Elevated Blood Glucose Levels Research Articles

Glucokinase regulatory protein rs780094 polymorphism is associated with type 2 diabetes mellitus, dyslipidemia, non-alcoholic fatty liver disease, and nephropathy

In this editorial, we comment on the article by Liu et al published in the recent issue of the World Journal of Diabetes (Relationship between GCKR gene rs780094 polymorphism and type 2 diabetes with albuminuria). Type 2 diabetes mellitus (T2DM) is a chronic disorder characterized by dysregulated glucose homeostasis. The persistent elevated blood glucose level in T2DM significantly increases the risk of developing severe complications, including cardiovascular disease, re-tinopathy, neuropathy, and nephropathy. T2DM arises from a complex interplay between genetic, epigenetic, and environmental factors. Global genomic studies have identified numerous genetic variations associated with an increased risk of T2DM. Specifically, variations within the glucokinase regulatory protein (GCKR) gene have been linked to heightened susceptibility to T2DM and its associated complications. The clinical trial by Liu et al further elucidates the role of the GCKR rs780094 polymorphism in T2DM and nephropathy development. Their findings demonstrate that individuals carrying the CT or TT genotype at the GCKR rs780094 locus are at a higher risk of developing T2DM with albuminuria compared to those with the CC genotype. These findings highlight the importance of genetic testing and risk assessment in T2DM to develop effective preventive strategies and personalized treatment plans.

The significance of precise diabetes diagnosis: a case of euglycemic diabetic ketoacidosis induced by the introduction of empagliflozin with simultaneous reduction of insulin dosage

Euglycemic diabetic ketoacidosis (euDKA) is a rare but severe metabolic complication of diabetes mellitus characterised by elevated anion gap metabolic acidosis despite normal or mildly elevated blood glucose levels. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have emerged as effective antidiabetic medications, yet their use is associated with an increased risk of euDKA, especially when coupled with insulin dose reduction. We present the case of a 50-year-old male with a 20-year history of diabetes mellitus, initially managed with insulin and metformin, who developed euDKA following the introduction of empagliflozin and sitagliptin alongside a reduction in insulin therapy. Despite normoglycaemia the patient exhibited symptoms of ketoacidosis, including chronic fatigue, polydipsia, and polyuria. Diagnostic workup revealed metabolic acidosis, elevated inflammatory markers, acute kidney injury and ketonuria. Subsequent specialised laboratory tests confirmed type 1 diabetes mellitus (T1DM) with the presence of anti-glutamic acid decarboxylase (anti-GAD) antibodies and the absence of C-peptide secretion. Management involved fluid therapy, intravenous insulin and glucose administration. This case underscores the diagnostic challenges of euDKA and emphasises the importance of differentiating between T1DM and T2DM, as management strategies vary significantly. Patient education on insulin therapy and injection techniques is crucial to prevent complications such as improper insulin delivery and dose reduction, which can precipitate euDKA. In conclusion, clinicians should be vigilant for euDKA in patients on SGLT2 inhibitors, particularly when insulin dose reduction is involved. Comprehensive patient education and accurate differentiation between diabetes types are essential for timely diagnosis and optimal management, thereby reducing the risk of severe complications.

The Association between Dietary Intake and Lifestyle Patterns of People with Type 2 Diabetes Mellitus in Manipur, India

The aim of the study was to examine the association between dietary intake and lifestyle pattern of diabetes patients in Manipur. Tribal and non tribal respondents between 45-64 years of age were randomly selected from the Regional Institute of Medical Sciences (RIMS) Hospital Manipur. Total number of 200 study subjects, 100 tribal and 100 non tribal subjects constituted the study. The information was collected on socio-demographic profile, clinical, anthropometric measurements and dietary intakes of the patients by using interview schedule and 24-hour dietary recall methods. The data were analyzed and tabulated using statistical tools such as frequency, percentage, mean, standard deviation and Pearson’s correlation test. The key results indicate that alcohol consumption, elevated triglycerides levels, low energy, oils and sugar intake were notably linked with the prevalence of diabetes. Additionally, low calcium intake, particularly among non tribal individuals, demonstrated a significant correlation with elevated Fasting Blood Glucose (FBG) levels, suggesting a potential risk factor for Type 2 diabetes. Moreover, low calcium intake among the non-tribal community was associated with increased Post Prandial (PP) test results, indicating a rise in post-meal glucose levels. Notably, tribal energy intake and non-tribal protein consumption were significantly associated with HbA1c levels, reflecting their impact on glycemic control.

