Fasting blood glucose (FBG) is a significant risk factor for in-hospital mortality in acute coronary syndrome (ACS). This study examines the relationship between FBG levels and outcomes in ACS patients with different glycemic statuses.

Data from 50,365 ACS patients in the CCC-ACS Project (2014-2019) were analyzed in a prospective cohort study. Patients were categorized into three groups based on diabetes history and HbA1c levels: Group A (good), Group B (intermediate), and Group C (poor) glycemic status. A non-linear relationship between FBG and mortality was found. The lowest mortality risks were associated with FBG levels of 4.96 mmol/L (Group A), 5.71 mmol/L (Group B), and 7.44 mmol/L (Group C). Elevated FBG levels were linked to increased mortality risk in all groups: Group A (OR: 1.17), Group B (OR: 1.14), and Group C (OR: 1.10), all p < 0.001. The model showed moderate accuracy (AUC: 0.78 for Groups A/B, 0.80 for Group C)·In Group A, each unit increase in FBG raised the mortality risk by 1.08 times compared to Group B (OR: 1.08, 95 % CI: 1.03-1.14, p = 0.002) and by 1.07 times compared to Group C (OR: 1.07, 95 % CI: 1.03-1.12, p = 0.002).

In ACS patients, elevated FBG is an independent risk factor for in-hospital mortality, regardless of glycemic status. Different glycemic statuses have varied optimal glycemic targets. The effect of FBG on mortality differs across glycemic groups, with patients in good glycemic status facing the highest mortality risk as FBG increases.

The current study aimed to investigate which one or certain combinations of preoperative comorbidities were associated with higher risk of postoperative delirium.

This propensity-score-matched cohort study analyzed a retrospective dataset of elderly patients undergoing surgery at the First Medical Center of the Chinese PLA General Hospital from January 2014 to April 2019. Univariate risk factors were selected by logistic regression, and then the combinations of these univariate factors were compared.

We identified 1034 older patients developed postoperative delirium (POD) within seven days after surgery, and 3102 patients without POD were matched by propensity score matching analysis at a ratio of 1:3 for those with POD. Eight preoperative comorbidities, including hypertension, diabetes, atrial fibrillation, cerebrovascular disease, Parkinson's disease, epilepsy, depression, and chronic obstructive pulmonary disease (COPD) were more common in patients diagnosed with POD after surgery than those without POD. Patients with POD were more likely to concurrently suffer from the combinations of hypertension and cerebrovascular disease, or hypertension and COPD.

Several preoperative comorbidities are associated with a higher risk of POD in older surgical patient. Those suffering from combinations of preoperative comorbidities were more likely to develop POD, and hypertension plays a central role in these combinations.

Type 2 diabetes (T2D) is a persistent illness that has a high incidence rate. Still, there is no conclusive evidence on effectively improving blood sugar levels in patients through physical therapy. This study examined the regulatory effects of different intensities of low-intensity pulsed ultrasound (LIPUS) on T2D by stimulating brown adipose tissue (BAT). Eight-week-old C57BL/6J mice were divided into six groups (n = 10 per group): Control sham (C-Sham), Control-LIPUS (C-LIPUS), T2D-sham (T2D-Sham), T2D groups treated with LIPUS at spatial average-temporal-average intensity (Isata) of 60mW/cm² (T2D-L-60), 80mW/cm² (T2D-L-80), and 100mW/cm² (T2D-L-100). T2D models were induced by intraperitoneal injection of 40 mg/kg streptozotocin (STZ) three times after 12 wks of high-fat diet (HFD). The T2D-LIPUS group received LIPUS stimulation for 20 minutes per day for 6 weeks. The LIPUS stimulation had a duty cycle of 20%, a frequency of 1 MHz, and Isata of 60mW/cm², 80mW/cm², 100mW/cm². Subsequently, glucose tolerance tests (GTT) and insulin tolerance tests (ITT) were performed, and body fat content in mice was analyzed using nuclear magnetic resonance (NMR). Metabolic changes were monitored using metabolic cages. The results indicated that 80mW/cm² intensity level significantly improved glucose tolerance, insulin sensitivity, and metabolic function after LIPUS exposure. Significant reductions in body fat content and enhanced thermogenesis were observed, highlighting the potential of LIPUS in T2D management. This provides the basis for the dose study of LIPUS in the treatment of T2D.

The effects of sodium-glucose co-transporter 2 inhibitors (SGLT-2i) on dementia risk have not been assessed in the Chinese population. We aimed to assess the association between the use of SGLT-2i and dementia incidence in a mainland Chinese population.

A target trial of SGLT-2i vs. dipeptidyl peptidase 4 inhibitors (DPP-4i) was emulated, with cohorts of type 2 diabetes mellitus patients who were new users of SGLT-2i or DPP-4i being assembled using the Yinzhou Regional Health Care Database. Inverse probability of treatment weighting (IPTW) was applied to control potential confounding, and a Cox model was used to estimate the hazard ratio (HR) of the association between the use of SGLT-2i and incident dementia.

The final cohort included 47 335 new users of DPP-4i or SGLT-2i. In the primary analysis, the incidence of dementia was 500.2 and 347.5 per 100 000 person-years in users of DPP-4i and SGLT-2i, respectively. SGLT-2i use was associated with a reduced risk of incident dementia after adjusting for potential confounding using IPTW, with an HR of 0.74 (95% CI, 0.60-0.93). The results were generally consistent in various subgroup analyses and sensitivity analyses.

The use of SGLT-2i is associated with a decreased risk of dementia incidence in the study population in mainland China.

Nano-chaperones represent an innovative therapeutic approach targeting amyloid aggregation in Alzheimer's disease (AD) and Type-2 diabetes mellitus (T2DM), two diseases linked by similar pathogenic mechanisms involving protein misfolding and insulin resistance. Current treatments primarily address symptoms, yet nano-chaperones can potentially intervene at the molecular level by mimicking natural chaperone proteins to prevent or reverse amyloid aggregation. In AD, nano-chaperones target amyloid-beta (Aβ) peptides, reducing neurotoxicity and preserving neuronal function, while in T2DM, they inhibit islet amyloid polypeptide (IAPP) aggregation, alleviating cytotoxic stress on pancreatic β-cells. These nanoparticles exhibit a dual capacity for cellular penetration and selectivity in interacting with misfolded proteins, showing promise in mitigating the shared amyloidogenic pathways of both diseases. Preclinical studies have demonstrated significant reductions in amyloid toxicity with potential applications in crossing the blood-brain barrier (BBB) to enhance central nervous system (CNS) delivery. Nano-chaperones transformative role in developing multi-targeted precision therapies for complex diseases is highlighted, underscoring their capacity to modulate disease progression through targeted biomimetic interactions. Nano-chaperone designs for clinical application focus on enhancing therapeutic efficacy and safety. This innovative approach may redefine treatment paradigms for amyloid-related diseases, offering a new frontier in personalized medicine.

