Antidiabetic Treatment Research Articles

Antioxidant and antidiabetic potential of Cystoseira myrica-mediated green metallic zinc nanoparticles using the algal extract: synthesis and characterization

Abstract Cystoseira myrica marine macroalgae (CSR) were used to produce metallic zinc nanoparticle composites by utilizing the phytochemicals naturally found in the algae. This involves homogenizing the residuals of CSR (10 g), zinc nitrate solution (5 M; 100 ml), and methanol liquid extract (100 ml) at 30 °C for 24 h of sonication and stirring, followed by filtration and drying. This resulted in a hybrid bio-composite (Zn/CSR), which demonstrated strong antioxidant and antidiabetic properties when compared to zinc oxide (ZnO) and CSR used separately. The Zn/CSR hybrid showed excellent antioxidant activity against common radicals such as DPPH (91.5 ± 1.66%), nitric oxide (90.4 ± 1.2%), ABTS (92.2 ± 1.9%), and O2 ·− (27.8 ± 1.12%) (p < 0.05), performing better than the standard antioxidant, ascorbic acid. Regarding its antidiabetic properties, the Zn/CSR composite significantly inhibited key enzymes involved in diabetes, including both commercial enzyme forms (α-amylase (80.3 ± 1.65%), α-glucosidase (96.6 ± 1.11%), amyloglucosidase (95.8 ± 1.3%)) and their crude intestinal forms (α-amylase (72.3 ± 1.5%), α-glucosidase (94.2 ± 1.7%)) (p < 0.05). This improvement increases the impact of the green CSR extract in reducing the agglomeration behaviors of the loaded metal and the formation of a capping layer from the phytochemicals on its surface, in addition to the beneficial effects of the CSR as substrate, which enhances the biological functions of the loaded metal and its interaction interfaces. The Zn/CSR composite also outperformed commercial miglitol drugs and slightly surpassed acarbose in effectiveness. Given the high cost and potential side effects of current medications, the Zn/CSR composite could be a cost-effective alternative for antioxidant and antidiabetic treatments. These findings also emphasize the role of CSR-derived phytochemicals and algae residues in enhancing the biological activity of the metal nanoparticles.

Empaglifozin modifies the arterial stiffness in type-2 diabetic patients: a preliminary report.

Abstract Background Sodium-glucose cotransporter-2 (SGLT2) inhibitors demonstrated beneficial effects on cardiovascular and renal events in patients with type 2 diabetes mellitus. The mechanisms underlying these effects are not fully elucidated. Aim of this study was to investigate whether empagliflozin is able to modify the arterial stiffness in type 2 diabetic patients. Methods Pulse wave velocity (PWV) and other parameters of arterial stiffness were assessed before and after adding empagliflozin to a traditional antidiabetic treatment in 16 consecutive T2DM outpatients folowed for 3 months. Arterial stiffness were evaluted using SphygmoCor ECEL measuring the pulse waveform of the arterial pulse moving from tha descending aorta to the femoral artery (PWV). Data obtained from the diabetic population has been compared to 16 T2DM outpatients not treated with SGLT2 inhibitors. Results In the two groups differences according gender distribution or duration of diabetes mellitus did not emerge. However the empagliflozin group was younger compared to controls (64.1±8.68 vs 74.45±8.13, P < 0.05). Empagliflozin treatment significantly decreased HbA1c after 12 weeks of treatment (7.9±0.78 vs 7.04±1.09%, P < 0.008.). After 12 weeks’ treatment, empagliflozin significantly improved PWV compared to controls not treated with SGLT2-i (ΔPWVV -0.68±1.1 vs 0.89±1,6 p <0.004, P = 0.0065 with age and HbA1c as covariates). Moreover body weight significantly decreased in the empagliflozin group (86.75±16.16 vs 81.71±16.5 kg, p =0.001) compared to controls (in whom remained unchanged) as long as BMI (30.48±5.4 versus 28.75±5.66 kg/m2, P < 0.002) compared to controls (in whom remained unchanged). Estimated glomerular filtration rate (eGFR) remained unchanged in the two groups during the study whereas urine Albumin to Creatinine ratio significantly improved using empagliflozin (17.8±46.8 vs 12.2±35.7 mg/mmol, P = 0.049). Conclusion In this ‘real clinical practice’ experience, the potential effect of empagliflozin treatment on arterial stiffness in T2DM patients was extensively investigated. Arterial stiffness was significantly decreased adding empaglifozin to the traditional treatment and this result has been obtained after 3-month. Significantly improvement in urine Albumin to Creatinine ratio might suggest an amelioration of endothelial function in those patients that could be involved in reducing arterial stiffness.