Regulation of Oxidative Stress and Apoptosis in Streptozotocin-Induced Diabetic Rats by Egyptian Sidr Honey.

Diabetesmellitusis a global health issuecharacterized by hyperglycemia which leads over time to severe damage to numerous tissues.The present study aimed to estimate the effect of Egyptian Sidr honey against streptozotocin-induced diabetes in rats. Diabetic rats were treated with Sidr honey daily for 4 consecutive weeks. The biochemical profile of blood samples was measured. Furthermore, the activity of antioxidant enzymes, nitric oxide (NO), and malonaldehyde (MDA) were examined in liver and pancreas tissues. Moreover, the expression of Bax, Caspase-3, and Bcl2 proteins were measured. Results revealed that the capability of Sidr honey to decline the elevated blood glucose and fructosamine levels compared to diabetic rats. Also, the honey decreased the levels of NO and MDA. Furthermore, it regulated the antioxidant enzymes activity. Moreover, it reduced the expression levels of Caspase-3 and Bax while increased the Bcl2 level. In conclusion, Sidr honey can regulate hyperglycemia, oxidative stress, apoptosis, and antioxidant enzymes in STZ-induced diabetic rats.

Interaction of serotonin/GLP-1 circuitry in a dual preclinical model for psychiatric disorders and metabolic dysfunction

Isolation of rodents throughout adolescence is known to induce many behavioral abnormalities which resemble neuropsychiatric disorders. Separately, this paradigm has also been shown to induce long-term metabolic changes consistent with a pre-diabetic state. Here, we investigate changes in central serotonin (5-HT) and glucagon-like peptide 1 (GLP-1) neurobiology that dually accompany behavioral and metabolic outcomes following social isolation stress throughout adolescence. We find that adolescent-isolation mice exhibit elevated blood glucose levels, impaired peripheral insulin signaling, altered pancreatic function, and fattier body composition without changes in bodyweight. These mice further exhibited disruptions in sleep and enhanced nociception. Using bulk and spatial transcriptomic techniques, we observe broad changes in neural 5-HT, GLP-1, and appetitive circuits. We find 5-HT neurons of adolescent-isolation mice to be more excitable, transcribe fewer copies of Glp1r (mRNA; GLP-1 receptor), and demonstrate resistance to the inhibitory effects of the GLP-1R agonist semaglutide on action potential thresholds. Surprisingly, we find that administration of semaglutide, commonly prescribed to treat metabolic syndrome, induced deficits in social interaction in group-housed mice and rescued social deficits in isolated mice. Overall, we find that central 5-HT circuitry may simultaneously influence mental well-being and metabolic health in this model, via interactions with GLP-1 and proopiomelanocortin circuitry.

Effect of High-Sucrose Diet on the Occurrence and Progression of Diabetic Retinopathy and Dietary Modification Strategies.

As the most serious of the many worse new pathological changes caused by diabetes, there are many risk factors for the occurrence and development of diabetic retinopathy (DR). They mainly include hyperglycemia, hypertension, hyperlipidemia and so on. Among them, hyperglycemia is the most critical cause, and plays a vital role in the pathological changes of DR. High-sucrose diets (HSDs) lead to elevated blood glucose levels in vivo, which, through oxidative stress, inflammation, the production of advanced glycation end products (AGEs) and vascular endothelial growth factor (VEGF), cause plenty of pathological damages to the retina and ultimately bring about loss of vision. The existing therapies for DR primarily target the terminal stage of the disease, when irreversible visual impairment has appeared. Therefore, early prevention is particularly critical. The early prevention of DR-related vision loss requires adjustments to dietary habits, mainly by reducing sugar intake. This article primarily discusses the risk factors, pathophysiological processes and molecular mechanisms associated with the development of DR caused by HSDs. It aims to raise awareness of the crucial role of diet in the occurrence and progression of DR, promote timely changes in dietary habits, prevent vision loss and improve the quality of life. The aim is to make people aware of the importance of diet in the occurrence and progression of DR. According to the dietary modification strategies that we give, patients can change their poor eating habits in a timely manner to avoid theoretically avoidable retinopathy and obtain an excellent prognosis.

