Diabetes Drug Research Articles

Bilateral septic acromioclavicular arthritis in a farm worker with high suspicion of zoonotic disease: a case report

Abstract Introduction We report the case of a 54-year-old male with the rare entity of bilateral septic acromioclavicular (AC) arthritis with osteomyelitis of the lateral clavicle with methicillin-susceptible Staphylococcus aureus (MSSA). The glenohumeral joint was affected as well. The patient was immunocompetent with no history of diabetes or intravenous drug abuse. There is a high possibility of a transmission from farm animals. Material and methods The case files including laboratory measurements, imaging and documentation were used to reassess the case and complete the case report. Regular clinical follow-up was done in our outpatient clinic. We compared our case with the literature and existing guidelines. Results We report this rare entity of bilateral septic AC arthritis to ensure early diagnosis and proper treatment in the future. In comparison to the existing guidelines, we followed similar treatment concepts. The outcome of our patient was satisfactory despite a pre-existing rotary cuff tear, which might need further treatment in the future. Conclusion This report of a rare case can help to understand this infectious disease in the future and help establish treatment guidelines. In farm workers, one should be highly suspicious of transmission through animals and establish a quick and effective treatment as we did in this case.

Single-cell transcriptomics of human organoid-derived enteroendocrine cell populations from the small intestine.

Gut hormones control intestinal function, metabolism and appetite, and have been harnessed therapeutically to treat type 2 diabetes and obesity. Our understanding of the enteroendocrine axis arises largely from animal studies, but intestinal organoid models make it possible to identify, genetically modify and purify human enteroendocrine cells (EECs). This study aimed to map human EECs using single-cell RNA sequencing. Organoids derived from human duodenum and ileum were genetically modified using CRISPR-Cas9 to express the fluorescent protein Venus driven by the chromogranin-A promoter. Fluorescent cells from CHGA-Venus organoids were purified by flow cytometry and analysed by 10X single-cell RNA sequencing. Cluster analysis separated EEC populations, allowing an examination of differentially expressed hormones, nutrient-sensing machinery, transcription factors and exocytotic machinery. Bile acid receptor GPBAR1 was most highly expressed in L-cells (producing glucagon-like peptide 1 and peptide YY), long-chain fatty acid receptor FFAR1 was highest in I-cells (cholecystokinin), K-cells (glucose-dependent insulinotropic polypeptide) and L-cells, short-chain fatty acid receptor FFAR2 was highest in ileal L-cells and enterochromaffin cells, olfactory receptor OR51E1 was notably expressed in ileal enterochromaffin cells, and the glucose-sensing sodium glucose cotransporter SLC5A1 was highly and differentially expressed in K- and L-cells, reflecting their known responsiveness to ingested glucose. The organoid EEC atlas was merged with published data from human intestine and organoids, with good overlap between enteroendocrine datasets. Understanding the similarities and differences between human EEC types will facilitate the development of drugs targeting the enteroendocrine axis for the treatment of conditions such as diabetes, obesity and intestinal disorders. KEY POINTS: Gut hormones regulate intestinal function, nutrient homeostasis and metabolism and form the basis of the new classes of drugs for obesity and diabetes. As enteroendocrine cells (EECs) comprise only ∼1% of the intestinal epithelium, they are under-represented in current single-cell atlases. To identify, compare and characterise human EECs we generated chromogranin-A labelled organoids from duodenal and ileal biopsies by CRISPR-Cas9. Fluorescent chromogranin-A positive EECs were purified and analysed by single-cell RNA sequencing, revealing predominant cell clusters producing different gut hormones. Cell clusters exhibited differential expression of nutrient-sensing machinery including bile acid receptors, long- and short-chain fatty acid receptors and glucose transporters. Organoid-derived EECs mapped well onto data from native intestinal cell populations, extending coverage of EECs.

