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Background: The triglyceride-glucose (TyG) index is recognized as an alternative measure of insulin resistance (IR) and has been linked to the risks of cardiovascular disease (CVD) and mortality. This study aimed to evaluate whether the association between the TyG index and CVD mortality is influenced by the use of antidiabetic and hypolipidemic agents, given their potential modifying effects on the TyG index., Methods: Participants from the National Health and Nutrition Examination Survey (1999-2018) were included in the study. Mortality outcomes were tracked through linkage with National Death Index records until December 31, 2019. Data on the use of antidiabetic and hypolipidemic medications (including prescribed insulin, diabetic pills, and cholesterol-lowering agents) were self-reported by participants., Results: A total of 5,046 adults (representing 42,753,806 individuals, weighted mean age 61.08 years [SE: 0.24]; 49.35% female) were analyzed. The TyG index was significantly associated with all-cause and CVD mortality, and these associations were modified by the use of antidiabetic and hypolipidemic agents (p < 0.01). Significant interactions were observed between the TyG index and the use of these agents for mortality outcomes after full adjustments (p-value for interaction < 0.05). Exposure-effect analysis revealed a U-shaped relationship between TyG index levels and the risks of all-cause and CVD mortality in participants using these agents, while a linear positive relationship was observed in participants not using these agents., Conclusions: The use of antidiabetic and hypolipidemic agents modify the association between the TyG index and all-cause and CVD mortality. These findings suggest that future studies on the TyG index and its relationship with CVD and mortality should account for the modifying effects of these agents., Competing Interests: Declarations. Ethics approval and consent to participate: The study protocol was approved by the NHANES Institutional Review Board and implemented in accordance with the Declaration of Helsinki, with all NHANES participants providing signed informed consent. Consent for publication: The authors have no relevant conflicts of interest to disclose. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Pre-established anaesthetic protocols in animal models might unexpectedly interfere with the main outcome of scientific projects and therefore they need to account for the specific research goals. We aimed to optimize the anaesthetic protocol and animal handling strategies in a diabetes-related-study exemplifying how the anaesthetic approach must be adjusted for individual research targets. Aachen minipigs were used as a model to test long-lasting skin glucose sensors for diabetic human patients. A total of 6 animals participated in two or three rounds of experiments. Each round lasted 2 months, with a maximum of 2 rounds per year. In each round, animals were anaesthetised 4 times: for glucose sensors insertion, twice for glucagon stress tests (GST), and a last time for removal of sensors. Acepromazine (ACE) was compared to medetomidine (MED) in association with butorphanol (BUT) and Ketamine (KET) and 4 parameters were analysed to define the optimum anaesthetic protocol including: sedation level, anaesthesia duration, effects on blood glucose and safety. ACE-BUT demonstrated a weaker sedative effect but reduced overall experimental time, minimized anaesthetic risk and minimally interfered with the glucose metabolism. The improvement obtained by animal conditioning and handling strategies applied in this study were not objectively estimated, although the aversion behavior was completely abolished. Based on the analysed parameters, the use of acepromazine is proposed to be superior when Aachen Minipigs are used specifically as a model for diabetes-related studies, albeit the recommendations for the anaesthesia of minipigs suggest otherwise., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Soares et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The benefit of aspirin in primary prevention for atherosclerotic cardiovascular diseases (ASCVD) is questionable due to bleeding complications. We analyzed the Korean National Health Insurance data to compare the efficacy and overall bleeding of sarpogrelate, an antiplatelet agent with lower bleeding risk, versus aspirin in high-/very-high-risk diabetic populations without prior ASCVD. The primary endpoint was net adverse clinical events (NACE), defined as a composite of efficacy and overall bleeding. The efficacy was a composite of all-cause death, myocardial infarction (MI) and stroke, whereas overall bleeding included intracranial hemorrhage (ICH) and gastrointestinal (GI) bleeding. A total of 10,778 high-/very-high-risk diabetic patients (9550 on aspirin, 1228 on sarpogrelate) were analyzed. After propensity score matching, sarpogrelate was linked to a lower incidence of NACE (HR:0.71; 95% CI 0.57-0.88), mainly driven by 62% reductions in overall bleeding (0.38; 0.17-0.81), a composite of 64% and 72% lower rate of GI bleeding and ICH, respectively. Additionally, there was no significant differences in MI or stroke between groups. In high- or very-high-risk diabetic patients without ASCVD, sarpogrelate use was associated with net clinical benefit mainly due to the reduction of significant reduction in overall bleeding events., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

The challenges associated with prolonged healing or non-healing of chronic diabetic wounds contribute significantly to the increased incidence of lower limb amputation. A pivotal factor in the impediment of healing is the reduced production of endogenous nitric oxide (NO) due to the hyperglycemic microenvironment typical of chronic diabetes. While both endogenous and exogenous NO have been shown to promote the healing process of diabetic wounds, the direct application of NO in wound management is limited due to its gaseous nature and the risk of explosive release. This review summarizes recent advances of nanodressings incorporating NO donors in the treatment of diabetic wounds, detailing the specific conditions under which these nanodressings facilitate NO release, with a focus on the beneficial effects of NO, strategies for its supplementation, and the challenges encountered in the clinical translation of NO donors as a clinically viable nanomedicine in the context of improving diabetic wound healing., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Diabetes mellitus (DM) is a global health problem. Adherence to intensive insulin therapy is necessary to achieve better glycemic control in types 1 and 2 DM. This study aimed to evaluate the extent of adherence to insulin therapy, its predictors and to identify barriers to its adherence., Method: This was a cross-sectional survey among adult (≥18 years) diabetic patients who are currently using insulin, either alone or in combination with an oral antidiabetic regimen, and seeking primary care at Kwame Nkrumah University of Science and Technology Hospital in Ghana. A total of one hundred and eight-six patients were conveniently sampled, and interviewed. Insulin adherence was determined using the Medication Adherence Reporting Scale-5. Descriptive statistics, a chi-square test of independence, and a multiple logistic regression analysis were performed using STATA version 14 (StataCorp, TX USA)., Results: The majority of the patients interviewed were over 60 years (40.32%); female (61.83%); married (68.82%); and had completed secondary education (48.39%). 67.20% of the patients were adherent to insulin therapy. Adherence level was associated with age (p = 0.020), marital status (p = 0.001), employment status (p = 0.012), type of DM (p<0.001), regular follow-up (p = 0.007) and comorbidities (p = 0.002) and was only predicted by the type of DM (aOR = 14.82 C.I 1.34-163.50, p-value = 0.028)., Conclusion: Adherence to insulin therapy among our study population was suboptimal, which is a concern considering the associated increased risk of complications. Adherence assessment and counselling by healthcare professionals to address barriers to poor adherence must be continually undertaken to achieve optimal glycemic control., Impact of Findings on Practice Statements: Continuous adherence assessment and counselling must be offered to all diabetes mellitus patients on insulin therapy as part of their ambulatory care to help improve outcomes.Using the Medication Adherence Reporting Scale-5 to determine patient adherence levels is an easy-to-use and an inexpensive method; however, it should be used with caution due to the potential for misclassification.Efforts must be made to provide appropriate strategies to deal with barriers to insulin adherence at ambulatory care clinics as part of the individualized comprehensive diabetic care to reduce diabetic complications., Competing Interests: The authors have declared no competing interests exist., (Copyright: © 2025 Sefah et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Emerging evidence indicates that immune checkpoint inhibitor-induced diabetes mellitus (ICI-DM) might be more common than initially reported, and more different clinical pictures associated with ICI-DM were described., Objective: The aim of our study was to identify the clinical characteristics and possible predictive factors of ICI-DM., Methods: We conducted a retrospective review of patients who received immune checkpoint inhibitors (ICI) at West China Hospital, Sichuan University until June 2023. Patients were reviewed at death or on 7 May 2024. We applied logistic regression to study the associations between clinical characteristics and ICI-DM., Results: Our study included 8,199 participants who received ICI between October 2014 and June 2023. Among them, 1,077 patients (13.14%) developed ICI-DM according to diagnostic criteria based on guidelines. By excluding patients influenced by glucocorticoids or immunosuppressants, ICI-DM was observed in 713 of 8,199 (8.70%) patients. In all patients, hypertension, hyperlipidemia, using glucocorticoids or immunosuppressants, lung cancer, and using more than one pathway of ICI were associated with a higher risk of ICI-DM. However, the risk factors for ICI-DM in patients without the influence of glucocorticoids or immunosuppressants were only hypertension, hyperlipidemia, and pancreatic lesions. In all patients and those patients without the influence of glucocorticoids and immunosuppressants, hypertension and hyperlipidemia may increase the risk for ICI-DM., Conclusions: This large, real-world cohort demonstrates that the incidence of ICI-DM may be underestimated in previous literature. Blood glucose monitoring is needed in patients receiving ICI therapy., Clinical Trial Registration: https://www.chictr.org.cn, identifier ChiCTR2300075974., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Zhan, Long, He, Huang, Wu, Xu, Mo and Xu.)

