Medicine
Diabetes and its Silent Partner: A Critical Review of Hyperinsulinemia and its Complications
In this complex realm of diabetes hyperinsulinemia is no longer regarded as just a compensatory response to insulin resistance but rather has evolved into an integral feature. This comprehensive review provides a synthesis of the current literature including various aspects associated with hyperinsulinemia in diabetic complications. Hyperinsulinemia has been shown to be more than just a compensatory mechanism and the key findings demonstrate how hyperinsulinism affects the development of cardiovascular events as well as microvascular complications. Additionally recognizing hyperinsulinemia as a modifiable factor the diabetes management paradigm shifts towards cognitive ones that consider the use of lifestyle modifications in combination with newer pharmacotherapies and precision medicine approaches. These findings have crucial implications for the clinical work requiring a careful appreciation of hyperinsulinemia's changing aspects as well as incorporation in personalized treatment protocol. In addition the review focuses on bigger issues related to public health showing that prevention and early diagnosis will help reduce the burden of complications. Research implications favor longitudinal studies biomarker discovery and the study of emerging treatment modalities; clinical practice should adopt global evaluations patient education and precision medicine adaptation. Finally this critical review provides an overview of the underlying processes of hyperinsulinemia in diabetes and its overall health effects.
Exploring the Therapeutic Potential of Anti-VEGF Drugs for the Management of Diabetic Retinopathy: An Overview
The discovery of antivascular endothelial growth factor medications has resulted in a substantial change in diabetic retinopathy treatment. The most common cause of diabetic retinopathy blindness is Diabetic Macular Edema. The pathophysiology of Diabetic Macular Edema is thought to include the well-known pro-angiogenic and pro-permeability factor vascular endothelial growth factor. Over the past decade drugs that impede the functions of vascular endothelial growth factors have established themselves as a standard-of-care treatment for a range of ocular ailments and improved patients' clinical results with diabetic retinopathy and Diabetic Macular Edema and their frequency has grown exponentially with the introduction of these agents Pegaptanib Ranibizumab and Aflibercept which are approved for ophthalmic indications while Bevacizumab is used off-label. These medications delivered intravitreally have halted the vascular development of diabetic retinopathy. Various randomized trials have proven that antivascular endothelial growth factor medication is safe and effective in preserving vision. Following an extensive period of preclinical development aimed at enhancing and defining its biological impacts these drugs were shown in clinical trials to be effective in treating diabetic retinopathy and other ophthalmic conditions. Data from various sources suggest that Pegaptanib Ranibizumab and Aflibercept are costly while Bevacizumab is cost-effective and in low and middle-income nations it is thus a desirable therapy choice. However issues with compounding counterfeiting and off-label usage restrict its availability in many nations. The pharmacology pharmacokinetics pharmacodynamics adverse effects and contraindications of antivascular endothelial growth factor agents are discussed and the results of clinical trials evaluating their efficacy are summarized.
An Updated Review on Diabetic Nephropathy: Potential Mechanisms, Biomarkers, Therapeutic Targets and Interventional Therapies
Diabetic nephropathy (DN) the primary risk factor for end-stage kidney disease (ESKD) that requires dialysis or renal transplantation affects up to 50% of individuals with diabetes.
In this article potential mechanisms biomarkers and possible therapeutic targets will be discussed as well as their interventional therapies.
A literature review was done from databases like Google Scholar PUBMED-MEDLINE and Scopus using standard keywords “Diabetic Nephropathy” “Biomarkers” “Pathophysiology” “Cellular Mechanism” “Cell Therapy” “Treatment Therapies” from 2010-2023. It has been studied that metabolic as well as hemodynamic pathways resulting from hyperglycemia act as mediators for renal disease.
We identified 270 articles of which 210 were reviewed in full-text and 90 met the inclusion criteria. Every therapy regimen for the prevention and treatment of DN must include the blocking of ANG-II action. By reducing inflammatory and fibrotic markers brought on by hyperglycemia an innovative approach to halting the progression of diabetic mellitus (DN) involves combining sodium-glucose cotransporter-2 inhibitors with renin-angiotensin-aldosterone system blockers. When compared to taking either medicine alone this method works better. AGEs protein kinase C (PKC) and the renin-angiotensin aldosterone system (RAAS) are among the components that are inhibited in DN management strategies.