Comparatively tested potential risk factors across survivors and non-survivors critically patients

Background: The risk factors associated with mortality in critically ill patients have been the subject of numerous studies. However, a considerable amount of variation is evident when one considers the dispersion of patients, the geographical spread, and the classification of healthcare establishments. Aim: The purpose of this study was to compare potential risk factors between Survivors and Non-Survivors, including demographics, anthropometrics, kidney and liver indices, complete blood counts, and biochemical assays. Patients whose condition is critical. Methods: An ICU retrospective investigation was conducted in Jordan, where critically ill patients with surgical and medical conditions were examined. Using the Electronic Medical Record System (Hakeem), the study analysed data and classified patients into two cohorts according to their survival status. Demographic information, clinical characteristics, insulin administration rate, blood glucose levels, dosing schedules for vasopressors, and the burden of comorbidities were all included in the data. The research was granted approval by the Institutional Review Board committee of the Royal Medical Services, Jordan. Results: The research examined the male-to-female ratios among COVID-19 patients and classified them into six distinct age groups. A significant proportion of critical patients, ranging in age from 50 to 60, exhibited elevated corrected sodium levels and a diminished normontraemia status. Higher albumin levels and mean arterial pressures were associated with survivors, whereas a greater proportion of non-survivors were underweight and had a low BMI. A normal temperature was observed in the majority of critically ill patients, whereas non-survivors exhibited elevated fractional blood glucose levels and estimated creatinine clearances. The research emphasises the significance of treatment outcomes and patient demographics. Conclusion: SI may be a more accurate prognostic indicator than non-septic patients due to the effect of norepinephrine, a vasopressor, on heart rate and systolic blood pressure, which may account for the difference in SI values between the two groups.

In Vitro Test of Leilem Leaf Ethanol Activity on β-Glucosidase Enzyme Inhibition

Diabetes is a chronic metabolic disease with signs of elevated blood glucose levels. One of the targets of antidiabetic drugs is to inhibit the enzyme α-/β-glucosidase which works in the process of glucose absorption. Leilem plant (Clerodendrum minahassae Teisjm. & Binn.) is well known and used as a dish and medicine for several diseases in Minahasa and has potential as an antidiabetic agent. This study aimed to determine the activity of ethanolic extract of leilem leaves in inhibiting β-glucosidase enzyme. The extract was prepared with 96% ethanol. Antidiabetic properties were measured by β-glucosidase enzyme inhibitory activity. The inhibitory concentration (IC50) values of the extract compared tp acarbose were 28,229 and 13,716. Ethanol extract of leilem leaves inhibits β-glucosidase enzyme. Keywords : β-glucosidase; ethanol extract; in vitro; leilem leaf

Knowledge and Attitude Towards Insulin Therapy in Type 2 Diabetes Mellitus Patients and Associated Factors at an Adult Endocrine Clinic of SPHMMC Addis Ababa Ethiopia