Diabetes imposes a global healthcare burden, with Type 2 Diabetes Mellitus (T2DM) escalating due to demographic shifts and lifestyle changes. Combination therapies offer promise in managing T2DM, yet patient adherence remains a challenge. This scoping review aims to explore patient adherence to combination therapies in T2DM management.

This scoping review followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews guidelines. Electronic databases including PubMed, Scopus, and Web of Science were searched until July 10, 2024. Studies focused on patients with T2DM prescribed oral combination therapies were included. Data extraction and synthesis were conducted to identify adherence patterns, influencers, and strategies.

The review identified nine eligible studies spanning from 2004 to 2021, primarily retrospective cohort and cross-sectional designs. Adherence assessment methods varied, with medication possession ratio being the most common. Both dual (loose-dose) and fixed-dose combination therapies were explored. Adherence rates varied across studies and therapies, influenced by factors such as glycemic control, weight management, economic considerations, complexity of regimens, and demographic factors. Bibliometric analysis revealed diverse geographic origins of the included studies and varied adherence assessment methods. Dual therapy regimens demonstrated adherence rates ranging from 49% to 80.8%, while FDC therapies showed adherence rates ranging from 60.3% to 98.9%. Factors influencing adherence included glycemic control, weight management, economic considerations, complexity of regimens, and demographic factors.

Patient adherence to oral combination therapies in diabetes management is complex, affected by clinical, economic, and psychosocial factors. Addressing these issues is crucial for enhancing treatment outcomes and alleviating the burden of diabetes. A patient-centered approach and innovative strategies can empower patients to adhere to medication regimens, improving health outcomes and quality of life.

Diabetic neuropathy (DN) is a prevalent and debilitating complication of diabetes mellitus, significantly impacting patient quality of life and contributing to morbidity and mortality. Affecting approximately 50% of patients with diabetes, DN is predominantly characterized by distal symmetric polyneuropathy, leading to sensory loss, pain, and motor dysfunction, often resulting in diabetic foot ulcers and lower-limb amputations. The pathogenesis of DN is multifaceted, involving hyperglycemia, dyslipidemia, oxidative stress, mitochondrial dysfunction, and inflammation, which collectively damage peripheral nerves. Despite extensive research, disease-modifying treatments remain elusive, with current management primarily focusing on symptom control. This review explores the complex mechanisms underlying DN and highlights recent advances in diagnostic and therapeutic strategies. Emerging insights into the molecular and cellular pathways have unveiled potential targets for intervention, including neuroprotective agents, gene and stem cell therapies, and innovative pharmacological approaches. Additionally, novel diagnostic tools, such as corneal confocal microscopy and biomarker-based tests, have improved early detection and intervention. Lifestyle modifications and multidisciplinary care strategies can enhance patient outcomes. While significant progress has been made, further research is required to develop therapies that can effectively halt or reverse disease progression, ultimately improving the lives of individuals with DN. This review provides a comprehensive overview of current understanding and future directions in DN research and management.

To determine the effect of red blood cell (RBC) lifespan variability on glycosylated hemoglobin (HbA1c) measurements in type 2 diabetes mellitus (T2DM) individuals and develop a mathematical model for adjusting HbA1c values.

We tracked glucose levels in 516 T2DM patients from Chu Hsien-I Memorial Hospital, categorized into Construction (n = 416) and Internal (n = 100) cohorts. Additionally, 165 participants from Tianjin diabetic retinopathy screening cohort, serving as the Independent cohort. RBC lifespan was determined using the CO breath test, and Hemoglobin glycation variation index (HGI) was calculated from the difference between measured and estimated HbA1c (eHbA1c). Model efficacy was evaluated using AUC, accuracy, sensitivity, and specificity.

An inflection in the HGI-RBC lifespan model occurred at 66 days, with HbA1c underestimation when RBC lifespan was below 90 days, notably in the ≤ 66 days group. This underestimation increased the risk of cardiovascular and peripheral neuropathy complications. To rectify the impact of the shorter RBC lifespan in T2DM patients, the correction formula was established as HbA1c(c) = -0.05629×RBC lifespan + 1.127×HbA1c + 3.178 (R = 0.7360) in the ≤ 66 day lifespan group and HbA1c(c) = -0.004772 × RBC lifespan + 0.7569 × HbA1c + 2.394 (R = 0.7344) in the 67 to 89 day group. The corrected HbA1c models exhibited satisfactory predictive performance in all cohorts.

Accurate adjustment for the effects of RBC lifespan on HbA1c values in T2DM patients is expected to enhance blood glucose management and the efficacious prevention and treatment of diabetes-associated complications.

Chu Hsien-I Memorial Hospital of Tianjin Medical University, identifier ChiCTR2100046557.

Aloe-emodin (AE) has drawn interest due to its potential activity against type II diabetes mellitus (T2DM). However, the mechanisms underlying its antidiabetic activity are not well explored. Using network pharmacology, molecular docking and molecular dynamics simulation studies, we investigated its molecular mechanisms in the management of T2DM. Potential target genes of AE were predicted using the Swiss Target Prediction (http://www.swisstargetprediction.ch/) database. The GeneCards, OMIM and DisGeNET databases were used to compile a comprehensive list of genes associated with T2DM. A compound-disease-target network was constructed, and protein-protein interaction networks were analysed to identify hub genes. Finally, molecular docking and interaction analysis between AE and the identified proteins were performed using AutoDock tools. Investigation of AE targets and genes associated with T2DM identified 32 overlapping genes. Gene ontology studies revealed that AE may exert its anti-diabetic effects by modulating glucose metabolism and enhancing cellular response to glucose. Furthermore, KEGG pathway analysis suggested that AE influences these processes by targeting pathways related to apoptosis, insulin resistance, and T2DM signaling. The core target proteins identified were TNF, ALB, TP53, PPARG, BCL2, CASP3, and EGFR. AE interaction with each of these proteins exhibited a binding energy of > - 5 kcal/mol, with TNF showing the lowest binding energy (- 7.75 kcal/mol). Molecular dynamics simulation further validated the molecular docking results with TNF and EGFR exhibiting a strong affinity for AE and forming stable interactions. AE exerts its antidiabetic activity through multiple mechanisms, with the most significant being the amelioration of pancreatic β-cell apoptosis by binding to and inhibiting the actions of TNFα. Further cellular and molecular studies are needed to validate these findings.

The online version contains supplementary material available at 10.1007/s40203-025-00337-1.