A real-world data analysis investigating the cardioprotective effects of glucagon-like peptide-1 receptor agonists among people with type 2 diabetes in England

Abstract Background Cardiovascular disease (CVD) is a common and major complication of type 2 diabetes (T2D). Anti-diabetic therapy aims to lower blood glucose, with primary clinical trial endpoints for new antidiabetic entrants focused on HbA1c. Research suggests some glucose-lowering drugs, including glucagon-like peptide-1 receptor agonists (GLP-1 RAs), can have a cardioprotective effect in people with T2D.1,2 Purpose To compare the real-world risk of major adverse cardiovascular event (MACE) in people with T2D treated with GLP-1 RAs compared to dipeptidyl peptidase-4 (DPP-4) inhibitors or basal insulin. Methods We conducted a retrospective cohort study using linked primary care data from the Clinical Practice Research Datalink Aurum, secondary care Hospital Episode Statistics and Office for National Statistics death registrations. We included patients aged ≥18 years with T2D at high-risk or very-high-risk of CVD (as defined by the European Society of Cardiology) who had ≥2 prescriptions of either GLP-1 RA (dulaglutide, liraglutide, and semaglutide), DPP-4 inhibitor (as part of line 4 therapy) or basal insulin from 01/01/2014-31/12/2018. We excluded those pregnant at therapy initiation or with type 1 diabetes. Follow-up started at second prescription of relevant therapy and ended at the earliest of two years later, pregnancy, death, end of primary care record, or 31/12/2019. We used data from patients’ medical histories to define baseline characteristics. We calculated the incidence of MACE per 100,000 person-years (PY), defined as non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death. We used Cox proportional hazards regression, using LASSO to select confounding clinical variables including BMI, prior MACE and intercurrent antidiabetic treatments, to estimate risk difference of MACE among those treated with 1) GLP1-RA and DPP-4 inhibitor and 2) GLP1-RA and basal insulin. Results We included 63,237 patients, among whom the patients treated with GLP1-RA were younger and a higher proportion were obese or severely obese than those treated with DPP-4 inhibitor or basal insulin (Table 1). The incidence of MACE was highest in those treated with DPP-4 inhibitor (high-risk 1,503.0/100,000 PY; very-high-risk 6,000.7/100,000 PY) followed by basal insulin (high-risk 1,396.9/100,000 PY; very-high-risk 5,707.1/100,000 PY), and lowest in those treated with GLP1-RA (high-risk 377.1/100,000 PY; very-high-risk 1,946.1/100,000 PY). After adjustment, the risk of MACE among patients treated with GLP1-RA was still significantly lower than those treated with either DPP-4 inhibitor (high-risk aHR: 0.42, 95% CI 0.21-0.86 and very-high-risk aHR: 0.65, 95% CI 0.58-0.73) or those treated with basal insulin (high-risk aHR: 0.36, 95% CI 0.18-0.72 and very-high-risk aHR: 0.72, 95% CI 0.64-0.81). Conclusion(s) Our study supports clinical trial and other observational research studies which find a cardioprotective effect of GLP-1 RA use in people with T2D.

Parallel improvement of arterial stiffness with weight loss following intensification of antidiabetic treatment

Abstract Background Arterial stiffness is a marker that can flag increased cardiovascular disease risk in patients with type 2 Diabetes Mellitus (T2DM), while weight management plays a crucial role for the management of glycemic control and prevention of complications in these patients. Purpose To investigate the effects of novel antidiabetic agents on arterial stiffness in T2DM patients as well as potential associations with their weight status before and after treatment. Patients and Methods We enrolled 118 consecutive patients under stable antidiabetic therapy. According to their physician they start treatment with an additional antidiabetic agent; either dipeptidyl peptidase-4 inhibitor (DPP-4i, n=19), or glucagon like peptide-1 receptor agonist (GLP-1RA, n=50) or sodium/glucose cotransporter-2 inhibitor (SGLT-2i, n=49). Body Mass Index (BMI) along with carotid-femoral pulse wave velocity (PWV) as a biomarker of arterial stiffness were measured at baseline and 3 months after treatment intensification. Results There were no differences between the study groups regarding their sex, age and other traditional risk factors or the values of PWV and BMI at baselined (p=NS for all). All groups achieved better glycemic control in terms of HbA1c values between baseline and follow-up; from 7.4±1.2% to 7.4±1.2% in the DPP4i group (p<0.001 for all), from 8.6±0.7% to 6.7±0.8% in the GLP-1RA group (p=0.07) and from 7.7±1.1% to 6.7±0.7% in the SGLT-2i group (p<0.001). PWV showed a decrease from 10.6±2.7 to 9.0±1.6 m/sec (p=0.001) in the DPP4-i group, from 11.2±2.5 to 9.3±2.2 m/sec (p<0.001) in the GLP-1RA group and from 10.7±2.4 to 8.9±2.0 m/sec (p=0.001) in the SGLT-2i group as presented in Figure 1. Regarding BMI, a reduction in the values between groups from baseline to follow-up was also observed; from 27.4±5.3 to 26.1±5.0 kg/m2 for the DPP-4i group, from 33.6±4.9 to 31.5±4.6 kg/m2 for the GLP-1RA group, from 31.8±5.5 to 30.5±5.6 kg/m2 for the SGLT-2i group (p<0.001 for all). Moreover, in the entire study population there was significant correlation between PWV and BMI improvement following treatment initiation (rho=0.247, p=0.007) (Figure 2). Conclusion Diabetes mellitus treatment intensification with GLP1-RA or SGLT-2i or DPP4i, ameliorated arteriosclerosis, improved PWV and BMI while there is significant association between BMI and PWV improvement.Changes in PWV values among the groupsCorrelation between deltaBMI & deltaPWV

