further studies in this field may open new therapeutic avenues to prevent or arrest/reduce both the development of diabetes and progression of its complications.
REVIEW | doi:10.20944/preprints202301.0096.v1
Subject: Medicine And Pharmacology, Endocrinology And Metabolism Keywords: Diabetes Mellitus; Diabetic Complications; Pyroptosis; Bibliometrics
Online: 5 January 2023 (03:37:02 CET)
Objective: To visualize and analyze the published literature on diabetes and pyroptosis based on a bibliometric approach, so as to provide a comprehensive picture of the hot research directions and dynamic progress in this field. Methods: This study was based on the web of science core collection database to conduct a comprehensive search of the published literature in the field of diabetes and Pyroptosis from January 1985 to August 2022, including the published research literature in this field, as well as a visual analysis of the number of citations, year of publication, journal, author, research institution, country, and research topic. Results: A total of 139 literature on research related to diabetes and cellular scorch from 2011 to 2022 were retrieved, with a total of 3009 citations and a maximum of 255 citations for a single article, which had a first authorSchmid-Burgk, JL The first author of this article is from Germany; among 20 publishing countries, China leads with 100 articles; among 222 publishing institutions, Harbin Medical University leads with 18 articles and 184 citations; among 980 authors, Chen, X from China tops the list of high-impact authors with 5 articles and 29 citations; Among the 98 journals, "CELL DEATH DISEASE" ranked first in both volume and high impact journals with 4 articles and 29 citations; among 349 keywords, "pyroptosis" ranked first with a cumulative frequency of 65 times. The cluster analysis was divided into three categories, chronic complications of diabetes and pyroptosis (67 articles), diabetes and pyroptosis (60 articles), and diabetes combined with other diseases and pyroptosis (12 articles), and the number of articles related to diabetes and its chronic complications increased rapidly from 2019, among which, diabetic cardiomyopathy (27 articles) had the highest number of articles. Conclusions: Based on a comprehensive analysis of published literature in the field of diabetes and pyroptosis from 2011-2022, this study achieved a visual analysis of studies with significant and outstanding contributions to the field, thus framing a picture showing the development and changes in the field. At the same time, this study provides research information and direction for clinicians and investigators to conduct diabetes and pyroptosis related research in the future.
CASE REPORT | doi:10.20944/preprints202207.0045.v1
Subject: Medicine And Pharmacology, Endocrinology And Metabolism Keywords: Diabetic Foot Ulcer; Amniotic Membrane Allograft
Online: 4 July 2022 (09:32:17 CEST)
Management of diabetic foot ulcers (DFUs) presents challenges to even the most experienced wound care providers. Because of the chronic, non-healing nature of many DFUs, advances in the treatment and care of this disease process are particularly relevant. This case study aims to report the efficacy of the application of dehydrated amniotic membrane allograft (DAMA) to a diabetic foot ulcer. The patient in this study is a 44-year-old male who presented with an aggressive infection on his right foot, which resulted in an open wound of 18 months duration. This patient received weekly applications of dual-layer DAMA over seven weeks. Upon examination at the initial application, the wound was classified as a Wagner grade 3 with necrosis of the underlying muscle. Upon inspection at the final visit, the wound was closed entirely. The results that were shown include improvements in the size, depth, edges, necrotic tissue amount, and epithelization of the wound. This case study demonstrates that the ap-plication of DAMA has the potential to augment the body’s natural DFU healing response; however, future nonrandomized and randomized controlled trials are needed to establish its efficacy further.
REVIEW | doi:10.20944/preprints202305.2187.v1
Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: diabetes mellitus; blood-brain barrier disruption; dysglycemia; hyperglycemia; insulin resistance; neurodegenerative disease; diabetic complications; dementia, diabetic encephalopathy
Online: 31 May 2023 (10:05:10 CEST)
Diabetes mellitus is one of the most common metabolic diseases worldwide, and its long-term complications include neuropathy, referring both to the peripheral and to the central nervous system. Detrimental effects of dysglycemia, especially hyperglycemia, on the structure and function of blood-brain barrier (BBB) seem to be a significant backgrounds of diabetic neuropathy pertaining to the central nervous system (CNS). Effects of hyperglycemia, including excessive glucose influx to insulin independent cells, may induce oxidative stress and secondary innate immunity dependent inflammatory response which can damage cells within the CNS, thus promoting neurodegeneration and dementia. Advanced glycation end products (AGE) may exert similar, pro-inflammatory effects through activating receptors for advanced glycation end products (RAGE), as well as some pattern-recognition receptors (PRR). Moreover, long-term hyperglycemia can promote brain insulin resistance, which may in turn promote Aβ aggregate accumulation and tau hyperphosphorylation. This review is focused on a detailed analysis of the effects mentioned above towards the CNS, with special regard to mechanisms taking part in the pathogenesis of central long-term complications of diabetes mellitus initiated by the loss of BBB integrity.
REVIEW | doi:10.20944/preprints202309.1108.v1
Subject: Medicine And Pharmacology, Endocrinology And Metabolism Keywords: hypoglycaemia; spontaneous hypoglycaemia; neuroglycopaenia; non-diabetic; adult
Online: 19 September 2023 (03:50:47 CEST)
Although adult spontaneous (non-diabetic) hypoglycaemia is rare, its recognition is important for the preventative or curative treatment of the underlying cause. Establishing Whipple’s triad; low blood glucose, neuroglycopaenia and resolution of neuroglycopaenia on increasing blood glucose levels to normal or above, is essential to verify hypoglycaemia. Awareness that hypoglycaemia may occur in severely ill patients is important for its prevention. Further investigation in such cases is unnecessary unless another cause of hypoglycaemia is suspected. Patients are often asymptomatic and normoglycaemic at review. History of medication, self-medication, access to hypoglycaemic drugs, alcohol and comorbidity may provide aetiological clues. The investigation involves obtaining blood samples during symptoms for laboratory glucose measurement or provoking fasting or postprandial hypoglycaemia as directed by symptoms. If confirmed, insulin, c-peptide, proinsulin, beta-hydroxybutyrate are analysed in hypoglycaemic samples. These will classify hypoglycaemia due to non-ketotic hyperinsulinaemia, non-ketotic hypoinsulinaemia and ketotic hypoinsulinaemia and direct investigations to identify the underlying cause. There are, however, many pitfalls, which may mislabel healthy individuals as “hypoglycaemic” or misdiagnose treatable or preventable causes of spontaneous hypoglycaemia. Clinical acumen and appropriate investigations will mostly identify hypoglycaemia and its cause.
ARTICLE | doi:10.20944/preprints202306.1881.v1
Subject: Medicine And Pharmacology, Endocrinology And Metabolism Keywords: diabetes; diabetic foot; hospital admission; limb salvage
Online: 27 June 2023 (10:18:13 CEST)
The study aims to evaluate the rate of readmission in patients affected by diabetic foot ulcers (DFUs), causes and the outcomes of patients requiring a new hospitalization. This study is a retrospective observational study including consecutive patients requiring hospitalization since January 2019 to September 2022 due to a DFU. Once they were discharged, patients were regularly followed as outpatients. After 6 months of follow-up, the rate of hospital readmission for a diabetic foot problem was recorded. According to the readmission or not, patients were divided in two groups, readmitted and not readmitted patients respectively. Hence, all patients were followed for six months more and outcomes for the two groups were analyzed and compared. The mean age was 6812yrs, with a prevalence of male (72.6%); the majority of patients were affected by type 2 diabetes (>90%) with a mean diabetes duration of approximately 20yrs. After 6 months of follow-up, 68 (21.9%) patients were readmitted. The main reason of hospital readmission were the presence of critical limb ischaemia (CLI) in the contralateral limb (6.1%), the recurrence of CLI in the previous treated limb (4.5%) and the onset of new infected DFU in the contralateral foot (4.5%). Readmitted patients reported lower rate of healing (51.5vs89.2%,p<0.0001) and higher rate of major amputation (10.3vs4.5%,p=0.04) in comparison to not readmitted patients. CLI and dialysis resulted independent predictors of hospital readmission. Hospital readmission is frequent issue among patients with DFUs, increasing the risk of non-healing and major amputation. CLI resulted the main cause of new hospitalization.
ARTICLE | doi:10.20944/preprints202306.0626.v1
Subject: Medicine And Pharmacology, Internal Medicine Keywords: diabetic kidney injury; inflammation; systemic inflammatory index
Online: 8 June 2023 (10:26:17 CEST)
Background: The systemic inflammatory index (SII) is a new inflammatory marker that has been the subject of various studies in diseases with chronic inflammation. Diabetic nephropathy is also a disease that goes with chronic inflammation. We aimed to evaluate the relationship be-tween SII and diabetic nephropathy. Methods: Patients with diabetes who applied to our outpatient clinic are included in the study. Diabetic patients are divided into two groups: those with diabetic nephropathy and those with-out. In addition, healthy individuals who applied to our clinic for general check-ups during these dates are included as control group. The SII values and other characteristics of the three study groups are compared. Results: The median SII value for those with DKI was 584 (178-4819); for those without DKI, it was 282 (64-618); and for the control group, it was 236 (77.5-617) (p<0.001). SII was significantly and positively correlated with BMI, weight, blood glucose, HbA1c, CRP and creatinine, and neg-atively correlated with glomerular filtration rate (GFR) value. The SII value higher than 336 has 75% sensitivity and 70% specificity in detecting DKI. Conclusion: The SII value could predict diabetic kidney injury in diabetics and it could be used as an adjunctive diagnostic tool.
ARTICLE | doi:10.20944/preprints202211.0159.v1
Subject: Medicine And Pharmacology, Endocrinology And Metabolism Keywords: care wound; wound diabetic; honey; staphylococcus aureus
Online: 9 November 2022 (01:07:32 CET)
Background : Diabetic wounds are very easy to experience complications in the form of infection due to bacterial invasion, and sugar conditions blood which tall encourage the growth of bacteria.Bacteria that can cause infection in diabetic wounds wrong one is staphylococci aureus . Wound diabetes can treated with honey. Honey contains antibacterial , antioxidant and hydrogen peroxide properties that help kill bacteria dangerous. Objective : The purpose of this study was to determine the effect of the wound dressing contains honey against bacterial colonization Staphylococcus aureus on wound diabetic . Methods : The research design used is pre-experimental with o ne-group pre-test and post-test design . Sampling method using consecutive sampling as many as 7 respondents. Results : Analysis data use test dependent t-test and obtained score p value 0.000 ( p value < = 0.05), so could concluded there is influence care wound use honey to colonization bacteria Staphylococcus aureus in wounds diabetic Diabetes Mellitus patients in the region work Public health center Banjarmasin . Conclusion : best Use honey as product care wound because nature the antibacterial which could prevent infection and speed up process healing wound .