Pre-existing diabetes raises the likelihood of Parkinson's disease (PD), according to epidemiological and animal research. Our study aimed to investigating the likely neuroprotective effect of metformin (Met) and/or semaglutide (Sem) in model of PD in male diabetic rats and the possible underlying mechanism. Type 2 diabetes (T2DM) was induced by giving high-fat diet (HFD) for 3 weeks followed by a single streptozotocin (STZ) injection (40 mg/kg, i.p., once dose) followed by injection of 9 doses of rotenone every 48 ± 2 h for induction of PD. Met and/or Sema were administered to DM+PD via gastric gavage once daily for 4 weeks. In comparison with the DM+PD group, Met and/or Sem significantly lowered blood glucose levels, HOMA-IR, HbA1C, cholesterol, triglycerides, and LDL with significantly increased insulin and HDL levels. In addition, there was enhanced brain antioxidant status with lower oxidative-inflammatory stress biomarkers associated with improved rat cognitive, locomotor, and olfactory functions. A significant downregulation of caspase 3 and GFAP with concomitant upregulation of NRF2 protein expressions were observed in treated groups. Overall, co-treatment with Met and Sem elicited more efficacy than that of the individual regimen. When combined, the results of this study have demonstrated for the first time that Met and Sem work in concert to create neuroprotection in PD model of male diabetic rats compared to when taken separately. The study's findings indicate that Met and/or Sem have a restorative effect on T2DM and PD-induced changes in neurobehavioral and biochemical/molecular indices ascribed to the improvement of endogenous antioxidant systems, decreased lipid peroxidation, suppression of oxidative/inflammatory stress, and-most importantly-regulation of Nrf2 and caspase 3.

The association between dipeptidyl peptidase-4 inhibitors (DPP-4i) exposure and the risk of colorectal cancer (CRC) in patients with type 2 diabetes mellitus (T2DM) is unclear.

This meta-analysis aims to investigate the relationship between DPP-4i exposure and the incidence of CRC in patients with T2DM.

A systematic review and meta-analysis.

A comprehensive search of electronic databases, including PubMed, Web of Science, EMBASE, and ScienceDirect, was conducted up to March 2024. The studies including randomized clinical trials (RCTs), cohort studies, and case-control studies were retrieved. The odds ratio (OR) was calculated using Stata 12.0 statistical software. The primary outcome assessed was the incidence of CRC.

This meta-analysis incorporated six retrospective cohort studies and two case-control studies. The findings indicate that the incidence of CRC in the DPP-4i exposure group was significantly higher than that in the control group (OR = 1.11, 95% CI: 1.02-1.21, p = 0.013). Subgroup analysis revealed that both male (OR = 2.07, p < 0.001) and female participants (OR = 1.49, p = 0.05) in the DPP-4i exposure group exhibited a significantly higher incidence of CRC compared to the control group. Among participants younger than 65 years, the incidence of CRC was markedly elevated in the exposure group (OR = 2.81, p < 0.001). Furthermore, when the exposure duration was less than 1 year, the CRC incidence in the exposure group surpassed that of the control group (OR = 1.24, p = 0.005). When sulfonylureas (SU) were used as control drugs, the incidence of CRC was higher in the exposure group (OR = 1.10, p = 0.017).

There is a potential correlation between DPP-4i exposure and increased incidence of CRC in T2DM patients. This association appears to be influenced by gender, age, duration of exposure, and the choice of control medications. Therefore, attention should be paid to colorectal diseases when DPP-4i is employed in the clinic.

The meta-analysis has been registered with the International Prospective Register of Systematic Reviews (PROSPERO). The registration number is CRD42024535292.

This review explores the promising potential of repurposing type 2 diabetes (T2D) medications for the treatment of Parkinson's disease (PD), highlighting the shared pathophysiological mechanisms between these two age-related conditions, such as oxidative stress, mitochondrial dysfunction, and ferroptosis. The overlap suggests that existing diabetes drugs could target the common pathways involved in both conditions. Specifically, the review discusses how T2D medications, including metformin (Met), peroxisome-proliferator-activated receptor gamma (PPAR-γ) agonists, sodium-glucose cotransporter-2 (SGLT2) inhibitors, incretins, and dipeptidyl-peptidase 4 (DPP-4) inhibitors, can improve mitochondrial function, reduce neuroinflammation and oxidative stress, and potentially inhibit ferroptosis. The connection between ferroptosis and existing treatments, including diabetes medication, are only beginning to be explored. The limited data can be attributed also to the complexity of mechanisms involved in ferroptosis and Parkinson's disease and to the fact that the specific role of ferroptosis in Parkinson's disease pathogenesis has not been a primary focus until recent. Despite the promising preclinical evidence, clinical findings are mixed, underscoring the need for further research to elucidate these drugs' roles in neurodegeneration. Repurposing existing diabetes medications that have well-established safety profiles for Parkinson's disease treatment could significantly reduce the time and cost associated with drug development and could offer a more comprehensive approach to managing Parkinson's disease compared to treatments targeting a single mechanism.

People with type 2 diabetes mellitus who have clinical inertia often struggle to control their blood sugar levels and do not receive timely treatment intensification. Strict glycemic control has advantages, but many patients with diabetes are unable to reach their target blood sugar levels. The study's main objective was to determine the prevalence of clinical inertia in patients with type 2 diabetes at Debre Tabor Comprehensive Specialized Hospital(DTCSH) in Ethiopia.

An institutional based, cross-sectional research design was used at Debre Tabor Comprehensive Specialized Hospital from November 20/2023 to January 30/2024. A structured questionnaire modified from various medical records and literatures were used to gather data. A logistic regression model was also employed after the Hosmer-Lemeshow goodness-of-fit test was checked to find contributing variables to clinical inertia. A threshold of p < 0.05 was considered statistically significant.

In total, 287 samples were included in the research. The occurrences of clinical inertia 31.4% (95%CI: 25.9 - 36.8) were obtained from 90 patients. Aged patients (AOR = 1.103; 95% CI, 1.034 - 1.176; P = 0.003), medication fee (AOR = 4.955; 95% CI, 1.284 - 14.127; P = 0.020), medication nonadherence (AOR = 4.345; 95% CI, 2.457 - 15.537; P = 0.001), increase number of medication (AOR = 4.205; 95% CI, 2.657- 6.655; P ≤ 0.001), poor glycemic control (AOR = 2.253; 95% CI, 1.673 - 3.033; P ≤ 0.001) were more likely to have clinical inertia.

One-third of patients experienced clinical inertia. Age, glycemic control, medication non-adherence, treatment fee, and number of medications were found to be strongly correlated with clinical inertia. More precise knowledge of the clinical inertia and the associated therapies is necessary to tackle this issue more effectively.