Background: Previous studies demonstrated that diabetes remission can occur during intensive intervention and in real-world settings. However, the impact of diabetes remission in real-world settings on the incidence of cardiovascular disease (CVD) remains unclear., Methods: This retrospective cohort study included 299,967 individuals aged 20-72 years who underwent multiple checkups between 2008 and 2020 and completed ≥ 3 years of follow-up. Patients were divided into four groups according to changes in glycated hemoglobin levels and the use of diabetes medications during the 1-year baseline period: diabetes mellitus (DM)+/no remission, DM+/remission, DM-/no progression, and DM-/progression. The risk of CVD was evaluated using multivariable Cox regression analysis., Results: The median follow-up period was 5.0 years. The rates of CVD in the DM+/no remission, DM+/remission, DM-/no progression, and DM-/progression groups were 7.96, 4.76, 1.99, and 5.47 per 1000 person-years, respectively. Compared with DM+/no remission, DM+/remission reduced the risk of CVD [hazard ratio (HR) = 0.71, 95% confidence interval (CI) = 0.57-0.89]. Meanwhile, the HR for CVD in the DM+/remission group was 0.75 (95% CI = 0.56-0.99) for change in BMI ≤ 0%, versus 0.66 (95% CI = 0.45-0.96) for change in BMI > 0%., Conclusions: In a real-world setting without intensive intervention, diabetes remission decreased the risk of CVD by approximately 30% regardless of changes in BMI, suggesting that diabetes remission can prevent CVD without weight loss in routine care and emphasizing the importance of achieving remission., Competing Interests: Declarations. Ethics approval and consent to participate: The Ethics Committee of Niigata University approved this study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Diabetes mellitus (DM) is an important risk factor for the development of active tuberculosis (TB). QuantiFERON-TB Gold Plus (QFT-P), white blood cell count (WBC) assays and monocyte-to-lymphocyte ratio (MLR) reflect the inflammatory reactions associated with TB and offer the potential to monitor TB treatment to allow a better management of the disease. The aim of this study was to assess the influence of DM on the respective performances of QFT-P and WBC assays in their capacities to monitor the treatment of drug-sensitive pulmonary TB (TBP). The QFT-P and WBC were prospectively compared between TB patients with and without DM at inclusion (D0), at the end of treatment (M6) and two months after the end of treatment (M8). After laboratory measurement of glycated hemoglobin (HbA1c), the patients were categorized into two groups: the TBP (n=43) and the TBDM (n=30) groups. The TBDM patients were characterized by an elevated Mycobacterium tuberculosis -specific QFT-P IFN-γ response after TB treatment compared to the TBP group (p<0.001 and p<0.05, respectively, after TB1 and TB2 antigens stimulation). A significantly higher proportion of positive QFT-P tests was observed in the TBDM group compared to the TBP group (91.3% vs 64.1%) at the end of the treatment (p=0.03). MLR analysis showed a decrease of MLR value after TB treatment for both diabetic and nondiabetic TB patients (p<0.001 and p<0.05). These data reflected from immune-host based tests used to monitor the TB treatment, seemed to further suggest that TB with concomitant DM is associated with a persistent inflammatory response after TB treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Ranaivomanana, Razafimahefa, Ndiaye, Razafimahatratra, Ramamonjisoa, Herindrainy, Raherison, Raherinandrasana, Rakotonirina, Hoffmann, Ratovoson and Rakotosamimanana.)

Objectives: Stroke is a major cause of death and disability globally, especially among diabetic patients. In this study, we aim to scrutinise the effects of metformin on the clinical outcomes of stroke in diabetic patients., Design: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines., Data Sources: PubMed, Embase and Web of Science databases were searched between their inception and 5 December 2023., Eligibility Criteria for Selecting Studies: Studies investigating the effect of metformin on the clinical outcomes of stroke in patients with diabetes were included., Data Extraction and Synthesis: The effect of metformin on the clinical outcomes of stroke in patients with diabetes was identified using combined ORs and 95% CIs., Results: A total of 11 studies involving 18 525 participants were included in this review. Pooled analysis has demonstrated that prestroke metformin use could reduce the probability of poor course after stroke by 34% in diabetes mellitus (DM) patients (OR=0.66, 95% CI: 0.61 to 0.72) and reduce the probability of death by 43% (OR=0.57, 95% CI: 0.51 to 0.64)., Conclusions: Prestroke metformin use is beneficial for the improvement of clinical outcomes in patients who had a stroke with DM, although the potential bias should be carefully considered., Prospero Registration Number: CRD42024496056., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

This narrative review examines the dynamic interplay between carbohydrate intake and diabetes medications, highlighting their combined molecular and clinical effects on glycemic control. Carbohydrates, a primary energy source, significantly influence postprandial glucose regulation and necessitate careful coordination with pharmacological therapies, including insulin, metformin, glucagon-like peptide (GLP-1) receptor agonists, and sodium-glucose cotransporter-2 (SGLT2) inhibitors. Low-glycemic-index (GI) foods enhance insulin sensitivity, stabilize glycemic variability, and optimize medication efficacy, while high-GI foods exacerbate glycemic excursions and insulin resistance. Continuous glucose monitoring (CGM) offers real-time insights to tailor dietary and pharmacological interventions, improving glycemic outcomes and reducing complications. Despite advancements, gaps persist in understanding nutrient-drug interactions, particularly with emerging antidiabetic agents. This review underscores the need for integrating carbohydrate-focused dietary strategies with pharmacotherapy to enhance diabetes management. Future research should prioritize clinical trials leveraging CGM technology to explore how glycemic index, glycemic load, and carbohydrate quality interact with newer diabetes medications. Such studies can refine evidence-based recommendations, support individualized care plans, and improve long-term outcomes. Addressing systemic barriers, such as limited access to dietitians and CGM technology in underserved regions, is critical for equitable care. Expanding the roles of community health workers and training healthcare providers in basic nutrition counseling can bridge gaps, promoting sustainable and inclusive diabetes management strategies. These efforts are essential for advancing personalized, effective, and equitable care for individuals with diabetes.

Background: This study aimed to analyze the changing trend of diabetes drugs clinical trials in China during 2013-2023, and provided a reference for the research and development of diabetes drugs., Methods: Diabetes drug clinical trial data were obtained from the registration and information disclosure platform of the National Medical Products Administration (NMPA) between January 1, 2013, and December 31, 2023. Trends of clinical trials on diabetes drugs were systematically analyzed in terms of characteristics, trial design, time trends, drug type, and indications., Results: From 2013 to 2023, a total of 1,256 diabetes drugs clinical trials have been registered on the NMPA platform, of which 1056 were chemical drugs and 184 were biological products. The indications are mainly type 2 diabetes mellitus (n=1237, 98.49%). Among them, 838 clinical trials have been completed, 379 were proceeding, and 39 have been terminated or suspended. There were 42 international multi-center clinical trials, and the remaining 1034 clinical trials were domestic. Bioequivalence trials were 691, accounting for 55.02%, followed by 340 phase I clinical trials and 169 phase III clinical trials. The leading units were mostly distributed in eastern China. The proportion of clinical trial sponsorship from domestic pharmaceutical companies is higher than that from overseas companies., Conclusions: China has made significant advancements in diabetes drug research and development over the past decade. However, problems such as serious drug homogeneity, and insufficient innovation have become increasingly prominent. The government, clinical trial institutions, and pharmaceutical companies must collaborate to promote the high-quality development of drug clinical trials., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Ma, Zhao, Lin, Zhang, Wu, Tao, Shi and Li.)

Background: Although commercially developed automated insulin delivery (AID) systems have recently been approved and become available in a limited number of countries, they are not universally available, accessible, or affordable. Therefore, open-source AID systems, cocreated by an online community of people with diabetes and their families behind the hashtag #WeAreNotWaiting, have become increasingly popular., Objective: This study focused on examining the lived experiences, physical and emotional health implications of people with diabetes following the initiation of open-source AID systems, their perceived challenges, and their sources of support, which have not been explored in the existing literature., Methods: We collected data from 383 participants across 29 countries through 2 sets of open-ended questions in a web-based survey on their experience of building and using open-source AID systems. Narratives were thematically analyzed, and a coding framework was identified through iterative alignment., Results: Participants consistently reported improvements in glycemia, physical health, sleep quality, emotional impact on everyday life, and quality of life. Knowledge of open-source AID systems was largely obtained through the #WeAreNotWaiting community, which was also the primary source of practical and emotional support. The acquisition of the components to build an open-source AID system and the technical setup were sometimes problematic., Conclusions: The #WeAreNotWaiting movement represents a primary example of how informed and connected patients proactively address their unmet needs, provide peer support to each other, and obtain results through impactful, user-driven solutions. Alongside providing evidence on the safety and efficacy of open-source AID systems, this qualitative analysis helps in understanding how patients' experiences and benefits range from psychosocial improvements to a reduction in the burden of managing diabetes., International Registered Report Identifier (irrid): RR2-10.2196/15368., (©Bryan Cleal, Yanbing Chen, Mandy Wäldchen, Hanne Ballhausen, Drew Cooper, Shane O'Donnell, Christine Knoll, Niklas Krug, Klemens Raile, Tebbe Ubben, Adrian Tappe, Dana Lewis, Ingrid Willaing, Timothy Skinner, Katarina Braune. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 06.01.2025.)