REVIEW | doi:10.20944/preprints202202.0353.v1
Subject: Biology And Life Sciences, Endocrinology And Metabolism Keywords: Diabetic; Chronic Kidney Disease; Metformin; Acidosis Lactate
Online: 28 February 2022 (09:28:33 CET)
Background: Diabetes Mellitus is a metabolite disorder with parameters of high blood sugar levels. In the management of diabetes can be used the drug metformin is the gold of choice to achieve a therapeutic effect and rarely causes side effects of the drug, but it still has debate view. However, if used in excessive doses for patients with kidney disease, it will be contraindicated with side effects such as lactic acidosis. Objective: This study aims to evaluate the side effect of Metformin for diabetic kidney diseases (DKD) patients. Method: This study used the Narrative Review Method that was obtained from 2011 to 2021, in the English language from PubMed, Google Scholar, and Cochrane Library. Results: Metformin is at the forefront of the treatment of type 2 diabetes mellitus (DM2). Metformin is likely to have lactic acidosis-related adverse effects in chronic kidney disease (CKD) patients, such as increased arterial lactate. Lactic acidosis is defined as an increase in arterial lactate with an indicator of more than five mmol/L and an arterial blood pH of less than 7.35. Metformin-induced lactate levels are considered to be below the parameters. DKD risk factors can be conceptually classified as several susceptibility factors, initiation factors, and developmental factors. The two most prominent risk factors are hyperglycemia and hypertension. Conclusion: Metformin can increase lactate levels in CKD patients but is still below the parameters of lactic acidosis. This study may have some weaknesses and requires further prospective research to validate the results.
COMMUNICATION | doi:10.20944/preprints202106.0364.v2
Subject: Medicine And Pharmacology, Endocrinology And Metabolism Keywords: Diabetic foot infection; Sonication Method; Microbiological diagnosis.
Online: 24 November 2021 (11:51:36 CET)
We hypothesized that biofilm production occurs on stainless steel when incubated with tissue specimens in thioglycolate broth media (TBM). In a diabetic foot infection (DFI) cohort, applying the Kirschner wire and conventional methods were more sensitive than applying only the latter (CI 90%; 0.167 versus 0.375).
ARTICLE | doi:10.20944/preprints201809.0282.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: silver nanoparticles; green synthesis; anti diabetic; cytotoxic
Online: 16 September 2018 (10:02:14 CEST)
Background. Nanotechnology is promising field for generating new applications. A green synthesis of nanoparticles through biological methods using plant extract have a reliable and ecofriendly approach to improve our global environment. Methods. Silver nanoparticles (AgNPs) were synthesized using aqueous extract of Anagalis arvensis L and silver nitrate and were physicochemically characterized. Results. The stability of AgNPs toward acidity, alkalinity, salinity and temperature showed that they remained stable at room temperature for more than two months. The SEM and TEM analysis of the AgNPs showed that they have a uniform spherical shape with an average size in the range of 40–78 nm. Further 1-Dibhenyl-2-Picrylhydrazl radical in Anagalis arvensis L.mediated AgNPs showed a maximum activity of 98% at concentration of 200μg/mL. Hydrogen peroxide scavenging assay in Anagalis arvensis L. mediated AgNPs showed a maximum activity of 85% at concentration of 200μg/mL. Reducing power of Anagalis arvensis L.Ag NPs exhibited a higher activity of 330 μg/mL at concentration of 200 μg/mL. These NPs have cytotoxic effects against brine shrimp (Artemia salina) nauplii with a value of 53% LD 178.04μg/mL. Conclusion. The AgNPs synthesized using Anagalis arvensis L. extract demonstrate a broad range of applications.
REVIEW | doi:10.20944/preprints202308.2062.v1
Subject: Medicine And Pharmacology, Endocrinology And Metabolism Keywords: diabetic kidney disease; proteinuria; pathophysiological mechanism; drug therapy
Online: 31 August 2023 (03:22:20 CEST)
Diabetic kidney disease (DKD) is one of the leading causes of end-stage renal disease worldwide and significantly increases the risk of premature death due to cardiovascular diseases. Elevated urinary albumin levels are an important clinical feature of DKD. Effective control of albuminuria not only delays glomerular filtration rate (GFR) decline but also markedly reduces cardiovascular disease risk and all-cause mortality. New drugs for treating DKD proteinuria, including sodium-glucose cotransporter 2 inhibitors (SGLT2i), mineralocorticoid receptor antagonists (MRAs), and endothelin receptor antagonists (REAs), have shown significant efficacy. Auxiliary treatment with proprietary Chinese medicine has also yielded promising results; however, it also faces a broader scope for development. The mechanisms by which these drugs treat albuminuria in patients with DKD should be described more thoroughly. The positive effects of combination therapy with two or more drugs in reducing albuminuria and protecting the kidneys warrant further investigation. Therefore, this review explores the pathophysiological mechanism of albuminuria in patients with DKD, the value of clinical diagnosis and prognosis, new progress and mechanisms of treatment, and multidrug therapy in patients who have type 2 diabetic kidney disease (T2DKD), providing a new perspective on the clinical diagnosis and treatment of DKD.
ARTICLE | doi:10.20944/preprints202308.0952.v1
Subject: Biology And Life Sciences, Food Science And Technology Keywords: phlorotannin; starch digestion; edible seaweed; anti-diabetic effect
Online: 11 August 2023 (13:20:28 CEST)
Seaweeds, notably cochayuyo (Durvillaea incurvata), are recognized for their rich macro- and micronutrient content, along with their inhibitory effects on the α-glucosidase enzyme. The present study aims to evaluate the effectiveness of this inhibition in actual starchy food products under in vitro gastrointestinal conditions. The study utilized freeze-dried cochayuyo, extracted using hot pressurized liquid extraction with 50% ethanol at 120 C and 1500 psi. The inhibition mechanism of α-glucosidase was determined, and the polyphenol composition of the extract was analyzed using Ultra-High-Performance Liquid Chromatography. The study further evaluated the extract’s impact on starch digestibility, total phenolic content, and antioxidant capacity in noodles as representative starchy food under gastrointestinal conditions. The results indicate that the α-glucosidase inhibition mechanism is mixed. Phenolic compounds, primarily tetraphloroethol, could contribute to this anti-enzymatic activity. The extract was observed to decrease starch digestibility, indicated by a lower rate constant (0.0158 vs. 0.0261 min-1) and digested starch at an infinite time (77.4 vs. 80.5 g/100 g). A significant increase (~1200 vs. ~390 µmol TROLOX/100 g) in antioxidant activity was also noted during digestion when the extract was used. Thus, the study suggests that the cochayuyo extract can reduce starch digestion and enhance antioxidant capacity under gastrointestinal conditions.
ARTICLE | doi:10.20944/preprints202307.1457.v1
Subject: Chemistry And Materials Science, Medicinal Chemistry Keywords: Anti-diabetic; Alpha amylase; Adhatoda vasica; Molecular docking
Online: 21 July 2023 (10:09:28 CEST)
Background: Diabetic patients are more likely to experience morbidity and mortality as a result of microvascular complications such as retinopathy, neuropathy, nephropathy, and stroke. There are many synthetic anti-diabetic agents available which are expensive and have undesirable pathological effects. Thus, it is essential to look for cost-effective, natural, and safe antidiabetic agents. The aim of this study was to screen phytoconstituent and evaluate the in-vitro and in-silico α-amylase inhibitory activity of ethanolic extract of Adhatoda vasica leaves. Method: The extraction of Adhatoda vasica leaves was performed with ethanol through Soxhlet extraction process. Different concentrations (0.1 mg/ml to 1 mg/ml) of ethanolic extract, Acarbose, and Sitagliptin, were prepared and all concentrations were evaluated for α-amylase inhibitory activity through the spectrophotometric method. Molecular docking (AutodockVina 1.2.0) and toxicity profiling (SToPToX web server) studies were performed. Results: The plant extract showed highest inhibition of α-amylase (56.763±0.0035) at a concentration of 1 mg/ml. This inhibitory activity was supported by the in-silico study. Vasicoline (C5) and quercetin (C9), active constitute of plant Adhatoda vasica, showed the best binding energy of 8.3 and 8.0 Kcal/mol respectively with α-amylase enzyme (PDBID: 4W93). Toxicity study revealed the safety profile of plant extract. Conclusion: It was concluded that Adhatoda vasica leaves possess some bioactive compounds which are responsible for controlling blood glucose levels and its identification, purification, and isolation may lead to the development of newer therapeutic agent with lesser side effects.
ARTICLE | doi:10.20944/preprints202306.0862.v1
Subject: Medicine And Pharmacology, Endocrinology And Metabolism Keywords: Diabetic nephropathy; ultrasonography; echointensity; type 2 diabetes mellitus
Online: 13 June 2023 (02:51:30 CEST)
The objective of this study is to assess the hepatic/renal and splenic/renal echointensity ratios in ultrasonography in patients with and without diabetic nephropathy. This retrospective study included patients with diabetes mellitus who underwent ultrasound examinations at our hospital between January 2023 and May 2023. Ultrasound examinations done with renal cortical echogenicity and cortico-medullary differentiation by using B-mode ultrasonography. The hepatic/renal and splenic/renal echo intensity ratios were compared among study groups (diabetic patients with diabetic nephropathy and without nephropathy). The diabetic nephropathy group exhibited significantly higher right renal echointensity and left renal echointensity compared to the non-nephropathic group. Additionally, the splenic/renal echointensity ratio and hepatic/renal echointensity ratio were significantly lower in the diabetic nephropathy group. Urinary microalbumin levels was significantly correlated with Right renal echointensity (r=0.65, p<0.001) and Left renal echointensity (r=0.69, p<0.001). There was also a significant inverse correlation between urinary albumin and splenic/renal echointensity ratio (r=-0.58, p<0.001). Ultrasonography, specifically the assessment of hepatic/renal and splenic/renal echointensity ratios, shows promise as a non-invasive and cost-effective method for evaluating morphological changes in the kidneys in patients with diabetic nephropathy. These findings suggest that ultrasonography can be a valuable tool for monitoring the progression of diabetic nephropathy and contributing to its early detection and management.
REVIEW | doi:10.20944/preprints202305.0932.v1
Subject: Medicine And Pharmacology, Ophthalmology Keywords: Diabetes; diabetic retinopathy; ocular surface; retina; immunity; inflammation
Online: 12 May 2023 (11:00:32 CEST)
Diabetes is a prevalent global health issue associated with significant morbidity and mortality. Diabetic retinopathy (DR) is a well-known inflammatory, neurovascular complication of diabetes and a leading cause of preventable blindness in developed countries among working-age adults. However, the ocular surface components of diabetic eyes are also at risk of damage due to uncontrolled diabetes, which is often overlooked. Inflammatory changes in the corneas of diabetic patients indicate that inflammation plays a significant role in diabetic complications, much like in DR. The eye´s immune privilege restricts immune and inflammatory responses, and the cornea and retina have a complex network of innate immune cells that maintain immune homeostasis. Nevertheless, low-grade inflammation in diabetes contributes to immune dysregulation. This article aims to provide an overview and discussion of how diabetes affects the ocular immune system’s main components, immune-competent cells, and inflammatory mediators. By understanding these effects, potential interventions and treatments may be developed to improve the ocular health of diabetic patients.