Thus it can be concluded that the multifactorial condition of DN needs to be treated at an early stage. Novel therapies with a combination of cell therapies and diet management are proven to be effective in the management of DN.
Impact of SGLT2 Inhibitors on Renal Function in Type 2 Diabetic Patients with Coronary Artery Disease Undergoing Percutaneous Intervention: A Systematic Review and Meta-Analysis
Contrast agents directly cause kidney toxicity in patients who are candidates for percutaneous intervention having cardiovascular disease with type 2 diabetes.
This meta-analysis aims to assess the effects of SGLT2i on renal function in individuals undergoing percutaneous intervention.
The databases used for the search included Google Scholar PubMed Cochrane Central Registry of Controlled Trials and Scopus. We considered randomized controlled and observational studies published from January 2013 to August 2023. Eligibility to include the studies was assessed independently. The Cochrane modified data extraction form and Joanna Briggs Institute were used to extract the data. The quality of the studies was evaluated using the Cochrane risk of bias tool and the Newcastle-Ottawa scale. The GradePro software was used to measure the certainty of the evidence.
The pooled estimate showed a substantial reduction in serum creatinine levels at 48 and 72 hours post-PCI who received SGLT2i (MD -9.57; 95% CI -18.36 -0.78; p-value 0.03 and MD -14.40; 95% CI -28.57 -0.22; p-value 0.05). There was a decrease in the occurrence of the CI-AKI among SGT2i users (RR: 0.46; 95% CI: 0.32 0.67; p value< 0.0001). No substantial difference was observed in the number of patients requiring hemodialysis; however a lower proportion of patients among SGLT2i users required hemodialysis (RR: 0.88; 95% CI: 0.19 4.07; p-value = 0.87).
The use of SGLT2i confers substantial beneficial effects on kidney function and reduces the occurrence of contrast-induced acute kidney injury among diabetes patients undergoing PCI procedures with cardiovascular disease.
The Effect of a Vegan Diet on the Health Indicators and Outcomes of Patients with Type 2 Diabetes Mellitus
Recently there has been a notable increase in interest in various forms of vegetarianism which may be due to the growing prevalence of health issues such as Type 2 Diabetes Mellitus (T2DM). Adhering to a vegan diet may have positive health outcomes. As a result we conducted a review article to gather data from previous research studies on the effects of a vegan diet on different aspects of managing patients with T2DM.
We searched the PubMed website for research studies on how a vegan diet affects the outcomes of patients with T2DM. The research studies were categorized according to the type of data collected such as prevalence incidence body weight insulin resistance glycemic control and lipid profile.
It was found that following a vegetarian diet can significantly reduce the risk of mortality from heart disease. Additionally studies have demonstrated that a vegetarian diet is linked to several improvements in T2DM. However long-term weight loss plans and managing T2DM is a comprehensive intervention that includes caloric restriction exercise and behavioral modification.
Incorporating a vegan diet can be a valuable factor to consider in managing T2DM as it can offer numerous benefits such as increased insulin sensitivity weight loss and reduced blood sugar levels. It helps to reduce cholesterol levels LDL and triglyceride levels which are all risk factors associated with T2DM. By reducing these risk factors the vegan diet can improve the overall health of T2DM patients.
Integration of Diabetes Mellitus and Hypertension on Major Cardiovascular Events: An Experience From a 15-year Follow-up Cohort Study in EMR
Patients with hypertension and diabetes are more susceptible to cardiovascular diseases (CVD) and mortality. This study aimed to evaluate the individual and combined effects of hypertension and diabetes on cardiovascular events and mortality in a Middle Eastern population-based cohort.
Fifteen-year follow-up data were collected for 6323 adults aged 35 years and older who were free from CVD at baseline. The subjects were categorized into different groups according to hypertension and diabetes at baseline. Cox proportional hazards regression was implemented to estimate hazard ratios (HRs) of hypertension and diabetes for cardiovascular events (CVE) CVD mortality and all-cause mortality. Population-attributable hazard fraction (PAHF) was used to assess the proportion of hazards of CVE and mortality attributable to hypertension or diabetes.
The incidence rates (95% CI) of CVE CVE mortality and all-cause mortality in the total population were 13.77(12.84-14.77) 3.01(2.59-3.49) and 9.92(9.15-10.77) per 1000 persons per year respectively. The HR of hypertension for CVE in the diabetic population was 1.98 (1.47-2.66) with a PAHF of 27.65(15.49-39.3). When the HRs and PAHF of diabetes were evaluated in hypertensive patients they were statistically significant for CVE CVE mortality and all-cause mortality.