Background: The effect of antidiabetic agents on mortality outcomes is unclear for individuals with diabetes mellitus (DM) who are hospitalized for COVID-19., Purpose: To examine the relationship between antidiabetic agent use and clinical outcomes in individuals with DM hospitalized for COVID-19., Methods: A systematic review of the literature (2020-2024) was performed across five databases. Included articles reported primary research (English) reporting clinical outcomes of adult patients (≥18 yrs.) with DM receiving antidiabetic agents who were hospitalized for COVID-19. Following PRISMA guidelines articles underwent independent dual review. Quality appraisal was completed for included studies. Independent reviewers used a structured data extraction form to retrieve relevant data. Aggregated data were synthesized by treatment regimen and reported descriptively. Random effects meta-analyses were performed to assess relative risk and prevalence of mortality., Results: After removing duplicates, title and abstract screening of 4,898 articles identified 118 articles for full-text review and 35 articles were retained for analysis. Included articles were primarily from China (15/35, 43%) and retrospective in nature (31/35, 89%). Fourteen studies (40%) assessed multiple antidiabetic agents, fifteen studies (42%) focused on metformin, three studies (9%) assessed the use of DPP-4 inhibitors, and three single studies (9%) investigated the use of insulin, TZD, and SGLT2 inhibitors. Despite differences among studies, the overall relative risk of mortality among metformin and DPP-4 inhibitor users was 0.432 (95% CI = 0.268-0.695, z = 3.45, p < 0.001) and the overall prevalence of mortality among all antidiabetic users was 16% (95% CI = 13%-19%, z = 10.70, p < 0.001)., Conclusions and Implications: Synthesis of findings suggest that patients who remained on oral agents (with/without supplemental insulin therapy) exhibited decreased mortality and lower inflammatory markers. Results indicate that individuals with DM should continue oral antidiabetic agents with additional basal insulin as needed to improve glycemic control and reduce mortality. Further work is needed to uncover mechanism(s) and clarify medical management approaches., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Keels, McDonald, Lee and Dwyer.)

Diabetes mellitus (DM), a global disease that significantly impacts public health, has become increasingly common over time. In this review, we aim to determine the potential benefits of St. John's Wort (SJW) as an adjunct therapy for DM. We gathered information from studies conducted in vitro, in vivo, and in humans. In vitro studies investigated the concentrations of SJW extracts capable of inhibiting certain enzymes or factors involved in the inflammatory pathway, such as the β-signal transducer and activator of transcription 1, nuclear factor κB, methylglyoxal, and oxidative stress (OS). The extract was found to have positive effects on OS and anti-inflammatory properties in DM, suggesting it could serve as a protective agent against diabetic vascular complications, cell damage, and apoptosis. According to in vivo research, the essential components of the extract can stimulate thermogenesis in adipose tissue, inhibit several key inflammatory signaling pathways, and delay the early death of pancreatic β cells, all of which contribute to combating obesity. The extract may also help treat prediabetes and significantly reduce neuropathic pain. Human studies have also confirmed some of these results. However, some of the plant's side effects need further investigation through clinical research before it can be used to treat DM.

This review describes our current understanding of the role of the mitochondria in the repurposing of the anti-diabetes drugs metformin, gliclazide, GLP-1 receptor agonists, and SGLT2 inhibitors for additional clinical benefits regarding unhealthy aging, long COVID, mental neurogenerative disorders, and obesity. Metformin, the most prominent of these diabetes drugs, has been called the "Drug of Miracles and Wonders," as clinical trials have found it to be beneficial for human patients suffering from these maladies. To promote viral replication in all infected human cells, SARS-CoV-2 stimulates the infected liver cells to produce glucose and to export it into the blood stream, which can cause diabetes in long COVID patients, and metformin, which reduces the levels of glucose in the blood, was shown to cut the incidence rate of long COVID in half for all patients recovering from SARS-CoV-2. Metformin leads to the phosphorylation of the AMP-activated protein kinase AMPK, which accelerates the import of glucose into cells via the glucose transporter GLUT4 and switches the cells to the starvation mode, counteracting the virus. Diabetes drugs also stimulate the unfolded protein response and thus mitophagy, which is beneficial for healthy aging and mental health. Diabetes drugs were also found to mimic exercise and help to reduce body weight.

Background: The advantages of insulin degludec 100 U/mL (IDeg100) in the treatment of diabetes mellitus (DM) include consistent release, predictable glucose-lowering effect, and minimal day-to-day variability., Hypothesis/objectives: To describe the use of IDeg100 in dogs with DM, level of diabetic control and adverse effects., Animals: Thirty-three client-owned dogs with DM., Methods: A prospective, multi-institutional, uncontrolled study of newly diagnosed or previously insulin-treated, with or without comorbidities and with or without concurrent medications. Clinical signs and continuous glucose monitoring data were monitored and guided insulin dose adjustments. A per-protocol analysis was performed., Results: The final dose of IDeg100 in dogs was 1.3 U/kg (median, range, 0.4-2.2) achieved in 14 days (median, range, 3-32). Seventy-nine percent (26/33) of the dogs had comorbidities with 42% (11/26) having more than 1 comorbidity. Sixty-four percent (21/33) of dogs were receiving concurrent medications with 62% (13/21) receiving more than 1 non-insulin medication. Seventy-six percent (25/33) were scored as having excellent/very good DM control. From baseline to study exit, dogs showed improvements in both ALIVE DM clinical score (from 3 [0-8, 96.49% CI (2-5)] to 1 [0-7, 96.49% CI (1-2)]; P = .0007) and average 3-day interstitial glucose (from 332.8 ± 68.7 mg/dL, 95% CI [308.8-357.2] to 229.0 ± 56.3 mg/dL [CI 209.0 - 248.9]; P < .0001)., Conclusions and Clinical Importance: Insulin degludec 100 U/mL is effective for the treatment of dogs with DM. Eighty-four percent (28/33) of dogs responded to once daily dose of IDeg100 with low frequency of clinical hypoglycemia., (© 2025 The Author(s). Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Objectives: To analyze the cost-effectiveness of the use of a specialized oral nutritional supplement (ONS) with proline, arginine, vitamins, and micronutrients to stimulate the healing of chronic wounds in patients with and without diabetes mellitus., Methods: This is a quantitative study on cost-effectiveness. This model used a decision-tree model followed by a budget impact analysis from the Brazilian public healthcare system's perspective. For this analysis, the population and data from a randomized trial of an oral specialized-ONS-containing supplement were considered. For budget impact analysis, an epidemiologic approach was used to estimate the eligible population. The eligible population comprised 3 different groups: patients with pressure ulcers, patients with vascular ulcers, and patients with diabetic feet. The budget impact analysis used the results of the cost-effectiveness analysis., Results: The results demonstrate that the use of specialized ONS, when compared with control ONS, proved to be cost saving (cheaper and more effective), considering the presence of predictive scar factor. The aggregated budget impact analysis results shows that the total reduction of costs after 5 years is USD 332 628 437.00., Conclusions: The use of a specialized ONS was cost-effective in the healing of chronic wounds, when compared with control. The budget impact analysis showed a significant decrease in costs in a 5-year time horizon for the management of pressure ulcers, vascular ulcers, and diabetic feet., Competing Interests: Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material section., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

This study explores novel therapeutic avenues for diabetes, a global health concern marked by elevated blood glucose levels. We investigated the anti-diabetic potential of Gymnema Sylvestre's bioactive compounds, including Gymnemic acid I, Stigmasterol, Deacylgymnemic acid, Beta-Amyrin acetate, Longispinogenin, Gymnemic acid II, Gymnemic acid, Gymnemic acid X, Gymnemaside VI, Phytic acid and Gymnemic acid X. Employing network pharmacology, molecular docking and molecular dynamics (MD), we elucidated the potential mechanism of action. SwissTargetPrediction identified targets for bioactive constituents, while DisGeNET provided diabetes-related targets. A GeneVenn diagram revealed 397 common potential targets for diabetes management. The protein-protein interaction network, constructed via the STRING database, underwent topological analysis in Cytoscape, identifying AKT1, SRC, TNF, PPARG and IL1B as top targets. Gene ontology analysis using FunRich identified crucial roles of screened targets in integrin family cell surface interactions and glypican pathways for diabetes management. Molecular interactions and binding affinities with the top target, AKT1, were assessed, with Gymnemic acid I displaying the least binding energy (-9.813) with H- and non-H-bond interactions. Molecular dynamics simulations provided insights into the distinct behaviours of Gymnemic acid I within the protein complex. In conclusion, our study elucidates the potential anti-diabetic mechanism of Gymnemic acid I, underscoring the need for further in vitro, in vivo and clinical studies to validate our findings., (© 2025 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Objectives: Diabetes constitutes a prevalent condition posttransplant, imposing a substantial burden on solid organ transplant recipients, including increased risk of graft loss and reduced overall survival. Consequently, the implementation of effective glycemic control strategies is vital. Tirzepatide, the first dual glucosedependent insulinotropic polypeptide/glucagon-like peptide-1 receptor coagonist, represents a novel therapeutic option in the general population; however, further data are needed to support its use in solid-organ transplant recipients., Materials and Methods: In this retrospective chart review, we examined a cohort of 41 heterogenous patients who were undergoing tirzepatide therapy after solid-organ transplant in Abu Dhabi, United Arab Emirates, from January 2017 to January 2024., Results: Within our study cohort, the median time elapsed from transplant to tirzepatide therapy commencement was 2.91 years (range, 1.04-4.38 y), with use that lasted for a median follow-up duration of 11 months (range, 7-13 mo) until date of data collection. Tirzepatide facilitated optimal glycemic control, elicited significant weight reductions, and improved renal function without adversely affecting graft function or patient survival, showing an adverse effect profile similar to that of the general population, as shown in the literature., Conclusions: Tirzepatide represents a promising therapeutic avenue for management of posttransplant diabetes mellitus and type 2 diabetes mellitus in solidorgan transplant recipients.