Drug-loaded poly(lactic-co-glycolic acid) (PLGA) scaffolds were fabricated using a mold-less technique to investigate whether the combined delivery of both Y15 (FAK inhibitor) and metformin would result in enhanced effects on cell viability compared to the release of each drug alone for the treatment of platinum-resistant ovarian cancer (PROC).

Scaffolds were fabricated using an easy and economical mold-less technique that combined PLGA and the drugs (i.e. metformin and/or Y15) in tetraglycol and injected in PBS, to form a globular morphology.

The exposure of cells to metformin and Y15 resulted in a significantly enhanced cytotoxic efficacy compared to single-drug treatment with either metformin or Y15. When the drugs were delivered using the PLGA scaffolds, the combination of the two drugs was significantly more cytotoxic compared to scaffolds containing metformin only and Y15 only.

The combination of metformin and Y15 can result in an increase in antitumor activity in PROC cells through apoptosis. The delivery of both drugs from the PLGA biomaterial scaffold allowed for a more enhanced combinational effect compared to the utilization of free drugs (without a scaffold) and should be further explored as a promising treatment of PROC.

The aim of this review was to discuss the use and concerns of diabetes agents, clinical targets, and key aspects to be considered in the management of patients with type 2 diabetes mellitus (T2DM), and at high risk or established cardiovascular disease (CVD).

The recent European and American guidelines recommended SGLT2 inhibitors and GLP-1 receptor agonists as the preferred first-line diabetes agents in patients with T2DM and CVD. This is a paradigm shift from using metformin as first-line therapy. Amid their widespread use, however, there are also concerns about their side effects. With the rapidly growing diabetes regimens available, questions arise about how best to approach the management of patients with T2DM and CVD.

To reduce CVD morbidity and mortality in patients with T2DM and at high or very high risk for CVD, the two key diabetes agents SGLT2i and/or GLP1-based therapies should be offered. Although lacking cardiovascular benefit, other diabetes agents remain necessary for many patients with T2DM for their glucocentric effects; Metformin and pioglitazone are useful in severe insulin resistance, while insulin therapy is often necessary in advanced diabetes; GLP1-RA is cautioned in patients with active gastrointestinal and mental health conditions, while DPP4 inhibitor is likely a well tolerated option in a challenging psychosocial setting. Other important aspects that should be considered include obesity, chronic kidney disease, women's cardiovascular health, and psychosocial factors.

Background Type 2 diabetes mellitus (T2DM) is a prevalent chronic metabolic disease in Saudi Arabia, with a prevalence rate of approximately 25%. Traditional blood glucose monitoring methods, such as finger stick tests, provide limited insights into blood glucose measurements and fluctuations contributing to clinical inertia. The advent of continuous glucose monitoring (CGM) systems, such as the FreeStyle Libre glucose monitoring system, has transformed diabetes management by offering comprehensive exposure of glucose data to healthcare providers. Objective This study aims to evaluate the impact of the FreeStyle Libre glucose monitoring system on diabetes management intensification and treatment progression provided by healthcare specialists among T2DM patients in primary healthcare settings in Riyadh, Saudi Arabia. Methods An observational, retrospective, 24-week, two-arm study was conducted at Prince Sultan Military Medical City. The study involved 188 T2DM patients who were either using standard capillary glucose monitoring or transitioned to the FreeStyle Libre system, and it was based on clinical discretion rather than randomization. The primary outcomes were to evaluate the effect of FreeStyle Libre on treatment intensification provided by healthcare providers and changes in HbA1c levels. Data analysis included descriptive statistics and hypothesis testing using R software. Results Participants using the FreeStyle Libre glucose monitoring system experienced higher rates of medication intensification, and the use of insulin correction doses, and a significant reduction in median HbA1c levels was observed at three months (9.19% vs. 9.6%, p=0.047). However, at six months, the median HbA1c further reduced to 9.07%, though the difference between groups was not statistically significant. Despite these improvements, healthcare provider visits due to hyperglycemia were higher in the FreeStyle Libre group (p<0.001). There were no significant differences in hypoglycemia-related visits between the two groups (p=0.09). Conclusion The FreeStyle Libre glucose monitoring system was associated with increased treatment intensification and a significant reduction in HbA1c at three months compared to standard glucometers. However, by six months, the reduction in HbA1c was no longer statistically significant between groups. The increased healthcare provider visits in the FreeStyle Libre group may be attributed to heightened glucose monitoring awareness rather than the true worsening of hyperglycemia. While CGM offers advantages in diabetes management, its impact on long-term glycemic control remains uncertain. Further research is needed to confirm these findings, assess patient adherence, and evaluate the long-term effectiveness of continuous glucose monitoring in diabetes care.

Hepatic insulin resistance is a fundamental phenomenon observed in both Type 2 diabetes (T2D) and metabolic (dysfunction) associated fatty liver disease (MAFLD). The relative contributions of nutrients, hyperinsulinemia, hormones, inflammation, and other cues are difficult to parse in vivo as they are convoluted by interplay between the local and systemic events. Here, we used a well-established human liver microphysiological system (MPS) to establish a physiologically-relevant insulin-responsive metabolic baseline and probe how primary human hepatocytes respond to controlled perturbations in insulin, glucose, and free fatty acids (FFAs).

Replicate liver MPS were maintained in media with either 200 pM (normal) or 800 pM (T2D) insulin for up to 3 weeks. Conditions of standard glucose (5.5 mM), hyperglycemia (11 mM glucose), normal (20μM) and elevated FFA (100 μM), alone and in combination were used at each insulin concentration, either continuously or reversing back to standard media after 2 weeks of simulated T2D conditions. Hepatic glucose production, activation of signaling pathways, insulin clearance, transcriptome analysis, and intracellular lipid and bile acid accumulation were assessed.

Hyperinsulinemia alone induces insulin resistance after one week of exposure, while hyperglycemia and increased FFAs significantly exacerbate this phenotype. Hyperinsulinemia, along with elevated glucose and FFAs, transcriptionally predisposes hepatocytes to insulin resistance through altered metabolic and immune signaling pathways. The phenotypes observed in hyperinsulinemia and nutrient overload are partially reversible upon return to normophysiologic conditions.

Our enhanced in vitro model, replicating multiple aspects of the insulin-resistant condition, offers improved insights into disease mechanisms with relevance to human physiology.

To evaluate the efficacy and safety of add-on dapagliflozin in patients with type 2 diabetes mellitus (T2D) who had inadequate glycaemic control with metformin and linagliptin.

A total of 235 patients with inadequate response to metformin (≥1000 mg/day) plus linagliptin (5 mg/day) were randomized to receive either dapagliflozin/linagliptin fixed-dose combination (FDC [AJU-A51]) 10/5 mg/day (n = 117) or linagliptin 5 mg plus placebo (n = 118) for 24 weeks. After the main treatment period, patients who received linagliptin plus placebo were treated with AJU-A51 for an additional 28 weeks. Change in glycated haemoglobin (HbA1c) from baseline to Week 24 was the primary endpoint.