Prevalence of Diabetic Retinopathy Among Diabetic Patients from Northeastern Bulgaria.

Diabetic retinopathy (DR) is a leading cause of visual impairment globally among working-aged individuals. This study aims to update data on DR prevalence in Bulgaria. The present cross-sectional study was conducted between 1 January 2022 and 1 January 2023, using a local diabetes registry from the city of Varna as a sampling framework. In total, 587 diabetic patients underwent DR examination. Data included demographics, diabetes type/duration, treatment, and ophthalmic history. DR status was assessed using indirect slit-lamp biomicroscopy or digital fundus photography, graded by the International Clinical Diabetic Retinopathy Scale. Of 587 participants, 13 were excluded due to cataract-related ungradable images. The median age was 65 years (IQR 56-73), with a slight female predominance (54%). The overall prevalence of any DR was 39.9% (95% CI 35.9-44.0), with non-proliferative DR (NPDR) at 27.5%, proliferative DR (PDR) at 7.3%, and macular edema (DME) at 5%. Type 1 diabetes patients had significantly higher DR prevalence (68.8%) than type 2 (34.1%, p < 0.001). Men exhibited higher DR prevalence. Age and diabetes duration correlated positively with DR prevalence. Insulin treatment was associated with higher DR prevalence (55.6%) than oral antidiabetic treatment (22.5%, p < 0.001) for type 2 diabetes patients. Among those diagnosed with DR, 70.9% received treatment, mainly laser therapy. These findings provide epidemiological insights for future research and emphasize the need for a comprehensive national DR screening program in Bulgaria. Technological advancements enable proactive measures to mitigate DR-related visual impairment and blindness, including widespread screening, even in rural areas.

The effect of antidiabetic drugs on bone metabolism: a concise review.

Diabetes mellitus (DM) is a complex metabolic disorder characterized by chronic hyperglycemia, which derives from either insufficient insulin production [type 1 diabetes mellitus (T1DM)] or both impaired insulin sensitivity along with inadequate insulin production [type 2 diabetes mellitus (T2DM)] and affects millions of people worldwide. In addition to the adverse effects of DM on classical target organs and tissues, skeletal health can also be adversely affected. There is considerable evidence linking DM with osteoporosis. The fracture risk in patients with DM differs upon the type of diabetes, and it appears to be related to the type of anti-diabetic treatment. Antidiabetic drugs may have various effects on bone health. Most of them have neutral or even favorable effects on bone metabolism with the exception of thiazolidinediones (TZDs). Some studies suggest that TZDs may have negative impact on bone health by decreasing bone formation and increasing the fracture risk. There are also limited studies linking the use of canagliflozin, a Sodium-glucose contransporter-2 inhibitor (SGLT2i), with increased fracture risk. On the other hand, therapies that are based on incretin effect, like Dipeptidyl peptidase-4 inhibitors (DPP-4i) and Glucagon-like peptide-1 receptor agonizts (GLP-1RAs) might have positive effects on bone health by promoting bone formation. Herein we review the impact of antidiabetic drugs on bone health, highlighting the potential benefits and risks associated with these medications in an attempt to contribute to the development of personalized treatment strategies for individuals with DM.