Our study indicated that the joint effect of diabetes and hypertension is the dramatic increased risk of CVE. A considerable fraction of the excess risk of CVE in patients with diabetes was attributable to hypertension on the other hand diabetes was associated with a substantial hazard fraction of CVE and mortality in hypertensive patients.
The Role of Dietary Anthocyanins for Managing Diabetes Mellitus-Associated Complications
Diabetes mellitus (DM) is an intricate metabolic disorder marked by persistent hyperglycemia arising from disruptions in glucose metabolism with two main forms type 1 and type 2 involving distinct etiologies affecting β-cell destruction or insulin levels and sensitivity. The islets of Langerhans particularly β-cells and α-cells play a pivotal role in glucose regulation and both DM types lead to severe complications including retinopathy nephropathy and neuropathy. Plant-derived anthocyanins rich in anti-inflammatory and antioxidant properties show promise in mitigating DM-related complications providing a potential avenue for prevention and treatment. Medicinal herbs fruits and vegetables abundant in bioactive compounds like phenolics offer diverse benefits including glucose regulation and anti-inflammatory antioxidant anticancer anti-mutagenic and neuroprotective properties. Anthocyanins a subgroup of polyphenols exhibit diverse isoforms and biosynthesis involving glycosylation making them potential natural replacements for synthetic food colorants. Clinical trials demonstrate the efficacy and safety of anthocyanins in controlling glucose reducing oxidative stress and enhancing insulin sensitivity in diabetic patients emphasizing their therapeutic potential. Preclinical studies revealed their multifaceted mechanisms positioning anthocyanins as promising bioactive compounds for managing diabetes and its associated complications including retinopathy nephropathy and neuropathy.
Machine Learning and Augmented Intelligence Enables Prognosis of Type 2 Diabetes Prior to Clinical Manifestation
The global incidence of type 2 diabetes (T2D) persists at epidemic proportions. Early diagnosis and/or preventive efforts are critical to attenuate the multi-systemic clinical manifestation and consequent healthcare burden. Despite enormous strides in the understanding of pathophysiology and on-going therapeutic development effectiveness and access are persistent limitations. Among the greatest challenges the extensive research efforts have not promulgated reliable predictive biomarkers for early detection and risk assessment. The emerging fields of multi-omics combined with machine learning (ML) and augmented intelligence (AI) have profoundly impacted the capacity for predictive preventive and personalized medicine.
This paper explores the current challenges associated with the identification of predictive biomarkers for T2D and discusses potential actionable solutions for biomarker identification and validation.
The articles included were collected from PubMed queries. The selected topics of inquiry represented a wide range of themes in diabetes biomarker prediction and prognosis.
The current criteria and cutoffs for T2D diagnosis are not optimal nor consider a myriad of contributing factors in terms of early detection. There is an opportunity to leverage AI and ML to significantly enhance the understanding of the underlying mechanisms of the disease and identify prognostic biomarkers. The innovative technologies being developed by GATC are expected to play a crucial role in this pursuit via algorithm training and validation enabling comprehensive and in-depth analysis of complex biological systems.
GATC is an emerging leader guiding the establishment of a systems approach towards research and predictive personalized medicine. The integration of these technologies with clinical data can contribute to a more comprehensive understanding of T2D paving the way for precision medicine approaches and improved patient outcomes.
Cell Therapies and Gene Therapy for Diabetes: Current Progress
The epidemic of diabetes continues to be an increasing problem and there is a need for new therapeutic strategies. There are several promising drugs and molecules in synthetic medicinal chemistry that are developing for diabetes. In addition to this approach extensive studies with gene and cell therapies are being conducted. Gene therapy is an existing approach in treating several diseases such as cancer autoimmune diseases heart disease and diabetes. Several reports have also suggested that stem cells have the differentiation capability to functional pancreatic beta cell development in vitro and in vivo with the utility to treat diabetes and prevent the progression of diabetes-related complications. In this current review we have focused on the different types of cell therapies and vector-based gene therapy in treating or preventing diabetes.
