Dysfunction Insulin Research Articles

Ruellia tuberosa L. Leaf Extract Improves Histopathological Damages in Kidneys of Alloxan-Induced Diabetic Rats

Background: Diabetes mellitus is a Non-Communicable Disease (NCD) characterized by hyperglycemia and insulin dysfunction, leading to redox imbalance and increased Reactive Oxygen Species (ROS). This oxidative stress condition can lead to kidney damage. While drugs like metformin are commonly used to treat diabetes, they can also cause damage to the kidney. Therefore, exploring natural alternatives, such as Ruellia tuberosa L. leaves, is important to minimize side effects and protect kidney function.Methods: This study used a Completely Randomized Design (CRD) with five treatments and five replications. The negative control group received distilled water, while the positive control group was injected with alloxan (150 mg/kgBW) and treated with metformin (50 mg/kg BW). Treatment groups (P1, P2, and P3) received alloxan (150 mg/kg BW) and Ruellia tuberosa L. extract at doses of 200, 400, and 800 mg/kg BW, respectively. Data were analyzed using the Kruskal-Wallis test, and if the extract showed an effect on the kidney condition, post hoc analysis with the Mann-Whitney test was performed.Results: The results of the study showed that there was kidney damage characterized by glomerular necrosis, degeneration of tubular cells, and necrosis of renal tubular cells due to alloxan induction. However, giving Ruellia tuberosa L. extract at doses of 200, 400, and 800 mg/kgBW can prevent kidney damage.Conclusion: The data analysis results indicate that the Ruellia tuberosa L. leaf extract can prevent kidney damage in alloxan-induced diabetic white rats, with the recommended effective dose of 800 mg/kgBW.Keywords: Alloxan, Degeneration, Diabetes, Necrosis, Tubules

The effect of active compounds in herbal plants on increasing salivary pH in patients with Type 2 Diabetes Mellitus

Background: Diabetes mellitus is a chronic disease caused by insulin dysfunction characterized by hyperglycemia. Diabetes mellitus can be classified into four, namely type I diabetes mellitus, type II diabetes mellitus, other specific types of diabetes, gestational diabetes. Diabetes mellitus can cause complications in the dental and oral area, such as Xerostomia, dental caries, periodontitis, periodontal abscesses, and fungal infections of the mouth. Objective: This study aims to determine the effect of active ingredients in herbal plants on the pH of saliva in people with type II diabetes mellitus. Methods: The research design used is a literature review. Discussion: The literature studied states that the content of flavonoids in different types of herbal plants can increase the pH of saliva in patients with type II diabetes mellitus. The manifestation of type II diabetes mellitus is an increase in glucose levels in the saliva that can be metabolized by oral cavity bacteria so that it produces acid and lowers the pH of the saliva. Increasing the pH of saliva to neutral can be done by providing extracts from herbal plants that contain flavonoids. Conclusion: The active ingredients of flavonoids in herbal plants can restore the pH of saliva to normal in people with type II diabetes mellitus.

HUBUNGAN KEBIASAAN MENGKONSUMSI MINUMAN BERENERGI DENGAN STATUS DIABETES MELITUS TIPE 2 PADA SOPIR TAKSI DI KOTA PONTIANAK

Diabetes is one of the leading non-communicable diseases causing mortality worldwide. Type 2 diabetes mellitus is characterized by elevated blood sugar levels due to insulin dysfunction, influenced by behaviors such as energy drink consumption. This study aims to examine the relationship between energy drink consumption habits and type 2 diabetes mellitus status among taxi drivers in Pontianak City.This research employed a cross-sectional design involving 31 taxi drivers as participants. Data collected through interviews revealed that among respondents consuming energy drinks ≤4 times per week, 64.51% were in the normal category with no prediabetes cases. Conversely, in the group consuming >4 times per week, 12.90% were in the normal category, and 22.58% in the prediabetes category. Bivariate analysis using the Chi-square test demonstrated a significant relationship between energy drink consumption habits and type 2 diabetes mellitus status (p-value 0.001 < α 0.005). These findings indicate that the frequency of energy drink consumption contributes to type 2 diabetes mellitus status among taxi drivers in Pontianak City.

The involvement of the dysfunctional insulin receptor signaling system in long COVID patients with diabetes and chronic pain and its implications for the clinical management using taVNS.