<i>Background:</i> Diabetes Mellitus (DM), a chronic disease characterized by elevated blood glucose levels, is associated with severe complications. Type 2 DM (T2DM), the most prevalent form of DM in adults, is characterized by varying degrees of insulin deficiency or resistance. The prevention or delay of macrovascular and microvascular problems associated with DM depends on achieving appropriate glycemic control. The percentage of T2DM patients failing to reach glycemic targets keeps rising even with the expanded availability of numerous anti-hyperglycemic drugs and evidence-based treatment guidelines. The delay in treatment intensification despite inadequate glucose control—often referred to as clinical or therapeutic inertia-contributes significantly to this trend.<i> Objective:</i> This study aims to evaluate the understanding and perceptions of insulin therapy among patients with T2DM. The study focuses on patients under follow-up care at the Adult Endocrine Clinic of St. Paul Hospital Millennium Medical College.<i> Method and Material:</i> An institutional-based, cross-sectional study was carried out from January to March 2021 to evaluate knowledge and attitudes regarding insulin therapy and related factors. A structured questionnaire was used for interviews with a representative sample of 271 T2DM patients who are receiving follow-up care at the endocrine clinic at SPHMMC. The SPSS, version 25, was the software utilized. The statistical significance of the relationship between the dependent and independent variables was assessed using a 95% confidence interval and a p-value less than 0.05.<i> Results:</i> The majority of the respondents were between the ages of 56 and 65, with a mean age of 57.35 years. More than half of the participants, accounting for 231 (85.2%) of the total, were from urban areas. Out of the 271 respondents, approximately 85.6% demonstrated poor knowledge of insulin therapy, and around 37.6% exhibited negative attitudes towards it. Factors such as age, occupation, and a history of long-term Oral Antidiabetic Drug use were found to be associated with the level of knowledge about insulin. In addition to these factors, marital status and a family history of insulin use were found to be associated with patients’ attitudes towards insulin. <i>Conclusions:</i> Our study identified a significant knowledge gap about insulin usage among T2DM patients in the designated study area. We recommend the implementation of regular, structured health education programs, delivered by trained health professionals. This approach is expected to enhance both the knowledge and attitudes toward insulin usage among patients attending follow-up sessions at the SPHMMC diabetic clinic.

Blood glucose fluctuation and in-hospital mortality among patients with acute myocardial infarction: eICU collaborative research database.

To assess the relationship between glycemic variability, glucose fluctuation trajectory and the risk of in-hospital mortality in patients with acute myocardial infarction (AMI). This retrospective cohort study included AMI patients from eICU Collaborative Research Database. In-hospital mortality of AMI patients was primary endpoint. Blood glucose levels at admission, glycemic variability, and glucose fluctuation trajectory were three main study variables. Blood glucose levels at admission were stratified into: normal, intermediate, and high. Glycemic variability was evaluated using the coefficient of variation (CV), divided into four groups based on quartiles: quartile 1: CV≤10; quartile 2: 10<CV≤20; quartile 3: 20<CV≤30; quartile 4: CV>30. Univariate and multivariate Cox regression models to assess the relationship between blood glucose levels at admission, glycemic variability, glucose fluctuation trajectory, and in-hospital mortality in patients with AMI. 2590 participants were eventually included in this study. There was a positive relationship between high blood glucose level at admission and in-hospital mortality [hazard ratio (HR) = 1.42, 95%confidence interval (CI): 1.06-1.89]. The fourth quartile (CV>30) of CV was associated with increased in-hospital mortality (HR = 2.06, 95% CI: 1.25-3.40). The findings indicated that only AMI individuals in the fourth quartile of glycemic variability, exhibited an elevated in-hospital mortality among those with normal blood glucose levels at admission (HR = 2.33, 95% CI: 1.11-4.87). Additionally, elevated blood glucose level was a risk factor for in-hospital mortality in AMI patients. Glycemic variability was correlated with in-hospital mortality, particularly among AMI patients who had normal blood glucose levels at admission. Our study findings also suggest early intervention should be implemented to normalize high blood glucose levels at admission of AMI.

Synthesis and molecular docking studies of new aryl imeglimin derivatives as a potent antidiabetic agent in a diabetic zebrafish model

Diabetes mellitus (DM) is a persistent, progressive, and multifaceted disease characterized by elevated blood glucose levels. Type 2 diabetes mellitus is associated with a relative deficit in insulin mainly due to beta cell dysfunction and peripheral insulin resistance. Metformin has been widely prescribed as a primary treatment option to address this condition. On the other hand, an emerging glucose-reducing agent known as imeglimin has garnered attention due to its similarity to metformin in terms of chemical structure. In this study, an innovative series of imeglimin derivatives, labeled 3(a–j), were synthesized through a one-step reaction involving an aldehyde and metformin. The chemical structures of these derivatives were thoroughly characterized using ESI–MS, 1H, and 13C NMR spectroscopy. In vivo tests on a zebrafish diabetic model were used to evaluate the efficacy of the synthesized compounds. All compounds 3(a–j) showed significant antidiabetic effects. It is worth mentioning that compounds 3b (FBS = 72.3 ± 7.2 mg/dL) and 3g (FBS = 72.7 ± 4.3 mg/dL) have antidiabetic effects comparable to those of the standard drugs metformin (FBS = 74.0 ± 5.1 mg/dL) and imeglimin (82.3 ± 5.2 mg/dL). In addition, a docking study was performed to predict the possible interactions between the synthesized compounds and both SIRT1 and GSK-3β targets. The docking results were in good agreement with the experimental assay results.