AJU-A51 significantly reduced HbA1c levels (from 7.93% ± 0.82% to 7.11% ± 0.61%) compared with linagliptin plus placebo (from 7.80% ± 0.71% to 7.87% ± 0.94%), with a least squares mean difference of -0.88% (95% confidence interval -1.07 to -0.68; p < 0.0001) at 24 weeks. The AJU-A51 group had a significantly higher proportion of patients who achieved HbA1c <7.0% at Week 24 than the control group (44.8% vs. 18.6%; p < 0.001). The AJU-A51 group maintained glycaemic efficacy up to 52 weeks, whereas the control group showed a substantial reduction in HbA1c after switching to AJU-A51 in the extension study period. Both groups had similar incidence of treatment-emergent and serious adverse events, and no cases of symptomatic hypoglycaemia were reported.

Dapagliflozin and linagliptin FDC (AJU-A51) showed potent glucose-lowering effects, with good tolerability, in patients with T2D who had poor glycaemic control on metformin and linagliptin (ClinicalTrials.gov [NCT06329674]).

Introduction: Concerns have been raised that glucagon-like peptide 1 receptor agonists (GLP1-RAs) may increase the risk of thyroid cancer, but evidence remains conflicting. We therefore investigated if GLP1-RA use, compared with use of dipeptidyl peptidase-4 inhibitors (DPP-4is), was associated with thyroid cancer risk in patients with type 2 diabetes. Methods: This multisite cohort study with subsequent meta-analysis included six population-based databases from Canada (Ontario), Denmark, Norway, South Korea, Sweden, and Taiwan. Study populations comprised patients with type 2 diabetes between 2007 and 2023. Cox regression models estimated hazard ratios (HR) and 95% confidence intervals (CIs) for thyroid cancer among GLP1-RA users compared with DPP-4is. Models were weighted using standardized mortality ratio weights generated from time-specific propensity scores. Site-specific HRs were pooled using a fixed-effects model. Results: We identified 98,147 users of GLP1-RA and 2,488,303 users of DPP-4i, with the median follow-up among users of GLP1-RA ranging from 1.8 to 3.0 years. Overall, use of GLP1-RA relative to use of DPP-4i was not associated with an increased risk of thyroid cancer (pooled weighted HR 0.81, CI 0.59-1.12). Similarly, we observed no increased risk in thyroid cancer with increasing cumulative dose of GLP1-RA among GLP1-RA ever-users. Subgroup analysis of types of thyroid cancer was not possible. Results remained consistent across a range of supplementary analyses. Discussion: In this large multisite study, utilizing data from six population-based databases, we found no evidence that GLP1-RA use is associated with an increased risk of thyroid cancer with follow-up ranging from 1.8 to 3.0 years, providing some reassurance to patients and clinicians about the short-term safety of these drugs. Nevertheless, evidence was insufficient to rule out excess risk with long-term use, due to the short follow-up.

The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, an interprofessional expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.

According to most guidelines, dietary interventions are essential in the management of diabetes. Fasting has emerged as potential therapeutic regimes for diabetes. The proof-of-concept study and the fasting in diabetes treatment trial are the first to explore the clinical impact of the Fasting Mimicking Diet (FMD) in patients with type 2 diabetes mellitus. Their results showed that FMD cycles improve glycemic management and can be integrated into usual care complementary to current guidelines. This economic evaluation aims to assess the 10-year quality-of-life effects, cost implications, and cost-effectiveness of adding a 3-year FMD program to diabetes standard care in diabetic population on dual or triple medications at baseline from the perspective of the US payer.

We constructed a microsimulation model in TreeAge using a published US-specific diabetes model. The model was populated using FMD effectiveness outcomes and publicly available clinical and economic data associated with diabetes complications, use of diabetes medications, hypoglycemia incidence, direct medical costs in 2021 USD, quality of life, and mortality. All benefits were discounted by 3%.

This cost-utility analysis showed that the FMD program was associated with 11.4% less diabetes complications, 67.2% less overall diabetes medication use, and 45.0% less hypoglycemia events over the 10-year simulation period. The program generated an additional effectiveness benefit of 0.211 quality-adjusted life year and net monetary benefit of 41 613 USD per simulated patient. Thus, the FMD program is cost saving.

These results indicate that the FMD program is a beneficial first-line strategy in T2DM management.

Objective. In this retrospective observational study, we aimed to evaluate the impact of insulin degludec/insulin aspart (IDegAsp) treatment on glycemic status, metabolic parameters, and weight/body mass index (BMI) change at a single tertiary diabetes center in Turkey. Methods. We conducted a retrospective cohort study of patients with type 2 diabetes who received IDegAsp treatment between October 2018 and November 2019 at the diabetes outpatient clinic. The patients who had inadequate responses (HbA1c ≥8%) to at least 3 months of experienced insulin (± oral antidiabetic drug [OAD]) treatment were included into the study. Results. One hundred patients (61% females) with a mean age of 61.7±10.0 years (range; 39-88 years) were analyzed. Mean fasting plasma glucose and HbA1c levels decreased by 3rd, 6th, 9th, and 12th months (p=0.010, p=0.007, p=0.027, and p=0.090, respectively and p<0.001, p<0.001, p<0.001, and p=0.001, respectively). Mean body weight and BMI values increased in the 3rd (83.1±15.6 kg and 31.6±5.7 kg/m2, repecitvely) and 6th (87.0±15.4 kg and 32.3±5.3 kg/m2, resepctively) months, although the changes were not statistically significant (p=0.10 and p=0.08, respectively). However, mean body weight returned to baseline levels by the 9th (80.8±17.0 kg and 30.5±6.4 kg/m2, respectively) and 12th (79.5±13.5 kg and 30.5±5.7 kg/m2, respectively) months (p=0.074 and p=0.400, respectively). Conclusions. IDegAsp can provide a significant decrease in HbA1c in a real-life setting. Although weight gain was observed in the first months of the treatment, this effect disappeared over time and decreased to the baseline levels.

A double bond between the nitrogen and carbon atoms characterizes a wide class of compounds known as Schiff bases. The flexibility of Schiff bases is formed from several methods and may be combined with alkyl or aryl substituents. The group is a part of organic compounds, either synthetic or natural, and it serves as a precursor and an intermediate in drugs that have therapeutic action. The review focuses on molecular docking and structure-activity relationship (SAR) analysis for antidiabetic effects of the different nonmetal Schiff bases. Many studies have found that Schiff bases are used as linkers in an extensive range of synthesized compounds and other activities. Thus, this current study aims to give the scientific community a thoughtful look at the principal ideas put forward by investigators regarding antidiabetic actions exhibited by certain Schiff-based derivatives, as this review covered many aspects, including docking and SAR analysis. For individuals who intend to create novel antidiabetic compounds with Schiff bases as pharmacophores or physiologically active moieties, it will be an invaluable informational resource.