In clinical terms, chronic pain is the most prevalent sequela resulting from COVID-19, which is induced by the novel coronavirus (SARS-CoV-2), while type 2 diabetes mellitus (T2D) is the most common comorbidity. This triangular relationship can be attributed to the dysfunction of the insulin receptor signaling system (IRSS) in both central and peripheral systems. Patients with T2D are essentially more susceptible to SARS-CoV-2 infection due to the widespread expression of angiotensin converting enzyme 2 (ACE2) in their pancreatic beta cells, which serves as the cellular port for the SARS-CoV-2 to infect and enter the cell. This infection can exacerbate chronic pain and insulin resistance for various reasons. Peripherally, once infected, the virus can cause damage to peripheral nerves and pancreatic β-cells, further exacerbating pain and glucose metabolism conditions. Additionally, in the central nervous system, dysfunctional IRSS is closely linked to chronic pain. Over the past few years of the COVID-19 pandemic, an increasing body of evidence suggests that insulin and other medications currently used in clinical practice for hyperglycemia control may not be safe for treating these patients. Therefore, we need a proper approach for the treatment of chronic pain in long COVID patients, especially patients with T2D. This review presents evidence that transcutaneous auricular vagal nerve stimulation (taVNS) may provide a viable treatment option for chronic pain and metabolic dysfunction by improving the function of IRSS in both the central nervous system and peripheral tissues.

Examining the Shared Attributes of Diabetes Mellitus and Parkinson's Disease: A Literature Review

There is a progressive disorder of the brain in Parkinson's Disease (PD), and there seems to be an association, although less clearly defined, with Type 2 Diabetes Mellitus (T2D). There is now mounting evidence that the critical mechanisms common to both diseases include insulin resistance and dysfunction of mitochondria, oxidative stress and chronic inflammation. These can be implied to play a role in the pathogenesis of neuronal damage in PD, particularly dopaminergic neurons. Such convergent biological mechanisms will be used in this study to create predictive models of Parkinson's disease using machine learning approaches. For instance, this model will focus on markers such as insulin resistance, mitochondrial function, levels of oxidative stress, and inflammation, among others, while calculating the likelihood of Parkinson's. It will classify those at higher risk of neurodegeneration by using clinical data-blood sugar levels, insulin sensitivity, inflammatory protein profiles, oxidative stress markers.

Improvement of the method for the diagnosis of insulin resistance in horses

The diagnosis of equine metabolic syndrome has become an essential focus for many specialists, particularly in recent years. The primary risk factor for the development of metabolic syndrome is insulin dysfunction, which leads to both insulin resistance and hyperinsulinemia. This article addresses the pressing issue of diagnosing insulin resistance in horses. Modern diagnosis of equine metabolic syndrome is based on clinical examination, case history, and especially laboratory tests that evaluate various aspects of insulin resistance, along with other metabolic disorders, such as hyperglycemia. The main laboratory diagnostic methods include intravenous and oral dynamic glucose tolerance tests, which help assess insulin response to the introduction of carbohydrate components into the animal's body and the hormonal system's reaction to them [3]. The objective of the study was to explore the possibility of modifying the oral glucose tolerance test by using a domestically produced IG 42 invert syrup for diagnosing insulin resistance in horses. The article provides a detailed description of the research materials and methods, as well as the results of the test conducted on horses. It is noted that the use of the modified oral glucose tolerance test could be applied in practical veterinary medicine for diagnosing insulin resistance in horses. Based on the study results, it was established that the oral sugar test using IG 42 syrup could be employed in practical research to assess insulin resistance in horses by analyzing the dynamics of glucose and insulin concentrations. Future research will focus on evaluating the specificity and informativeness of this test in comparison with intravenous and combined glucose tolerance tests

Effects of insulin resistance and β-cell function on diabetic complications in Korean diabetic patients.