Practical method in the diagnosis of diabetic ketoacidosis: end-tidal carbon dioxide

Objectives: Diabetic ketoacidosis (DKA) poses a life-threatening risk in uncontrolled diabetes. Current diagnostic criteria rely on invasive measures, leading to potential delays in treatment initiation. This study aimed to assess the diagnostic utility of noninvasive end-tidal carbon dioxide (EtCO2) measurements in DKA patients. Methods: A prospective, cross-sectional study was conducted in a tertiary-level Emergency Medicine Clinic from January 2021 to January 2023. Participants included adults with DKA symptoms and those with stable vital signs as controls. EtCO2 levels were measured using a capnograph device. Diagnostic criteria for DKA were blood glucose ≥250 mg/dL, ketonuria, ketonemia, and metabolic acidosis (pH&amp;lt;7.3 or bicarbonate &amp;lt;15 mEq/dL). Statistical analysis was performed using SPSS Statistics. Results: Of 730 participants, 120 had DKA, 410 did not, and 200 served as controls. EtCO2 levels significantly differed between DKA, non-DKA, and control groups (P&amp;lt;0.05). EtCO2 correlated with pH, lactate, base deficit, and bicarbonate (P&amp;lt;0.05). ROC analysis showed an AUC of 0.86 for EtCO2 in diagnosing DKA (P&amp;lt;0.01), with 91.67% sensitivity and 74.39% specificity at a cut-off value 23.7. Conclusion: This study suggests that EtCO2 measurement is a valuable noninvasive tool for diagnosing and assessing the severity of DKA in the emergency department. An EtCO2 threshold of &amp;lt;23.7 could prompt consideration of DKA in patients with elevated blood glucose levels. More extensive multicenter studies are warranted to validate these findings further. EtCO2 measurement could facilitate early DKA diagnosis and improve patient outcomes.

Exploring the link between obesity and hypothyroidism in autoimmune thyroid diseases: a metabolic perspective.

Background: The management of primary hypothyroidism demands a comprehensive approach that encompasses both the implications of autoimmune thyroid disease and the distinct effects posed by obesity and metabolic irregularities. Despite its clinical importance, the interplay between obesity and hypothyroidism, especially in the context of metabolic perspectives, is insufficiently explored in existing research. This study endeavors to classify hypothyroidism by considering the presence of autoimmune thyroid disease and to examine its correlation with various metabolic obesity phenotypes. Method: This research was conducted by analyzing data from 1,170 individuals enrolled in the Thyroid Disease Database of Shandong Provincial Hospital. We assessed four distinct metabolic health statuses among the participants: Metabolically Healthy No Obese Metabolically Healthy Obese Metabolically Unhealthy No Obese and Metabolically Unhealthy Obese Utilizing logistic regression, we investigated the association between various metabolic obesity phenotypes and hypothyroidism. Results: The study revealed a significant correlation between the Metabolically Unhealthy Obese (MUO) phenotype and hypothyroidism, particularly among women who do not have thyroid autoimmunity. Notably, the Metabolically Unhealthy No Obese (MUNO) phenotype showed a significant association with hypothyroidism in individuals with thyroid autoimmunity, with a pronounced prevalence in women. Furthermore, elevated levels of triglycerides and blood glucose were found to be significantly associated with hypothyroidism in men with thyroid autoimmunity and in women without thyroid autoimmunity. Conclusion: Effective treatment of hypothyroidism requires a thorough understanding of the process of thyroid autoimmune development. In patients without concurrent thyroid autoimmunity, there is a notable correlation between obesity and metabolic issues with reduced thyroid function. Conversely, for patients with thyroid autoimmunity, a focused approach on managing metabolic abnormalities, especially triglyceride levels, is crucial.