ARTICLE | doi:10.20944/preprints202003.0060.v1
Subject: Medicine And Pharmacology, Dietetics And Nutrition Keywords: Alcaligenes faecalis; Diabetic foot ulcer; extensive-drug resistant
Online: 4 March 2020 (10:34:23 CET)
Background: Diabetic foot ulcers are an increasingly common complex problem and are associated with a very considerable health care burden. Diabetic foot ulcer with Alcaligenes faecalis infection is rarely reported in the literature. We report a case series of diabetic foot ulcer with Alcaligenes faecalis infection treated at our facility. Methods: We conducted a retrospective analysis of all patients with diabetic foot ulcer with Alcaligenes faecalis infection seen from January 2014 to April 2019. We analyzed the clinical characteristics, ulcer lesion classification, comorbidities, prior intravenous antibiotic use within three months, wound culture, antibiotics sensitivity test, and clinical outcomes of these patients. Results: Eight cases of diabetic foot ulcer with Alcaligenes faecalis infection were seen in five males and three females. The mean age was 54.6 years. All patients had other comorbidities, and all ulcer lesions were of chronic duration ( more than 14 days ). All wound cultures revealed polymicrobial infection, with two cases of diabetic foot with extensive-drug resistant Alcaligenes faecalis infection found in 2019. All patients needed intravenous antibiotic therapy and surgical interventions for the chronic ulcer lesion. The wound failed to heal in three patients. Conclusions: All diabetic foot ulcers with Alcaligenes faecalis infection were of chronic duration ( more than 14 days ) and had polymicrobial infection. Extensive-drug resistant Alcaligenes faecalis emerged in 2019. Definitive antibiotic therapy is necessary for all infected wounds and should be based on both the culture results and susceptibility data. All patients will need appropriate wound care, and most will need rapid surgical intervention for an optimal outcome.
ARTICLE | doi:10.20944/preprints201810.0489.v1
Subject: Physical Sciences, Biophysics Keywords: diabetes mellitus; blood glucose; kidney; diabetic neuropathy; pancreas
Online: 22 October 2018 (10:45:08 CEST)
This present study was designed to find out whether the acankoreagenin showed the antidiabetic and renoprotective effects in streptozotocin (STZ)-induced diabetic nephropathy (DN) rats. Type I diabetes was induced by a single intraperitoneal injection of STZ (70 mg/kg). At the end of the experiment, rats were euthanized and serum/plasma was separated for the determination of glucose, insulin, glycated hemoglobin A1c (HbA1c), C-peptide, biochemical parameters, and kidney function. One kidney was used for determining glutathione, superoxide dismutas, malondialdehyde, and tumor necrosis factor-alpha levels. The other kidney and pancreas were used for histopathological studies and immunohistochemical measurement of transforming growth factor beta (TGF-β) or NF-κB. Acankoreagenin (2 mg/kg) treatments led to a significant reduction in blood glucose assessed via oral glucose tolerance test (OGTT) in diabetic rats at 2 h. The treatment also resulted in improved body weight, decreased HbA1c, restored lipid profile, and renal oxidative stress. By inhibiting NF-κB, the release of proinflammatory cytokines was suppressed and by inhibiting TGF-β, the renal fibrosis was suppressed in STZ-induced diabetic rat model. Histopathological injury was also observed in pancreatic and renal tissues. These findings support the beneficial effect of acankoreagenin treatment in DN, which could be attributed to its antidiabetic and renoprotective effects.
REVIEW | doi:10.20944/preprints202209.0165.v1
Subject: Medicine And Pharmacology, Endocrinology And Metabolism Keywords: Diabetic foot; Diabetic neuropathies; Peripheral arterial disease; Foot ulcer; Gait; Walking; Postural balance; Wearable electronic devices; Gait analysis; Digital technology
Online: 13 September 2022 (09:28:22 CEST)
People with diabetic foot frequently exhibit poor gait and balance. However, there is no review to inform digital biomarkers of poor gait and balance related to diabetic foot, measurable by wearables outside traditional gait laboratories. Such information could assist in designing remote patient monitoring platform to track changes in gait and balance dysfunction among people with diabetic foot for timely referral and intervention. Accordingly, we conducted a web-based review using PubMed. Our search was limited to human subjects and English-written papers published in peer-reviewed journals. We identified 20 papers in this review. We found preliminary evidence of digital biomarkers of gait and balance dysfunction in people with diabetic foot, measured by wearables, such as slow gait speed, large gait variability, unstable gait initiation, and large body sway. However, due to heterogeneities in included papers in terms of study design, movement tasks, and small sample size, more studies are recommended to confirm this preliminary evidence. Additionally, based on our review, we recommend establishing appropriate strategies to successfully implement wearable-based assessment into clinical practice for diabetic foot care.
REVIEW | doi:10.20944/preprints202306.1245.v1
Subject: Medicine And Pharmacology, Endocrinology And Metabolism Keywords: diabetic kidney disease; metabolic-associated fatty liver disease; biomarker
Online: 16 June 2023 (13:36:04 CEST)
Metabolic-associated fatty liver disease (MAFLD) and diabetic kidney disease (DKD) share various pathophysiological factors, and epidemiological evidence suggests that these two diseases are associated. Albuminuria and the estimated glomerular filtration rate, which are conventional biomarkers of DKD, are reportedly associated with the risk or severity of MAFLD. Recently, novel DKD biomarkers reflecting renal tubular injury have been introduced to complement conventional DKD markers. In this article, we looked at previous studies that showed an association between MAFLD and DKD and also reviewed the significance of DKD biomarkers as predictive risk factors for MAFLD.
ARTICLE | doi:10.20944/preprints202111.0219.v1
Subject: Medicine And Pharmacology, Psychiatry And Mental Health Keywords: Diabetic Ketoacidosis; Mental health; Type 1 diabetes; Transition; Glycemia
Online: 12 November 2021 (12:04:43 CET)
The transition of people from paediatric to adult diabetes services is associated with worsening glycaemia and increased diabetes-related hospitalisation. This study compared the clinical characteristics of those with and without mental health conditions among attenders at a diabetes young adult clinic diabetes before and after changes in service delivery. Retrospective review of 200 people with diabetes attending a Sydney public hospital over eight years corresponding to the period before (2012-2016) and after (2017-2018) restructuring of a clinic for young adults aged 16-25 years. Characteristics of those with and without mental health conditions (depression, anxiety, diabetes related distress, eating disorders), were compared. Among clinic attenders (type 1 diabetes n=184, 83.2%), 40.5% (n=89) had a mental health condition particularly, depression (n=57, 64%), which was higher among Indigenous than non-Indigenous people (5.6% vs 0.8% p=0.031) but similar between diabetes type. Over eight years, those with, compared with those without a mental health condition had higher HbA1c at the last visit (9.4%[79 mmol/mol] vs 8.7% [71 mmol/mol], p=0.027), the proportion with diabetic ketoacidosis (DKA 60.7% vs 42.7%,p=0.009), smoking (38.4 vs 13.6%,p=0.009), retinopathy (9.0 vs 2.3%,p=0.025), multiple DKAs (28.4 vs 16.0%,p=0.031) were significantly higher. Having a mental health condition was associated with 2.02 (95% Confidence intervals 1.1-3.7) fold increased risk of HbA1c ≥ 9.0%[75mmol/mol]. Changes to the clinic were not associated with improvements in mental health condition (39.0% vs 32.4%, p=0.096). In conclusion, we found that mental health conditions, particularly depression, are common in this population and are associated with diabetes complications. Diabetes type and clinic changes did not affect the reported mental health conditions. Additional strategies are required to reduce complication risks among those with mental health conditions. .
COMMUNICATION | doi:10.20944/preprints202007.0654.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Anti-diabetic; hyperglycaemia; hypoglycaemic; Vernonia amygdalina; Type-2 diabetes
Online: 27 July 2020 (00:32:27 CEST)
Nine components (C1-C9) were isolated from chloroform fraction of fractionated methanol extracts of Vernonia amygdalina leaves (FMEVA) by column chromatography. All the components C1 to C9 were purified and screened for hypoglycaemic activities in type-2 diabetic rats. The most potent hypoglycaemic component was elucidated on the basis of extensive spectroscopic (1D-, 2D-NMR, GC-MS, FTIR) data analysis. The Component C5 was found to be the most potent hypoglycaemic in reducing blood glucose by 12.55 ± 3.55% at 4 h post-oral administration, when compared to the positive (18.07 ± 1.20%) and negative (-1.99 ± 0.43%) controls. The spectroscopic data analysis reveals that the isolated compound has a structure consistent with 11β,13-dihydrovernolide. The isolated compound is part of the hypoglycaemic components present in V. amygdalina leaves that is responsible for the anti-diabetic activities. Further research is needed in the development of this compound or its derivatives for pharmaceutical use.
ARTICLE | doi:10.20944/preprints201909.0343.v1
Subject: Biology And Life Sciences, Animal Science, Veterinary Science And Zoology Keywords: uric acid levels; aloxan; diabetic rat; Muntingia calabura L.
Online: 30 September 2019 (08:02:58 CEST)
Background and objectives: This study were designed to determine uric acid concentration and renal histopathology of M. calabura L. stem bark extract in diabetic rats and to compare the natural product of M. calabura L. stem bark extract with allopurinol. Materials and Methods: A completely randomized design was used for the experiment which consisted of 6 treatment groups, each consisting of 4 rats, as follows: 1) NR, normal rat; 2) KN, diabetic rat (negative control); 3) KP, diabetic rats given allopurinol 10 mg/kg body weight; 4) EM150, diabetic rats given the test extract 150 mg/kg body weight/day; 5) EM300, diabetic rats given the test extract 300 mg/kg body weight/day; and 6) EM450, diabetic rats given the test extract 450 mg/kg body weight/ day. Results: The results showed that M. calabura L. stem bark extract decrease (p<0.05) uric acid levels in diabetic rats and no specific damage to renal proximal tubular cells was seen. Conclusions: It was concluded that M. calabura L. stem bark extract has a potential as an antihyperuricemic in diabetic rats. The recommended does was 300 mg/kg body weight to provide a significant effect on reducing the uric acid level in diabetic rats. Our findings support the use of this plant as a treatment for gout and other inflammatory diseases.
ARTICLE | doi:10.20944/preprints201804.0350.v1
Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: 1-DNJ; diabetic cardiomyopathy; fibrosis; N-glycosylation; α1,6-fucosylation
Online: 27 April 2018 (06:13:25 CEST)
The traditional Chinese drug Bombyx Batryticatus mori.L (BBm) which is also named the white stiff silkworm has been widely used in Chinese clinics for thousands of years. It is famous for its antispasmodic and blood circulation promoting effects. Cardiomyocyte hypertrophy, interstitial cell hyperplasia and myocardial fibrosis are closely related to the N-glycosylation of key proteins. To examine the alterations of N-glycosylation that occur in diabetic myocardium during the early stage of the disease and clarify the therapeutic effect of 1-DNJ extracted from BBm, we used the db/db mouse model and an approach based on hydrophilic chromatography solid-phase extraction integrated with an LC-MS/MS identification strategy to perform a site-specific N-glycosylation analysis of left ventricular cardiomyocyte proteins. AGEs, hydroxyproline, CTGF and other serum biochemical indicators were measured with ELISA. In addition, the α1,6-fucosylation of N-glycans was profiled with LCA lectin blots and FITC-labelled lectin affinity histochemistry. The results indicated that 1-DNJ administration obviously downregulated myocardium protein N-glycosylation in db/db mice. The expression levels of serum indicators and fibrosis-related cytokines were reduced significantly by 1-DNJ in a dose-dependent manner. The glycan α1,6-fucosylation level of the db/db mouse myocardium was elevated, and the intervention effect of 1-DNJ administration on N-glycan α1,6-fucosylation was significant. To verify this result, the well-known TGF-β/smad2/3 pathway was selected, and core α1,6-fucosylated TGFR-βⅡ was analysed semi-quantitatively with western blotting. The result supported the conclusions obtained from LCA lectin affinity histochemistry and lectin blot analysis. The expression level of FUT8 mRNA was also detected, and the results showed that 1-DNJ administration did not cause obvious inhibitory effects on FUT8 expression. Therefore, the mechanism of 1-DNJ to relieve the DCM-associated fibrosis can be concluded as the inhibition of N-GlcNAc formation and the reduction of substrate concentration.