Current prevalence of rotator cuff tear in Type 2 diabetes mellitus patients and its association with type of diabetic drug regime (OHA’S vs. insulin therapy) – A prospective study

Background: A prospective study to assess the prevalence of rotator cuff (RC) tears in patients with Type 2 diabetes mellitus. Aims and Objectives: The purpose of this study is to assess the prevalence of RC tear in Type 2 diabetes mellitus patients presenting with shoulder pain to the outpatient clinic. Materials and Methods: A total of 100 diabetic patients with shoulder pain and restriction of movements formed the study group and were prospectively studied using magnetic resonance imaging and were evaluated with regard to the presence of RC tear. The factors that were analyzed included HBA1C levels, duration of diabetes, and type of diabetic medication. All these factors were evaluated with regard to their correlation with RC tear. Results: In our study, we found that the prevalence of RC tear was 37% and there seemed to be a significant correlation between HBA1C levels (P=0.007) as well as prolonged duration of diabetes (P=0.006) with RC tear. It has been established in our study that the occurrence of RC tear is lesser in oral hypoglycemic agents group as compared to insulin group in treating diabetic patients. Conclusion: One independent risk factor for RC tear is diabetes. The prevalence of RC tear is higher in the diabetic population with increased HBA1c levels and prolonged duration of diabetes mellitus. Metformin usage in diabetes mellitus has been associated with reduced incidence of RC tear due to diminished impregnation of advanced glycation end products with in the RC tendon.

Utilization of basic diabetes mellitus services among adult patients with diabetes mellitus at Mbarara Regional Referral Hospital diabetes clinic, Uganda: a cross-sectional study.

Utilization of diabetic care services remains a challenge among adult patients in low- and middle-income countries. Optimal utilization of diabetic care services could reduce morbidity and mortality and delay the development of long-term complications. This study assessed the utilization of basic diabetic care services and associated factors among diabetes mellitus patients at Mbarara Regional Referral Hospital in Western Uganda. We enrolled 208 patients with either type 1 or 2 diabetes mellitus in a cross-sectional study between June and August 2022 at Mbarara Regional Referral Hospital, Uganda. Consecutive sampling was used to select patients with diabetes mellitus who attended the diabetes clinic based on their scheduled date of appointment. Optimal utilization of basic diabetic services was defined as receiving at least three of the four core services: health education, assessment of vital signs (blood sugar, blood pressure, and body mass index), assessment of diabetic complications, and diabetic drug refills. Modified Poisson regression analysis was used to assess the determinants of utilization of basic diabetic services in STATA version 14.0. Three-quarters of the study participants were female patients (75.0%), and the median (inter-quartile range, IQR) age was 52 (43, 56). Moreover, 62.0% [95% confidence interval (CI): 55.3-68.7] self-reported to have utilized basic diabetic care services. In the adjusted analysis, waiting longer than 120 min to receive any service [adjusted prevalence ratio (aPR) 0.46, 95% CI 0.27-0.80), being 45-54 years old (aPR 1.48, 95% CI:1.11-1.98), and being 55-60 years old (aPR, 1.38, 95% CI: 1.02 1.86)] were significantly associated with the utilization of basic diabetic care services. Utilization of basic diabetic care services among adult patients remains sub-optimal. Age and waiting time were significantly associated with the utilization of diabetic care services. Interventions should be directed toward shortening the waiting time in service delivery at diabetes clinics.

Metabolic Outcomes of Changing From Rilpivirine/Tenofovir Disoproxil Fumarate/Emtricitabine to Rilpivirine/Tenofovir Alafenamide/Emtricitabine: A Longitudinal Study.