Controlling autoimmune diabetes onset by targeting Protease-Activated Receptor 2

BackgroundType 1 diabetes (T1D) is a challenging autoimmune disease, characterized by an immune system assault on insulin-producing β-cells. As insulin facilitates glucose absorption into cells and tissues, β-cell deficiency leads to elevated blood glucose levels on one hand and target-tissues starvation on the other. Despite efforts to halt β-cell destruction and stimulate recovery, success has been limited. Our recent investigations identified Protease-Activated Receptor 2 (Par2) as a promising target in the battle against autoimmunity. We discovered that Par2 activation’s effects depend on its initial activation site: exacerbating the disease within the immune system but fostering regeneration in affected tissue. MethodsWe utilized tissue-specific Par2 knockout mice strains with targeted Par2 mutations in β-cells, lymphocytes, and the eye retina (as a control) in the NOD autoimmune diabetes model, examining T1D onset and β-cell survival. ResultsWe discovered that Par2 expression within the immune system accelerates autoimmune processes, while its presence in β-cells offers protection against β-cell destruction and T1D onset. This suggests a dual-strategy treatment for T1D: inhibiting Par2 in the immune system while activating it in β-cells, offering a promising strategy for T1D. ConclusionsThis study highlights Par2's potential as a drug target for autoimmune diseases, particularly T1D. Our results pave the way for precision medicine approaches in treating autoimmune conditions through targeted Par2 modulation.

Metabolic and Skeletal Characterization of the KK/Ay Mouse Model-A Polygenic Mutation Model of Obese Type 2 Diabetes.

Type 2 diabetes (T2D) increases fracture incidence and fracture-related mortality rates (KK.Cg-Ay/J. The Jackson Laboratory; Available from: https://www.jax.org/strain/002468 ). While numerous mouse models for T2D exist, few effectively stimulate persistent hyperglycemia in both sexes, and even fewer are suitable for bone studies. Commonly used models like db/db and ob/ob have altered leptin pathways, confounding bone-related findings since leptin regulates bone properties (Fajardo et al. in Journal of Bone and Mineral Research 29(5): 1025-1040, 2014). The Yellow Kuo Kondo (KK/Ay) mouse, a polygenic mutation model of T2D, is able to produce a consistent diabetic state in both sexes and addresses the lack of a suitable model of T2D for bone studies. The diabetic state of KK/Ay stems from a mutation in the agouti gene, responsible for coat color in mice. This mutation induces ectopic gene expression across various tissue types, resulting in diabetic mice with yellow fur coats (Moussa and Claycombe in Obesity Research 7(5): 506-514, 1999). Male and female KK/Ay mice exhibited persistent hyperglycemia, defining them as diabetic with blood glucose (BG) levels consistently exceeding 300mg/dL. Notably, male control mice in this study were also diabetic, presenting a significant limitation. Nevertheless, male and female KK/Ay mice showed significantly elevated BG levels, HbA1c, and serum insulin concentration when compared to the non-diabetic female control mice. Early stages of T2D are characterized by hyperglycemia and hyperinsulinemia resulting from cellular insulin resistance, whereas later stages may feature hypoinsulinemia due to β-cell apoptosis (Banday et al. Avicenna Journal of Medicine 10(04): 174-188, 2020 and Klein et al. Cell Metabolism 34(1): 11-20, 2022). The observed hyperglycemia, hyperinsulinemia, and the absence of differences in β-cell mass suggest that KK/Ay mice in this studyare modeling the earlier stages of T2D. While compromised bone microarchitecture was observed in this study, older KK/Ay mice, representing more advanced stages of T2D, might exhibit more pronounced skeletal manifestations. Compared to the control group, the femora of KK/Ay mice had higher cortical area and cortical thickness, and improved trabecular properties which would typically be indicative of greater bone strength. However, KK/Ay mice displayed lower cortical tissue mineral density in both sexes and increased cortical porosity in females. Fracture instability toughness of the femora was lower in KK/Ay mice overall compared to controls. These findings indicate that decreased mechanical integrity noted in the femora of KK/Ay mice was likely due to overall bone quality being compromised.

Phenotypes of streptozotocin-induced gestational diabetes mellitus in mice.