Diabetes mellitus is characterized by insulin resistance (IR) and dysfunctional insulin secretion from pancreatic β-cells. However, little research has been conducted on the relationship between IR and β-cell function in relation to diabetic complications among Korean diabetic patients. This study aimed to examine the differential associations between IR and β-cell function and various diabetic complications among Korean diabetic patients. The analysis employed a common data model (CDM). IR and β-cell function were quantified using the homeostasis model assessment for insulin resistance (HOMA-IR) and β-cell function (HOMA-β), respectively. Hazard ratios for diabetic nephropathy, diabetic retinopathy, and cardiovascular disease (CVD) events were calculated. The study cohort consisted of 2,034 diabetic patients aged over 20 years who visited EUMC between January 2001 and December 2019. Among diabetic patients in the highest quartile of HOMA-IR, the adjusted hazard ratio for total CVD events was 1.76 (95% confidence interval [CI], 1.20-2.57) compared with those in the lowest quartile of HOMA-IR (P = 0.004). In contrast, diabetic patients in the lowest quartile of HOMA-β exhibited an adjusted hazard ratio of 3.91 (95% CI, 1.80-8.49) for diabetic retinopathy compared to those in the highest quartile of HOMA-β (P = 0.001). Insulin resistance and β-cell function exhibited different associations with diabetic complications among Korean diabetic patients. Specifically, lower β-cell function was associated with an increased risk of diabetic retinopathy, whereas higher IR was associated with an increased risk of CVD events. Individuals with pronounced IR should prioritize CVD prevention measures, and those with significant β-cell dysfunction may benefit from early, intensive surveillance for diabetic retinopathy.

Optimized Proteomic Analysis of Insulin Granules From MIN6 Cells Identifies Scamp3, a Novel Regulator of Insulin Secretion and Content.

Pancreatic β-cells in the Islets of Langerhans are key to maintaining glucose homeostasis, by secreting the peptide hormone insulin. Insulin is packaged within vesicles named insulin secretory granules (ISGs), that have recently been considered to have intrinsic structures and proteins that regulate insulin granule maturation, trafficking, and secretion. Previously, studies have identified a handful of novel ISG-associated proteins using different separation techniques. Here, this study combines an optimized ISG isolation technique and mass spectrometry-based proteomics, with an unbiased protein correlation profiling and targeted machine learning approach to uncover 211 ISG-associated proteins with confidence. Four of these proteins: Syntaxin-7, Synaptophysin, Synaptotagmin-13 and Scamp3 have not been previously ISG-associated. Through colocalization analysis of confocal imaging we validate the association of these proteins to the ISG in MIN6 and human β-cells. We further validate the role for one (Scamp3) in regulating insulin content and secretion from β-cells for the first time. Scamp3 knock-down INS-1 cells show a reduction in insulin content and dysfunctional insulin secretion. These data provide the basis for future investigation of Scamp3 in β-cell biology and the regulation of insulin secretion.

Drug Repurposing for Thioredoxin Interacting Protein Through Molecular Networking, Pharmacophore Modelling, and Molecular Docking Approaches

Background: Diabetes Mellitus (DM) has emerged as one of the major causes behind global all-cause mortality between the age group of 20-79 years. Thioredoxin Interacting Protein (TXNIP) is a naturally occurring protein that primarily acts by binding to TRX protein, thereby inhibiting its ability to maintain the cellular reduced environment and subsequent oxidative stress, which leads to dysfunctional insulin production and pancreatic islet beta cell apoptosis. Objective: By inhibiting the levels of TXNIP, a search for new molecules was carried out by employing an in-silico approach. Methods: Molecular networking study was carried out using Cytoscape, wherein previously FDAapproved drugs were screened to check their ability to interact with TXNIP. This provided 14 drug molecules, which along with 11 previously obtained drug molecules that inhibit TXNIP, were subjected to pharmacophore generation. A pharmacophore was generated using the PharmaGist web server, which when visualised showed two hydrogen bond acceptors and one aromatic ring. Based on the generated pharmacophore model, we carried out virtual screening using ZINCPharmer. A total of 116 HITs were generated based on this pharmacophore model. We then subjected the 116 molecules to Molecular Docking against TXNIP (PDB: 4GEI) by using PyRx and the standard molecules, metformin and rosiglitazone. Results: Compared to the standard, we found 10 molecules that had a better binding affinity towards TXNIP. These 10 molecules were further taken for ADMET studies. From this, all 10 compounds showed good significant ADMET properties. Conclusion: From the preliminary studies, these 10 molecules showed good activity in the reversal of diabetes mellitus by reducing the levels of TXNIP.

Incretin-based therapy: a new horizon in diabetes management.