People living with human immunodeficiency virus (HIV, PLWH) are aging, and there are growing concerns regarding combined antiretroviral therapy (cART)-associated negative metabolic consequences. We aimed to investigate the metabolic outcomes of PLWH by replacing rilpivirine (RPV)/tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) with RPV/tenofovir alafenamide (TAF)/FTC. This retrospective study enrolled PLWH who changed from RPV/TDF/FTC to RPV/TAF/FTC between January 2019 and September 2023. Metabolic profiles were compared 1 year before and 3 years after changing cART using Cochran's Q and one-way ANOVA. The independent risk factors for metabolic syndrome were analyzed using logistic regression. A total of 182 patients were enrolled. The prevalence of metabolic syndrome has increased from 28% to 40.7%. The prevalence of hypertension and abnormal lipid levels significantly increased in the first year after changing cART, but the prescription of medicine for dyslipidemia increased in the second year (p = 0.025) and that for hypertension increased in the third year (p < 0.001). In addition to the criteria, body mass index (BMI) before changing cART was the only predictor of metabolic syndrome in the third year (OR 1.36; 95% CI 1.19-1.55; p < 0.001). The prevalence of metabolic syndrome and BMI did not increase significantly during the second and third years. A gradually higher prevalence of metabolic syndrome among PLWH occurred with changes from RPV/TDF/FTC to RPV/TAF/FTC but plateaued beyond 2 years. However, fewer drugs for dyslipidemia, diabetes, and hypertension were prescribed within the first year after changing cART.

Community-level responses and environmental fate of metformin in freshwater mesocosms.

The type 2 diabetes drug metformin is among the most frequently prescribed, dispensed, and consumed pharmaceuticals worldwide; and its heavy use and poor breakdown means it is consequently detected in various wastewater treatment plant (WWTP) effluents and surface waters. The resulting environmental concentrations of metformin can have adverse impacts on aquatic ecosystems. An 8-week in-lake mesocosm experiment was conducted in a freshwater boreal lake at the IISD-Experimental Lakes Area (Ontario, Canada) to determine the environmental fate and effects of metformin. Mesocosms were assigned to nominal concentrations of 0, 5, or 50μgL-1 metformin, in replicates of four. Biotic communities (i.e. microbial, phytoplankton, zooplankton, benthic macroinvertebrate) were assessed and complementary Lemna gibba and Daphnia magna bioassays were conducted in the laboratory. Metformin was extremely stable during the 8-week experiment, with mean measured concentrations of 0.00, 5.42, and 42.79μgL-1 in mesocosm surface waters for the 0, 5, and 50μgL-1 treatments, respectively. While trace amounts of metformin were detected in mesocosm sediments, the compound was primarily found in the water column. After over 1year following metformin additions, the mean loss of metformin from surface water was 94.0% and 91.0% for the 5 and 50μgL-1 treatment groups, respectively. No adverse effects of metformin treatment on the diversity, abundance, or biomass of microbial, phytoplankton, zooplankton, or benthic macroinvertebrate communities were found. Additionally, no survival or reproductive effects were observed in the 21-d Daphnia magna bioassays and no significant effects were observed in the 7-d Lemna gibba growth assays. No substantial metformin transformation to guanylurea was observed in mesocosm surface waters or sediments, likely due to a lack of bacterial degradation occurring within mesocosms relative to WWTPs.

HPR169 Impact of Recent US Pricing Policy on the Price of Diabetes Drugs in the US

HPR169 Impact of Recent US Pricing Policy on the Price of Diabetes Drugs in the US

COLONOSCOPY-RELATED NEPHROPATHY

Colonoscopy is a widely used tool for the diagnosis and treatment of colon disease [1]. It is the gold standart to visualize the large bowel [2]. Acute phosphate nephropathy (APhN) is a clinical entity which causes acute and subsequent chronic renal failure after exposure to oral sodium phosphate (OSP) bowel purgatives. APhN is seen as a result of oral sodium phosphate use in patients undergoing bowel cleansing before colonoscopy [3]. Generally, patients who will undergo colonoscopy are given 45 ml of OSP twice, starting 12-24 hours before the procedure. After intestinal absorption, elevated urea and creatinine, transient hyperphosphatemia, hypocalcemia, hypernatremia, hyponatremia, hypokalemia and high anion gap metabolic acidosis may also be observed [4]. Advanced age, ACEi/ARB use, acute or chronic kidney disese or the presence of a kidney transplant, retention of OSP resulting from poor bowel motility or colitis, female gender, volume depletion, hypertension, diabetes, and diuretic, lithium, or nonsteroidal anti-inflammatory drug use are considered as risk factors [5]. This case report describes a patient who developed nephropathy and required urgent observation and treatment after phosphate administration before colonoscopy.