Gestational diabetes mellitus (GDM) in human patients disrupts glucose metabolism post-pregnancy, affecting fetal development. Although obesity and genetic factors increase GDM risk, a lack of suitable models impedes a comprehensive understanding of its pathology. To address this, we administered streptozotocin (STZ, 75 mg/kg) to C57BL/6N mice for two days before pregnancy, establishing a convenient GDM model. Pregnant mice exposed to STZ (STZ-pregnant) were compared with STZ-injected virgin mice (STZ-virgin), citrate buffer-injected virgin mice (CB-virgin), and pregnant mice injected with citrate buffer (CB-pregnant). STZ-pregnant non-obese mice exhibited elevated blood glucose levels on gestational day 15.5 and impaired glucose tolerance. They also showed fewer normal fetuses compared to CB-pregnant mice. Additionally, STZ-pregnant mice had the highest plasma C-peptide levels, with decreased pancreatic islets or increased alpha cells compared to CB-pregnant mice. Kidneys isolated from STZ-pregnant mice did not display histological alterations or changes in gene expression for the principal glucose transporters (GLUT2 and SGLT2) and renal injury-associated markers. Notably, STZ-pregnant mice displayed decreased gene expression of insulin-receiving molecules (ISNR and IGFR1), indicating heightened insulin resistance. Liver histology in STZ-pregnant mice remained unchanged except for a pregnancy-related increase in lipid droplets within hepatocytes. Furthermore, the duodenum of STZ-pregnant mice exhibited increased gene expression of ligand-degradable IGFR2 and decreased expression of GLUT5 and GLUT12 (fructose and glucose transporters, respectively) compared to STZ-virgin mice. Thus, STZ-pregnant mice displayed GDM-like symptoms, including fetal abnormalities, while organs adapted to impaired glucose metabolism by altering glucose transport and insulin reception without histopathological changes. STZ-pregnant mice offer a novel model for studying mild onset non-obese GDM and species-specific differences in GDM features between humans and animals.

The efficacy and safety of perioperative glucocorticoid for total knee arthroplasty: a systematic review and meta-analysis

BackgroundAn increasing number of individuals undergo total knee arthroplasty (TKA), which can result in pain, limited motor function and adverse complications such as infection, nausea and vomiting. Glucocorticoids have been shown anti-inflammatory and antiemetic effects, but can also elevate blood glucose levels and increase the risk of wound infection. Thus, it is essential to investigate the efficacy and safety of glucocorticoid usage in TKA.MethodA comprehensive systematic search of PubMed, Medline, EMBASE, Cochrane databases, to identify relevant randomized controlled trials (RCTs) of glucocorticoid application in TKA. The primary outcomes assessed were the postoperative pain assessment. Secondary outcomes included the range of motion in knee joint, levels of inflammatory cytokines, adverse complications, and the length of hospital stay.ResultsThirty-six randomized controlled trials were included in the final analysis. The glucocorticoid group exhibited significant reduction in the resting VAS scores on postoperative days 1, 2 (POD1, 2)and postoperative 3 months (POM3), as well as decreased morphine consumption on POD1 and increased range of motion (ROM) in knee joint on POD1, 3. Additionally, the glucocorticoid group exhibited decreased levels of postoperative inflammatory cytokines and the incidence of PONV along with a shorter length of hospital stay. The blood glucose concentration was significantly increased in the glucocorticoid group on POD1 compared with the control group. While the blood glucose on POD2 and occurrence of postoperative adverse complications were similar between two groups including wound infection and venous thrombosis. The periarticular injection analgesia (PIA) group demonstrated lower VAS scores on POD2 comparing to the systemic administration (SA) group according to two studies. However, there was no significant difference of the resting VAS on POD1 and POD2 between PIA and SA group across all studies.ConclusionPerioperative glucocorticoids treatment in TKA significantly reduced short-term pain score and opioid-use which was probably not patient relevant. The application of glucocorticoids in TKA implied a beneficial trend in analgesic, anti-inflammatory, and antiemetic effects, as well as improved range of motion and shortened hospital stay. While it will not increase the risk of continued high glucose, postoperative wound infection and venous thrombosis.