Rates of obesity continue to rise, including in older adults. Use of medication for obesity in the elderly has been considered controversial, due to concerns around potential progression of age-related sarcopenia and a general lack of evidence for its use in this age group. Within this review, we describe the general considerations when prescribing obesity pharmacotherapy for older adults living with obesity. We evaluate in detail the anti-obesity medications currently licenced in Europe, with emphasis on the available efficacy, safety and cardiovascular outcome data gathered from study of older people. Finally, we discuss future directions and avenues of research.

The focus on repurposing readily available, well-known drugs for new, creative uses has grown recently. One such medication is metformin, a drug commonly used to manage diabetes, which shows a favorable correlation between its use and lower cancer morbidity and death. Numerous investigations and clinical trials have been conducted to evaluate the possible application of metformin as an anticancer medication in light of this conclusion.

This study used 'pathway/gene-set analysis' Gene2drug, a resource for Gene Ontology (GO), and DepMap to determine whether metformin would be potentially advantageous for treating cancer.

A total of 1826 tumor cell lines were analyzed using the Drug Sensitivity (Primary Purposing Primary Screening) 19Q4 Tool.

9 genes from 402 genes, SGPL1, CXCR6, ATXN2L, LAMP3, RTN3, BTN2A1, FOXM1, NQO1, and L1TD1 in 1826 cancer cell line showed statistical sensitivity to metformin.

This in-silico study showed the sensitivity of specific cancer cell lines to metformin. Therefore, holding promises for metformin and tumor-targeted treatment strategies. It is recommended, however, to conduct further research into its potential effectiveness and mechanism of action.

Diabetes Mellitus (DM) is the most hazardous public health challenge requiring engineering study to prevent disease complications. In this paper, a Sorensen-based diabetic model is presented in which the insulin-glucose process of a Type 1 patient is maintained by considering other factors such as physical characteristics and changes in mental aspects of the diabetic patient. The purpose of the research is to include a non-linear model of a patient with diabetes who is affected by stress, meals, exercise, and Insulin Sensitivity (IS), and a suitable RECCo controller is designed as a notable recent innovation that implements the concept of ANYA fuzzy rule-based system, which is an online adaptive type of controller that is used in this research work with an uncertainty case of the condition, where the blood glucose must be regulated. To ensure the performance of the proposed controller, a simple insulin pump is designed in a practical case, and a hardware experiment is conducted. The result of the hardware is analyzed and shows the success of the implementation of the controller in blood glucose regulation, thereby preventing complications such as hypoglycemia and hyperglycemia. The comparison analysis of RECCo was performed with other types of controllers, such as MPC and MRAC. The accuracy of the model was validated using the N-BEATS algorithm with a data-set collected from the simulated model, which is around 98%.

In the ACCORD study, participants with the haptoglobin (Hp) 2-2 phenotype and glycated hemoglobin (HbA1c) ≥ 8.0% had a higher risk of coronary artery disease (CAD) compared to those with HbA1c 7.0-7.9%. However, this association was not observed in participants without the Hp2-2 phenotype. The optimal glycemic target for CAD prevention for the Hp phenotypes remains uncertain and may vary based on demographic and clinical factors.

To investigate how reaching clinically relevant HbA1c targets relates to the risk of CAD in different Hp phenotype groups among a diverse cohort of individuals with T2DM (the Look AHEAD study, HbA1c ≤ 11% at baseline).

Cox regression models with time-varying covariables were used to quantify the association between time-varying achieved HbA1c (< 6.5%, 6.5-6.9%, and ≥ 8.0% compared to 7.0-7.9%), updated at years 1-4, 6, 8, and 10, and incident CAD in the Hp2-2 (n = 1,587) and non-Hp2-2 (n = 2,944) phenotypes separately. Further pre-specified subgroup analyses by age, sex, history of cardiovascular disease (CVD), race, and diabetes duration were performed in each Hp phenotype group separately.

Compared with HbA1c 7.0-7.9%, having HbA1c < 6.5% was associated with a 29% lower CAD risk among participants with the non-Hp2-2 phenotype (adjusted HR 0.71, 95% CI 0.55-0.90). In subgroup analyses, this association was present in participants with the non-Hp2-2 phenotype who were male (0.60, 0.44-0.83), who did not have a history of CVD (0.65, 0.47-0.90), who were aged ≥ 65 years (0.64, 0.44-0.94), who were White (0.68, 0.51-0.91), or who had diabetes duration > 10 years (0.58, 0.35-0.95). HbA1c ≥ 8.0% was associated with CAD risk only among participants with the Hp2-2 phenotype who had a history of CVD (1.79, 1.00-3.20). No associations were found between the other HbA1c targets and CAD risk when participants with the Hp2-2 phenotype were grouped together or divided into subgroups.

The differences in our results compared to our previous findings may be due to variations in the study populations and factors associated with weight loss, making it difficult to draw definitive conclusions. Our current findings should be considered in the context of hypothesis generation, and ideally, will encourage additional research in this field.

Bone fragility is a recognized complication of type 2 diabetes mellitus (T2DM), increasing patient morbidity. Thus, the development of an effective intervention to prevent diabetic bone fragility is urgently needed. As lifestyle intervention represents an effective option for diabetes management, it may have an impact on bone health. While studies have shown a beneficial effect of dietary fiber in T2DM management, its effect on bone health is still unclear. Thus, we investigated the impact of a high-fiber diet on bone and glucose control in men and women with T2DM. Forty-five T2DM patients (HbA1c: 6.5% ± 0.49%, age: 74 ± 7.29 yr) scheduled for hip arthroplasty were randomly assigned to follow a high-fiber diet (38 g/day) or to make no diet changes for 12 wk. Interestingly, BMI decreased by 4% (p <.0001) and HbA1c by 3.4% (p <.0001) in the high-fiber diet group, but did not decrease in the control group. However, serum concentration of the bone formation marker procollagen type 1 amino-terminal propeptide (P1NP) decreased by 8.6 % in the high-fiber diet group (p =.0004), whereas it remained unchanged in the control group. In contrast, similar to the control group, serum concentration of the bone resorption marker C-terminal telopeptide of type I collagen (CTX) concentrations did not change in the high-fiber diet group. Bone microCT analysis revealed no changes in trabecular and cortical bone parameters between the high-fiber diet and control groups. Similarly, real-time (RT)-PCR analysis in bone tissue showed no changes in the gene expression of Wnt pathway-related genes (Sost, Dkk-1, Wnt10b, and Lef-1), bone formation markers (Runx2, Col1a1, and Ocn), and inflammatory cytokines (IL-6, IL-8, TNF-α, and IL-10) between the two groups. Our findings suggest that 12-wk high-fiber diet intervention improves metabolic outcomes in patients with T2DM. However, it may reduce bone formation without affecting bone microarchitecture or Wnt pathway regulation.