Diabetes is a prevalent and serious metabolic disorder affecting millions globally, and it poses extensive health risks due to elevated blood glucose levels. One promising approach for managing diabetes is the inhibition of α-glucosidase, an enzyme that plays a crucial role in carbohydrate metabolism. Targeting α-glucosidase can help delay glucose absorption, thus controlling postprandial blood sugar spikes. Dihydropyrimidones, a core structural class present in various biologically active natural compounds, have been recognized for their diverse therapeutic potential, including anti-diabetic properties. In this study, we evaluated a library of previously synthesized 37 Dihydropyrimidone derivatives to assess their potential as α-glucosidase inhibitors. We identified 34 derivatives with significant inhibitory activity, exhibiting IC 50 values in the range of 5.30-56.72 µM. Among these, compounds 2, 4-7, 9-11, 13-16, 31, 32, and 33 demonstrated high potency, with IC 50 values below 20 µM; the most active compound, 5, achieved an IC 50 of 5.30 µM. A detailed kinetic study on compound 5 revealed a competitive inhibition mode with a Ki value of 16.10 ± 0.0075 µM. Additionally, cytotoxicity assays confirmed that compound 5 is non-toxic to BJ cell lines, underscoring its safety for therapeutic use. The computational studies further supported the inhibitory potential by illustrating key interactions and binding affinities between the Dihydropyrimidone derivatives and the α-glucosidase, highlighting these compounds as promising candidates for diabetes management., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Diabetes mellitus (DM) prevalence is rising worldwide. Current therapies comprising subcutaneous insulin injections can cause adverse effects such as lipodystrophy, local reactions like redness and swelling, fluid retention, and allergic reactions. Nanoparticle carriers for oral insulin are groundbreaking compared to existing methods because they are non-invasive treatments, showing operational convenience, controlled release profile, and ability to simulate the physiological delivery route into the bloodstream. These systems improve patient adherence and have demonstrated the potential to lower blood glucose levels in DM. We present a systematic review and meta-analysis aimed at compiling relevant data to pave the way for developing innovative nano- and microparticles for the oral delivery of insulin. Our analysis of 85 articles revealed that the diminution of glucose levels is not proportional to the administered insulin dosage, which ranged from 1 to 120 International Units (IU). The meta-analysis data indicated that 25 IU of encapsulated porcine insulin did not produce a statistically significant outcome (p = 0.93). In contrast, a dosage of 30 IU was efficacious in eliciting an optimal hypoglycemic effect compared to excipient controls. Parameters such as a high degree of encapsulation (~ 90%), particle size (200-400 nm), and polydispersity index (0.086-0.3) are all associated with lower blood glucose levels. These parameters were also significant in the linear regression analysis. Among the excipients employed, chitosan emerged as a prevalent excipient in formulations due to its biocompatible and biodegradable properties and its ability to establish stable polymeric matrices. Even though oral insulin administration is a promising therapeutic method, it cannot guarantee preclinical safety and therapeutic efficacy yet in regulating glucose levels in diabetic conditions., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Chronic wounds in diabetic patients experience significant clinical challenges due to compromised healing processes. Hypoxia-inducible factor-1 alpha (HIF-1α) is a critical regulator in the cellular response to hypoxia, enhancing angiogenesis and tissue restoration. Nevertheless, the cellular response to the developed chronic hypoxia within diabetes is impaired, likely due to the destabilization of HIF-1α via degradation by prolyl hydroxylase domain (PHD) enzymes. Researchers have extensively explored HIF-1α activation as a potential pathway for diabetic wound management, focusing mainly on deferoxamine (DFO) as a potent agent to stabilize HIF-1α. This review provides an update of the other recent pharmacological agents managing HIF-1α activation, including novel PHD inhibitors (roxadustat and daprodustat) and Von Hippel-Lindau protein (VHL) antagonists, which could be potential alternatives for the local treatment of diabetic wounds. Furthermore, it highlights how localized delivery via advanced nanostructures can enhance the efficacy of these novel therapies. Importantly, by addressing these points, the current review can offer a promising area for research. Given that, these novel drugs have minimal applications in diabetic wound healing, particularly in the context of local application through nanomaterials. This gap presents an exciting opportunity for further investigation, as combining these drugs with localized nanotechnology could avoid undesired systemic side effects and sustain drug release within wound site, offering a transformative platform for diabetes wound treatment., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Saber et al.)

Diabetes-related foot infections(DFI), including diabetes-related foot osteomyelitis, are generally treated with systemic antibiotics. However, systemic antibiotics are often overused and administered for excessively long periods, making patients more susceptible to multidrug-resistant bacteria. Local antibiotics may be beneficial to DFI patients. This article reviews the advantages and disadvantages, types and clinical evidence of local antibiotics in the treatment of DFI, and points out the research gaps and future research direction in this field. This article aims to provide a reference for clinicians in formulating anti-infectious treatment plans for DFI.

CD73, an important metabolic and immune escape-promoting gene, catalyzes the hydrolysis of adenosine monophosphate (AMP) to adenosine (ADO). AMP has anti-inflammatory and vascular relaxant properties, while ADO has a strong immunosuppressive effect, suggesting that CD73 has pro-inflammatory and immune escape effects. However, CD73 also decreased proinflammatory reaction, suggesting that CD73 has a positive side to the body. Indeed, CD73 plays a protective role in diabetes, while with age, CD73 changes from anti-atherosclerosis to pro-atherosclerosis. The upregulation of CD73 with agents, including AGT-5, Aire-overexpressing DCs, Aspirin, BAFFR-Fc, CD4+ peptide, ICAs, IL-2 therapies, SAgAs, sCD73, stem cells, RAD51 inhibitor, TLR9 inhibitor, and VD, decreased diabetes and atherosclerosis development. However, the downregulation of CD73 with agents, including benzothiadiazine derivatives and CD73 siRNA, reduced atherosclerosis. Notably, many CD73 agents were investigated in clinical trials. However, no agents were used to treat diabetes and atherosclerosis. Most agents were CD73 inhibitors. Only FP-1201, a CD73 agonist, was investigated in clinical trials but its further development was discontinued. In addition, many lncRNAs, circRNAs, and genes are located at the same chromosomal location as CD73. In particular, circNT5E promoted CD73 expression. circNT5E may be a promising target for agent development. This mini-review focuses on the current state of knowledge of CD73 in diabetes, atherosclerosis, and its potential role in agent development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Zhao, Li, Wang, Wang, Wu, Huang, Xing and Chen.)

Aims: To present a study protocol for the development of an intervention to enhance safe insulin use for older or frail adults undergoing a surgical admission to hospital., Design: Following the United Kingdom's Medical Research Council and National Institute for Health and Care Research Frameworks for development and evaluation of complex interventions; this qualitative study will use a co-design approach using design thinking, to develop a theoretical model for the intervention., Methods: Non-participatory observations, interviews and co-design workshops will be conducted with older or frail individuals with diabetes, their caregivers and healthcare staff responsible for their care during surgical admissions at a single National Health Service hospital in England. We will utilise their experiences and perspectives to establish priorities and generate ideas for the development of a conceptual model aimed at supporting the insulin safety review process in hospitals. Data will be analysed using framework analysis. People with diabetes were involved in the design of this study. The protocol was approved by the East-Midlands-Derby Research Ethics Committee (24/EM/0022). Study registered on Open Science Framework: https://osf.io/4wvu5., Results: Results of this study will be shared with study participants and disseminated through presentations at conferences/meetings and peer-reviewed publications., Conclusion: This article outlines the methodology for the planned study which will employ a novel methodology to tackle the problem of hospital insulin safety. Its findings will contribute to a better understanding of the multiple interacting components implicated in hospital insulin use (patient, staff, context) and support further work around system-based strategies to enhance insulin safety resilience in hospital., Competing Interests: Christina Lange Ferreira; Sara Donetto; Jyothish Govindan; Angus Forbes; Kirsty Winkley: no known conflicts of interest. Hellena Habte-Asres: received speaker honoraria from AstraZeneca and Bayer., (Copyright: © 2024 Lange Ferreira et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Diabetes mellitus (DM) has a millennia-long history, with early references dating back to ancient Egypt and India. However, it was not until the 20th century that the connection between diabetes and insulin was fully understood. The sequencing of insulin in the 1950s initiated the convergence of biotechnology and diabetes management, leading to the development of recombinant human insulin in 1982. This marked the start of peptide-based therapies in DM. Recombinant peptides for DM treatment: Numerous recombinant peptides have been developed since, starting with modified insulin molecules, with the aim of bettering DM management through fine-tuning the glycemic response to insulin. Peptide-based therapies in DM have expanded substantially beyond insulin to include agonists of Glucagon-like peptide-1 receptor and Glucose-dependent insulinotropic polypeptide receptor, glucagon receptor antagonists, and even peptides exerting multiple receptor agonist effects, for better metabolic control. Insulin pumps, continuous glucose monitoring, and automated insulin delivery systems: The development of modern delivery systems combined with real-time glucose monitoring has significantly advanced diabetes care. Insulin pumps evolved from early large devices to modern sensor-augmented pumps with automated shutoff features and hybrid closed-loop systems, requiring minimal user input. The second-generation systems have demonstrated superior outcomes, proving highly effective in diabetes management. Islet cell transplantation, organoids, and biological pancreas augmentation represent innovative approaches to diabetes management. Islet cell transplantation aims to restore insulin production by transplanting donor beta cells, though challenges persist regarding graft survival and the need for immunosuppression. Organoids are a promising platform for generating insulin-producing cells, although far from clinical use. Biological pancreas augmentation relies on therapies that promote beta-cell (re)generation, reduce stress, and induce immune tolerance. Further biotechnology-driven perspectives in DM will include metabolic control via biotechnology-enabled tools such as custom-designed insulin hybrid molecules, machine-learning algorithms to control peptide release, and engineering cells for optimal peptide production and secretion.