Diabetes mellitus, a metabolic syndrome characterized by hyperglycemia and insulin dysfunction, often leads to serious complications such as neuropathy, nephropathy, retinopathy, and cardiovascular disease. Incretins, gut peptide hormones released post-nutrient intake, have shown promising therapeutic effects on these complications due to their wide-ranging biological impacts on various body systems. This review focuses on the role of incretin-based therapies, particularly Glucagon-like peptide-1 (GLP-1) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors, in managing diabetes and its complications. We also discuss the potential of novel agents like semaglutide, a recently approved oral compound, and dual/triple agonists targeting GLP-1/GIP, GLP-1/glucagon, and GLP-1/GIP/glucagon receptors, which are currently under investigation. The review aims to provide a comprehensive understanding of the beneficial impacts of natural incretins and the therapeutic potential of incretin-based therapies in diabetes management.

Age-dependent impact of streptozotocin on metabolic endpoints and Alzheimer's disease pathologies in 3xTg-AD mice

Alzheimer's disease (AD) is a multifactorial neurodegenerative disease with a complex origin, thought to involve a combination of genetic, biological and environmental factors. Insulin dysfunction has emerged as a potential factor contributing to AD pathogenesis, particularly in individuals with diabetes, and among those with insulin deficiency or undergoing insulin therapy. The intraperitoneal administration of streptozotocin (STZ) is widely used in rodent models to explore the impact of insulin deficiency on AD pathology, although prior research predominantly focused on young animals, with no comparative analysis across different age groups. Our study aimed to fill this gap by analyzing the impact of insulin dysfunction in 7 and 23 months 3xTg-AD mice, that exhibit both amyloid and tau pathologies. Our objective was to elucidate the age-specific consequences of insulin deficiency on AD pathology.STZ administration led to insulin deficiency in the younger mice, resulting in an increase in cortical amyloid-β (Aβ) and tau aggregation, while tau phosphorylation was not significantly affected. Conversely, older mice displayed an unexpected resilience to the peripheral metabolic impact of STZ, while exhibiting an increase in both tau phosphorylation and aggregation without significantly affecting amyloid pathology. These changes were paralleled with alterations in signaling pathways involving tau kinases and phosphatases. Several markers of blood-brain barrier (BBB) integrity declined with age in 3xTg-AD mice, which might have facilitated a direct neurotoxic effect of STZ in older mice.Overall, our research confirms the influence of insulin signaling dysfunction on AD pathology, but also advises careful interpretation of data related to STZ-induced effects in older animals.

Temporal multiscale modeling of biochemical regulatory networks: Calcium-regulated hepatocyte lipid and glucose metabolism

Hepatocyte lipid and glucose metabolism is regulated not only by major hormones like insulin and glucagon but also by many other factors, including calcium ions. Recently, mitochondria-associated membrane (MAM) dysfunction combined with incorrect IP3-receptor regulation has been shown to result in abnormal calcium signaling in hepatocytes. This dysfunction could further lead to hepatic metabolism pathology. However, the exact contribution of MAM dysfunction, incorrect IP3-receptor regulation and insulin resistance to the calcium-insulin-glucagon interplay is not understood yet. In this work, we analyze the role of abnormal calcium signaling and insulin dysfunction in hepatocytes by proposing a model of hepatocyte metabolic regulatory network with a detailed focus on the model construction details besides the biological aspect. In this work, we analyze the role of abnormal calcium signaling and insulin dysfunction in hepatocytes by proposing a model of hepatocyte metabolic regulatory network. We focus on the model construction details, model validation, and predictions. We describe the dynamic regulation of signaling processes by sigmoid Hill function. In particular, we study the effect of both the Hill function slope and the distance between Hill function extremes on metabolic processes in hepatocytes as a model of nonspecific insulin dysfunction. We also address the significant time difference between characteristic time of glucose hepatic processing and a typical calcium oscillation period in hepatocytes. Our modeling results show that calcium signaling dysfunction results in an abnormal increase in postprandial glucose levels, an abnormal glucose decrease in fasting, and a decreased amount of stored glycogen. An insulin dysfunction of glucose phosphorylation, glucose dephosphorylation, and glycogen breakdown also cause a noticeable effect. We also get some insight into the so-called hepatic insulin resistance paradox, confirming the hypothesis regarding indirect insulin action on hepatocytes via dysfunctional adipocyte lipolysis.

