Combination therapy is one of the key strategies for managing type 2 diabetes mellitus (T2DM). The combined administration of insulin and exendin-4 can improve glycemic control, reduce the risk of hypoglycemia, and alleviate weight gain in T2DM patients. However, the co-administration of these two drugs is currently restricted to subcutaneous injection, which undoubtedly imposes pain and treatment burden on patients. Herein, we developed a dual-nanoparticle-hydrogel-based microneedle (MN) patch for the co-delivery of insulin and exendin-4. Insulin-loaded nanoparticles (iNPs) formed by weaker boronic ester bonds and exendin-4-loaded nanoparticles (eNPs) formed by stronger boronic ester bonds were co-encapsulated within a glucose-sensitive hydrogel for the fabrication of an MN patch. This design enabled the MN patch to dynamically release these two drugs in response to different blood glucose levels (BGLs). Under normoglycemic conditions, insulin was predominantly released to maintain fasting blood glucose homeostasis. In the case of postprandial hyperglycemia, both insulin and exendin-4 were released simultaneously, thereby exerting a synergistic and highly effective hypoglycemic effect. In vivo studies in T2DM mice demonstrated that the MN patch treatment effectively reduced BGLs, maintained normal blood glucose control for more than 28 hours without hypoglycemia risk, and improved glucose tolerance. In summary, this MN patch exhibits excellent therapeutic effects and clinical translation potential, offering a promising strategy for the long-term and safe treatment of T2DM.

Cryopreservation of stem cell-derived aggregates for type 1 diabetes cell therapy: Considerations and challenges.

Glycated hemoglobin A1c (HbA1c) is a key biomarker for monitoring long-term glycemic control in diabetic patients, reflecting average blood glucose levels over a two- to three-month period. This study presents the development of a novel hybrid biosensor for HbA1c detection, based on a high-affinity anti-HbA1c variable new antigen receptor (vNAR) isolated from a naïve freshwater stingray library. vNAR domains offer remarkable stability and adaptability for integration into biosensing platforms. The hybrid nanobiosensor combines voltammetric detection with chemiluminescence resonance energy transfer (CRET) to enhance sensitivity. The hybrid nanobiosensor (rGO-AuNPs-APBA-vNAR) operates either in solution or on solid substrates with a Minimum Detectable Quantity (MDQ) of 1.5 ng. On a solid substrate, HbA1c binds to the immobilized vNAR on the hybrid nanobiosensor surface, triggering an electrochemical signal or strong SERS peaks. In solution, the hybrid nanobiosensor is detected via a chemiluminescence-based luminol oxidation reaction in the presence of HbA1c. This vNAR-based hybrid nanobiosensor shows strong potential for clinical HbA1c diagnostics, offering rapid, sensitive, and patient-friendly monitoring to support improved diabetes management and healthcare outcomes.

Using nationally representative data from the China Health and Retirement Longitudinal Study (CHARLS), in this study, we examined cross-sectional and retrospective cohort study associations between blood glucose status and shoulder pain in middle-aged and older Chinese adults. A total of 13,523 participants aged ≥ 45 years were included in the cross-sectional analysis and classified into high or normal blood glucose groups. A total of 8,440 participants without shoulder pain were recruited from the CHARLS at baseline in 2011 were followed up in 2015. The prevalence of shoulder pain was 13.0% in the overall population, with an increased prevalence of 18.0% among individuals with high blood glucose. High blood glucose was significantly associated with shoulder pain, with an odds ratio = 1.41 (95% CI 1.15–1.73). Over 4 years, 996 new cases of shoulder pain were identified, and high blood glucose increased risk with an odds ratio = 1.58 (95% CI 1.20–2.07). High blood glucose is a risk factor for shoulder pain, supporting the importance of blood sugar control to reduce shoulder pain among patients with high blood glucose in middle-aged and older Chinese adults.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-026-47880-1.