Point of care creatinine testing for early detection of renal dysfunction in Tanzanian HIV patients: a study protocol

BackgroundRenal dysfunction (RD) is more prevalent among people living with HIV (PLHIV) in sub-Saharan Africa (SSA) due to factors such as co-infections, hypertension, diabetes, and nephrotoxic antiretroviral drugs like tenofovir. Early detection of RD is critical but limited by resource constraints in many SSA countries, including Tanzania. Point-of-care (POC) tests, such as the Stat-Sensor Creatinine test by Nova Biomedical, present a cost-effective and non-invasive option for early detection. This study will evaluate the diagnostic performance of the Stat-Sensor creatinine test in detecting renal dysfunction in HIV care and treatment clinics (CTCs) in Tanzania. It will be conducted for a period of six months, from November 2024 to April 2025.MethodologyThe study will measure point-of-care creatinine using a rapid creatinine dipstick against the standard serum creatinine test. The diagnostic performance and agreement to diagnose renal dysfunction will be assessed using a standardized statistical approach: Bland-Altman analysis and linear mixed-effects models to test agreement between creatinine dipstick tests with serum creatinine. Receiver operating characteristics (ROC) statistics will be used to test the diagnostic performance of the creatinine dipstick test to diagnose renal dysfunction.DiscussionWe hypothesize that POC creatinine testing will show strong diagnostic performance, providing a reliable, rapid, and cost-efficient alternative for RD detection, leading to better patient outcomes and integration of POC tests into routine HIV care.Ethical clearanceThe study protocol was reviewed and approved by the Muhimbili University of Health and Allied Sciences Research and Publication committee in June 2024 with reference number, MUHAS-REC-05-2024-2275.

PREVALENCE OF HAND OR WRIST-RELATED PAIN AND ITS FUNCTIONAL LIMITATION AMONG HEALTHCARE PRACTITIONERS

Background: Work-related hand and wrist injuries are among the most common occupational traumas, particularly affecting healthcare practitioners due to prolonged manual tasks and repetitive movements. These injuries significantly impact the practitioners' functional abilities and overall productivity. Addressing this issue is critical not only to enhance the health and well-being of healthcare workers but also to maintain high standards of patient care. This study aimed to evaluate the prevalence of hand and wrist pain and its associated functional limitations among healthcare practitioners. Objective: To assess the prevalence and impact of hand and wrist pain on functional limitations among healthcare practitioners in diverse healthcare settings. Methods: A cross-sectional study was conducted between March 2024 and July 2024, involving 70 healthcare practitioners aged 21 to 35 years from Madinah Teaching Hospital, Faisalabad International Hospital, Civil Hospital, Sahil Hospital, and Prime Care Hospital. Approval was obtained from the Ethical Institutional Review Board (Ref: TUF/IRB/329/24). Participants were selected using purposive sampling, including those with at least one year of clinical experience and a minimum of four working hours per day. Data were collected using validated tools: Pain Rated Wrist/Hand Evaluation (PRWHE), Numeric Pain Rating Scale (NPRS), and Michigan Hand Outcome Questionnaire (MHOQ). Exclusion criteria included unhealed fractures, arthritis, neurological disorders, neoplasms, diagnosed diabetes mellitus, smoking or drug abuse &gt;2 years, and systemic conditions affecting musculoskeletal function. Results: The PRWHE, NPRS, and MHOQ showed mean values of 31.57 (SD 18.75), 3.64 (SD 1.75), and 66.25 (SD 12.29), respectively. Functional domains of MHOQ recorded percentages for Function (59.42%), Activities of Daily Living (70.06%), Work (58.28%), Pain (36.35%), Aesthetics/Appearance (83.75%), and Satisfaction (61.85%). Urologists demonstrated the highest pain levels (PRWHE: 41.64; NPRS: 4.57) and lowest functional outcomes (MHOQ: Function: 50.71%). Surgeons exhibited the highest overall hand functionality (MHOQ: 69.16%), while nurses and dentists reported significant limitations in pain and work-related capabilities. Conclusion: The study identified a considerable prevalence of hand and wrist pain and associated functional limitations among healthcare practitioners. These findings underscore the necessity of ergonomic interventions and workplace modifications to alleviate musculoskeletal strain and improve the well-being and productivity of healthcare workers.