Cetagliptin is a novel dipeptidyl peptidase-4 (DPP-4) inhibitor developed for the treatment of patients with type 2 diabetes (T2D). Several phase 1 studies have been conducted in China. Modelling and simulation were used to obtain cetagliptin dose for phase 3 trials in T2D patients.

A pharmacokinetic (PK)/pharmacodynamic (PD) model and model-based analysis of the relationship between hemoglobin A1c (HbA1c) and dosage was explored to guide dose selection of cetagliptin for phase 3 trials. The PK/PD data were derived from four phase 1 clinical studies, and sitagliptin 100 mg was employed as a positive control in studies 1, 3, and 4.

The PK profiles of cetagliptin were well described by a two-compartment model with first-order absorption, saturated efflux, and first-order elimination. The final PD model was a sigmoid maximum inhibitory efficacy (Emax) model with the Hill coefficient. The final model accurately captured cetagliptin PK/PD, demonstrated by goodness-of-fit plots. Based on weighted average inhibition (WAI), the relationship between HbA1c and dose was well displayed. Cetagliptin 50 mg once daily or above as monotherapy or as add-on therapy appeared more effective in HbA1c reduction than sitagliptin 100 mg. Cetagliptin 50 mg or 100 mg once daily was selected as the dose for phase 3 trials of cetagliptin in T2D patients.

The PK/PD model supports dose selection of cetagliptin for phase 3 trials. A model‑informed approach can be used to replace a dose-finding trial and accelerate cetagliptin's development.

This nationwide cohort study evaluated the impact of sodium-glucose co-transporter-2 inhibitors (SGLT2i) on patients with type 2 diabetes mellitus (T2DM) after ischaemic stroke (IS), aiming to compare clinical outcomes between SGLT2i-treated patients and those not receiving SGLT2i.

Utilizing Taiwan's National Health Insurance Research Database, we identified 707 patients with T2DM treated with SGLT2i and 27 514 patients not treated with SGLT2i after an IS, respectively, from 1 May 2016 to 31 December 2019. Propensity score matching was applied to balance baseline characteristics. The follow-up period extended from the index date (3 months after the index acute IS) until the independent occurrence of the study outcomes, 6 months after discontinuation of the index drug, or the end of the study period (31 December 2020), whichever came first.

After propensity score matching, compared with the non-SGLT2i group (n = 2813), the SGLT2i group (n = 707) exhibited significantly lower recurrent IS rates (3.605% per year vs. 5.897% per year; hazard ratio: 0.55; 95% confidence interval: 0.34-0.88; p = 0.0131) and a significant reduction in all-cause mortality (5.396% per year vs. 7.489% per year; hazard ratio: 0.58; 95% confidence interval: 0.39-0.85; p = 0.0058). No significant differences were observed in the rates of acute myocardial infarction, cardiovascular death, heart failure hospitalization, or lower limb amputation.

Our findings indicate significantly lower risks of recurrent IS and all-cause mortality among patients with T2DM receiving SGLT2i treatment. Further studies are required to validate these results and investigate the underlying mechanisms behind the observed effects.

Insulin utilization pattern varies greatly in type 2 diabetes mellitus (T2DM) patients. Clinical inertia in treatment intensification hinders glycemic control in T2DM management. This study investigated insulin prescription trends and various predictors among insulin naive, user, and insulin inertia (II) patients in T2DM.

A retrospective analysis of T2DM patient records from the diabetes clinic at a tertiary care center was conducted. Data on socio-demographics, anthropometry, disease characteristics, comorbidities, adherence, and medication prescribing patterns were collected. Analysis was done using tests of significance, odds ratio (OR), and multivariate logistic regression.

A total of 950 records were analyzed, with 17.3% of patients identified as insulin users (IU), 70.9% being insulin-naïve (IN), and 11.8% having II. IUs had significantly higher glycemic levels including HbA1c, fasting, postprandial, and random blood sugars compared to the other groups. Higher HbA1c levels were associated with significantly increased odds of insulin usage (OR: 3.46, confidence interval (CI): 1.94-6.16), while individuals taking sulfonylureas had lower odds of insulin usage (OR: 0.27, CI: 0.08-0.91). A significant association was also seen with the total number of oral antidiabetic drugs prescribed (four drugs; OR: 15.6, and five drugs; OR: 9.1). Other factors did not show a significant association. The regression model showed HbA1c level as low as 7.9% could indicate a future insulin requirement in 22% of patients.

The study outlines differences in characteristics and parameters among T2DM patients who require or do not require insulin and highlights the challenges in insulin initiation in Indian T2DM patients. Findings on II underscore the need for timely treatment intensification.

The impact of comprehensive risk factor control on heart failure (HF) risk and HF-free survival time in individuals with type 2 diabetes (T2D) was evaluated in this study.

This prospective study included 11,949 individuals diagnosed with T2D, matched with 47,796 non-T2D control study participants from the UK Biobank cohort. The degree of comprehensive risk factor control was assessed on the basis of the major cardiovascular risk factors, including blood pressure, BMI, LDL cholesterol, hemoglobin A1c, renal function, smoking, diet, and physical activity. Cox proportional hazards models were used to measure the associations between the degree of risk factor control and HF risk. Irwin's restricted mean was used to evaluate HF-free survival time.

During a median follow-up of 12.3 years, 702 individuals (5.87%) with T2D and 1,402 matched control participants (2.93%) developed HF. Each additional risk factor controlled was associated with an average 19% lower risk of HF. Optimal control of at least six risk factors was associated with a 67% lower HF risk (hazard ratio [HR] 0.33; 95% CI 0.20, 0.54). BMI was the primary attributable risk factor for HF. Notably, the excess risk of HF associated with T2D could be attenuated to levels comparable to those of non-T2D control participants when individuals had a high degree of risk factor control (HR 0.66; 95% CI 0.40, 1.07), and they exhibited a longer HF-free survival time.

Comprehensive management of risk factors is inversely associated with HF risk, and optimal risk factor control may prolong HF-free survival time among individuals with T2D.

Through the lens of self-determination theory, this quantitative study investigates how patient-provider collaboration through perceived shared decision-making (SDM) and autonomy support impact type 2 diabetes (T2D) outcomes.

We sampled 474 individuals over 18 years old who self-identified as having T2D. Completed and valid responses were received from 378 participants from two separate groups in an online survey. Data was analyzed using the IBM Statistical Package for Social Sciences (SPSS), AMOS package, version 28, and Mplus, version 8.8.