Pancreatic diseases, typically including pancreatic cancer, pancreatitis, and diabetes, pose enormous threats to people's lives and health. To date, therapeutics with high therapeutic efficacy and low side effects are still challenging. With the development of nanotechnology, nanomaterials have successfully been applied in pancretic disease treatment. Here, we first introduce the diversity of nanomaterials and the effects of their different physicochemical properties on pancreatic function. Following this, we analyze the potential of nanomaterials to enhance pancreatic targeting by overcoming the challenges of traditional delivery methods through surface modifications, structural adjustments, and optimized drug loading. Then, we introduce the application of structurally optimized nanomaterials to pancreatic-related diseases. For instance, on pancreatic cancer (as drug delivery platforms, for the promotion of radiation therapy, and as multifunctional tools), pancreatitis (as drug delivery systems, anti-inflammatory and anti-fibrotic agents), and diabetes (as insulin delivery carriers, for protecting pancreatic β cells, and for improving insulin resistance). Through analysis of the progress of current research, we summarize how nanomaterials can enhance treatment efficacy while minimizing side effects. Finally, we look forward to the prospects of nanomaterials in pancreatic disease treatment.

Diabetes Mellitus is a significant global public health burden. Although medication adherence is an inevitable consideration in managing and curing the disease, medication price is the major barrier to patients in Nepal, like any other low- and middle-income countries. Prescribing in brand-name inhibits the possibility of accessing cost-effective generic alternatives in Nepal. This study aimed to explore and examine price variations among the oral hypoglycaemic medicines (OHMs) available in the country and their distribution in various medicine-related characteristics. A cross-sectional study was conducted using a convenient sample of five tertiary care hospital pharmacies in Kathmandu, publicly accessible online pharmacy websites, and a government database to list the OHMs available in Nepal. The study determined price variations and statistically tested the association between these variations and the characteristics of the medicines. Fourteen OHMs were available as 57 generic medicine items with different formulations in Nepal. The maximum of 484.82% of price variation was found. Fourteen, fifteen and eighteen OHMs have variations of over 100%, more than 10 rupees and no price change, respectively. Except for Dipeptidyl Peptidase-IV (DPP-4) Inhibitors and Thiazolidinediones (TZDs), all other categories of OHMs have >100% of price variation in medicine items. Although Nepal itself produces most of the available OHMs, the available OHMs have price variations. Most fixed dose combinations showed no reduction in cost compared to their component medicine's mean price. This study presented and discussed the price variation scenario of OHMs with their medicine-related characteristics to develop and implement effective drug policies and programs that can address medication price-related issues to ensure access to OHMs without placing an economic burden on patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Shrestha et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Diabetes mellitus (DM) is increasingly recognized as a possible consequence of statin therapy. Secondary analysis of randomized clinical trials and limited observational cohort analyses have suggested that women may be more likely than men to experience statin-associated DM. No analyses of real-world drug safety data addressing this question have been published., Research Design and Methods: This was a retrospective pharmacovigilance analysis of spontaneously reported adverse drug events (ADEs) submitted to the Food and Drug Administration Adverse Event Reporting System between January 1997 through December 2023. We analyzed cases that mentioned atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, or simvastatin in aggregate as well as cases reporting atorvastatin, pravastatin, rosuvastatin, simvastatin individually. DM events were identified using the Medical Dictionary for Regulatory Activities. We used the proportional reporting ratio to identify increased rates of statin-associated DM events in women and men compared with all other medications, and the reporting OR to compare reporting rates in women versus men., Results: A total of 18,294,814 ADEs were reported during the study period. Among statin-associated ADEs, 14,874/519,209 (2.9%) reports mentioned DM in women compared with 7,411/489,453 (1.5%) in men, which were both significantly higher than background (0.6%). Statins were the primary-suspected or secondary-suspected cause of the ADE significantly more often in women than men (60 vs 30%), and reporting rates were disproportionately higher in women than in men for all statins. (reporting OR 1.9 (95% CI 1.9 to 2.0)). The largest difference in reporting of statin-associated DM between women and women was observed with atorvastatin., Conclusions: Analysis of post-marketing spontaneous ADE reports demonstrated a higher reporting rate of DM-associated with statin use compared with other medications with a significantly higher reporting rate in women compared with men. Future studies should consider mechanisms of statin-associated DM moderated by sex., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The co-occurrence of breast cancer and diabetes presents complex clinical challenges, as each condition may influence the progression and management of the other, potentially worsening patient outcomes. This study aims to examine the association between insulin use and the risks of all-cause mortality, breast cancer-specific mortality, and recurrence in diabetic patients with breast cancer., Methods: A systematic review and meta-analysis were conducted using studies identified from multiple databases, including Web of Science, Scopus, PubMed, Cochrane, Google Scholar, and Embase. The meta-analysis approach was used to estimate the relative risk (RR) of the relationship between insulin use and the risks of all-cause mortality, breast cancer-specific mortality, and recurrence in diabetic patients with breast cancer. Heterogeneity among studies was assessed using statistical tests such as the Chi-square test, I2, and forest plots. Meta-regression and sensitivity analyses were performed to explore sources of heterogeneity. The quality of the included studies was assessed using the Newcastle-Ottawa Scale checklist. Data were analyzed using Stata version 17 (Stata Corp, College Station, Texas)., Results: Data from 22 studies conducted between 2002 and 2023, with a total of 159,674 participants, were analyzed. Nineteen studies were rated as high quality, and three as moderate quality. Diabetic patients with breast cancer who received insulin had a 1.65 (95% CI: 1.36-2.02; P < 0.001; I2 = 89.7%) times higher risk of overall mortality compared to those who did not use insulin. Meta-regression revealed that sample size and study quality were significant contributors to heterogeneity (P ≤ 0.10). Furthermore, insulin use was associated with a 1.22 (95% CI: 1.05-1.42; P = 0.009; I2 = 37.9%) times higher risk of breast cancer-specific mortality. For breast cancer recurrence, insulin use was associated with a 1.45 (95% CI: 1.19-1.77; P < 0.001; I2 = 3.4%) times higher risk. Sensitivity analysis confirmed the stability of the results across all outcomes., Conclusion: This meta-analysis provides strong evidence that insulin use in diabetic patients with breast cancer is associated with increased risks of overall mortality, breast cancer-specific mortality, and recurrence. These findings underscore the need for careful consideration of insulin therapy in this patient population., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Loktionova et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Diabetes mellitus (DM) increases the risk of cardiovascular diseases (CVD) significantly. Statins are recommended for all diabetic patients aged ≥ 40 years to alleviate this risk., Objectives: This study aimed to determine the status of the implementation of the recommendations of lipid management strategies for diabetic patients., Methods: In this cross-sectional study, 500 patients with DM, aged ≥ 40 referring to a public pharmacy with at least one diabetic medication in their prescription, were enrolled. Patients' demographics, lipid panel data, medications, personal and family history of atherosclerotic cardiovascular disease (ASCVD), and risk factors for ASCVD were documented. The appropriateness of stain dosing intensity was judged based on the American Diabetes Association (ADA) guideline., Results: The mean ± SD of the age of patients was 61.39 ± 10.49 years. Among patients, 238 (47.6) were men. More than half of the patients were subject to receiving primary prevention (59.8%, n = 299). For 80.8% (n = 404) of patients, a statin, most frequently atorvastatin (61.8%), was prescribed. The appropriate statin dose based on the guideline for 470 patients (94%), was high-intensity statin. In 70.6% (n = 353) of patients, lipid management was not in accordance with the guideline. Patients with ASCVD were more likely to receive the statins and the appropriate doses compared to patients without ASCVD (p-value < 0.001)., Conclusion: Despite a relatively high percentage of patients who received statins, the lipid management in most patients was not in accordance with the guideline. The profound problem was the suboptimal dosage of statins. Investigating the reasons and barriers of the appropriate management can be helpful. Additionally, since patients without ASCVD who should receive statins for primary prevention were significantly less likely to receive statins and evidence-based doses, more attention is needed for this population., Competing Interests: Declarations Ethics approval and consent to participate The study was approved by the ethics committee of TUMS.Patients were enrolled if they were willing to participate in the study. Consent for publication Not applicable. Competing interests The authors have no competing interests to declare that are relevant to the content of this article. Conflicts of interest The authors have no relevant financial or non-financial interests to disclose., (© 2024. The Author(s), under exclusive licence to Tehran University of Medical Sciences.)

Background: Evidence shows that diabetes raises the probability of contracting COVID-19 and associated complications. We hypothesize that metformin, being pleiotropic, may improve COVID-19 in diabetics., Methods: A retrospective cohort study was conducted with 421 COVID-19 patients with diabetes, hospitalized between 1st April 2020 and 31st March 2022 in a tertiary-care hospital. Patients with metformin or its combination constituted the study cohort (SC; n  = 221), while other antidiabetics constituted the reference cohort (RC; n  = 200)., Results: SC and RC were matched for mean age ± SD (SC: 53.3 ± 5.7 vs. RC: 54.3 ± 8.2 years). The mean length of hospitalization (days) was significantly shorter in SC (9.0 ± 5.7) than in RC (12.7 ± 6) ( p  < 0.02). Metformin use was associated with reduction in mortality risk (OR: 0.106, 95% CI = 0.039-0.287; p  < 0.001). Moreover, SC also improved levels of LDH (OR: 0.243, 95% CI = 0.104-0.566; p  < 0.001), CRP (OR: 0.281, 95% CI = 0.120-0.659; p  < 0.004), and D-dimer (OR: 0.220, 95% CI = 0.089-0.539; p  < 0.001) than RC. The calculated number needed to treat for metformin was 3.1., Conclusion: Metformin users have a decrease in hospital stay and mortality rates and improvement in LDH, CRP, and D-dimer levels. Therefore, metformin might protect against mortality in COVID-19 with diabetes.