Extracellular glucose and dysfunctional insulin receptor signaling independently upregulate arterial smooth muscle TMEM16A expression.

Diabetes alters the function of ion channels responsible for regulating arterial smooth muscle membrane potential, resulting in vasoconstriction. Our prior research demonstrated an elevation of TMEM16A in diabetic arteries. Here, we explored the mechanisms involved in Transmembrane protein 16A (TMEM16A) gene expression. Our data indicate that a Snail-mediated repressor complex regulates arterial TMEM16A gene transcription. Snail expression was reduced in diabetic arteries while TMEM16A expression was upregulated. The TMEM16A promoter contained three canonical E-box sites. Electrophoretic mobility and super shift assays revealed that the -154 nt E-box was the binding site of the Snail repressor complex and binding of the repressor complex decreased in diabetic arteries. High glucose induced a biphasic contractile response in pressurized nondiabetic mouse hindlimb arteries incubated ex vivo. Hindlimb arteries incubated in high glucose also showed decreased phospho-protein kinase D1 and TMEM16A expression. In hindlimb arteries from nondiabetic mice, administration of a bolus dose of glucose activated protein kinase D1 signaling to induce Snail degradation. In both in vivo and ex vivo conditions, Snail expression exhibited an inverse relationship with the expression of protein kinase D1 and TMEM16A. In diabetic mouse arteries, phospho-protein kinase D1 increased while Akt2 and pGSK3β levels declined. These results indicate that in nondiabetic mice, high glucose triggers a transient deactivation of the Snail repressor complex to increase arterial TMEM16A expression independently of insulin signaling. Conversely, insulin resistance activates GSK3β signaling and enhances arterial TMEM16A channel expression. These data have uncovered the Snail-mediated regulation of arterial TMEM16A expression and its dysfunction during diabetes.NEW & NOTEWORTHY The calcium-activated chloride channel, TMEM16A, is upregulated in the diabetic vasculature to cause increased vasoconstriction. In this paper, we have uncovered that the TMEM16A gene expression is controlled by a Snail-mediated repressor complex that uncouples with both insulin-dependent and -independent pathways to allow for upregulated arterial protein expression thereby causing vasoconstriction. The paper highlights the effect of short- and long-term glucose-induced dysfunction of an ion channel expression as a causative factor in diabetic vascular disease.

Biochemical changes to the inner ear contributing to diabetes-induced hearing loss: possible pharmacological targets for therapy.

Biochemical alterations due to diabetes development and progress are complex and diabetes-associated injury to various tissues has been well reported. Nevertheless, a close investigation of the literature demonstrates limited coverage regarding these biochemical and molecular alterations within the inner ear and their impact on the vestibulocochlear environment. A closer look at these may reveal pharmacological targets that could alleviate the severity of disease in patients. Tight control of glucose levels within the highly metabolic inner ear structures is crucial for their physiology and function. Impaired glucose homeostasis is well known to occur in vestibulocochlear malfunctioning. Moreover, the involvement of insulin signalling, and glucose transporters were recently confirmed in vestibulocochlear structures and are believed to play a crucial role in auditory and vestibular functions. Oxidative overload, glucolipotoxicity, perturbed blood rheology, endothelial dysfunction, compromised microvascular supply, and neurotoxicity are reported in many diabetic complications such as nephropathy, retinopathy, and diabetic neuropathy and are incriminated in the disruption of blood labyrinth barrier as well as vestibulocochlear neuritis. Dysfunctional insulin signalling was recently reported in the Organ of Corti. Insulin resistance in the inner ear niche warrants further studies to verify and uncover new pharmacological targets to manage this debilitating condition better.

Influence of Maqian essential oil on gut microbiota and immunoresponses in type 1 diabetes: In silico study