Diabetes-related cardiovascular diseases carry high rates of disability and mortality, and their medical costs are prohibitively expensive. Shifting management upstream is imperative. The risk of cardiovascular and cerebrovascular diseases in diabetic populations exists prior to the onset of diabetes. Can lifestyle interventions targeting the prevention of diabetes in people with pre-diabetes also extend to reducing cardiovascular risk? The Daqing Diabetes Prevention Study (DQDPOS) in China provided a definitive answer, though regrettably, this was not corroborated by comparable studies in the United States. Consequently, this has prevented the cardiovascular and diabetes communities from reaching consensus regarding early intervention strategies for cardiovascular disease. By 2024, the European Cardiovascular Community still did not include prediabetes in its cardiovascular disease management population. By late 2025, two landmark studies from China and the United States of America (DQDPOS and DPPOS) reported that individuals with prediabetes who achieved normal blood glucose levels experienced a substantial reduction in the risk of heart failure and cardiovascular mortality compared to those who did not normalize plasma glucose levels. It is hoped this new finding will spur the cardiovascular community to develop more proactive strategies for intensifying glycaemia control in prediabetic populations to reduce cardiovascular risk. Given the prediabetic population in China exceeding 300 million, effective cardiovascular risk management in this population would benefit the reduction of cardiovascular risk across the entire population.

Modified Huanglian Wendan Decoction improves prediabetic renal injury by activating the AMPK/ULK1 pathway to restore autophagy and suppress inflammation.

This study examined the effects of coffee berry pulp (CBP) extract on hepatic lipid accumulation and blood lipid levels in mice fed on a high-fat, high-fructose (HFHF) diet. Male C57BL/6J mice were divided into the following four groups and fed their respective diets for 15 weeks: normal diet, HFHF diet, and HFHF diet supplemented with 100 or 200 mg/kg body weight CBP extract. CBP inhibited weight gain and normalized blood glucose and insulin levels. CBP supplementation also inhibited lipid and lipoprotein accumulation in the liver, thereby effectively regulating triglyceride (TG) levels in both the blood and liver. Analysis of liver lipid metabolism revealed that CBP suppressed the increased messenger RNA (mRNA) expression of sterol regulatory element-binding protein-1C induced by HFHF and downregulated both mRNA and protein levels of peroxisome proliferator-activated receptor-γ. Liver X receptor regulation occurred at the mRNA level, and the adenosine monophosphate-activated protein kinase (AMPK)/phosphorylated AMPK ratio was modulated at the protein level. Among the lipid catabolic enzymes, adipose TG lipase expression was specifically modulated by CBP treatment. These findings suggest that CBP supplementation modulates key hepatic lipid regulators and reduces blood and liver TG accumulation. Although CBP shows promise in regulating TG synthesis and storage in a mouse model, further studies, including clinical validation, are required to confirm its potential as a treatment for human non-alcoholic fatty liver disease.

The healthy donor effect (HDE) refers to the lower mortality observed among blood donors compared to the general population. While HDE arises due to healthier individuals being more likely to donate, the extent to which it is influenced by genetic differences remains unclear. To elucidate the genetic basis of HDE, we conducted a genome-wide association study (GWAS) involving 53,688 active blood donors with extensive donation histories and 228,060 controls from biobank cohorts within the FinnGen project. We identified 46 fine-mapped genome-wide significant loci associated with several health-related endpoints, plasma protein levels and laboratory measurements. Genetic correlation analyses across FinnGen endpoints revealed that blood donors are genetically protected against several diseases beyond those affecting donation eligibility. Using the correlated endpoints as exposures in multivariable Mendelian randomization (MVMR) to inform priors for Bayesian GWAS, we found that 25 of the fine-mapped loci exert a direct effect on blood donorship (BD) rather than acting through disease mediation, suggesting a genetic contribution to maintaining a health state conducive to long-term donation. We also performed MVMR analyses of laboratory traits. The results indicated that normal liver function, blood glucose, and low inflammation independently increase the likelihood of becoming a blood donor, while iron levels showed no causal relationship. Functional enrichments among the proteins regulated by the 46 fine-mapped variants included mainly red cell antigen-related cell adhesion processes. In conclusion, our findings demonstrate that HDE is partly explained by genetic factors, involving both direct health-promoting effects and indirect eligibility selection.

Therapeutic potential of alginate-stabilized silver nanoparticles encapsulating nitrogen-containing heterocyclic derivative mitigates inflammation and fibrosis in L-arginine induced in vivo zebrafish model of chronic pancreatitis.