A review on the impact of the worldwide shortage of glucagon-like peptide-1 medications on control of diabetic patients

Glucagon-like peptide 1 receptor agonists (GLP-1 RA) have shown promising benefits in improving outcomes for patients with type 2 diabetes, particularly those affected by obesity-related complications such as cardiovascular disease, cardiometabolic disorders, and heightened cancer risks, posing significant public health challenges. Notably, GLP-1 RA have been recognized for their potential to achieve up to a 15% weight reduction over a span of two years, making them a preferred choice in specific conditions for diabetic patients with a body mass index (BMI) above 27. However, widespread public interest, particularly amplified through social media, has intensified the demand for GLP-1 RA due to their weight loss properties, thereby straining global supplies and fostering a black market among non-diabetic individuals seeking these effects. This heightened attention has prompted various medical regulatory bodies worldwide to enact strategies and policies aimed at alleviating shortages. Measures include minimizing new prescriptions of GLP-1 RA, exploring alternative medications within the GLP-1 RA category, carefully transitioning patients to other anti-diabetic treatments and managing patient expectations. These efforts appear effective in managing overall outcomes amid ongoing supply challenges. This narrative review provides a focused evaluation of how these GLP-1 RA medication shortages have impacted type 2 diabetic patients around the world and their overall diabetic outcomes.

Antidiabetic Treatment and Prevention of Ischemic Stroke: A Systematic Review

Background: Diabetes mellitus (DM) is a prevalent disease in the general population and also a well-established risk factor for the development of ischemic stroke. Patients who have been diagnosed with diabetes have a 20% higher risk for developing ischemic stroke in comparison to non-diabetic individuals. The aim of the current systematic review is to provide the latest evidence regarding the association between antidiabetic treatment and the prevention of ischemic stroke. Methods: A comprehensive search in scientific literature databases PUBMED, COCHRANE, and SCOPUS was conducted. The studies that were deemed as eligible for this review were those that examined the clinical benefits of therapeutic strategies in terms of preventing ischemic strokes. Results: A total of 32 studies met the established selection criteria. The included studies showed that pioglitazone treatment significantly reduced the risk for recurrent stroke in patients with DM. Furthermore, in the context of primary prevention, the improvement in glycemic control after treatment with the glucagon-like peptide-1 receptor agonists (GLP-1RA) semaglutide and dulaglutide was associated with a reduction in the risk of ischemic stroke in diabetic subjects. Metformin monotherapy may reduce stroke risk, while dipeptidyl peptidase 4 inhibitors, sodium-glucose co-transporter 2 inhibitors, and insulin do not seem to affect the incidence of stroke. Conclusions: The findings of the present systematic review suggest that pioglitazone and GLP-1RA may decrease the risk of stroke. Further studies are needed to provide additional data regarding the preventive effect of novel antidiabetic drugs, such as dual glucose-dependent insulinotropic polypeptide/GLP-1RA agents, on stroke.

Development and Characterization of Ethanolic Extract of Cleome gynandra L. Loaded Solid Lipid Nanoparticles for the Management of Diabetes Mellitus

The bioactive components of the botanical remedy Cleome gynandra L., which is famous for its antidiabetic effects, were extracted using ethanol. To improve its stability, bioavailability, and therapeutic potential, the extract was subsequently encapsulated within solid lipid nanoparticles (SLNs) using a high-pressure homogenization method with varying concentrations of lipids. Zeta potential, entrapment efficiency, kinetics of drug release, and particle size were among the numerous characteristics of the SLNs that were thoroughly examined. One important measure for determining whether bioactive compounds were successfully encapsulated within the SLNs is the entrapment efficiency. An impressive entrapment efficiency of more than 82.13% was shown by the optimized formulation F4. The optimized formulation F4 exhibited a mean particle size ranging from 243.5 to 261.7 nm, according to particle size analysis. This size range is ideal for improving cellular uptake and bioavailability. A negative charge was observed in the zeta potential measurements, which means that the SLNs are stable and do not aggregate. A PDI of 0.416 provided additional evidence of the nanoparticles’ stability and uniformity. A sustained release of about 62.57% over 7 hours was shown in the in-vitro drug release profile data, indicating a long-lasting therapeutic effect. Improved therapeutic efficacy of antidiabetic treatment and more stable blood glucose levels are both benefits of the sustained release profile. The in-vitro results of formulation F4 suggest that SLNs have the good stability, bioavailability, and therapeutic potential of C. gynandra L.’s ethanolic extract when used as a delivery system.

Assessing Cardiovascular Target Attainment in Type 2 Diabetes Mellitus Patients in Tertiary Diabetes Center in Romania.