Knowledge and Associated Factors of Diabetes Mellitus among HIV Clients Living with Diabetes in Eastern Uganda: A Cross-sectional Study

Introduction: Poor diabetes knowledge among diabetes clients living with HIV remains a big public health challenge in Africa. Effective self-management of diabetes requires clients to be knowledgeable about the recommended diets, exercises, drugs, lifestyle modifications, and possible diabetes complications. The proportion of diabetes clients living with HIV with poor diabetes knowledge is on the rise in Eastern Uganda. Poor level of diabetes knowledge among clients is a serious threat to individual health, and Knowledge is essential for effective control of diabetes, as it allows the patient to play an active and cooperative role in planning and monitoring the therapeutic, which promotes informed decisions Aim: This study, conducted from May to June 2024, assessed the level of diabetes knowledge and its associated factors among diabetes clients living with HIV in Eastern Uganda. Study Design: A cross-sectional study was conducted in Mbale and Soroti Regional Referral Hospitals in Eastern Uganda from May to June 2024. Materials and Methods: The sample size was 267 registered participants though ten didn’t participate. Random sampling was done to select eligible registered participants. Electronic data collection was done by trained research assistants under the supervision of the principal investigator. All the research assistants were trained in data quality management. Ethical approval was obtained from Busitema University REC. The diabetes knowledge questionnaire was used to gather the data, and Stata version 14 was used for analysis. Univariate analysis and Binary logistic regression were used to identify associated factors. P &lt;0.05 was considered statistically significant at a 95% confidence interval. Results: A total of 257 participants in Mbale and Soroti Hospitals participated in this study. The majority 152(59.1%) were females and 156(60.7%) of these participants were above the age of 50 years. The married were 59.1%. Only 20.2% had tertiary education. More than half (58.4%) had a below-average level of knowledge regarding diabetes, 78.2% did not know how diabetes is managed and 58.4% were not aware of the common diabetes complications. In addition, 49.80% were not knowledgeable about the recommended diabetes tests, and 46.30% were not knowledgeable about the diets. Conclusions: The level of knowledge about diabetes is low among diabetes people living with HIV at Mbale and Soroti Hospitals in Eastern Uganda. No factor was found to be significantly associated with low diabetes knowledge. Routine diabetes education by the facility's health workers is encouraged and the focus should be on recommended diabetes tests, diets, drugs and possible complications. Contribution: Identifies specific areas to be strengthened in diabetes education.

Antidiabetic Activity Test of Fe(III) Complex Compound with Arginine Ligand in Male Mice (Mus Musculus L.)