Context: Diabetic kidney disease (DKD) is a prominent complication arising from diabetic microangiopathy, and its prevalence and renal impact have placed it as the primary cause of end-stage renal disease. Traditional Chinese Medicine (TCM) has the distinct advantage of multifaceted and multilevel therapeutic attributes that show efficacy in improving clinical symptoms, reducing proteinuria, protecting renal function, and slowing DKD progression. Over recent decades, extensive research has explored the mechanisms of TCM for preventing and managing DKD, with substantial studies that endorse the therapeutic benefits of TCM compounds and single agents in the medical intervention of DKD., Objective: This review lays the foundation for future evidence-based research efforts and provide a reference point for DKD investigation., Methods: The relevant literature published in Chinese and English up to 30 June 2023, was sourced from PubMed, Cochrane Library, VIP Database for Chinese Technical Periodicals (VIP), Wanfang Data, CNKI, and China Biology Medicine disc (CBM). The process involved examining and summarizing research on TCM laboratory tests and clinical randomized controlled trials for DKD treatment., Results and Conclusions: The TCM intervention has shown the potential to inhibit the expression of inflammatory cytokines and various growth factors, lower blood glucose levels, and significantly affect insulin resistance, lipid metabolism, and improved renal function. Furthermore, the efficacy of TCM can be optimized by tailoring personalized treatment regimens based on the unique profiles of individual patients. We anticipate further rigorous and comprehensive clinical and foundational investigations into the mechanisms underlying the role of TCM in treating DKD.

Non-healing wounds are long-term complications of diabetes mellitus (DM) that increase mortality risk and amputation-related disability and decrease the quality of life. Nitric oxide (NO·)-based treatments (i.e., use of both systemic and topical NO· donors, NO· precursors, and NO· inducers) have received more attention as complementary approaches in treatments of DM wounds. Here, we aimed to highlight the potential benefits of NO·-based treatments on DM wounds through a literature review of experimental and clinical evidence. Various topical NO·-based treatments have been used. In rodents, topical NO·-based therapy facilitates wound healing, manifested as an increased healing rate and a decreased half-closure time. The wound healing effect of NO·-based treatments is attributed to increasing local blood flow, angiogenesis induction, collagen synthesis and deposition, re-epithelization, anti-inflammatory and anti-oxidative properties, and potent broad-spectrum antibacterial effects. The existing literature lacks human clinical evidence on the safety and efficacy of NO·-based treatments for DM wounds. Translating experimental favors of NO·-based treatments of DM wounds into human clinical practice needs conducting clinical trials with well-predefined effect sizes, i.e., wound reduction area, rate of wound healing, and hospital length of stay., (Copyright © 2024 Copyright: © 2024 Medical Gas Research.)

Major depressive disorder (MDD) and diabetes mellitus (DM) remain among the most prevalent diseases and the most significant challenges faced by medicine in the 21st century. The frequent co-occurrence and bidirectional relationship between the two conditions necessitates the identification of treatment strategies that benefit both. The purpose of this study was to systematically review and meta-analyze data on the efficacy and safety of agomelatine (AGO) in the treatment of patients with depression with comorbid diabetes to explore its potential mechanism of action in both diseases and its impact on diabetic parameters. Following PRISMA guidelines, a total of 11 studies were identified, both preclinical and clinical trials. Agomelatine has shown great potential as a treatment option for patients with diabetes and comorbid depression and anxiety. In addition to improving depressive and anxiety symptoms, it is also beneficial in glycemic control. A meta-analysis demonstrated a statistically significant reduction in glycated hemoglobin (HbA1C) and fasting blood glucose (FBG) levels following AGO administration over a period of 8-16 weeks. The administration of agomelatine was found to result in a significantly greater reduction in HbA1C than that observed with the selective serotonin reuptake inhibitor (SSRI) medications (namely fluoxetine, sertraline, and paroxetine) during 12-16 weeks of therapy. Furthermore, AGO has been found to be at least as effective as SSRIs in reducing depressive symptoms and more effective than SSRIs in reducing anxiety symptoms. The safety of such treatment is similar to SSRIs; no severe adverse events were reported, and the incidence of some side effects, such as insomnia and sexual dysfunction, are even less often reported. Particularly promising is also its potential action in improving some diabetic complications reported in preclinical trials. This might be through mechanisms involving the reduction in oxidative stress, anti-inflammatory effects, and potentially noradrenergic or NMDA receptor modulation. Further clinical studies on larger sample sizes, as well as elucidating its mechanisms of action, especially in the context of diabetic complications, are needed. Research should also focus on identifying the patient subpopulations most likely to benefit from agomelatine treatment.

Glucokinase (GCK) is an essential enzyme for blood glucose homeostasis. Because of its importance in glucose metabolism, GCK is considered an attractive target for the development of antidiabetic drugs. However, a viable therapeutic agent has still to emerge, prompting efforts to improve understanding of the complex regulation and biological effects of GCK. Using the vertebrate organism zebrafish, an attractive model to study metabolic diseases and pharmacological responses, we dissected the complexities of gck regulation and unraveled effects of Gck modulation. We found that while gck expression in zebrafish islet cells is constitutive, gck expression in the liver is regulated by nutritional status, confirming similarity to the mammalian system. A combination of transgenic gck reporter lines and our diabetes model, the pdx1 mutant, allowed monitoring of gck expression under pathological conditions, revealing reduced gck expression and activity in the liver, which was unresponsive to nutrient stimulation, and decreased expression in the islet due to the reduced number of β-cells. Gck activation substantially ameliorated hyperglycemia in pdx1 mutants, without inducing oxidative stress responses in liver or islet. In-depth characterization of Gck activity and regulation at the cellular level in a whole-organism diabetes model clarifies its applicability as a drug target for therapies., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: We explored the changes in metabolic dysfunction-associated steatotic liver disease (MASLD) severity over time by analyzing data from the placebo arms of randomized controlled trials (RCTs), focusing on the presence of diabetes., Methods: RCTs on MASLD that included a placebo arm were identified using a systematic search of the literature. Primary outcomes were changes in hepatic steatosis and fibrosis., Results: The meta-analysis included 8 RCTs involving 386 patients without diabetes and 24 RCTs involving 637 patients with diabetes. The pooled estimate of mean change in steatosis grade was - 0.1 in patients without diabetes, and - 0.37 in patients with diabetes (P = 0.066). The mean change in fibrosis stage was 0.05 in patients without diabetes, and - 0.03 in patients with diabetes (P = 0.359). The mean change in nonalcoholic fatty liver disease activity score was - 0.55 in patients without diabetes, and - 1.50 in patients with diabetes (P = 0.100). The mean change in ALT and AST were significantly larger in patients without diabetes compared to those with diabetes (P < 0.05)., Conclusion: Placebo treatment had a greater effect in improving liver steatosis in patients with diabetes compared to those without. These findings highlight the importance of tailored treatment strategies in MASLD, particularly considering diabetes status., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Conflict of interest: The authors declare that they have no conflicts of interest relevant to this work. Financial support: This research was supported in part by grants from the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (grant numbers 2018R1A5A2025286 and 2022R1I1A1A01065244). The sponsors had no role in study design, data collection and analysis, decision to publish, or manuscript preparation. The funding source was not involved in the design or implementation of the study. Trial registration number: This study was registered with PROSPERO (registration number: CRD42023455528)., (© 2024. The Author(s).)

Diabetes mellitus (DM) is a significant risk factor for various cancers, with the impact of anti-diabetic therapies on cancer progression differing across malignancies. Among these therapies, metformin has gained attention for its potential anti-cancer effects, primarily through modulation of the AMP-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) pathway and the induction of autophagy. Beyond metformin, other conventional anti-diabetic treatments, such as insulin, sulfonylureas (SUs), pioglitazone, and dipeptidyl peptidase-4 (DPP-4) inhibitors, have also been examined for their roles in cancer biology, though findings are often inconclusive. More recently, novel medications, like glucagon-like peptide-1 (GLP-1) receptor agonists, dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) agonists, and sodium-glucose co-transporter-2 (SGLT-2) inhibitors, have revolutionized DM management by not only improving glycemic control but also delivering substantial cardiovascular and renal benefits. Given their diverse metabolic effects, including anti-obesogenic properties, these novel agents are now under meticulous investigation for their potential influence on tumorigenesis and cancer advancement. This review aims to offer a comprehensive exploration of the evolving landscape of glucose-lowering treatments and their implications in cancer biology. It critically evaluates experimental evidence surrounding the molecular mechanisms by which these medications may modulate oncogenic signaling pathways and reshape the tumor microenvironment (TME). Furthermore, it assesses translational research and clinical trials to gauge the practical relevance of these findings in real-world settings. Finally, it explores the potential of anti-diabetic medications as adjuncts in cancer treatment, particularly in enhancing the efficacy of chemotherapy, minimizing toxicity, and addressing resistance within the framework of immunotherapy.