Diversity and homeostasis of gut bacterial composition is highly associated with the pathogenesis of insulin dysfunction and type 1 diabetes melittus (T1D), hence emerged in parallel with the activation of autoimmunity. We aimed to study the bioactive potential of essential oil from Zanthoxylum myriacanthum var. pubescens Huang (Maqian) through computational approaches. Twelve chemical constituents derived from Maqian essential oil were docked with selected proteins (i.e., 3pig, 1kho, 7dmq, 4m4d, 2z65, 4glp, and 3fxi) in which are involved in gut microbiota modulation in T1D. Subsequently, the prediction of bioavailability properties of the small molecules were evaluated. Among all chemical constituents, the post-docking interaction analysis demonstrated that α-phellandrene exhibits the strongest binding affinity and induces gut microbiota modulation with β-fructofuranosidase from Bifidobacterium longum. The current result revealed the potential of 3-Carene and α-Pinene in inducing specific changes in gut microbiota downregulating Clostridium perfringens and quenching Leptotrichia shahii respectively. β-Pinene possess exceptionally strong binding affinity that effectively disrupt the interaction between lipopolysaccharide and its cognate receptors, while α-Phellandrene was exhibited the uppermost binding affinity with TLR4/MD2 and could likely target TLR4 stimulating lipopolysaccharide. Our results are the first to report on the gut microbiota modulation effects of α-Phellandrene and β-Phellandrene via actions on LPS binding to CD14 and the TLR4 co-receptor signaling. In conclusion, our findings based on computational approaches, small molecules from Maqian present as promising agents which could regulate inflammatory response and modulate gut microbiota in type 1 diabetes mellitus.

Cannabis sativa L. Fixed Oil and Its Nanoemulsion: Effect on Diabetes and Dyslipidemia Induced in Rats

Background: Diabetes Mellitus (DM) is a syndrome that interferes with energy metabolism and is caused by a decrease and dysfunction of insulin, leading to chronic hyperglycemia. DM associated with dyslipidemia is a severe health risk, increasing the chance of cardiovascular events, such as acute myocardial infarction and stroke. The Cannabis sativa L. fixed oil (CSO) is composed of unsaturated fatty acids and can be crucial in treating metabolic alterations. In addition, the nanoemulsion of C. sativa oil (NCS) has advantages in optimizing treatments. Objectives: This study aimed to evaluate the effects of treatments with CSO and its nanoemulsion (NCS) on induced diabetes and dyslipidemia in Wistar rats. Materials and methods: CSO’s physical-chemical and chromatographic characterization was performed, followed by the preparation of an NE containing 6% CSO. DM was induced in Wistar rats by intraperitoneal injection of streptozotocin (STZ) at a 55 mg/kg dose. Four days later, animals with blood glucose levels exceeding 300 mg/dL were considered diabetic. The rats were then divided into five groups ( n = 5) and treated orally. The groups included a normoglycemic control group (NOR), a diabetic control group, a group treated with metformin (100 mg/kg), a group treated with CSO (400 mg/kg), and a group treated with nanoemulsion (NCS 200 mg/kg). Subsequently, the pancreas’s clinical, biochemical, and histopathological parameters were evaluated. Results: In the chemical profile of CSO, it was observed the majority composition of palmitoleic (14.58%), oleic (12.50%), linoleic (42.40%), and linolenic (8.55%) acids. The results demonstrated that the induction of DM by STZ could reproduce the typical symptoms and clinical signs of DM. It was observed that treatments with CSO and NCS showed a significant improvement ( p < .001) in polydipsia, polyuria, and loss of body mass, as well as a significant reduction ( p < .001) of glucose levels in urine and blood and serum lipids. Histopathology of the pancreas revealed that treatment with CSO and NCS showed an increase in the number of cells in the islets of Langerhans and a decrease in regions devoid of cells, indicating possible cell regeneration. Moreover, insulin levels were significantly increased ( p < .05) in the preferred groups. With dyslipidemia induced by Triton (Tyloxapol), it was observed that the treatment with CSO and NCS significantly decreased the levels of triglycerides ( p < .05) and cholesterol ( p < .001), as well as low-density lipoproteins (LDL) ( p < .01). Conclusion: Treatment with CSO and NCS under the conditions of this study demonstrated an anti-diabetic effect and the ability to act in the reduction of triglyceride, cholesterol, and LDL levels. In this respect, treatments with CSO and NCS act in the control of DM, as well as in the prevention of cardiovascular diseases.