Type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) share a bidirectional link, and the innovative antidiabetic molecules GLP-1 Ras and SGLT-2is have proven cardiac and renal benefits, respectively. This study aimed to evaluate CV risk categories, along with lipid-lowering and antidiabetic treatments, in patients with T2DM from a real-life setting in Romania. A cross-sectional evaluation was conducted on 405 consecutively admitted patients with T2DM in an ambulatory setting, assessing them according to the 2019 ESC/EAS guidelines for moderate, high, and very high CV risk categories. The average age of the group was 58 ± 9.96 years, with 38.5% being female. The mean HbA1C level was 7.2 ± 1.7%. Comorbidities included HBP in 88.1% of patients, with a mean SBP and DBP of 133.2 ± 13.7 mm Hg and 79.9 ± 9 mm Hg, respectively, and obesity in 66.41%, with a mean BMI of 33 ± 6.33 kg/m2. The mean LDL-C levels varied by CV risk category: 90.1 ± 34.22 mg/dL in very high risk, 98.63 ± 33.26 mg/dL in high risk, and 105 ± 37.1 mg/dL in moderate risk. Prescribed treatments included metformin (100%), statins (77.5%), GLP-1 Ras (29.4%), and SGLT-2is (29.4%). In Romania, patients with T2DM often achieve glycemic control targets but fail to meet composite targets that include glycemic, BP, and lipid control. Additionally, few patients benefit from innovative glucose-lowering therapies with proven cardio-renal benefits or from statins.

Prevalence of obesity and cardiovascular disease in adults with type 2 diabetes and use of diabetes medication in Germany: A claims data study.

To identify the prevalence of cardiovascular disease (CVD) and obesity in patients with type 2 diabetes (T2D) in Germany and to evaluate if antidiabetic treatment patterns varied by comorbidity status. Patients with T2D (aged ≥18 years) were identified during the study period (2014-2020) from medical claims of 4.5 million publicly insured German residents and divided into different cohorts based on CVD and/or obesity diagnosis. Annual prevalence and incidence were estimated for each study year, while characteristics and treatments were assessed in 2020. Data were extrapolated to the German population by age and sex. The prevalence of T2D in 2020 was 11.4%. Among patients with T2D, 53.0% had CVD, 39.3% had obesity, and 20.9% had CVD and obesity. Since 2014, CVD increased by 1.4%, obesity by 4.5%, and CVD with obesity by 2.7% in patients with T2D. The incidence of T2D in 2020 was 1.0% (42.9% had CVD, 37.9% had obesity, and 15.8% had CVD and obesity). Among the prevalent T2D population in 2020, 4.9% received glucagon-like peptide-1 receptor agonists (GLP-1RAs), 9.7% received sodium-glucose cotransporter-2 (SGLT2) inhibitors, and 13.0% received GLP-1 RAs and/or SGLT2 inhibitors. Of those with CVD, 12.9% received GLP-1 RAs and/or SGLT2 inhibitors (without CVD, 13.2%). Of those with obesity, 19.4% received GLP-1RAs and/or SGLT2 inhibitors (without obesity, 9.0%). In this retrospective claims database study, more than two thirds of patients with T2D also had CVD, obesity, or both CVD and obesity. GLP-1 RA and SGLT2 inhibitor use remained low.

TNFα and IL-8 vitreous concentrations variations with two antidiabetic therapies in patients with proliferative diabetic retinopathy: an observational study

BackgroundAntidiabetic therapies are effective, but could indirectly modify the inflammatory response in the ocular microenvironment; therefore, a study was developed to evaluate the inflammatory cytokine profile in the vitreous humor of diabetic patients with retinopathy under treatment with antidiabetic drugs.MethodsObservational, comparative, retrospective, cross-sectional study. Interleukins 1β, 6, 8, 10, and tumor necrosis factor-alpha (TNFα) were evaluated in the vitreous humor obtained from patients with type 2 diabetes mellitus, proliferative diabetic retinopathy, and concomitant retinal detachment or vitreous hemorrhage, and who were already on antidiabetic treatment with insulin or metformin + glibenclamide. The quantification analysis of each cytokine was performed by the cytometric bead array (CBA) technique; medians and interquartile ranges were obtained, and the results were compared between groups using the Mann-Whitney U test, where a p-value < 0.05 was considered significant.ResultsThirty-eight samples; quantification of TNFα concentrations was higher in the group of patients administered insulin, while interleukin-8 was lower; in the metformin + glibenclamide combination therapy group, it occurred inversely. In the stratified analysis, the highest concentrations of interleukin-8 and TNFα occurred in patients with vitreous hemorrhage; however, the only statistical difference existed in patients with retinal detachment, whose TNFα concentration in the combined therapy group was the lowest value found (53.50 (33.03–86.66), p = 0.03). Interleukins 1β, 6, and 10 were not detected.ConclusionInterleukin-8 and TNFα concentrations are opposite between treatment groups; this change is more accentuated in patients with proliferative diabetic retinopathy and vitreous hemorrhage, where the highest concentrations of both cytokines are found, although only TNFα have statistical difference.