Background: Diabetes mellitus and thyroid dysfunction are prevalent endocrine disorders that impose enormous burdens on patients and countries. However, access to essential medicines remains inadequate in many low-income countries. This study evaluated medications' availability, price, and affordability for these conditions., Methods: A cross-sectional study was conducted at health facilities in the South Wollo zone in 2022. Following World Health Organization (WHO)/Health Action International (HAI) guidelines, 34 medicines were evaluated across 60 medicine outlets. Data were collected using a standardized tool adapted from WHO/HAI. Availability was measured by the percentage of facilities where the medicines were in stock. Prices were reported as median prices and median price ratios (MPR). Affordability was assessed based on the number of days' wages required for the lowest-paid government workers to cover the full course of therapy., Results: The availability of lowest-priced generic (LPG) diabetes and thyroid dysfunction medicines in the public sector was 24.4% and 28.7%, respectively. In private pharmacies, availability was 26.3% for diabetes and 21% for thyroid dysfunction medicines. Median prices for LPG medicines were higher in private pharmacies than in public health facilities, with 81.81% showing a statistically significant difference (p < 0.05). In private pharmacies, the prices of LPG diabetes (5, 71.43%) and thyroid dysfunction medicines (5, 83.33%) exceeded the reference price. None of the LPG diabetes and thyroid dysfunction medicines were affordable in either setting., Conclusions: The study revealed a very low availability of medicines and a financial burden on patients. Therefore, the government should improve the availability of these essential medicines and regulate their prices., Competing Interests: Declarations Ethics approval and consent to participate The Ethics Review Committee of Wollo University, College of Medicine and Health Sciences (CMHS 660/14) approved this research. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Suboptimal medication adherence among individuals with diabetes presents a significant challenge in low-income nations. Growing evidence demonstrates the effectiveness of text messaging interventions to enhance medication adherence. This study assesses the intention to use Short Messaging Service (SMS) based reminder services in promoting drug adherence among diabetic patients and associated factors in Addis Ababa, Ethiopia., Methods: An institution-based cross-sectional study was conducted from February 06, 2023, to March 27, 2023, in Addis Ababa, Ethiopia. A sample of 351 patients was selected using systematic random sampling. Structured questionnaires were used for data collection. Binary and multivariable logistic regression models were used to analyze the association between intention to use SMS reminders to promote drug adherence among individuals with diabetes and related factors., Results: A total of 333 respondents, with a 94.87% response rate, were interviewed for this study. The majority of respondents, 66.4 % (95% CI [61.9-71.2]), expressed an intention to use SMS-based reminder services to promote their drug adherence. Age < 45 years (AOR = 5.73, 95% CI [2.07-15.73]), higher educational level (AOR = 3.03, 95% CI [1.16-7.90]), type of diabetes (AOR = 3.71, 95% CI [1.16-7.90]), oral medication users (AOR = 2.99, 95% CI [1.42-6.32]), SMS as a preferred medium for communication (AOR = 2.86, 95% CI [1.17-7.00]) were deemed to be important variables linked to intention to use SMS reminders to promote drug adherence among individuals with diabetes., Conclusion: The findings suggest the majority of individuals with diabetes have intention to use SMS reminders to enhance adherence. This result indicates the potential for utilization of SMS reminders to enhance adherence to diabetic medications. Furthermore, the findings highlight the importance of tailored interventions that take into account patient characteristics and preferences as factors that influence intention when designing such an intervention., Competing Interests: The authors declare that they have no competing interests, (© 2024 Alem and Gulema.)

Purpose: To study epidemiology, complications, risk factors, clinical course and treatment patterns of diabetes, the Nanjing Diabetes Cohort (NDC) was established using anonymised electronic health records from 650 hospitals and primary care since 2020. This cohort provides valuable data for researchers and policy-makers focused on diabetes management and public health strategies., Participants: Diabetes was defined as having inpatient or outpatient encounters with a diagnosis of diabetes International Classification of Diseases-9/10 codes, any use of insulin or oral hypoglycaemic drugs, or one encounter with haemoglobin A1C >4.8 mmol/mol or 6.5%. Patients with diabetes have been continuously enrolled on hospitals and primary care in Nanjing since 2020. Demographic, medications and comorbidities data were extracted from clinical notes, diagnostic codes, labs, prescriptions and vital signs among different types of diabetes., Findings to Date: The NDC consisted of 1 033 904 patients from 1 January 2020 to 31 December 2022, the majority were male (50.62%) and from the Gulou district (30.79%). The clinical characteristics and medication usage of patients with type 1 diabetes, type 2 diabetes, gestational diabetes and other diabetes were assessed. The prevalences of hypertension, ischemic heart disease, and cerebrovascular disease were 49.72%, 17.85% and 24.90%, respectively., Future Plans: NDC will annually enrol eligible patients and include socioeconomic data in future updates. The data of NDC are maintained by the Department of Medical Informatics at Nanjing Medical University., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Immune checkpoint inhibitor-related diabetes mellitus (ICI-DM) is a rare complication that medical oncologists seldom encounter in routine practice. The sporadic nature and intrinsic complexity of ICI-DM make it challenging to analyze comprehensively in experimental settings. In this review, we examine phase 3 clinical trials on ICIs and published case reports of ICI-DM, aiming to summarize its incidence, clinical features, management, and prognosis. Phase 3 clinical trials reveal that the incidence of ICI-DM is higher with combination therapies, such as anti-PD-1 and anti-CTLA-4 or anti-PD-L1, compared to anti-PD-1 monotherapy. ICI-DM typically presents as severe hyperglycemia with a fulminant onset and is often associated with diabetic ketoacidosis, accompanied by unexpectedly low HbA1c and C-peptide levels. ICI-DM shares similarities with classic type 1 diabetes, particularly in terms of autoimmunity and genetic predisposition. This includes a high prevalence of islet autoantibodies and susceptibility to certain HLA haplotypes, often with concurrent endocrine gland dysfunction. This suggests that genetic susceptibility and exposure to ICIs may both be necessary for triggering islet autoimmunity and inducing ICI-DM. Notably, patients with positive islet autoantibodies, such as glutamic acid decarboxylase antibody and islet-associated antigen 2 antibody, tend to experience rapid onset of ICI-DM after ICI exposure. Although patients with ICI-DM generally show a high objective response rate to immunotherapy, a significant proportion also face the need to permanently discontinued treatment. Further research is urgently needed to determine whether permanent discontinuation of immunotherapy is necessary and whether this discontinuation negatively impacts overall survival., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhou, Yang, Li, Xue and Wan.)

The field of peptide drug research has experienced notable progress, with stapled peptides featuring stabilized α-helical conformation, emerging as a promising field. These peptides offer enhanced stability, cellular permeability, and binding affinity and exhibit potential in the treatment of diabetes and metabolic disorders. Stapled peptides, through the disruption of protein-protein interactions, present varied functionalities encompassing agonism, antagonism, and dual-agonism. This comprehensive review offers insight into the technology of peptide stapling and targeting of crucial molecular pathways associated with glucose metabolism, insulin secretion, and food intake. Additionally, we address the challenges in developing stapled peptides, including concerns pertaining to structural stability, peptide helicity, isomer mixture, and potential side effects., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: In patients with diabetes and monoclonal gammopathy of uncertain significance (MGUS), the impact of glucagon-like peptide-1 (GLP-1) receptor agonists on the natural history of MGUS is unknown. We aimed to assess the association of GLP-1 receptor agonist use in the progression of MGUS to multiple myeloma in patients with diabetes., Methods: This is a population-based cohort study of veterans diagnosed with MGUS from 2006 to 2021 with a prior diagnosis of diabetes. A validated natural language processing algorithm was used to confirm MGUS and progression to multiple myeloma. We performed 1:2 matching for individuals with and without GLP-1 receptor agonist exposure. The Gray test was performed to detect the difference in cumulative incidence functions for progression by GLP-1 receptor agonist use status. The association between time-varying GLP-1 receptor agonist use and progression was estimated through multivariable-adjusted hazard ratio using a stratified Fine-Gray distribution hazard model, with death as a competing event and stratum for the matched patient triad., Results: Our matched cohort included 1097 individuals with MGUS who had ever used GLP-1 receptor agonists and the matched 2194 patients who had never used GLP-1 receptor agonists. Overall, 2.6% of individuals progressed in the GLP-1 receptor agonist ever use group compared with 5.0% in the GLP-1 receptor agonist never use group. Cumulative incidence functions were statistically significantly different between the exposed and unexposed groups (P = .02). GLP-1 receptor agonist use vs no use was associated with decreased progression to multiple myeloma (hazard ratio = 0.45, 95% confidence interval = 0.22 to 0.93, P = .03)., Conclusions: For patients with diabetes and MGUS, GLP-1 receptor agonist use is associated with a 55% reduction in risk of progression from MGUS to multiple myeloma compared with no use., (© The Author(s) 2024. Published by Oxford University Press.)