Molecular Mechanisms Underlying the Therapeutic Potential of Plant-Based α-Amylase Inhibitors for Hyperglycemic Control in Diabetes
Diabetes mellitus (DM) arising from pancreatic β-cell dysfunction and disrupted alpha-amylase secretion manifests as hyperglycemia. Synthetic inhibitors of alpha-amylase like acarbose manage glucose but pose adverse effects prompting interest in plant-derived alternatives rich in antioxidants and anti-inflammatory properties.
The current review investigates plant-based alpha-amylase inhibitors exploring their potential therapeutic roles in managing DM. Focusing on their ability to modulate postprandial hyperglycemia by regulating alpha-amylase secretion it assesses their efficacy health benefits and implications for diabetes treatment.
This review examines plant-derived alpha-amylase inhibitors as prospective diabetic mellitus treatments using PubMed Google Scholar and Scopus data.
Plant-derived inhibitors including A. deliciosa B. egyptiaca and N. nucifera exhibit anti-inflammatory and antioxidant properties effectively reducing alpha-amylase levels in diabetic conditions. Such alpha-amylase inhibitors showed promising alternative treatment in managing diabetes with reduced adverse effects.
The current literature concludes that plant-derived alpha-amylase inhibitors present viable therapeutic avenues for diabetes management by modulating alpha-amylase secretion by regulating inflammatory oxidative stress and apoptotic mechanisms involved in the pathogenesis of diabetes. Further investigation into their formulations and clinical efficacy may reveal their more comprehensive diabetes therapeutic significance emphasizing their potential impact on glucose regulation and overall health.
Therapeutic Interventions for Diabetes Mellitus-associated Complications
Diabetes Mellitus (DM) is an alarming health concern affecting approximately 537 million people worldwide. As a leading cause of morbidity and mortality DM demands a comprehensive understanding of its diverse pathophysiological mechanisms and disease progression.
This traditional review has consolidated literature on the pathogenesis of hyperglycemia its progression into complications and advances in optimal treatment strategies. The literature in the last two decades has been reviewed using several keywords including “diabetes” “diabetes-associated complications” “novel therapeutic interventions for diabetes-associated diseases” “phyto-extracts as antidiabetic drugs” etc. in prominent databases such as PubMed Scopus Google Scholar Web of Science and ClinicalTrials.gov.
We have discussed macrovascular and microvascular complications such as atherosclerosis cardiovascular disease Peripheral Arterial Disease (PAD) stroke diabetic nephropathy retinopathy and neuropathy as well as various pharmacological and non-pharmacological interventions that are currently available for the management of DM. We have also focused on the potential of natural products in targeting molecular mechanisms involved in carbohydrate metabolism insulin production repair of pancreatic cells and reduction of oxidative stress thereby contributing to their antidiabetic activity. Additionally novel therapeutic approaches like genetic stem cell and immunomodulatory therapies have been explored. We have also discussed the benefits and limitations of each intervention emerging research and technologies and precision medicine interventions.
This review has emphasized the need for an improved understanding of these advancements which is essential to enhance clinicians' ability to identify the most effective therapeutic interventions.
The Multifaceted Role of the Polyphenol Curcumin: A Focus on Type 2 Diabetes Mellitus
Type 2 Diabetes Mellitus (T2DM) is a chronic metabolic disorder characterized by chronic hyperglycemia which often co-exists with other metabolic impairments. This condition can damage various tissues and organs resulting in the development of severe complications both microvascular such as retinopathy nephropathy and neuropathy and macrovascular responsible for an increased risk of cardiovascular diseases. Curcumin is the main bioactive molecule found in the rhizomes of turmeric. Many studies have reported curcumin to exhibit antioxidant anti-inflammatory anti-infectious and anti-cancer properties; thus there is an increasing interest in exploiting these properties in order to prevent the rise or the progression of T2DM as well as its possible associated conditions. In this review we have presented the current state-of-art regarding the clinical trials that have involved curcumin administration and analyzed the possible mechanisms by which curcumin might exert the beneficial effects observed in literature.
A Scoping Review of GIS Mapping of Type 1 Diabetes in Children: Identifying Current Gaps and Future Research Directions Using PRISMA-ScR
Type 1 Diabetes poses a significant public health threat especially in low-and-middle countries where resources are limited. The use of geographical information systems in diabetes research has shown the potential to reveal several epidemiological risk factors.