Glucagon-like peptide-1 analogs for Alzheimers disease -- A systematic meta-analysis

Alzheimers Disease (AD) poses a serious health concern especially for the aging population above the years of 65. An estimated 6 million Americans are diagnosed with Alzheimers Disease, and there are at least 50 million Alzheimers patients in the world. AD affects the daily life of these patients, yet there is no permanent cure. Current treatments involve cholinesterase inhibitors and NMDA-receptor agonists to help alleviate the symptoms. GLP-1 is a peptide often used in the treatment of diabetes. Since there are shared pathological features between diabetes and AD, such as insulin dysfunction and glucose metabolism dysregulation, GLP-1 may be a viable study for AD treatment. To perform a meta-analysis to investigate whether GLP-1 has a beneficiary effect on biological markers and cognitive outcome in AD patients. We searched the following electronic databases: EMBASE, MEDLINE, phycINFO, CINAHL, PubMed, Cochrane CENTRAL, and ClinicalTrials.gov. We only utilized Randomized Control Trials (RCTs) and clinical trials. We also searched with the following Medical Search Headings: Alzheimers Disease, Alzheimer, Alzheimers, and GLP-1. We included 2 randomized, double-blind, and placebo controlled clinical trials into our meta-analysis. We extracted the baseline and outcomes from the clinical trials and evaluated its risks of bias. Biological markers were measured by amyloid beta (A) accumulation, and cognitive outcomes were measured by the Wechsler Memory Scale - Fourth Edition (WMS-IV) and Mini Mental State Exam (MMSE). For one study, the WMS-IV was used to measure cognitive outcome. The other study measured cognitive outcome with the MMSE. Biological markers were measured by A accumulation in one study and with [11C]PIB tracer in another. There was no significant difference between the placebo and experimental group after the treatment period.

Serum albumin adjusted calcium and fluoride among type 2 diabetes mellitus patients.

The regulation of glucose-dependent insulin secretion in pancreatic β-cells relies on calcium concentration, making it a calcium-dependent process. Disruptions in calcium homeostasis may contribute to insulin dysfunction and disturbances in glucose homeostasis, potentially playing a role in the development of type 2 diabetes mellitus (T2DM). In T2DM patients, there may be changes in fluoride metabolism due to impaired renal function. Measurement of serum albumin-adjusted calcium and is crucial since changes in albumin levels can impact the accurate estimation of true calcium.

Causal association between antidiabetic drugs and erectile dysfunction: evidence from Mendelian randomization.

Antidiabetic drugs are widely used in clinical practice as essential drugs for the treatment of diabetes. The effect of hypoglycemic drugs on erectile dysfunction has not been fully proven due to the presence of multiple confounding factors. Two-sample Mendelian randomization (TSMR) was used to examine the causal effect of antidiabetic drugs (including metformin, insulin and gliclazide) on erectile dysfunction. We used five robust analytic methods, of which the inverse variance weighting (IVW) method was the primary method, and also assessed factors such as sensitivity, pleiotropy, and heterogeneity. Effect statistics for exposures and outcomes were downloaded from publicly available data sets, including open Genome-Wide Association Studies (GWAS) and the UK Biobank (UKB). In some of the hypoglycemic drug use, there was a significant causal relationship between metformin use and erectile dysfunction [Beta: 4.9386; OR:1.396E+02 (95% CI:9.13-2135); p-value: 0.0004), suggesting that metformin increased the risk of erectile dysfunction development. Also, we saw that gliclazide use also increased the risk of erectile dysfunction [Beta: 11.7187; OR:0.0125 (95% CI:12.44-1.21E+09); P value: 0.0125). There was no significant causal relationship between insulin use and erectile dysfunction [Beta: 3.0730; OR:21.6071 (95% CI:0.24-1942.38); p-value: 0.1806).Leave-one-out, MR-Egger, and MR-PRESSO analyses produced consistent results. The use of metformin and gliclazide have the potential to increase the risk of erectile dysfunction. There is no causal relationship between the use of insulin and erectile dysfunction.

Challenges and strategies in the treatment of juvenile type 2 diabetes: a case analysis

Type 2 diabetes mellitus is today the most common type of diabetes, characterized by insulin resistance and dysfunction of the beta cells of the pancreas. This condition is especially prevalent in adults, although in recent times it has increased significantly among young people. Factors such as obesity, lack of physical activity, poor sleep quality, family history are known contributors. The objective of this work is to develop effective intervention strategies and improve the management of the disease in adolescents. A case study was carried out and using the PESTEL method, strategies are proposed to comprehensively address the challenges associated with type 2 diabetes mellitus in adolescents, in addition to improving not only individual care but also the social and political environment that affects them youths