Diabetes mellitus is characterized by high blood sugar levels in the body. Treatment for type 1 diabetes mellitus is with insulin injections while treatment for type 2 diabetes mellitus generally uses oral medication. Currently, people are looking for diabetes drugs made from complex compounds using metals. The development of research and utilization of Fe(III) complex compounds is still limited, thus, in this study the synthesis of Fe(III) complex compounds with arginine ligands was carried out. The results of the research obtained a complex compound of Fe(III)-arginine with 96%, in the form of a brown gel with a sample weight of 0.5601 g. Characterization using a UV-Vis spectrophotometer showed absorption at a wavelength of 203 nm which indicated the absorption of the Fe(III)-arginine complex. The results of FTIR analysis showed a typical absorption of Fe–O and Fe–N bonds at a wavelength of 500–600 nm. The results of the calculation of the mice's body weight decreased when induced by alloxan. After 3 and 4 weeks, the mice's body weight returned to stability. The highest decrease in glucose levels was in dose 2, namely 100 μg/kg bw with a decrease in %GL of 66.72%. The results of this study show that the complex compound Fe(III) arginine can reduce blood glucose levels in mice.

Semaglutide promotes the transition of microglia from M1 to M2 type to reduce brain inflammation in APP/PS1/tau mice

A growing number of studies show that the diabetes drug Semaglutide is neuroprotective in Alzheimer’s disease (AD) animal models, but its mode of action is not fully understood. In order to explore the mechanism of Semaglutide, 7-month-old APP/PS1/tau transgenic (3xTg) mice and wild-type (WT) mice were randomly divided into four groups: control group (WT + PBS), AD model group (3xTg + PBS), Semaglutide control group (WT + Semaglutide) and Semaglutide treatment group (3xTg + Semaglutide). Semaglutide (25 nmol/kg) or PBS was administered intraperitoneally once every two days for 30 days, followed by behavioral and molecular experiments. The results show that Semaglutide can improve working memory and spatial reference memory of 3xTg-AD mice, promote the release of anti-inflammatory factors and inhibit the production of pro-inflammatory factors in the cortex and hippocampus, and reduce Aβ deposition in the hippocampal CA1 region of 3xTg mice. Semaglutide can inhibit the apoptosis of BV2 cells induced by Aβ1-42 in a dose-dependent manner and promote the transformation of microglia from M1 to M2, thereby exerting anti-inflammatory and neuroprotective effects. Therefore, we speculate that Semaglutide shows an anti-inflammatory effect by promoting the transformation of microglia from M1 to M2 type in the brain of 3xTg mice, and thus exerts a neuroprotective effect.

Spinal epidural abscess

Introduction. A spinal epidural abscess (SEA) is a rare but serious infectious disease characterized by the accumulation of pus in the spinal epidural space. This condition can lead to compression of the spinal cord and nerve roots, which, if diagnosis is delayed or mistaken, may result in persistent neurological deficits or even death. In recent decades, the incidence of SEA has been increasing, linked to an aging population, the spread of invasive medical procedures, and the rise of risk factors such as diabetes, obesity, and intravenous drug use. Diagnosing SEA is challenging due to its nonspecific symptoms; however, clinical awareness, along with early use of magnetic resonance imaging (MRI), enables timely detection and treatment. Clinical case description. A 55-year-old patient presented with complaints of weakness in all limbs and neck pain. The patient’s history began approximately four months earlier with a sore throat, followed by progressive limb weakness. MRI and CT imaging revealed an SEA at the C4-C5 level, causing spinal cord compression. The patient underwent C4 and C5 corpectomy, abscess removal and drainage, and stabilization with a cervical plate and autograft. In the postoperative period, the patient showed significant improvement; by discharge, the neurological deficit had substantially regressed. Conclusion. This review highlights the need to increase SEA awareness among healthcare professionals to facilitate early diagnosis and treatment initiation, particularly in high-risk patients. Despite advancements in treatment, mortality and neurological complications remain significant, underscoring the need for further research to optimize treatment strategies and improve outcomes for patients with SEA.

Adiponectin may play a crucial role in the metabolic effects of GLP-1RAs treatment in patients with Type 2 Diabetes Mellitus: a preliminary longitudinal study.