EVALUATION OF THE GLYCOREGULATION EFFICACY BEFORE AND AFTER TREATMENT WITH INSULIN DEGLUDEC IN PATIENTS WITH TYPE 2 DIABETES MELLITUS IN THE REPUBLIC OF NORTH MACEDONIA

Patients with type 2 diabetes mellitus (T2DM) who have unsatisfactory glycoregulation with concurrent use of basal insulin and oral hypoglycemics, should be switched to a more intensive therapy regime. To evaluate the efficacy of newly available insulin degludec 70/insulin aspart 30 (IDegAsp), we retrospectively analyzed glycoregulation in 131 patients with T2DM treated with this insulin. All 131 patients were with unsatisfactory glycoregulations, and were switched to IDegAsp from other insulins (except basal-bolus insulin regimen). After a mean period of 11.75±5 months of the treatment with IDegAsp, we found statistically significant improvement in fasting and postprandial glucose levels, and HbA1c (12.5±4.4 vs. 8.8±3.9mmol/l, 13.2±4.6 vs. 9.6±4.1mmol/l, 9.7±1.8 vs. 8.1±1.6%, p&lt;0.01, respectively). The total average daily dose of insulin units (IU) was the same, and there weren’t statistically significant differences in the frequency of hypoglycaemia (p&lt;0.05). From the results, we can conclude that patients with T2DM, who switched to IDegAsp from previous antidiabetic insulin treatment (except basal-bolus insulin regimen) had improved glycaemic control without increased insulin units, and without higher risk for hypoglycemia.

“Diabetes among tuberculosis patients in Bengaluru is alarming: Time to tackle it efficiently!”

ContextTuberculosis (TB) remains a major health challenge in India, with the country bearing the highest global burden. Co-existing with this epidemic is the surge in diabetes mellitus (DM) cases, earning India the title of "Diabetes Capital." AimThis study investigates the association between TB and DM, focusing on the feasibility and outcomes of screening TB patients for diabetes. It also explores the challenges and opportunities for integrated care of TB-DM comorbidities. Settingsand Design: This cross-sectional study was conducted in 32 tuberculosis units in the BBMP district of Bengaluru, Karnataka, India. Materials and methodsData were collected from TB laboratory registers and through interviews with National Tuberculosis Elimination Program (NTEP) healthcare providers. The study assessed the implementation of diabetes screening, challenges in the process, and suggestions for improvement. ResultsAs part of the Quantitative data, of the 17,052 presumptive TB cases examined, 41% were aware of their diabetes status. Diabetics constituted 14.61% of the presumptive cases. Of the diagnosed TB patients, 25.2% were found to be positive for DM as well. Qualitatively, healthcare providers highlighted operational challenges, mainly concerning the timing of blood sugar testing and the need for referral to higher-level facilities. They also emphasized the importance of generating awareness among communities and training healthcare workers for on-the-spot diabetes screening. ConclusionThe findings highlight the urgent need for improved screening of TB patients for diabetes, timely initiation of anti-diabetic treatment, and comprehensive healthcare services under one roof. Advocacy, communication, and social mobilization strategies should be intensified to create awareness of TB-DM comorbidities in the general population.

Drought stress enhances phytochemical, antioxidant, antidiabetic and anticancer properties in Pandanus tectorius

Global warming is responsible for increasing temperatures and reducing rainfall in many regions of the world. Due to insufficient rainfall or lack of water in the soil, plants experience a range of morphological and biochemical alterations when they are exposed to drought conditions. Interestingly, the cells of drought-stressed plants can serve as a potential source for discovering new drugs. These secondary metabolic products have important biological functions that determine how plants interact with the environment and help them accommodate alterations. Present research has shed light on the response of Pandanus tectorius induced drought stress at 8th and 16th days. The studies observed the levels of various secondary metabolites in plants under drought-induced stress. Among the secondary metabolites analyzed, total alkaloids exhibited the highest overall concentration at 26.19 ± 0.83a. Furthermore, the observations found that drought stress had a significant impact on the plant's secondary metabolism. This resulted in increased levels of total alkaloids, saponins, tannins, and phenolics compared to the control plant. Especially the concentration of phenolics showed the most significant increase, with a remarkable 64.99% rise observed at the 16th day of treatment. The concentration of phenolics reached (20.52 ± 0.181c) at this level. Moreover, compared to control, P. tectorius exhibits significant antioxidant, antidiabetic, anti-inflammatory, molecular docking, and anticancer effects against MDA-MB-231 human breast cancer cell line inhibitory concentration IC50 values (48.91 ± 0.95 μg/mL) at 16th day treated plants. Consequently, the positive responses of P. tectorius drought stress enhance secondary metabolites. This research focus on drought stress stimulus prompts an urge in the production of secondary metabolites in P. tectorius, leading to an increase in its anticancer and anti-diabetic properties and treatments for type-2 diabetes and against fighting for cancer with minimal side effects and helping prevent diseases.