Introduction: In kidney transplant (KT) recipients diabetes mellitus (DM) are associated with an increased mortality and a poorer graft survival. Glucagon-like peptide 1 receptor agonists (GLP1-RA) have demonstrated cardiovascular and renal benefits in the general population. However, there is lacking evidence in KT recipients., Objective: To analyze the efficacy and safety of glucagon-like peptide 1 receptor GLP1-RA in a cohort of KT recipients., Methods: Multicenter retrospective cohort study of KT patients with DM who started subcutaneous GLP1-RA in 3 hospitals in the province of Cádiz between February 2016 and July 2022. Estimated glomerular filtration rate (eGFR), proteinuria, and weight at baseline and after 6 and 12 months were collected. We analyzed glycemic control, blood pressure, lipid profile, and doses and trough levels of tacrolimus. We document episodes of acute rejection (AR), de novo donor-specific antibodies (dnDSA), and adverse effects., Results: During this period, 96 KT with DM started treatment with GLP1-RA, of which 84 had a minimum follow-up of 6 months and 61 were followed for 12 months. A significant reduction was observed in proteinuria (-19.1 mg/g, p = 0.000; -46.6 mg/g, p = 0.000), weight (-3.6 kg, p = 0.000; -3.6 kg, p = 0.000), glycosylated hemoglobin (-0.7%, p = 0.000; -0.9%, p = 0.000), systolic blood pressure (-7.5 mmHg, p = 0.013; -7.3 mmHg, p = 0.004), total cholesterol (-11.5 mg/dL, p = 0.001; -15.6 mg/dl, p = 0.002) and LDL cholesterol (-9.2 mg/dl, p = 0.002; -16.8 mg/dl, p = 0.000) at 6 months and 1 year of follow-up. The eGFR remained stable and the dose and trough levels of tacrolimus did not change. No episodes of AR or development of dnDSA were observed during follow-up., Conclusions: GLP1-RA in KT patients can be a safe and effective option for the management of DM in KT., (Copyright © 2023 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Increasingly, pharmacists are asked to incorporate social determinants of health (SDoH) identification and referral into clinical practice. However, to date, no studies have evaluated clinical changes from embedding SDoH screening into the delivery of comprehensive medication management (CMM) in patients with chronic conditions., Objective: To examine the clinical effectiveness of implementing a clinical pharmacist-led SDoH screening and referral process as part of CMM encounters across a network of 7 Federally Qualified Health Centers (FQHCs)., Methods: We used a retrospective cohort design to evaluate the effectiveness of integrating SDoH screening into CMM across a network of 7 FQHCs. A difference-in-difference approach was used to compare the effectiveness of CMM between patients with and without SDoH needs on the probability of achieving clinical control for blood pressure (<140 systolic/90 diastolic mm Hg) and diabetes (<9% hemoglobin A1c)., Results: Among 807 patients receiving CMM in 2023, 595 (74%) were screened for SDoH. 55.1% of patients screened had 1 or more SDoH, most commonly facing barriers related to insurance (22.0%), language (11.3%), transportation (9.1%), health behaviors (7.1%), income/employment (5.9%), and food insecurity (5.6%). Comparing patients with SDoH needs with those without, the proportion of patients controlled at baseline was 66.3% vs 72.3% for hypertension and 39.0% vs 75.4% for diabetes, respectively. Following a CMM encounter, the proportion of patients who achieved blood pressure control increased 7.6% more ( P = 0.225) among patients with SDoH needs than in those without SDoH, whereas diabetes control rates increased 13.3% more ( P = 0.143)., Conclusions: Although not statistically significant, the results of this pilot evaluation suggest the potential for meaningful clinical improvements from screening and referral of SDoH needs as a part of CMM encounters. These results should be corroborated using a larger, more robust study design.

Introduction: The management of chronic diabetes mellitus and its complications demands customized glycaemia control strategies. Polypharmacy is prevalent among people with diabetes and comorbidities, which increases the risk of adverse drug reactions. Clinical decision support systems (CDSSs) may constitute an innovative solution to these problems. The aim of our study was to conduct a systematic review assessing the value of CDSSs for the management of antidiabetic drugs (AD)., Materials and Methods: We systematically searched the scientific literature published between January 2010 and October 2023. The retrieved studies were categorized as non-specific or AD-specific. The studies' quality was assessed using the Mixed Methods Appraisal Tool. The review's results were reported in accordance with the PRISMA guidelines., Results: Twenty studies met our inclusion criteria. The majority of AD-specific studies were conducted more recently (2020-2023) compared to non-specific studies (2010-2015). This trend hints at growing interest in more specialized CDSSs tailored for prescriptions of ADs. The nine AD-specific studies focused on metformin and insulin and demonstrated positive impacts of the CDSSs on different outcomes, including the reduction in the proportion of inappropriate prescriptions of ADs and in hypoglycaemia events. The 11 nonspecific studies showed similar trends for metformin and insulin prescriptions, although the CDSSs' impacts were not significant. There was a predominance of metformin and insulin in the studied CDSSs and a lack of studies on ADs such as sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists., Conclusion: The limited number of studies, especially randomized clinical trials, interested in evaluating the application of CDSS in the management of ADs underscores the need for further investigations. Our findings suggest the potential benefit of applying CDSSs to the prescription of ADs particularly in primary care settings and when targeting clinical pharmacists. Finally, establishing core outcome sets is crucial for ensuring consistent and standardized evaluation of these CDSSs., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Nour Elhouda TLILI reports financial support was provided by National Center for Precision Diabetic Medicine. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Paeoniflorin (Pae) can improve diabetes mellitus (DM), especially endothelial dysfunction induced by high glucose (HG). Molecularly, the mechanism pertinent to Pae and DM lacks further in-depth research. Hence, this study determined the molecular mechanism of Pae in treating DM through network pharmacology. The target of Pae was analyzed by TCMSP database, and DM-related genes were dissected by Genecards database and Omim database. PPI network was constructed for cross targets through Cytoscape 3.9.1 and STRING platform. GO and KEGG analyses were carried out on the cross targets. Protein molecular docking verification was completed by AutoDockTools and Pymol programs. Human umbilical vein endothelial cells (HUVECs) were separately treated with HG, Pae (5, 10, 20 μM) and/or HRAS overexpression plasmids (oe-HRAS). The cell viability, apoptosis and the protein expressions of HRAS and Ras-GTP were evaluated. There were 50 cross targets between Pae and DM, and VEGFA, EGFR, HRAS, SRC and HSP90AA1 were the key genes identified by PPI network analysis. GO and KEGG analyses revealed signal paths such as Rap1 and Ras. Molecular docking results confirmed that Pae had a good binding ability with key genes. In HG-treated HUVECs, Pae dose-dependently facilitated cell viability, attenuated cell apoptosis, and dwindled the expressions of HRAS and Ras-GTP, but these effects of Pae were reversed by oe-HRAS. In conclusion, Pae regulates the viability and apoptosis of HG-treated HUVECs by inhibiting the expression of HRAS.

Objectives: Diabetes mellitus is a metabolic condition with hyperglycemia. Literature has shown a correlation between poor sleep quality and duration with an increased incidence of insomnia in diabetic individuals. The goal of this study was to determine the magnesium and potassium supplementation effect among diabetic individuals with insomnia., Methods: A randomized controlled trial (single blind) was conducted on 320 patients with diabetes; after 2 months of follow-up, 290 patients completed the trial. The Insomnia Severity Index (ISI) was used to assess the severity and duration of insomnia, before and after the trial. Tablets containing supplements were prepared: placebo (T1), magnesium (Mg, T2), potassium (K, T3), and a combination of Mg and K (T4). Melatonin and cortisol (sleep hormones) were measured from blood (serum) using an enzyme-linked immunosorbent assay (ELISA), before and after the trial., Results: The study included 93 (32.1%) male and 197 (67.9%) female participants. According to the analysis, there was a significant association between the treatment groups and ISI after the trial (post-trial), p = 0.0001. Analysis showed that there was significant association between pre- and post-serum cortisol levels in treatment groups 2, 3, and 4 (T2, T3, and T4) as p -values are 0.001, 0.001, and 0.001 respectively. Similar findings were observed for serum melatonin., Conclusions: The study revealed that magnesium, potassium, and magnesium and potassium combined had a significant effect on serum cortisol and melatonin levels (sleep hormones). In addition, supplementation significantly decreased the severity of insomnia among patients with diabetes by improving sleep duration., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Khalid, Bashir, Mehboob, Anwar, Ali, Hashim, Waseem and Basharat.)

Objectives: Diabetes is closely associated with risk of stroke and its adverse sequelae. Approximately 20%-33% of patients with stroke have diabetes. In China, however, it is unclear how stroke affects healthcare utilisation, medications and complications among people with diabetes. This study aimed to analyse the clinical characteristics, treatment options, medical expenses and complications of hospital outpatient healthcare associated with stroke in patients with diabetes in China., Design: A retrospective, multicentre, observational study., Setting: Beijing Municipal Medical Insurance Database, with data from 2016 to 2018., Participants: The study included patients with diabetes whose data included 2016-2018 outpatient medication records and who had Beijing medical insurance. Patients who did not have continuous prescription records for more than 2 months were excluded from the analysis. In total, 2 853 036 people with diabetes were included, and patients who had and did not have a stroke were compared., Results: In our study, 19.75%-22.30% of patients with diabetes suffered from stroke between 2016 and 2018. The average annual medical cost for a patient diagnosed with diabetes is ¥9606.65, and the cost increases to ¥13 428.39 when diabetes was combined with stroke; thus, stroke increases the medical cost for patients with diabetes by 39.78% (p<0.0001). Among patients with diabetes who had a stroke, 4.76 medications were used (1.8 hypoglycaemic drugs and 2.97 non-hypoglycaemic drugs); these numbers were significantly greater than for patients with diabetes who did not have a stroke receiving both hypoglycaemic drugs and non-hypoglycaemic drugs (p<0.0001). Among patients with diabetes who did not have a stroke, 3.58 medications were used (1.66 hypoglycaemic drugs and 1.92 non-hypoglycaemic drugs). Patients with diabetes who had a stroke also had significantly greater incidences of diabetic peripheral neuropathy, diabetic kidney disease, diabetic retinopathy and diabetic angiopathy than those who did not have a stroke (p<0.0001). These drugs and costs increased with the number of complications (p<0.0001). The increased medical costs for each specific complication are also listed. We also analysed the medical costs and medication regimens stratified by sex, age group and complications., Conclusions: Stroke is associated with a significant increase in complications and medications for patients with diabetes and greatly adds to the economic burden of these patients. Early identification of stroke risk factors in patients with diabetes, as well as targeted poststroke diabetes management, is crucial from a socioeconomic perspective for a comprehensive management and treatment of stroke in patients with diabetes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)