REVIEW | doi:10.20944/preprints202306.1909.v1
Subject: Medicine And Pharmacology, Endocrinology And Metabolism Keywords: Diabetic ketoacidosis; type 1 diabetes mellitus; pitfalls; children; diagnosis; management
Online: 27 June 2023 (12:51:47 CEST)
DKA represents an acute, severe complication of relative insulin deficiency and a common presentation of Type 1 Diabetes Mellitus (T1DM) primarily and, occasionally, T2DM in children and adolescents. It is characterized by the biochemical triad of hyperglycaemia, ketonaemia and/or ketonuria, and acidaemia. Clinical symptoms include dehydration, tachypnoea, gastrointestinal symptoms, and reduced level of consciousness, precipitated by a variably long period of polyuria, polydipsia and weight loss. The present review aims to summarize potential pitfalls in the diagnosis and management of DKA. A literature review was conducted using the Pubmed/Medline databases including articles published from 2000 onwards. Diagnostic challenges include differentiating between T1DM and T2DM, DKA and hyperosmolar hyperglycaemic state (HHS), or between DKA and alternative diagnoses presenting with overlapping symptoms, such as pneumonia, asthma exacerbation, urinary tract infection, gastroenteritis, acute abdomen and central nervous system infection. The mainstays of DKA management include careful fluid resuscitation, timely intravenous insulin administration and restoration of shifting electrolyte disorders and underlying precipitating factors. However, evidence suggests that optimal treatment remains a therapeutic challenge. Accurate and rapid diagnosis, prompt intervention and meticulous monitoring are of major importance to break the vicious cycle of life-threatening events and prevent severe complications during this potentially fatal medical emergency.
ARTICLE | doi:10.20944/preprints202112.0445.v1
Subject: Biology And Life Sciences, Food Science And Technology Keywords: omega-3; polyunsaturated fatty acids; painful diabetic neuropathy; metabolism; metabolomics
Online: 28 December 2021 (10:58:38 CET)
Background: Omega-3 polyunsaturated fatty acids (PUFAs) are increasingly reported to improve chronic neuroinflammatory diseases in peripheral and central nervous systems. Specifically, docosahexaenoic acid (DHA) protects nerve cells from noxious stimuli in vitro and in vivo. Recent reports link PUFA supplementation to improving painful diabetic neuropathy (pDN) symptoms. However, the molecular mechanism behind omega-3 PUFAs ameliorating pDN symptoms is lacking. Therefore, we sought to determine the distinct cellular pathways that omega-3 PUFAs dietary supplementation promotes in reducing painful neuropathy in type 2 diabetes mellitus (DM2) patients. Methods: Forty volunteers diagnosed with type 2 diabetes were enrolled in the "En Balance-PLUS" diabetes education study. The volunteers participated in weekly lifestyle/nutrition education and daily supplementation with 1,000 mg DHA and 200 mg eicosapentaenoic acid. The Short-Form McGill Pain Questionnaire validated clinical determination of baseline and post-intervention pain complaints. Laboratory and untargeted metabolomics analyses were conducted using blood plasma collected at baseline and after three months of participation in the dietary regimen. The metabolomics data was analyzed using random forest, hierarchical cluster, ingenuity pathway analysis, and metabolic pathway mapping. Results: We found that metabolites involved in oxidative stress and glutathione production shifted significantly to a more anti-inflammatory state post supplementation. Example of these metabolites include cystathionine (+90%), S-methylmethionine (+9%), glycine cysteine-glutathione disulfide (+157%) cysteinylglycine (+19%), glutamate (-11%), glycine (+11%) and arginine (+13.4%). In addition, the levels of phospholipids associated with improved membrane fluidity such as linoleoyl-docosahexaenoyl-glycerol (18:2/22:6) (+253 %) were significantly increased. Ingenuity pathway analysis suggested several key bio functions associated with omega-3 PUFA supplementation such as formation of reactive oxygen species (p = 4.38 × 10-4, z-score = -1.96), peroxidation of lipids (p = 2.24 × 10-5, z-score = -1.944), Ca2+ transport (p = 1.55 × 10-4, z-score = -1.969), excitation of neurons (p = 1.07 ×10-4, z-score = -1.091), and concentration of glutathione (p = 3.06 × 10-4, z-score = 1.974). Conclusion: The reduction of pro-inflammatory and oxidative stress pathways following omega-3 PUFAS supplementation is consistent with using omega-3 PUFAs as a complementary dietary strategy as part of the overall treatment of painful diabetic neuropathy.
ARTICLE | doi:10.20944/preprints201803.0030.v1
Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: 1-DNJ; diabetic cardiomyopathy; fibrosis; N-glycosylation; α 1,6-Fucosylation
Online: 5 March 2018 (04:08:49 CET)
The Chinese drug Bombyx Batryticatus mori.L which also named as the white stiff silkworm is widely used in clinics, due to the significant antispasmodic and promotional blood circulation effects. In addition, its hypoglycemic effect is also recognized in recent years. From a pathological point of view, the enzymatic glycosylation and non-enzymatic glycation both have important roles in regulating properties of proteins and are associated with Diabetes. With the db/db mouse model, we examined the alterations of N-glycosylation of diabetic myocardium at primary stage and clarify the differences in glycosylation of myocardium before and after with 1-DNJ treatment. Hydrophilic chromatography solid phase extraction enrichment and LC-MS/MS identification was applied to profile the alternations in protein glycosylation. Meanwhile, N-glycan α1, 6-fucosylation alterations were profiled with LCA lectin blot and FITC-labelled lectin affinity histochemistry. Our results showed that AGES, hydroxyproline, CTGF and other serum indicators and fibrosis related cytokines expressional levels were reduced significantly by 1-DNJ in a dose-dependent manner. In order to verify this result, the well-known pathway of TGF-β/smad2/3 was picked out and α1, 6-core fucosylated TGFR-βⅡwas semi-quantified with western blot method. The result sustained the conclusion from LCA lectin affinity histochemistry and lectin blot analysis. The expressional level of α1, 6-fucosyltransferase mRNA was increased in the myocardium of db/db mice, however, the 1-DNJ administration did not show obvious inhibitory effect on FU8 expression. This unexpected result can be interpreted as 1-DNJ plays the roles by reducing the concentration of substrate rather than inhibiting α1，6-fucose glycosyltransferase expression. Meanwhile, 1-DNJ crude extract from BBm with some flavonoids accompany can also play the roles of anti-oxidant, and all the chemicals protect the diabetic myocardium from hyperglycemia damage commonly.
REVIEW | doi:10.20944/preprints201907.0265.v2
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Aging; Alzheimer’s disease; brain insulin resistance; db/db diabetic mouse model; diabetic cognopathy; insulin resistance; metabolic syndrome; mixed dementia; obesity; type 2 diabetes mellitus
Online: 9 September 2019 (06:12:15 CEST)
Type 2 diabetes mellitus (T2DM) and late-onset Alzheimer’s disease-dementia (LOAD) are increasing in global prevalence and current predictions indicate they will only increase over the coming decades. These increases may be a result of the concurrent increases of obesity and aging. T2DM is associated with cognitive impairments associated with metabolic factors and increases the cellular vulnerability to develop the age-related increased risk of LOAD. This review addresses possible mechanisms due to obesity, aging, multiple intersections between T2DM and LOAD and mechanisms for the continuum of progression. Multiple ultrastructural images in female diabetic db/db models are utilized to demonstrate marked cellular remodeling changes of mural and glia cells and provide for the discussion of functional changes in T2DM. Throughout this review multiple endeavors to demonstrate how T2DM increases the vulnerability of the brain’s neurovascular unit (NVU), neuroglia and neurons are presented. Five major intersecting links are considered: i. aging (chronic age-related diseases); ii. metabolic (hyperglycemia - advanced glycation end-products and its receptor (AGE/RAGE) interactions and hyperinsulinemia – insulin resistance (a linking linchpin); iii. oxidative stress (reactive oxygen-nitrogen species); iv. inflammation (peripheral macrophage and central brain microglia); v. vascular (macrovascular accelerated atherosclerosis - vascular stiffening and microvascular NVU/neuroglial remodeling) with resulting impaired cerebral blood flow.
ARTICLE | doi:10.20944/preprints202309.0260.v1
Subject: Biology And Life Sciences, Food Science And Technology Keywords: antidiabetic; antioxidants; Coccinia grandis; herbal porridge, phototherapeutics; nano encapsulation; diabetic mellitus
Online: 5 September 2023 (07:48:30 CEST)
Diabetes mellitus is a cluster of metabolic diseases characterized by hyperglycemia. Since this epidemic growing worldwide, the usage of phototherapeutics to manage diabetes is vital. Coccinia grandis (Aka ivy gourd) belongs to cucumber family is identified as a most effective herb, especially for diabetes and many other disease conditions. Hence, an instant herbal porridge cube incorporating Coccinia grandis leaf powder was produced and sensory acceptability of the porridge was evaluated using trained panelists. The bioactive activity of Coccinia grandis leaf powder showed that 66.77±0.74 mg/g GAE of Total Phenolic Content, 27.65±6.79% of DPPH radical scavenging activity, 5.72% of alpha-amylase inhibition activity and 59.64% of alpha-glucosidase inhibition activity. The effect on postprandial blood sugar levels after consuming the developed porridge was measured using healthy adults and it was observed there was no blood sugar elevation during the 2 hours of time. As a further development, Coccinia grandis leaf extract was nano-encapsulated with food grade Sodium alginate and it was incorporated into the same porridge as a safe delivery method of bioactive compounds. In-vitro digestion assay was conducted and the results show that alpha-amylase inhibition activity for the gastric phase and alpha-glucosidase inhibition activity for the intestinal phase was higher in nano-encapsulated porridge. The study concludes that, consuming nano-encapsulated Coccinia grandis leaf extract with porridge is more beneficial for diabetic patients.
REVIEW | doi:10.20944/preprints202308.1440.v1
Subject: Medicine And Pharmacology, Endocrinology And Metabolism Keywords: Diabetes; Erectile dysfunction; microvascular complications; diabetic sexual health; men’s sexual health
Online: 21 August 2023 (08:21:21 CEST)
Erectile dysfunction (ED) is the inability to achieve or maintain an erection during sexual performance. ED is one of the most common and neglected complications of diabetes. Almost 35-75% of diabetic men around the world suffer from ED. Although the exact mechanism by which diabetes causes ED is not well understood. However, several studies suggested it may be related to damage to the nerve and vessels that supply the penis.