Movement disorders related to antidiabetic medications: a real-world pharmacovigilance study

BackgroundDiabetic Mellitus (DM) has progressively emerged as a worldwide health problem, leading to the widespread deployment of antidiabetic drugs as the primary therapy in the global population. The incidence of diabetes medications-related movement disorders (drMD) is noteworthy but underestimated by clinical practitioners. Research design and MethodsIn order to address the incidence of drMD in DM patients and realize the serious outcomes associated with drMD, we conducted a real-world pharmacovigilance study of 612,043 DM patients using the FDA Adverse Event Reporting System (FAERS) database from January 2004 to September 2023. Reporting Odd Ratio (ROR) was calculated to reflect the risk of drMD. A multivariable logistic regression analysis was employed to adjust crude ROR with the mixed factors including age, sex and various antidiabetic treatments. Afterward, a Mendelian Randomization (MR) study was performed to elucidate the underlying genetic correlation between the genetically proxied targets of antidiabetic drugs and motor disorders. ResultsAmong 11,729 cases of motor adverse events in DM patients, six categories of drMD were significantly associated with DM medications. Noticeably, metformin was revealed to drastically increase the incidence of parkinsonism (adjusted ROR:3.97; 95 %CI (3.03, 5.19), p = 5.68e-24), bradykinesia (adjusted ROR:1.69; 95 %CI (1.07,2.59), p = 0.02) and irregular hyperkinesia, including chorea, choreoathetosis and athetosis. Insulin/insulin analogues and GLP-1 analogues presented notably higher odds of tremor: the adjusted ROR (aROR) of insulin and GLP-1 analogue is respectively 1.24 (95 %CI (1.15,1.34), p = 2.51e-08) and 1.78 (95 %CI (1.65,1.91), p = 5.64e-54). The combined therapeutic effects of multiple genetic variants of metformin, especially AMP-activated protein kinase (AMPK) were markedly linked to a greater likelihood of developing secondary parkinsonism (OR:10.816, p = 0.049) according to MR analyses. ConclusionThe use of antidiabetic medications was significantly related to an increased incidence of movement disorders in DM patients. Moreover, MR analyses provided further genetic evidence for the pharmacovigilance study. This comprehensive investigation might help physicians recognize neurological adverse events associated with antidiabetic treatments and administer effective interventions.

Initiating or Switching to Insulin Degludec/Insulin Aspart in Adults With Type 2 Diabetes in the Philippines

Objectives. Blood glucose levels of the majority of Filipino patients with type 2 diabetes (T2D) remain uncontrolled. Insulin degludec/insulin aspart (IDegAsp) is a fixed‑ratio co-formulation of the long‑acting basal insulin degludec and the rapid-acting prandial insulin aspart. The real-world ARISE (A Ryzodeg® Initiation and Switch Effectiveness) study investigated clinical outcomes across six countries in people with T2D who initiated IDegAsp. This publication presents the clinical outcomes of the Filipino cohort from a subgroup analysis of the ARISE study. Methodology. This 26-week, open-label, non-interventional study examined outcomes in adults with T2D initiating or switching to IDegAsp (N=185) from other antidiabetic treatments per local clinical guidance. Results. Compared with baseline, there was a significant improvement in glycated hemoglobin at the end of study (EOS) (estimated difference [ED] −1.4% [95% confidence interval −1.7, −1.1]; P&lt;0.0001). Fasting plasma glucose (ED −46.1 mg/dL [−58.2, −34.0]; P&lt;0.0001) and body weight (ED −1.0 kg [−2.0, −0.1]; P=0.028) were significantly reduced at EOS compared with baseline. IDegAsp was associated with a decrease in the incidence of self-reported healthcare resource utilization. Adverse events were reported in eight (4.3%) participants. Conclusions. Initiating or switching to IDegAsp was associated with improved glycemic control, lower body weight, and lower HRU for people with T2D in the Philippines. No new, unexpected AEs were reported.

Disparity in Guideline-Based Antidiabetic Drugs Prescribing for Type 2 Diabetes Patients in Primary Healthcare Facilities Across China, 2017-2019.