Type 2 diabetes mellitus (T2DM) stands as the most prevalent metabolic disorder globally. T2DM entails numerous cardiovascular complications, which contribute significantly to morbidity, mortality, and increased public spending worldwide. The real challenge for new diabetes drugs lies not only in reducing blood glucose levels and glycated hemoglobin but also in preventing cardiovascular risk. Emerging receptor agonists for glucagon-like peptide-1 (GLP-1RAs) have demonstrated a pivotal role in diabetes management and mitigating cardiovascular risk. We conducted a 12-month longitudinal investigation evaluating the cardio-metabolic effects of GLP-1RAs on a cohort of 65 Caucasian patients diagnosed with T2DM who were scheduled for treatment with GLP-1RAs. Fifty-four T2DM patients successfully completed the 12-month study period, with 30 receiving dulaglutide and 24 receiving semaglutide. In our study population, GLP-1RAs resulted in several positive changes beyond the observed weight loss: a shift in fat distribution, indicated by a reduction in the percentage of visceral fat (1.21 vs. 1.17, p < 0.05); a significant decrease in LDL cholesterol levels (p < 0.05) and triglycerides (p < 0.01); and a significant increase in serum adiponectin levels (p < 0.05), potentially indicating a reduction in insulin resistance and inflammation. Additionally, we observed a significant decrease in microalbuminuria and media-intimal thickness at the carotid vessel level (p < 0.05). In patients with T2DM 1-year therapy with GLP-1RAs has a positive effect on the main determinants of cardiovascular risk including body weight, visceral fat, dyslipidemia, and atherosclerosis. Moreover, the increase in adiponectin may play a pivotal role in controlling the inflammatory state and the mechanisms of vascular damage.

Benchmarking the medication efficiency and technological progress of diabetes drugs.

Diabetes poses a serious global challenge, given its increasing prevalence, detrimental effects on public health, and substantial economic burden. Since 1950s, tens of drugs have been approved by the United States (US) Food and Drug Administration (FDA). In the past decade, the medical community and regulatory agencies have moved away from the glucose-centric paradigm and increasingly call for a holistic approach to assess different treatments' benefits and harms. This study aimed to assess the medication efficiency and technological progress of Type 2 Diabetes (T2D) drugs, by considering their physiological outcomes, including both benefits (i.e., glucose lowering and weight loss) and adverse effects (mortality), relative to dosing frequency. To derive medication efficiency, this study utilized data from the US FDA and prominent meta-analyses. Given that both the benefits and adverse effects of medications are multidimensional, this study employed a nonparametric frontier method, the data envelopment analysis (DEA) model, to integrate these factors into a measure of medication efficiency. Physiological outcomes could assume both positive and negative values. Adverse effects were regarded undesirable outputs. The DEA model was built under the framework of directional distance function and was able to handle negative and undesirable values which naturally arose in the case of T2D medications. The paper presented a ranking of 20 T2D drugs in terms of medication efficiency. Three of them were able to attain the highest medication efficiency, all of which were in the GLP-1 class, including oral Semaglutide, subcutaneous Semaglutide and Dulaglutide. However, the other two GLP-1 drugs, Lixisenatide and Liraglutide, were less efficient. The average medication efficiency of drugs approved post-2010 was significantly higher than pre-2010 drugs. High dose frequency, low HbA1c reduction and insignificant weight loss were the main driving factors behind inefficiencies. Overall, medication efficiency provided an alternative perspective on treatment effectiveness other than conventional measures such as cost-effectiveness.