Daily feeding frequency affects feed intake and body weight management of growing layers

The objective of this study was to investigate the effect of feeding behavior on feed intake and body weight in growing layers and the underlying mechanisms, thereby providing a scientific foundation for optimal feeding practices in growing layers' management. A total of 144 Hy-line brown growing layers of 10 wk old and similar body weight, were divided into 3 treatment groups with different feeding frequency and equal cumulative daily feeding amount: the once-a-day feeding group (F1) was fed at 9:00 am every day, with feeding amount of 150 g/layer; the twice-a-day feeding group (F2) were fed at 9:00 am and 13:00 pm every day, with each feeding amount of 75 g/layer; the 4 times-a-day feeding group (F4) were fed at 9:00 am, 11:00 am, 13:00 pm, and 15:00 pm every day, with each feeding amount of 37.5 g/layer. Pre-experiment lasted for 1 wk and formal experiment lasted for 8 wk. The results indicated that the daily feed intake and body weight were decreased (P < 0.05) while feed conversion ratio was not affected (P > 0.05) as daily feeding times increased. The glandular stomach proportion was significantly increased in twice-a-day feeding group, while liver proportion and ileum length were significantly increased in 4 times-feeding group (P < 0.05). Additionally, 4 times-feeding daily resulted in a significant elevation of blood glucose levels, which may have suppressed feed intake (P < 0.05). In 4 times-feeding group, the plasma triglyceride levels increased as feeding times, accompanied by a notable up-regulation in the mRNA level of appetite-suppressing gene, hypothalamic pro-opiomelanocortin (POMC) and glandular stomach ghrelin. This modulation effectively suppressed the subsequent feed intake and body weight. Therefore, 4 times feeding daily is recommended in growing layers' management, because it reduced the feed cost without affecting the feed conversion efficiency.

An Improved Ensemble Machine Learning Approach for Diabetes Diagnosis

Diabetes is recognized as one of the most detrimental diseases worldwide, characterized by elevated levels of blood glucose stemming from either insulin deficiency or decreased insulin efficacy. Early diagnosis of diabetes enables patients to initiate treatment promptly, thereby minimizing or eliminating the risk of severe complications. Although years of research in computational diagnosis have demonstrated that machine learning offers a robust methodology for predicting diabetes, existing models leave considerable room for improvement in terms of accuracy. This paper proposes an improved ensemble machine learning approach using multiple classifiers for diabetes diagnosis based on the Pima Indians Diabetes Dataset (PIDD). The proposed ensemble voting classifier amalgamates five machine learning algorithms: Decision Tree (DT), Logistic Regression (LR), K-Nearest Neighbor (KNN), Random Forests (RF), and XGBoost. We obtained the individual model accuracies and used the ensemble method to improve accuracy. The proposed approach uses a pre-processing stage of standardization and imputation and applies the Local Outlier Factor (LOF) to remove data anomalies. The model was evaluated using sensitivity, specificity, and accuracy criteria. With a reported accuracy of 81%, the proposed approach shows promise compared to prior classification techniques.

Congenital anatomical variants in human fetal embryological development and its risk factors in low-resource setting: A longitudinal study

Objectives We aimed to determine the variants of congenital anomalies in human fetal development using ultrasound diagnosis, its associated risk factors, and the outcome of such pregnancies. Material and Methods This longitudinal study was conducted at a secondary health facility in north-central Nigeria. A total of 250 consenting pregnant women between 12 and 28 weeks of gestation were recruited, and each had a detailed history taken, an ultrasound scan to screen for fetal congenital anatomic variants, packed cell volume (PCV), and a 75-g oral glucose tolerance test at 24–28 weeks of gestation. All participants were followed up until delivery, and data analysis was done with SPSS version 21.0 (Chicago, IL, USA). Results Ultrasound-diagnosed congenital anatomical malformations were found in 29 participants (11.6%), and all were confirmed at birth. Of the 29 cases with congenital malformation, 15 (51.7%) were males. Maternal characteristics that were significantly associated with the risk of fetal congenital anomalies included age (p &lt; 0.001), hypertension in pregnancy (p &lt; 0.001), ingestion of herbal medication during pregnancy (p &lt; 0.001), previous history of unexplained neonatal death (p &lt; 0.001), and elevated blood glucose level (p &lt; 0.001). Conclusion The study shows a high incidence of congenital anomalies, especially among pregnant women with medical disorders in pregnancy. Also, there is a need to discourage the use of herbal medications during pregnancy.