The purpose of this study is to evaluate the pattern, appropriateness, and cost of antidiabetic drugs prescribed for patients with Type 2 diabetes at primary healthcare facilities (PHFs) in China. We collected outpatient-visit prescriptions from 363 PHFs in 31 cities covering eastern, central, and western regions of China. The visits of adult patients with Type 2 diabetes diagnosis were collected and classified the antidiabetic medication pattern of each patient use as recommended or non-recommended according to Chinese guidelines. We then calculated the proportion of guideline-recommended patterns and the average monthly cost for each pattern, overall and by region. Of 33 519 prescriptions for Type 2 diabetes, most (73.9%) were for guideline-recommended antidiabetic treatments. The proportion of guideline-recommended prescriptions varied by region (eastern [75.9%], central [87.5%], and western [59.7%]). Metformin monotherapy was the most common guideline-recommended treatment in all three regions (eastern [20.1%], central [28.0%], and western [24.6%]). The most common non-guideline-recommended treatments were monotherapy of insulin (eastern [16.5%], central [5.1%], and western [25.7%]) and traditional Chinese antidiabetic medicines (eastern [5.6%], central [5.7%], and western [11.1%]). The average monthly costs were lower for guideline-recommended treatments compared to non-recommended treatments in all regions (eastern [13.6 ± 15.4 USD vs. 28.1 ± 22.0 USD], central [9.8 ± 10.9 USD vs. 28.7 ± 19.4 USD], and western [17.9 ± 21.4 USD vs. 30.3 ± 23.6 USD]). The majority of patients with Type 2 diabetes received guideline-recommended antidiabetic medications at PHFs in China, with only half of the prescriptions containing guideline-recommended metformin. Utilization of guideline-recommended therapies differed across regions. Tailored interventions to promote evidence-based antidiabetic prescribing are urgently needed, especially in the undeveloped western region.

Effectiveness of metformin pretreatment for stroke severity: A propensity score matching study.

Metformin pretreatment might have neuroprotective effects. We aimed to determine the therapeutic effects of the antidiabetic medication metformin on ischemic stroke severity and discharge outcomes. We analyzed data on 1303 ischemic stroke patients who were on antidiabetic medications from the Massachusetts General Hospital (MGH) Advanced Comprehensive Stroke Center dataset (n = 8943, 2012-2022). We applied propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) analyses to investigate the effect of current usage of metformin (versus alternate antidiabetic treatment) on acute stroke clinical severity and discharge outcomes. Of the 1303 patients who were on antidiabetic medications at the time of stroke admission, 730 (56%) were taking metformin. Metformin users were younger and more frequently had hypertension, whereas less frequently had prior CAD, AFib, and chronic kidney disease. The clinical features and laboratory values of the two groups were evenly distributed after PSM. Metformin-treated patients had statistically significant lower stroke severity on admission [National Institutes of Health Stroke Scale (NIHSS) (median, interquartile range) 3.0 (1.0-8.0) vs. 4.0 (2.0-11.3), p = 0.011], better functional independence at discharge (modified Rankin scale score 0-2, 36.3% vs. 25.4%, p < 0.001) and less in-hospital mortality (4.5% vs. 11.3%, p = 0.018). IPTW analysis results were consistent with PSM results. Among diabetic patients with acute ischemic stroke, metformin appears to confer neuroprotection. Our results extend previous findings to the general stroke population. Stroke patients with diabetes mellitus who were treated with metformin prior to stroke, even when combined with additional antidiabetic medications, experienced less severe strokes upon admission and had better functional outcomes during hospitalization.

Dorzagliatin: A Breakthrough Glucokinase Activator Coming on Board to Treat Diabetes Mellitus.

Dorzagliatin, an innovative dual-acting allosteric oral glucokinase activator that targets glucose homeostasis and insulin resistance, has gained approval for treating type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). The effectiveness of existing antidiabetic treatments in enhancing beta cell (β-cell) activity is restricted. Currently, there are no satisfactory medications available to address the fundamental deficiency in glucose sensing for glucokinase-maturity-onset diabetes of the young (GCK-MODY), which is caused by mutations in the glucokinase gene; researchers have embarked on glucokinase activators. Dorzagliatin enhances the affinity of glucokinase for glucose and glucose-sensing capacity, improves β-cell function, and reduces insulin resistance. Two phase 3 studies, an adjunct trial of dorzagliatin with metformin for T2DM patients and a monotherapy trial for drug-naïve T2DM patients, are key clinical trials that have shown a favorable safety and tolerability profile. They also demonstrated a rapid, sustained reduction in glycated hemoglobin (HbA1c) and a significant decrease in postprandial blood glucose. This review will summarize the substantial clinical evidence supporting the safety and efficacy of dorzagliatin in treating diabetes mellitus (DM) and clarify the molecular mechanisms underlying its action.