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Some diabetes drugs ‘linked to lower risk of kidney stones and gout’, study finds

Development and validation of a machine learning model for predicting drug-drug interactions with oral diabetes medications

Diabetes management is often complicated by comorbidities, requiring complex medication regimens that increase the risk of drug-drug interactions (DDIs), potentially compromising treatment outcomes or causing toxicity. Although machine learning (ML) models have made strides in DDI prediction, existing approaches lack specificity for oral diabetes medications and face challenges in interpretability. To address these limitations, we propose a novel ML-based framework utilizing the Simplified Molecular Input Line Entry System (SMILES) to encode structural information of oral diabetes drugs. Using this representation, we developed an XGBoost model, selecting molecular features through LASSO. Our dataset, sourced from DrugBank, included 42 oral diabetes drugs and 1,884 interacting drugs, divided into training, validation, and testing sets. The model identified 606 optimal features, achieving an F1-score of 0.8182. SHAP analysis was employed for feature interpretation, enhancing model transparency and clinical relevance. By predicting adverse DDIs, our model offers a valuable tool for clinical decision-making, aiding safer prescription practices. The 606 critical features provide insights into atomic-level interactions, linking computational predictions with biological experiments. We present a classification model specifically designed for predicting DDIs associated with oral diabetes medications, with an openly accessible web application to support diabetes management in multi-drug regimens and comorbidity settings.

Novel α-glucosidase Inhibitors Designed as Type 2 Diabetes Drugs by QSAR, Molecular Docking and Molecular Dynamics Simulation Methods.

Diabetes mellitus is a globally prevalent disease of significant concern. Alpha-glucosidase has emerged as a prominent target for the treatment of type 2 diabetes. In this study, 39 α-glucosidase inhibitors (AGIs) of tetrahydrobenzo[b]thiophene-2-ylurea derivatives to establish a stable and valid Topomer CoMFA model, with a cross-validation coefficient (q2) of 0.766 and a non-cross-validation coefficient (r2) of 0.960. Subsequently, the ZINC15 database was used to screen the fragments, based on which 13 novel inhibitor molecules with theoretically potentially high activity were designed. Molecular docking and molecular dynamics simulations to understand the binding status of the inhibitor molecules to the target proteins showed that amino acids ASP215, GLN279 and ARG442 may form hydrogen bonds with the ligands and therefore enhance the inhibitory effect of the small molecules. Additionally, MM/PBSA calculations indicate that the newly designed molecules exhibit more stable binding modes. These molecules also demonstrate favorable ADMET properties with potential as AGIs. The findings would provide valuable guidance and a theoretical foundation for the design and development of novel AGIs.

Polyphenol-rich Ocimum gratissimum leaf extract attenuates angiotensin-converting enzyme activity and impaired endothelial vascular function in diabetic rats

Endothelial vascular dysfunctions are prevalent among diabetic patients, significantly impacting their quality of life and prognosis. This study examined the effects of polyphenol-rich extracts from Ocimum gratissimum leaves on oxidative stress markers, serum lipid profiles, and angiotensin-converting enzyme activity in diabetic cardiac tissue. Forty Wistar rats (150–220 g) were divided into five groups: normal control, diabetic control, low-dose Ocimum gratissimum (122.46 mg/kg), medium-dose Ocimum gratissimum (244.98 mg/kg), and a positive control (standard diabetic drug). All rats except the normal control group were made diabetic via an intraperitoneal injection of 50 mg/kg streptozotocin, followed by 28 days of extract administration. Diabetes induction led to a significant (p&lt;0.05) disruptions in lipid profiles, oxidative stress markers, and ACE activity. Treatment with Ocimum gratissimum extracts at both doses significantly (p&lt;0.05) decreased triglyceride, low-density lipoprotein cholesterol, and very-low-density lipoprotein cholesterol levels while increasing high-density lipoprotein cholesterol. Lipid peroxidation marker, malondialdehyde, was significantly (p&lt;0.05) decreased, and antioxidant enzyme activities significantly (p&lt;0.005) improved. ACE activity was significantly (p&lt;0.05) reduced, approaching control levels. These results suggest that the polyphenol-rich extract of Ocimum gratissimum exerts antioxidant and cardio-protective effects, improving vascular functions in diabetic rats by improving lipid profiles, reducing oxidative stress, and suppressing ACE activity.