This scoping review aimed to identify the scope and extent of the current literature and explore its limitations on the geographical mapping of children with type 1 diabetes.
A scoping review was conducted using five electronic databases and included studies published between the years 2000 and 2023. The search terms included: “Type 1 Diabetes Mellitus” “GIS mapping” “Juvenile Onset Diabetes Mellitus” “Spatial Epidemiology” “Spatial Clustering” “Spatial analysis” and “Geographic information system”. Relevant full-text articles that met the inclusion criteria were selected for review.
The search identified 17 studies that met the criteria for inclusion in the review. More than half the studies were conducted before 2015 (n=11; 61%). All studies were conducted in High-Income Countries. More than 10 articles studied environmental factors 3 of them focused on the environment 6 of them included sociodemographic factors and 1 study incorporated nutrition (as a variable) in environmental factors. 2 studies focused on the accessibility of health services by pediatric patients.
Studies on type 1 diabetes highlight the complex relationship between incidence and risk suggesting comprehensive prevention and treatment. Geographical mapping has potential in low- and middle-income nations but further research is needed to develop innovative strategies. The importance of geomappping in understanding the risk factors for Type 1 Diabetes is highlighted in this scoping review which also suggests a possible direction for focused interventions particularly in settings with low resources.
Comorbidity of Depression and Diabetes: A Literature Review on Systemic Flaws in Healthcare and the Benefits of Collaborative Diagnosis and Treatment in Primary Care Settings
The increasing specialization and dispersion of healthcare systems have led to a shortage of resources to address comorbidities. Patients with coexisting mental and physical conditions are disadvantaged as medical providers often only focus on the patient's mental illness while neglecting their physical needs resulting in poorer health outcomes.
This study aimed to shed light on the systemic flaws in healthcare systems that contribute to suboptimal health outcomes in individuals with comorbid diseases including depression and diabetes. This paper also discusses the clinical and economic benefits of collaborative methods for diagnosing and treating depressive disorders in primary care settings.
A comprehensive literature review of the relationship between depression and diabetes was conducted. The outcomes of the literature review were carefully analyzed. Several databases were searched using keywords such as “diabetes” “depression” “comorbidity” “prevalence” “epidemiology” and “risk factors” using Google Scholar and PubMed as search engines. The review and research papers written between 1961 and 2023 were our main focus.
This study revealed improved depressive symptoms and better blood sugar and blood pressure control. Additionally individuals with comorbid depression and diabetes have higher direct and secondary medical costs. Antidepressants and psychological interventions are equally effective in treating depressive symptoms in patients with diabetes although they have conflicting effects on glycemic control. For individuals with comorbid diabetes and depression clear care pathways including a multidisciplinary team are essential for achieving the best medical and mental health outcomes.
Coordinated healthcare solutions are necessary to reduce the burden of illness and improve therapeutic outcomes. Numerous pathophysiological mechanisms interact with one another and may support the comorbidities of T2DM and depressive disorders could exacerbate the course of both diseases.
Characterization of Green Synthesized Nanoparticles with Anti-diabetic Properties. A Systematic Review
Plants are used in medicine because they are low-cost widely available and have few side effects (compared to pharmacological treatment). Plants have phytocompounds with antidiabetic properties that can be delivered using nanoparticles (NPs).
To describe the antidiabetic properties of green synthesized NPs (GSNPs) and their characterization methods.
Three databases were consulted using the terms “type 2 diabetes mellitus” “antidiabetic effects” “phytochemicals” “plants” and “nanoparticles.” Studies describing the antidiabetic effects (in vitro or animal models) of NPs synthesized by plant extracts and characterizing them through UV-Vis spectroscopy FTIR XRD SEM TEM and DLS were included.
16 studies were included. In vitro studies reported enzyme inhibition values between 11% (H. polyrhizus) and 100% (A. concinna) for alfa-amylase and between 41.1% (M. zapota) and 100% (A. concinna) for alfa-glucosidase. Animal studies with Wistar Albino rats having diabetes (induced by alloxan or streptozotocin) reported improved blood glucose triglycerides total cholesterol LDL and HDL after treatment with GSNPs. Regarding characterization NP sizes were measured with DLS (25-181.5 nm) SEM (52.1-91 nm) and TEM (8.7-40.6 nm). The surface charge was analyzed with zeta potential (-30.7 to -2.9 mV). UV-Vis spectroscopy was employed to confirm the formations of AgNPs (360-460 nm) AuNPs (524-540 nm) and ZnONPs (300-400 nm) and FTIR was used to identify plant extract functional groups.