Patient-provider collaboration through autonomy support improved treatment satisfaction (β = .16, ρ < .05) and self-management adherence (β = .43, ρ < .001). While collaboration through SDM improved treatment satisfaction (β = .25, ρ < .01), it worsened SM adherence (β = -.31, ρ < .001). The negative impact of SDM on self-management adherence was mitigated by our moderator, coping ability. However, coping ability minimally impacted treatment satisfaction and SM adherence when autonomous support was provided.

Autonomy support increases treatment satisfaction and self-management adherence. SDM enhances treatment satisfaction but may adversely affect self-management adherence. The study also suggests that coping ability can mitigate the negative effect of SDM on self-management adherence, although its influence is limited when autonomy support is provided by the provider.

For providers, SDM and autonomy support permits shared power over treatment decisions while fostering independence over self-management tasks. Providers should evaluate patients' coping ability and adapt their approach to care based on the patient's coping capacity.

To provide an overview of the primary outcomes and key clinical implications of the CANVAS Program and CREDENCE trial, which were event-driven, double-blind randomized controlled trials that established the efficacy and safety of canagliflozin in those with type 2 diabetes (T2D) and high cardiovascular risk (CV) or albuminuric chronic kidney disease (CKD).

The CANVAS programme (CANVAS and CANVAS-R trials) randomized 10 142 people with T2D and high CV risk to canagliflozin or placebo and followed them for a median of 126 weeks. The primary efficacy outcome was met, with canagliflozin treatment associated with a 14% reduction in major adverse CV events (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.75 to 0.97; p < 0.001) as compared to placebo. The CREDENCE trial randomized 4401 individuals with T2D and albuminuric CKD to canagliflozin or placebo and followed them for 109 weeks. The CREDENCE trial also met its primary endpoint; canagliflozin treatment was associated with a 30% reduction in the composite of kidney failure, sustained doubling of serum creatinine level, or death from kidney or CV causes (HR 0.70, 95% CI 0.59 to 0.82; p < 0.001). Substantial reductions in hospitalization for heart failure (CANVAS: HR 0.67, 95% CI 0.52 to 0.87; CREDENCE: HR 0.61, 95% CI 0.47 to 0.80) and other key CV and kidney outcomes were also identified. Relative clinical benefits were consistent across subgroups defined by baseline age, sex, kidney function and history of CV disease but absolute benefits were greatest in those at highest baseline risk. Total serious adverse events were less common with canagliflozin treatment. Concerns about amputation and fracture risk observed in the CANVAS Program were not seen in CREDENCE and appear to have been spurious chance findings.

Canagliflozin reduced important CV, kidney and mortality outcomes in those with T2D and high CV risk or CKD across diverse patient groups, with a good safety profile. Taken together with the other sodium-glucose cotransporter-2 inhibitor CV and renal outcomes trials, these landmark findings have changed the treatment landscape for patients worldwide.

The continual increase in global diabetic statistics portends decreased productivity and life spans, thus making it a disease of concern requiring more effective and safe therapeutic options. While several reports on antidiabetic plants, including Hura crepitans, are available, there is still a dearth of information on the holistic antidiabetic properties of H. crepitans and its associated complications. This study evaluated the antidiabetic potential of methanolic extract of Hura crepitans using in vitro, in vivo, and in silico approaches. The extract revealed a dose-dependent in vitro effect, with a 47.97 % and 65.34 % decrease in the fasting blood sugar levels of streptozotocin (STZ) induced diabetic rats at 150 and 300 mg/kg BW, respectively. Likewise, the extract increased serum and pancreatic insulin levels, and significantly ameliorated neuronal oxidative stress and inflammation by reducing the expression levels of cholinesterase, NF-κB, and COX-2 in the brain of hyperglycemic rats. Serum dyslipidemia, liver, and kidney biomarker indices, and hematological alterations in diabetic rats were also significantly attenuated by the extract. Several constituents, mainly terpenes, were identified in the extract. To further predict the drug-likeness, pharmacokinetics, and binding properties of the compounds, in silico analysis was conducted. Ergosta-2,24-dien-26-oicacid,18-(acetyloxy)-5,6-epoxy-4, 22-dihydroxy-1-oxo-,delta.-lactone-4.beta., displayed the highest docking scores for acetylcholinesterase, butyrylcholinesterases, alpha-amylase, and nuclear factor-kB with values of -12.4, -10.9, -10.3, and -9.4 kcal/mol, while ergost-25-ene-6,12-dione,3,5-dihydroxy-, (3.beta.,5.alpha.) topped for cyclooxygenase-2 (-9.0 kcal/mol). The top-ranked compounds also presented significant oral drug-likeness, pharmacokinetics, and safety properties. Altogether, our data provide preclinical evidence of the potential of Hura crepitans in ameliorating diabetes and its associated complications.

Many Australian adults are not receiving timely or effective diabetes management to prevent or delay the onset of diabetes related complications. Integrated care, a worldwide trend in healthcare reform, aims to reduce the fragmented delivery of health services and improve outcomes. This study aimed to test whether a specialist-led integrated model of care provided to a small subset of patients in general practices leads to spillover clinical improvements in all patients of the practice with type 2 diabetes.

Seventy-two general practice sites (clusters) in New South Wales, Australia received the Diabetes Alliance intervention, creating a non-randomised open cohort stepped wedge trial. The intervention comprised of case conferencing, delivered directly to a small proportion of adults with type 2 diabetes (n = 1,072) of the general practice sites; as well as practice feedback, education and training. Spillover clinical improvements were assessed on all adults with type 2 diabetes within the general practice sites (n = 22,706), using practice level data recorded in the MedicineInsight electronic database, compared before and after the intervention. Outcome measures included frequency of diabetes screening tests in line with the Annual Cycle of Care, and clinical results for weight, blood pressure, HbA1c, lipids, and kidney function.

Compared to before Diabetes Alliance, the odds of all practice patients receiving screening tests at or above the recommended intervals were significantly higher for all recommended tests after Diabetes Alliance (odds ratio range 1.41-4.45, p < 0.0001). Significant improvements in clinical outcomes were observed for weight (absolute mean difference: -1.38 kg), blood pressure (systolic - 1.12 mmHg, diastolic - 1.18 mmHg), HbA1c (-0.03% at the mean), total cholesterol (-0.11 mmol/L), and triglycerides (-0.02 mmol/L) (p < 0.05). There were small but significant declines in kidney function.

Integrated care delivered to a small subset of patients with type 2 diabetes across a large geographic region has spillover benefits that improve the process measures and clinical outcomes for all practice patients with type 2 diabetes.

ACTRN12622001438741; 10th November 2022, retrospectively registered: https://www.anzctr.org.au/ACTRN12622001438741.aspx .