ARTICLE | doi:10.20944/preprints202308.1008.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: diabetic vascular disease; endothelial cells; soluble vascular cell adhesion molecule 1
Online: 14 August 2023 (10:25:52 CEST)
Soluble cell adhesion molecules (sCAMs) are secreted ectodomain fragments of surface adhesion molecules, ICAM1 and VCAM1. sCAMs have diverse immune functions beyond their primary function, impacting immune cell recruitment and activation. Elevated sVCAM1 levels have been associated with poor cardiovascular disease (CVD) outcomes, supporting its role as a potential diagnostic marker and therapeutic target. Inhibiting sVCAM1 release or interaction with immune cells could offer cardioprotection in conditions such as diabetes. Membrane bound surface adhesion molecules are widely expressed in a wide variety of cell types with higher expression in endothelial cells (ECs), but the source of sCAMs in the circulation is not clear. Hypothesizing that endothelial cells (ECs) could be a potential source of sCAMs, this study investigated whether dysfunctional EC signaling mechanisms during diabetes cause VCAM1 ectodomain shedding. Our results from samples from a inducible diabetic mouse model revealed increased sVCAM1 plasma levels in diabetes. Protein analysis indicated upregulated VCAM1 expression and metalloproteases ADAM10 and ADAM17 in diabetic ECs. ADAMs are known for proteolytic cleavage of adhesion molecules, contributing to inflammation. GSK3β, implicated in EC VCAM1 expression, was found to be activated in diabetic ECs. GSK3β overexpression in control ECs increased ADAM10/17 and VCAM1. A GSK3β inhibitor reduced active GSK3β and VCAM1 ectodomain shedding. These findings suggest that diabetic ECs with elevated GSK3β activity led to VCAM1 upregulation and ADAM10/17-mediated sVCAM1 shedding. This mechanism underscores the potential therapeutic role of GSK3β inhibition in reducing the levels of circulating sVCAM1. The complex roles of sCAMs extend well beyond CVD. Thus, unraveling the intricate involvement of sCAMs in the initiation and progression of vascular disease particularly in diabetes, holds significant therapeutic potential.
REVIEW | doi:10.20944/preprints202305.1970.v1
Subject: Medicine And Pharmacology, Urology And Nephrology Keywords: Diabetic nephropathy; Hyperglycemia; Phytocompounds; End stage renal disease; Oxidative stress; Inflammation
Online: 29 May 2023 (05:03:27 CEST)
Diabetic nephropathy (DN), one of the primary consequences of diabetes mellitus, affecting many people worldwide. Diabetes affects yearly 463 million adults globally between the ages of 20 and 79, and is the main cause of death under the age of 60. ROS production rises during hyperglycemia and is crucial to the development of diabetic complications. Advanced glycation end products (AGEs) are produced excessively in a diabetic state and accumulate in the kidney, where they change renal architecture and impair renal function. Another important targeted pathway for the formation of DN includes NF-B, Nrf2, NLRP3, Akt/mTOR, and autophagy. About 40% of individuals with diabetes eventually acquire diabetic kidney disease and end stage renal disease that needs hemodialysis, peritoneal dialysis, or kidney transplantation, to survive. The current state of acceptable therapy for this kidney ailment is limited. The studies revealed that some naturally occurring bioactive substances might shield the kidney by controlling oxidative stress, renal fibrosis, inflammation, and autophagy. In order to provide new potential therapeutic lead bioactive compounds for contemporary drug discovery and clinical management of DN, this review was designed to examine the various mechanistic pathways by which current conventional plants derive phytocompounds that are effective for the control and treatment of DN.
REVIEW | doi:10.20944/preprints202304.1087.v1
Subject: Medicine And Pharmacology, Endocrinology And Metabolism Keywords: glucose transport; SGLT2 inhibitor; diabetic nephropathy; heart failure; chronic kidney disease
Online: 28 April 2023 (03:08:47 CEST)
The kidney and the heart work together in balancing the body circulation and although their physiology is based on strict inter dependence, their performance fulfills different aims. While the heart can rapidly increase its own oxygen consumption to comply with the wide changes in metabolic demand linked to body function, the kidney physiology is primarily designed to maintain a stable metabolic rate and has limited capacity to cope with any steep increase in renal metabolism. In the kidneys the glomerular population filters a large amount of blood and the tubular system has been programmed to reabsorb 99% of filtrate by reabsorbing sodium together with other filtered substances including all glucose molecules. Glucose reabsorption involves the sodium-glucose cotransporters SGLT2 and SGLT1 on the apical membrane in the proximal tubular section; it also enhances bicarbonate formation so as to preserve the acid-base balance. The complex work of reabsorption in the kidney is the main factor in renal oxygen consumption; analysis of renal glucose transport in disease states is providing better understanding of the renal physiology changes that occur when clinical conditions alter the neurohormonal response leading to an increase in glomerular filtration pressure. In this circumstance glomerular hyperfiltration occurs, imposing a higher metabolic demand on kidney physiology and causing progressive renal impairment. Albumin urination is the warning signal of renal engagement over-exertion and most frequently heralds heart failure development, regardless of disease etiology. The review analyzes the mechanisms linked to renal oxygen consumption, focusing on sodium-glucose management.
ARTICLE | doi:10.20944/preprints202301.0333.v1
Subject: Medicine And Pharmacology, Medicine And Pharmacology Keywords: diabetic foot osteomyelitis; biofilm; antimicrobial resistance; adverse effects; rifampicin; fluoro-quinolones
Online: 18 January 2023 (10:00:52 CET)
The choice of antibiotic regimens to use in patients presenting with diabetic foot osteomyelitis and their duration differs according to the situation. Antibiotics play a more important role in the medical option where no infected bone has been resected while their role is reduced but not negligible in the case of surgical options. Some studies have reported the presence of biofilm structures in bone samples taken from patients with diabetic foot osteomyelitis which raises the question of the place of anti-biofilm antibiotic regimens in this setting. During the last two decades, clinical studies have suggested a potential benefit for anti-biofilm antibiotics, mainly rifampicin against staphylococci and fluoroquinolones against gram-negative bacilli. No data from randomized controlled studies have however been reported so far. The present work provides a summary of the available data on the question of the place of anti-biofilm antibiotics for the treatment of diabetic foot osteomyelitis but also the potential limitations of such treatments.
Subject: Medicine And Pharmacology, Cardiac And Cardiovascular Systems Keywords: Diabetic Cardiomyopathy; Hyperglycemia; Ischemia/Reperfusion Injury; Metabolism; Mitochondria; Remote Conditioning; Exercise
Online: 17 March 2020 (08:52:25 CET)
Metabolic syndrome, diabetes and ischemic heart disease are among the leading causes of death and disability in Western countries. Diabetic cardiomyopathy is responsible for the most severe signs and symptoms. An important strategy for reducing the incidence of cardiovascular disease is regular exercise. Remote ischemic conditioning has some similarity with exercise, and can be induced by short periods of ischemia and reperfusion of a limb, and it can be performed in people who cannot exercise. There is abundant evidence that exercise is beneficial in diabetes and ischemic heart disease, but there is a need to elucidate the specific cardiovascular effects of emerging and unconventional forms of exercise in people with diabetes. Also, remote ischemic conditioning may be considered among the options to induce beneficial effects in these patients. The characteristics and interactions of diabetes and ischemic heart disease, and the known effects of exercise and remote ischemic conditioning in the presence of metabolic syndrome and diabetes, are analyzed in this brief review.
CONCEPT PAPER | doi:10.20944/preprints202308.1919.v1
Subject: Computer Science And Mathematics, Computer Vision And Graphics Keywords: Super-resolution; OCT-A; implicit neural representation; retina; diabetic retinopathy; opthalmic images
Online: 29 August 2023 (03:47:17 CEST)
There has been considerable progress in implicit neural representation to upscale an image to any arbitrary resolution. However, existing methods are based on defining a function to predict the RGB value from just four specific loci. Relying on just four loci is insufficient as it leads to losing fine details from the neighboring region(s). We show that by taking into account the semi-local region leads to an improvement in performance. In this paper, we propose applying a new technique called Overlapping Windows on Semi-Local Region (OW-SLR) to an image to obtain any arbitrary resolution by taking the coordinates of the semi-local region around a point in the latent space. This extracted detail is used to predict the RGB value of a point. We illustrate the technique by applying the algorithm to the Optical Coherence Tomography-Angiography (OCT-A) images and show that it can upscale them to random resolution. This technique outperforms the existing state-of-the-art methods when applied to the OCT500 dataset. OW-SLR provides better results for classifying healthy and diseased retinal images such as diabetic retinopathy and normals from the given set of OCT-A images. The project page is available at https://rishavbb.github.io/ow-slr/index.html
ARTICLE | doi:10.20944/preprints202108.0279.v1
Subject: Medicine And Pharmacology, Ophthalmology Keywords: Glaucoma; Diabetic Retinopathy; Convolution Neural Network (CNN); Vision Loss; Blindness; Machine Learning
Online: 12 August 2021 (15:36:51 CEST)
In the last few decades, glaucoma became the second biggest leading cause of irreversible vision loss. Because of its asymptotic growth, it is not properly diagnosed until the relatively late stage. To stop the severe damage by glaucoma it is needed to detect glaucoma in its early stages. Surprisingly diabetes also be the greatest cause of glaucoma. In the modern era, artificial intelligence makes great progress in the medical image processing field. Image analysis based on machine learning gives a huge success in diagnosis glaucoma without any misdiagnosis. The aim of this proposed paper is to create an automated process that can detect glaucoma and diabetic retinopathy. Here various Machine Learning models are used and results of these methods are presented.
ARTICLE | doi:10.20944/preprints202306.0202.v1
Subject: Medicine And Pharmacology, Internal Medicine Keywords: type 2 diabetes mellitus; diabetic neuropathy; inflammation; C reactive protein to albumin ratio
Online: 2 June 2023 (12:07:42 CEST)
Type 2 diabetes mellitus may be complicated with chronic complications including diabetic neuropathy (DN). Timely diagnosis is crucial in treatment and maybe reversal of this complication. C reactive protein to albumin ratio (CAR) is considered as a marker of inflammation in various diseases that characterized with acute or chronic inflammation. Since diabetic neuropathy and type 2 diabetes mellitus are also associated with chronic, low grade inflammation, we aimed to study CAR levels of type 2 diabetic subjects with diabetic neuropathy and to compare to those in patients without diabetic neuropathy. Type 2 diabetic patients presented to our institutional outpatient clinics were divided into two according to the presence of DN. Subjects with DN were listed as DN group and others were as non-DN group. Characteristics and laboratory data, including CAR, in DN and non-DN groups were compared. Median CAR of the DN and non-DN groups were 2,19 (0,2-49)% and 0,56 (0,02-5,8)%, respectively (p<0.001). CAR was significantly and positively correlated with age (r=0.15, p<0.001), weight (r=0.19, p=0.01), BMI (r=0.11, p=0.03), waist circumference (r=0.10, p=0.046), fasting plasma glucose (r=0.14, p=0.004), serum creatinine (r=0.25, p<0.001), triglyceride (r=0.17, p<0.001), and LDL-cholesterol (r=0.13, p=0.001) levels. Moreover, CAR was inversely correlated with eGFR levels (r=-0.16, p<0.001). The sensitivity and specificity of CAR (when higher than 1,02%) in predicting diabetic neuropathy were 78% and 73%, respectively (AUC: 0.84, p<0.001, 95% CI: 0,82-0,87). Moreover, high CAR level was an independent risk factor of diabetic neuropathy (p<0.001, OR: 1.34, 95% CI: 0.48-1.62). In conclusion, elevated CAR levels could be considered as a marker of diabetic neuropathy.