GSNP characterization (shape size zeta potential and others) is essential to know the viability and stability which are important to achieve health benefits for biomedical applications. Studies reported good enzyme inhibition percentages in in vitro studies decreasing blood glucose levels and improving lipid profiles in animal models with diabetes. However these studies had limitations in the methodology and potential risk of bias so results need careful interpretation.
An Overview on Diabetic Neuropathy
The term “Diabetic neuropathy” refers to a collection of clinical and subclinical symptoms caused by problems with the peripheral nervous system. Diabetes which affects approximately 381 million people worldwide is the source of dysfunction due to the emergence of microvascular complications. It is anticipated that in the next ten years Diabetic neuropathy will manifest in about 50% of patients who are currently diagnosed with diabetes. Clinical diagnosis can be established by getting a thorough patient history and exploring the symptoms to rule out alternative causes. Although distal symmetrical polyneuropathy or just is the most common and well-researched variant of the disorder this review will concentrate on it. The multifactorial pathogenesis is linked to various inflammatory vascular metabolic and neurodegenerative illnesses. The three fundamental molecular alterations that lead to the development of diabetic neuropathic pain are oxidative stress endothelial dysfunction and chronic inflammation. These three elements are crucial in the development of polyneuropathy because their combination might result in direct axonal damage and nerve ischemia. The purpose of this article was to provide a narrative review of diabetic neuropathy. We provide an overview of the most recent data on biomarkers the pathogenesis of the illness the most recent epidemiology of diabetic neuropathy and the existing screening and diagnosis outcome measures used in both clinical and research contexts.
Correlation between Serum 25 (OH) D Levels with Insulin Resistance and Metabolic Associated Fatty Liver Disease - A Retrospective Study based on Chinese Patients with Newly Diagnosed Type 2 Diabetes Mellitus
The objective of this study was to investigate the correlation between serum 25 hydroxyvitamin D [25(OH)D] levels and insulin resistance as well as metabolic associated fatty liver disease (MAFLD) in newly diagnosed with type 2 diabetes mellitus (T2DM) patients.
A retrospective analysis was conducted on 491 T2DM patients who were newly diagnosed between January 2017 and August 2022 at Peking University International Hospital. These patients were categorized into three groups based on their 25(OH)D levels.
The prevalence of MAFLD was significantly elevated in both the Vitamin D (VD) deficiency group and the VD insufficiency group compared to the VD sufficiency group (χ2 = 6.51 p<0.05). The patients in the VD sufficiency group had lower levels of insulin resistanceas assessed by the homeostasis model assessment when compared to the VD deficiency group and the VD insufficiency group (F = 8.61 p<0.05). Additionally the VD sufficiency group demonstrated higher levels of β cell function in comparison to the other two groups (p<0.05respectively).
A significant negative correlation was observed between 25(OH)D levels and insulin resistance as assessed by the homeostasis model assessment in T2DM patients (r = -0.33 p<0.05 for females; r = -0.32 p<0.05 for males).
In male patients 25(OH)D was identified as a protective factor against MAFLD(OR = 0.42;95%CI:0.19-0.95;p<0.05). Meanwhilein female patients 25(OH)D was also associated with a reduced risk of MAFLD (OR = 0.35;95%CI 0.17-0.89; p<0.05). Additionally the study determined that the threshold values for 25(OH)D were 15.06 ng/ml in female patients and 18.79 ng/ml in male patients for predicting MAFLD.
In newly diagnosed with T2DM patients the level of 25(OH)D may be related to insulin resistance and β cell secretion function independently and VD deficiency is an independent risk factor for MAFLD in patients with newly diagnosed T2DM.
In-Vitro and In-Silico Studies of Brevifoliol Ester Analogues against Insulin Resistance Condition
Brevifoliol is a diterpenoid that occurs naturally in the plants of Taxus genus and is widely used as chemotherapy agent for the management of cancer. A series of semisynthetic esters analogues of brevifoliol were prepared by Steglich esterification and attempted for their pharmacological potential against insulin resistance conditions using in-vitro and in-silico assays.
The aim of this study is to understand the pharmacological potential of eighteen semi‐synthetic analogs through Steglich esterification of Brevifoliol against insulin resistance condition.
In the in-vitro study insulin resistance condition was induced in skeletal muscle cells using TNF-α pro-inflammatory cytokine and these cells were treated with brevifoliol analogues. The most potent analouge was further validated using in-silico docking study against the tumor necrosis factor (TNF-α) (PDB ID: 2AZ5) and Human Insulin Receptor (PDB ID: 1IR3) using the Auto dock Vina v0.8 program.
Although all the analogues of Brevifoliol significantly exhibited the pharmacological potential. Among all analogue 17 was most potent in reversing the TNF-α induced insulin resistance condition in skeletal muscle cells and also to inhibit the production of TNF-α in LPS-induced inflammation in macrophage cells in a dose-dependent manner. Similarly in-silico molecular docking studies revealed that analogue 17 possesses a more promising binding affinity than the selected control drug metformin toward the TNF-α and insulin receptor.
These findings suggested the suitability of analogue 17 as a drug-like candidate for further investigation toward the management of insulin resistance conditions.
Efficacy of Adjunctive Local Antimicrobials to Non-Surgical Periodontal Therapy in Pocket Reduction and Glycemic Control of Patients with Type 2 Diabetes: A Network Meta-Analysis
This network meta-analysis [NMA] investigated the efficacy of adjunctive use of subgingivally delivered antimicrobials to non-surgical periodontal therapy [NSPT] in the glycemic control and periodontal pocket depth (PPD) reduction in patients with type 2 diabetes (T2D).
Seven databases grey literature and registry platforms were searched up to February 2024 to identify randomized clinical trials (RCT) fulfilling the eligibility criteria. The risk of bias was assessed through Cochrane’s tool (RoB 2). Two frequentist NMA were performed using a random-effects model to calculate mean differences (MD) as an effect measure and to quantitatively evaluate the glycated hemoglobin (HbA1c) and PPD. The certainty of evidence was assessed through the GRADE approach in a partially contextualized framework for interpreting results. Ten RCTs were included.
In total 261 patients were treated with eight different local antimicrobials adjuvants to NSPT (azithromycin gel clarithromycin gel tetracycline fiber or ointment chlorhexidine gel doxycycline nanospheres minocycline gel and satranidazole gel) while 249 patients received NSPT alone or associated to placebo. Considering PPD reduction (8 included studies) the best results were found after six months for satranidazole gel (MD -2.64 mm; 95%CI -3.56 -1.72; moderate evidence certainty). For HbA1c control (7 included studies) doxycycline gel (MD -0.80%; 95%CI -1.70 0.10) chlorhexidine gel (MD -0.68%; 95%CI -1.34 -0.02) and tetracycline fiber (MD -0.62%; 95%CI -0.85 -0.39) showed promising results after three months (low evidence certainty).
The adjunctive use of satranidazole gel probably reduces PPD after a 6-month follow-up while doxycycline gel chlorhexidine gel and tetracycline fiber may decrease HbA1c values in patients with T2D and periodontitis treated with NSPT after a 3-month follow up.
Diabetic Retinopathy-A Review
Diabetic Retinopathy is a vascular microvascular disease also called diabetic eye disease caused by microangiopathy leading to progressive damage of the retina and blindness. The uncontrolled blood glycemic level or sugar level results in diabetic retinopathy.
There are two stages of diabetic retinopathy: proliferative diabetic retinopathy and non-proliferative diabetic retinopathy. Symptoms of diabetic retinopathy often have no early warning signs even muscular edema which can cause rapid vision loss. Macular edema in which the blood vessels leak can also occur at any stage of diabetic retinopathy. Symptoms are darkened or distorted images and blurred vision that are not the same in both eyes. This review study primarily discusses the pathophysiology genetics and ALR AGEs VEGF EPO and eNOS involved in diabetic retinopathy.
The longer a person has diabetes the higher their risk of developing some ocular problems. During pregnancy diabetic retinopathy may also be a problem for women with diabetes. NIH are recommends that all pregnant women with diabetes have an overall eye examination. Diagnosis of diabetic retinopathy is made during an eye examination that comprises ophthalmoscopy or fundus photography and glow-in angiography for Fundus. Here we present a review of the current insights into pathophysiology in diabetic retinopathy as well as clinical treatments for diabetic retinopathy patients. Novel laboratory findings and related clinical trials are also analysed.