ARTICLE | doi:10.20944/preprints202305.2084.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: urinary extracellular vesicles,; exosomes; urine; diabetic kidney disease; reference genes; miRNA; mRNA; sequencing
Online: 30 May 2023 (08:23:23 CEST)
Urinary extracellular vesicles (uEV) hold non-invasive RNA biomarkers for genitourinary tract diseases. However, missing knowledge about reference genes and effects of pre-analytical choices hinder biomarker studies. We aimed to assess how pre-analytical variables (urine storage temperature, isolation workflow) affect diabetic kidney disease (DKD) -linked miRNAs or kidney -linked miRNAs and mRNAs (kidney-RNAs) in uEV isolates and to discover stable reference mRNAs across diverse uEV datasets. We studied nine raw and normalized sequencing datasets including healthy controls and individuals with prostate cancer or type 1 diabetes with or without albuminuria. We focused on kidney-RNAs reviewing literature for DKD-linked miRNAs from kidney tissue, cell culture and uEV/urine experiments. RNAs were analyzed by expression heatmaps, hierarchical clustering and selecting stable mRNAs with normalized counts (>200) and minimal coefficient of variation. Kidney-RNAs were decreased after urine storage at -20°C vs -80°C. Isolation workflows captured kidney-RNAs with different efficiencies. Ultracentrifugation captured DKD -linked miRNAs that separated healthy and diabetic macroalbuminuria groups. Eleven mRNAs were stably expressed across the datasets. Hence, preanalytical choices had variable effects on kidney-RNAs – analyzing kidney-RNAs complemented global correlation, which could fade differences in some relevant RNAs. Replicating prior DKD-marker results and discovery of candidate reference mRNAs encourages further uEV biomarker studies.
ARTICLE | doi:10.20944/preprints202306.1501.v1
Subject: Chemistry And Materials Science, Nanotechnology Keywords: Copper nanoparticles; Asparagus racemosus; Antioxidant; Anti-diabetic; Antifouling; Antibac-terial activity; Algae boom water
Online: 21 June 2023 (08:18:17 CEST)
The key objective of the experiment was to show the environmental based of copper nanoparticles which counters the growth of bacterial pathogens such as Pseudomonas aeruginosa, and Staphylococcus aureus. To begin with the experiments, root extract of Asparagus racemosus was used to synthesise Copper nanoparticles. To confirm the formation of Cu-NPs, it was subjected to characterization such as Ultra Violet analysis, X-ray Diffraction method, Fourier Transform Infrared Spectroscopy and Scanning electron microscope images. Later the antibacterial activity of Cu-NPs was studied by incorporating it into two bacterial pathogens (Pseudomonas aeruginosa and Staphylococcus aureus). The outcome displayed a satisfactory antibacterial activity against the bacterial pathogens by the biosynthesized copper nanoparticles. To boost up the enzyme inhibition property of the Cu NPs, Antioxidant and Antidiabetic assay were also performed. The biosynthesised Cu NPs displayed a satisfied result in Antifouling function. The result was used assessed with green algae bloom water.
ARTICLE | doi:10.20944/preprints202305.0451.v1
Subject: Chemistry And Materials Science, Biomaterials Keywords: Electrospun wound dressing; Skin tissue engineering; Regenerative medicine; Gelatin; Poly (glycerol sebacate); Diabetic wound
Online: 8 May 2023 (05:15:40 CEST)
Infectious diabetic wounds can result in severe injuries or even death. Biocompatible wound dressings offer one of the best ways to treat these wounds, but creating a dressing with suitable hydrophilicity and biodegradation rate can be challenging. To address this issue, we used the electrospinning method to create a wound dressing composed of poly(glycerol sebacate) (PGS) and gelatin (Gel). We dissolved the PGS and Gel in acetic acid (75 v/v%) and added EDC/NHS solution as a crosslinking agent. Our measurements revealed that the scaffolds' fiber diameter ranged from 180.2 to 370.6 nm, and all the scaffolds had porosity percentages above 70%, making them suitable for wound healing applications. Additionally, we observed a significant decrease (p < 0.05) in the contact angle from 110.8° ± 4.3° for PGS to 54.9° ± 2.1° for PGS/Gel scaffolds, indicating an improvement in hydrophilicity of the blend scaffold. Furthermore, our cell viability evaluations demonstrated a significant increase (p < 0.05) in cultured cell growth and proliferation on the scaffolds during the culture time. Our findings suggest that the PGS/Gel scaffold has potential for wound healing applications.
ARTICLE | doi:10.20944/preprints202212.0397.v2
Subject: Medicine And Pharmacology, Surgery Keywords: antibiotic therapy; diabetic foot infections; non-beta-lactam antibiotics; skin commensals; treatemet failures; associations with treatment failures
Online: 20 January 2023 (15:13:51 CET)
In diabetic foot infections (DFI), the clinically virulence of skin commensals are generally pre-sumed to be of low virulence. In this single-center study, we divided the wound isolates into two groups: skin commensals (coagulase-negative staphylococci, micrococci, corynebacteria, cutibacteria); and, pyogenicpathogenic pathogens, and followed the patients for ≥ 6 months. In this retrospective study among 1,018 DFI episodes (392 [39%] with osteomyelitis), we identified skin commensals as the sole culture isolates (without accompanying pyogenicpathogenic patho-gens) in 54 cases (5%). After treatment (antibiotic therapy [median of 20 days], hyperbaric oxy-gen in 98 cases [10%]), 251 episodes (25%) were clinical failures. Group comparisons between those growing only skin commensals and controls found no difference in clinical failure (17% vs 24 %, p=0.23) or microbiological recurrence (11% vs 17 %, p=0.23). The skin commensals were mostly treated with non-beta-lactam oral antibiotics. In multivariate logistic regression analysis, isolation of only skin commensals was not associated with failure (odds ratio 0.4, 95% confi-dence interval 0.1-3.8). Clinicians might wish to consider these isolates as potential pathogens when selecting a targeted antibiotic regimen, which may equally base on oral non-beta-lactam antibiotic agents susceptible to the corresponding skin pathogens.
REVIEW | doi:10.20944/preprints202212.0208.v1
Subject: Medicine And Pharmacology, Ophthalmology Keywords: Proliferative diabetic retinopathy; recurrent vitreous hemorrhage; diabetes duration; anemia; posterior vitreous; retinal laser photocoagulation
Online: 12 December 2022 (14:59:08 CET)
(Background) the aim was to determine related factors to recurrent vitreous hemorrhage (RVH) in a sample of proliferative diabetic retinopathy (PDR) patients. (Methods) A retrospective, review-based study. We studied 183 eyes from 121 type 2 diabetes patients with PDR. We recorded diabetes duration, history of hypertension, retinal photocoagulation status, the posterior vitreous status, the mean HbA1c, mean hemoglobin, the renal function, and the systemic complications related to diabetes. We also recorded the use of ranibizumab prior to vitrectomy and the following surgical variables: the application of segmentation and diathermy on fibrovascular proliferative tissue, the use of silicone oil, and the occurrence of surgical complications, to study which independent variables were significantly related to the presence of RVH. (Results) Duration of diabetes (P= 0.028), hemoglobin (P=0.02), status of the posterior vitreous (P=0.03), retinal photocoagulation (P=0.002) and use of segmentation surgery technique (P=0.003) have significant link to the presence of RVH. In addition, patients with diabetic polyneuropathy, myocardial infarction and ischemia in lower limbs had more vitreous hemorrhage events (p<0.001). (Conclusions) Patients with PDR and with longer diabetes duration, anemia, attached posterior vitreous, deficient retinal photocoagulation, and previously cardiovascular events, were more prone to RVH.
ARTICLE | doi:10.20944/preprints201805.0318.v1
Subject: Biology And Life Sciences, Food Science And Technology Keywords: microencapsulation; polyphenols; freeze-drying; antioxidant activity; in vitro dialyzability; in vitro anti-diabetic potential
Online: 23 May 2018 (08:11:46 CEST)
Microencapsulation of polyherbal formulation (PHF) extract was carried out by freeze drying method, by employing gum arabic (GA), gelatin (GE), and maltodextrin (MD) with their designated different combinations as encapsulating wall materials. Antioxidant components (i.e total phenolic contents (TPC),Total flavonoids contents (TFC), and total condensed contents (TCT)), antioxidant activity (i.e. DPPH, β-carotene & ABTS+ assays), moisture contents, water activity (aw), solubility, hygroscopicity, glass transition temperature (Tg), particle size, morphology, in vitro alpha-amylase and alpha-glucosidase inhibition and bioavailability ratios of the powders were investigated. Amongst all encapsulated products, TB (5% GA and 5% MD) and TC (10% GA) has proven to be the best treatments with respect to the highest preservation of antioxidant components and their antioxidant potential by DPPH and β-carotene assays and noteworthy for an ABTS+ assays, in addition, the aforesaid treatments also demonstrated lower moisture content, aw, particle size and higher solubility, hygroscopicity and glass transition temperature (Tg). All freeze dried samples showed irregular (asymmetrical) microcrystalline structures. Furthermore, TB and TC also illustrated the highest in vitro anti-diabetic potential due to great potency for inhibiting alpha-amylase and alpha-glucosidase activities. In the perspective of bioavailability, TA, TB and TC demonstrated the excellent bioavailability ratios (%).Futhermore, the phytochemo-profiling of ethanolic extract of PHF was also revealed to find out the bioactive compounds.
ARTICLE | doi:10.20944/preprints202304.0930.v3
Subject: Medicine And Pharmacology, Endocrinology And Metabolism Keywords: Multidisciplinary pain clinic; Diabetic foot; Amputation; Foot ulcer; Diabetes Mellitus; Economic evaluation; Cost Benefit Analysis
Online: 27 September 2023 (08:18:15 CEST)
Aims: Multidisciplinary diabetic foot clinics have been shown to be an effective therapeutic model for reducing major amputations and mortality rates. The aim of this article is to assess the economic impact of the implementation of a multidisciplinary diabetic foot clinic in a hospital in Barcelona, Spain. Methods: Observational cost-benefit study of all subjects with diabetes admitted with the diagnosis of a major amputation due to diabetic foot from 2010 to 2020. Direct and indirect costs were compared before and after the introduction of the multidisciplinary diabetic foot clinic. Results: The individual cost per patient with diabetic foot was €14,768 before the implementation of the unit. After the implementation of the clinic, the expected cost was reduced to €5,985 due to a 40% reduction in the probability of hospitalization. Overall, the implementation of the clinic resulted in cost savings per patient valued at €8,783, of which, €7,165 are related to hospital benefits. Conclusion: The results of this analysis contributes to the evidence suggesting that multidisciplinary diabetic foot clinics are cost-effective, by demonstrating that they have a positive impact on patient health while also reducing the utilization of healthcare resources.
REVIEW | doi:10.20944/preprints202307.0542.v1
Subject: Biology And Life Sciences, Other Keywords: eye health; visual impairment; age-related macular degeneration; glaucoma; retinitis pigmentosa; diabetic retinopathy; therapeutic strategies
Online: 10 July 2023 (08:29:38 CEST)
Visual impairment and blindness are a growing public health problem, as they reduce the quality of life of millions of people. The management and treatment of these diseases represent a scientific and therapeutic challenge, since the different cellular and molecular actors involved in the pathophysiology are still being identified. The visual system components, particularly the retinal cells, are extremely sensitive to genetic or metabolic alterations, and immune cells activated by insults contribute to biological events that culminate with vision loss and irreversible blindness. Several ocular diseases are linked to retinal cell loss, and diseases such as retinitis pigmentosa, age-related macular degeneration, glaucoma and diabetic retinopathy are characterized by pathophysiological hallmarks that represent possibilities to study and develop novel treatments for retinal cells degeneration. Here, we present a compilation of revisited information on retinal degeneration, including pathophysiologic and molecular features, biochemical hallmarks and possible directions for novel treatments, aiming to assist as a guide for innovative research. The expansion of knowledge of the mechanistic bases of the pathobiology of eye diseases, including information on the complex interactions of genetic predisposition, chronic inflammation, and environmental and aging-related factors will allow the identification of new therapeutic strategies.
ARTICLE | doi:10.20944/preprints202306.2099.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: retinal pigmented epithelium; rod outer segments; aerobic metabolism; oxidative stress; lipofuscin; antioxidants; diabetic retinopathy; hyperglycemia.
Online: 29 June 2023 (10:54:50 CEST)
Dysfunction of the retinal pigment epithelium (RPE) is associated with several diseases characterized by retinal degeneration, such as diabetic retinopathy (DR). However, it has recently been proposed that outer retinal neurons also participate in the damage triggering. Therefore, we have evaluated possible crosstalk between RPE and photoreceptors in priming and maintaining oxi-dative damage of the RPE. For this purpose, we used ARPE-19 cells as a model of human RPE, grown in normal (NG, 5.6 mM) or high glucose (HG, 25 mM), and unoxidized (UOx) or oxidized (Ox) mammalian retinal rod outer segments (OS). ARPE-19 cells were efficient at phagocytizing rod OS in both NG and HG settings. However, in HG, ARPE-19 cells treated with Ox-rod OS accumulated MDA and lipofuscins and displayed altered LC3, GRP78, and Caspase 8 expression, compared to untreated and UOx-rod OS-treated cells. Data suggest that early oxidative damage may originate from the photoreceptors and subsequently extend to the RPE, providing a new perspective to the idea that retinal degeneration depends solely on a redox alteration of the RPE.
REVIEW | doi:10.20944/preprints202212.0287.v1
Subject: Medicine And Pharmacology, Urology And Nephrology Keywords: green tea; EGCG; oxidative stress; acute kidney injury; chronic kidney disease; kidney stones; diabetic nephropathy
Online: 15 December 2022 (15:48:03 CET)
Kidney diseases are a global health problem, and their frequency is continuously increasing. Available treatments provide limited kidney protection. The protective effect of the green tea polyphenol epigallocatechin-3-gallate (EGCG) in several diseases have been extensively investigated. Experimental and clinical studies have shown that the antioxidant, anti-inflammatory, and anti-apoptotic properties of EGCG are promising for the treatment and/or prevention of kidney diseases. This review analyzes the available evidence on the effects, and the likely protective mechanisms of action, of EGCG in a broad spectrum of kidney diseases, including acute kidney injury, drug-induced nephrotoxicity, kidney stone disease, diabetic nephropathy, chronic kidney disease, and kidney fibrosis.
REVIEW | doi:10.20944/preprints202309.0163.v1
Subject: Medicine And Pharmacology, Medicine And Pharmacology Keywords: molecular hydrogen; diabetic kidney disease; mitochondrial dysfunction; oxidative stress; in-flammation; reactive oxygen species; medical application
Online: 4 September 2023 (11:16:33 CEST)
With the rapid increase in diabetes worldwide, the number of patients with diabetic kidney disease (DKD), a complication of diabetes mellitus, is also on the rise. DKD is a major cause of chronic kidney disease progressing to end-stage renal failure; however, current medical treatments for DKD do not achieve satisfactory outcomes. Molecular hydrogen (H2) is an antioxidant that selectively reduces hydroxyl radicals, a reactive oxygen species with a very potent oxidative capacity. H2 was recently shown to exert not only antioxidant, but also anti-inflammatory, cell lethality-regulating, and signal transduction-regulating effects, and is now being applied clinically. Many factors contribute to the onset and progression of DKD, with mitochondrial dysfunction, oxidative stress, and inflammation being strongly implicated. Recent preclinical and clinical trials reported that substances with antioxidant properties may slow the progression of DKD. Therefore, we conducted a literature review on animal models and human clinical trials in which H2 showed efficacy against various renal diseases. This literature review and our previous findings collectively suggest that H2 exerts therapeutic effects in patients with DKD by improving mitochondrial function. Future large-scale clinical studies are needed to confirm these findings.
ARTICLE | doi:10.20944/preprints201809.0529.v1
Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: hemodialysis; end stage renal disease; diabetes; motor performance; gait; balance; wearable; aging; frailty; diabetic peripheral neuropathy
Online: 27 September 2018 (04:19:43 CEST)
Motor functions are deteriorated by aging. Some conditions may magnify this deterioration. To examine whether hemodialysis (HD) process would negatively impact gait and balance beyond diabetes condition among mid-age adults (48-64 years) and older adults (65+ years). One hundred and ninety-six subjects (age=66.2±9.1 years, body-mass-index=30.1±6.4 kg/m2, female=56%) in 5 groups were recruited: mid-age adults with diabetes undergoing HD (Mid-age HD+, n=38) and without HD (Mid-age HD-, n=40); older adults with diabetes undergoing HD (Older HD+, n=36) and without HD (Older HD-, n=37); and non-diabetic older adults (Older DM-, n=45). Gait parameters (stride velocity, stride length, gait cycle time, and double support) and balance parameters (ankle, hip, and center of mass sways) were quantified using validated wearable platforms. Groups with diabetes had overall poorer gait and balance compared to the non-diabetic group (p<0.050). Among people with diabetes, the HD+ had significantly worsened gait and balance when comparing to the HD- (Cohen’s effect size d=0.63-2.32, p<0.050). Between-group difference was more pronounced among older adults with the largest effect size observed for stride length (d=2.32, p<0.001). Results suggested that deterioration in gait speed among the HD+ was correlated with age (r=-0.440, p<0.001), while this correlation was diminished among the HD-. Interestingly, results also suggested that poor gait in the Older HD- related to poor balance, while no correlation was observed between poor balance and poor gait among the Older HD+. Using objective assessments, results confirmed that the presence of diabetes can deteriorate gait and balance, and this deterioration can be magnified by HD process. Among non-HD people with diabetes, poor static balance described poor gait. However, among people with diabetes undergoing HD, age was a dominate factor describing poor gait irrespective of static balance. Results also suggested feasibility of using wearable platforms to quantify motor performance during routine dialysis clinic visits. These objective assessments may assist in identifying early deterioration in motor function, which in turn may promote timely intervention.
REVIEW | doi:10.20944/preprints201807.0454.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Carica papaya; fermented papaya preparation (FPP); free radical scavenging; antioxidant; oxidative stress; anti-diabetic; anti-carcinogenic
Online: 24 July 2018 (11:39:50 CEST)
The simplistic morphological characteristics of the Carica papaya, papaya or ‘pawpaw’ should not be the cause for underestimating its potential as a nutraceutical. The market for papaya has been expanding at a staggering rate, partly due to its applicability as a biofortified product, but mostly for its phytochemical properties and traditional health benefits. Recent characterization studies have showed that the entirety of papaya or using a formulation of fermented papaya promotion (FPP) displays effective free radical scavenging abilities, thought to be influenced by its phenolic, carotenoids, flavonoid or amino acid profile. Aiming at reducing the impact of free radical-induced oxidative damage in the human system, the antioxidant properties of FPP have been found to potently target a broad spectrum of diseases ranging from neurological impairments such as senile dementia to systemic diseases, to its interference at the cellular level and support of normal biological ageing processes. FPP has thus been extensively investigated for its ability to exert cellular protective effects and reduce oxidative stress via mitigation of genetic damage, lipid peroxidation and enzymatic inactivation in diseases. Oxidative stress reduction strategies using FPP and its holistic approach in disease prevention and management, with a focus on diabetes, cancer and cognitive health, contributes unequivocally to wellness in an aging population.
ARTICLE | doi:10.20944/preprints202305.1080.v1
Subject: Medicine And Pharmacology, Ophthalmology Keywords: diabetic macular edema; diabetes; visual acuity; optical coherence tomography; macular thickness; retinal thickness; anti-VEGF; corticosteroid; deviation
Online: 16 May 2023 (04:43:23 CEST)
The purpose of the study was to determine the “retinal thickness deviation” (RTD) in diabetic macular edema (DME) eyes treated with intravitreal therapy and to establish associations be-tween RTD and best-corrected visual acuity (BCVA). We conducted a retrospective study, in-cluding consecutive DME eyes undergoing intravitreal therapy with two years of follow-up. BCVA and central subfield thickness (CST) were collected at baseline, 12 months and 24 months of follow-up. RTD was calculated as the absolute difference between measured and normative CST values at each time point. Linear regression analyses were performed between RTD and BCVA and between CST and BCVA. One hundred and four eyes were included in the analysis. The RTD was 177.0 (117.2) μm at baseline, 97.0 (99.7) μm at 12 months and 89.9 (75.3) μm at 24 months of follow-up (P < .001). RTD showed a moderate association with BCVA at baseline (R2=0.134, p<0.001) and 12 months (R2=0.197, p<0.001), and a substantial association at 24 months (R2=0.272, p<0.001). The CST showed a moderate association with BCVA at baseline (R2=0.132, p<0.001) and 12 months (R2=0.136, p<0.001), while the association was weak at 24 months (R2=0.065, p=0.009). In conclusion, RTD showed a good association with visual outcome in DME eyes undergoing intravitreal treatment.
ARTICLE | doi:10.20944/preprints202110.0417.v1
Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: Diabetic wound; Achyranthes aspera; wound healing; burn wound; cotton; pellet granuloma; carrageenan-induced paw edema; Acute toxicity
Online: 27 October 2021 (14:16:41 CEST)
Introduction: Wound healing is a multifaceted biological process, and diabetic wounds add more complexity to it. In diabetic wounds, the combination of chloroform fractions of Achyranthes aspera L. (A.aspera) leaves with β-Glucans has not been investigated. The additive effect of these two (A.aspera + β-Glucans) would benefit the inflammatory phase of diabetic wounds, as improper treatment will lead to chronic injuries. Therefore, the goal of this research work was to assess the in-vivo wound healing and anti-inflammatory effects of a combination of chloroform fractions of A.aspera leaves and β-Glucans in a variety of wound models in STZ-induced diabetic rats. Methods: Preliminary phytochemical analyses of A.aspera were conducted to identify various phytoconstituents in the test extract. Acute and sub-acute dermal toxicity tests of A.aspera were carried out on mice and rats, respectively, to see whether there were any abnormalities. Excision and incision wound models, cotton pellet-induced granuloma models, rat paw edema and burn wounds were used to test wound healing and anti-inflammatory actions. To induce diabetes, streptozotocin (STZ) was administered intraperitoneally at a dosage of 65 mg/kg (i.p.). A.aspera (10% w/w) and β-Glucans (2% w/w) ointments were tested separately and in combination for wound healing activities. Silver sulfadiazine (1 % w/w) ointment was used to treat the positive control groups. Excision wound model rats that had been treated with basic ointment were used as negative controls, as were incision wound model rats that had not been treated. A.aspera (400 mg/kg, po) and β-Glucans (30 mg/kg, po) were tested separately and in combination for anti-inflammatory efficacy. Positive control groups were given indomethacin (10 mg/kg, po) for cotton pellet-induced granuloma and rat paw oedema models. Negative controls for both anti-inflammatory activity models were provided 2% Tween 80. The groups were made up of six rats, and the treatments were given topically and orally to assess wound healing and anti-inflammatory effects. The levels of hydroxyproline and hexosamine and the antioxidant enzymes (SOD and CAT) in the granulation tissue were measured in excision wound model. Healed excision wound skin was examined histopathologically. Results: The A.aspera and β-Glucans combination resulted in a significant percentage of wound contraction and a shorter epithelialization time (P<0.01). The combination was found to be the most effective, with the highest percentage of edema reduction (55 %; p<0.01). The combination also exhibited favourable hydroxylamine, hexosamine and anti-oxidant profiles supported by histopathology data. Conclusion: This research showed that the immunomodulatory effect of β-Glucans had significantly enhanced the wound healing, anti-inflammatory, and anti-oxidant potential of A.aspera in diabetic wounds.
REVIEW | doi:10.20944/preprints202308.2093.v1
Subject: Medicine And Pharmacology, Urology And Nephrology Keywords: semaphorin 3A; neuropilin-1; podocyte; diabetic nephropathy; acute kidney injury; chronic kidney injury; lupus nephritis; fibrosis; apoptosis; inflammation
Online: 31 August 2023 (02:53:48 CEST)
Kidney diseases are worldwide public health problems affecting millions of people. However, there are still limited therapeutic options against kidney diseases. Semaphorin 3A (SEMA3A) is the secreted and membrane-associated proteins, which regulate diverse functions, including immune regulation, cell survival, migration and angiogenesis, thus involving in the several pathogeneses of diseases, including eyes and neurons, as well as kidneys. SEMA3A is expressed in podocytes and tubular cells in the normal adult kidney, and recent evidence revealed that excess SEMA3A expression and subsequent signaling pathway aggravates kidney injury in a variety of kidney diseases, including nephrotic syndrome, diabetic nephropathy, acute kidney injury, and chronic kidney disease. In addition, several reports demonstrated that inhibition of SEMA3A ameliorated kidney injury via reduction of cell apoptosis, fibrosis and inflammation, thus SE-MA3A may be a potential therapeutic target for kidney diseases. In this review article, we summarized current knowledges regarding the role of SEMA3A signaling in kidney pathophysiology and their potential use in kidney diseases.
REVIEW | doi:10.20944/preprints202308.0806.v1
Subject: Public Health And Healthcare, Other Keywords: Hyperglycemic Hyperosmolar State (HHS); Diabetic Ketoacidosis (DKA); Hyperglycemia; Mixed HHS and DKA; Treatment protocols, Prognosis; Electrolyte imbalances; Patient management strategies
Online: 10 August 2023 (08:21:45 CEST)
This paper focuses on hyperglycemic hyperosmolar syndrome (HHS), a unique hyperglycemic state requiring divergent diagnosis and treatment approaches from diabetic ketoacidosis (DKA), despite some shared characteristics. We introduce the mnemonic DI-FF-ER-EN-CE-S to encapsulate unique HHS management and complications. 'DI' emphasizes the need to delay and reduce initial insulin therapy until serum glucose decline is managed by fluid resuscitation alone. 'FF' and 'ER' stress the importance of fluid and electrolyte replacement due to severe dehydration and imbalances. 'EN' denotes the potential for encephalopathy and the requirement for a controlled serum osmolality reduction. 'CE' indicates that cerebral edema is rare but necessitates aggressive fluid therapy. 'S' signifies systemic multiorgan failure. We categorize the associated risks into three mnemonic groups: the 3Rs (renal failure, respiratory distress, rhabdomyolysis), the 3Hs (heart failure, hypercoagulation, hyperthermia), and AP (arrhythmias, pancreatitis) to facilitate awareness and screening of HHS.
ARTICLE | doi:10.20944/preprints202101.0478.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: ocular drug delivery system; topical liposomes; posterior segment of the eye; safety and toler-ability; biologic activity; diabetic macular edema
Online: 25 January 2021 (10:48:51 CET)
Intravitreal injections (IVTs) of corticosteroids as triamcinolone acetonide (TA) are frequently used for the treatment of many vitreous and retinal disorders. However, IVTs are related to severe ocular complications. Lately, a topical ophthalmic TA loaded liposomes formulation (TALF) was designed to transport TA into the posterior segment of the eye when instilled in the ocular surface. To evaluate the safety, tolerability, and biologic activity of TALF, an animal study and a phase I clinical assay was performed. Moreover, four patients with diabetic macular edema (DME) were treated with TALF in order to explore the biologic activity of the formulation. No inflammation, lens opacity, swelling or intraocular pressure rising were recorded after the instillation of TALF in any of the animal or clinical study. Mainly, mild and transient adverse events such as dry eye (30%) and burning (30%) were reported. TALF improves significantly visual acuity and diminishes central foveal thickness in patients with DME. The current data demonstrate the safety, tolerability, and biologic activity of TALF. It seems that TALF can be used topically to treat vitreous and retinal diseases that respond to TA such as DME, avoiding the use of corticosteroids IVTs and its associated hazards.
REVIEW | doi:10.20944/preprints201709.0027.v1
Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: EVs; endothelial-derived microparticles; platelet-derived microparticles; non-invasive biomarkers; miRNAs signature; diabetes associated complications; micro-macrovascular damage; diabetic nephropathy
Online: 8 September 2017 (09:38:47 CEST)
Extracellular vesicles (EVs) represent a heterogeneous population of small vesicles, consisting of a phospholipidic bilayer surrounding a soluble interior cargo. Almost all cell types release EVs, thus they are naturally present in all body fluids. Among the several potential applications, EVs could be used as drug delivery vehicles in disease treatment, in immune therapy because of their immunomodulatory properties and in regenerative medicine. In addition to general markers, EVs are characterized by the presence of specific biomarkers (proteins, miRNAs) that allow the identification of their cell- or tissue-origin. For these features, they represent a potential powerful diagnostic tool to monitor state and progression of specific diseases. As regards, a large body of studies supports the idea that endothelial derived (EMPs) together with platelet-derived microparticles (PMPs) are deeply involved in the pathogenesis of diseases characterized by micro- and macrovascular damages, including diabetes. Existing literature suggests that the detection of circulating EMPs and PMPs and their specific miRNA profile may represent a very useful non-invasive signature to achieve informations about the onset of peculiar disease manifestations. In this Review, we discuss the possible utility of EVs in the early diagnosis of diabetes-associated microvascular complications, specifically related to kidney.
ARTICLE | doi:10.20944/preprints202305.0723.v1
Subject: Medicine And Pharmacology, Ophthalmology Keywords: retina organ culture; neuroretinal degenerative disease; oxidative stress; antioxidant; age-related macular degeneration (AMD); diabetic retinopathy (DR); Scutellarin; PEDF; GM-CSF; 4R
Online: 10 May 2023 (09:42:33 CEST)
Oxidative stress (OS) is involved in the pathogenesis of retinal neurodegenerative diseases like age-related macular degeneration (AMD) and diabetic retinopathy (DR) and an important target of therapeutic treatments. New therapeutics are tested in vivo despite limits in transferability and ethical concerns. Retina cultures using human tissue can deliver critical information and significantly reduce the number of animal experiments along with increased transferability. We cultured up to 32 retina samples derived from one eye, analyzed models’ quality, induced OS, and tested efficiency of antioxidative therapeutics. Bovine, porcine, rat, and human retinae were cultured in different experimental settings for 3-14 d. OS was induced by high-glucose or hydrogen peroxide (H2O2) and treated by Scutellarin, pigment epithelium-derived factor (PEDF), and/or granulocyte macrophage-colony stimulating factor (GM-CSF). Tissue morphology, cell viability, inflammation, and glutathione level were determined. Retina samples showed only moderate necrosis (23.83±5.05 increased to 27.00±1.66 AU PI-staining over 14 d) after 14 days in culture. OS was successfully induced (reduced ATP content of 288.3±59.9 vs. 435.7±166.8 nM ATP in controls); antioxidants reduced OS-induced apoptosis (from 124.20±51.09 to 60.80±319.66 cells/image after scutellarin-treatment). Enhanced mammalian animal and human retina cultures allow reliable, highly transferable research on OS-triggered age-related diseases and pre-clinical testing during drug development.
REVIEW | doi:10.20944/preprints202303.0500.v1
Subject: Medicine And Pharmacology, Ophthalmology Keywords: Oxidative stress and cell death; Reactive oxygen species; ROS; ROS cell death; autophagy; role of antioxidants; eye disease; cornea; lens; epithelium; retinal ganglion cells; retinal pigment epithelium; macular degeneration; antioxidants in the macula; oxidative stress prevention with antioxidants; lifestyle changes; digital eye strain; glaucoma; cataracts; dry eye disease; computer vision syndrome; digital eye strain; diabetic retinopathy; Vitamin A; Vitamin C; copper; glutathione; zinc; selenium; magnesium; blue light damage; UV light damage; blue light reactive oxygen species; autophagy; ferroptosis; ROS cell death; superoxide dismutase; optic nerve gliomas; food deserts; myopia; free radicals
Online: 29 March 2023 (03:33:55 CEST)
Increased screen time during the COVID-19 pandemic and the accelerated incorporation of technology into daily practices have directly contributed to the increased prevalence of eye disease. The human eye is not built for continual technological use and must adjust to exposure to digital screens. Overexposure to technology can result in eye strain and an increased risk of eye diseases such as myopia with complications later in life, including retinal tears, cataracts, and macular degeneration. As vision and ocular diseases become more prevalent, the study of eye diseases, including their causes and treatments, is especially relevant. There is a need to prevent ocular diseases before they become a burden to individuals, their families, and their communities by better understanding the pathophysiology of ocular diseases. Several ocular diseases are thought to be caused by imbalances in reactive oxygen species (ROS) and autophagy. ROS refers to a class of highly reactive oxygen-containing molecules that can undergo damaging reactions with other molecules in the cell. Autophagy is a cellular process of self-eating whereby damaged, harmful, or dead material in cells is broken down to maintain cellular homeostasis. This paper discusses the role of ROS and autophagy in the pathogenesis of computer vision syndrome (CVS), digital eye strain (DES), myopia, cataracts, glaucoma, diabetic retinopathy (DR), age-related macular degeneration (AMD), optic nerve crush injury (OCN), optic nerve gliomas, and retinoblastoma. Lifestyle changes such as limiting screen time, ensuring adequate exposure to evening sunlight, and using blue light protection measures or protective eyewear are important in the prevention of eye disease. Nutrition also contributes significantly to eye health. A balanced diet rich in vitamins and antioxidants may help to prevent ROS and autophagy imbalance-induced eye disease. Medical and surgical treatments become necessary when preventative measures fail. This paper also addresses how government measures to decrease the onset of eye disease, including targeted programs to increase access to fresh vegetables and fruits in food deserts, are a critical macro-level avenue to reduce eye disease prevalence in the US, which according to the National Eye Institute, costs $139 billion yearly.