Incretins such as glucagon-like-peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) play crucial roles in postprandial glucose management. Glucagon-like-peptide 1 and GIP stimulate insulin release in conjunction with meals and are responsible for up to 75% of the insulin secretion. Incretins are therefore very important for maintenance of normal blood glucose levels. Dairy foods are crucial for adequate nutrition at a young age, and skim milk powder in infant formula is frequently used. However, stored skim milk powder has been found to reduce the islet cell mass of the pancreas in experimental studies. The aim of this study was to investigate the potential effect of stored skim milk powder on incretin release from intestinal cells. Murine intestinal endocrine cells (STC-1) were incubated with fresh and stored skim milk powder, the latter containing 70-fold higher amounts of Maillard reactants. The cells' viability, proliferation, and release of incretins were measured after 24 h. Both the viability and proliferation of the STC-1 cells decreased significantly during incubation with stored skim milk powder. The release of GLP-1 and GIP was suppressed in a dose-dependent manner by stored skim milk powder compared with fresh milk powder. The clinical significance for the development of diabetes and obesity, due to this observed weak release of incretins induced by stored skim milk powder containing high amount of Maillard reactants, requires further studies.

The effect of orally administered gadolinium-europium orthovanadate nanoparticles (GdVO4:Eu3+ NPs) on the course and progression of diabetes and vascular malfunction in rats with type 2 diabetes (T2DM) was studied. Long-term GdVO4:Eu3+ NPs administration with drinking water for 28 days at a dose of 0.3-0.4mg/kg normalized blood glucose content and slightly increased the level of the insulin precursor, C-peptide. The glucose tolerance test demonstrated a decrease in the area under the glucose curve, a rise in fractional glucose clearance, and a return to normal glucose levels. The used T2DM model had no visible effect on endothelium-dependent vasodilator responses in the rat thoracic aorta. Administration of GdVO4:Eu3+ NPs also did not alter these responses. The results of the present study suggested that GdVO4:Eu3+ NPs have a positive effect on glucose homeostasis in experimental type 2 diabetes in rats, while the mechanisms underlying this effect require further investigation.

Prediabetes (PD), a reversible metabolic condition that precedes type 2 diabetes (T2DM), carries a high risk of progression to T2DM, but can be effectively treated by restoring normal blood glucose levels, mainly through lifestyle changes such as diet and physical activity. This study uses data from 21'023 patients from Canadian primary care Electronic Medical Records (EMRs), expanding a pre-existing clinical dataset by adding detailed information on drug prescriptions and smoking status, to train and compare different machine learning models to predict future normoglycemia, PD, or T2DM. The use of explainability techniques enhances our understanding of the progression from PD to T2DM, emphasizing the crucial role of blood sugar levels, body mass index, cholesterol levels and blood pressure in determining T2DM risk. These results highlight the potential of routinely collected clinical data to support early identification of high-risk individuals, enabling preventive interventions. Future studies should validate these findings in prospective cohorts and expand the set of investigated features to further improve the model's predictive performance and generalizability.

Diabetes is a highly prevalent chronic disease worldwide, and its early diagnosis is crucial for long-term monitoring and effective management. Sensitive identification and detection of glycated hemoglobin A1c (HbA1c), a key biomarker that reliably reflects average blood glucose levels over the past 2-3 months, play an important role in the long-term monitoring of diabetes. Here, we present a fluorescent and aptamer-based highly sensitive biosensor method for HbA1c detection employing a newly designed, target-triggered, and movable toehold-assisted proximal catalytic hairpin assembly (mt-pCHA) amplification strategy. The recognition of HbA1c by the aptamer triggers the release of DNA strands to activate the mt-pCHA process, in which the assembly hairpins are arranged in close proximity on the preassembled Y-shaped scaffolds to enhance their local concentrations for accelerating reaction kinetics. Furthermore, the introduction of a movable toehold optimizes the strand displacement pathway and suppresses the background leakage while preserving the catalytic efficiency. With the HbA1c-triggered initiation of mt-pCHA, numerous quenched fluorescent hairpins are unfolded in the assembly process, leading to significantly magnified fluorescence recovery for ultrasensitive detection of HbA1c. Experimental validation demonstrates a strong linear response over the range of 5 ng/mL-50 μg/mL for HbA1c with a detection limit of 4.66 ng/mL. The assay exhibits negligible cross-reactivity toward hemoglobin (Hb) and performs reliably in diluted human whole blood hemolysate samples. These results highlight its potential as a versatile biosensing platform for the sensitive detection of low-abundance protein biomarkers.

Glucose-responsive smart insulin delivery systems that mimic the pancreatic insulin release system can improve the health and quality of life of patients with diabetes. In this study, a spherical drug delivery carrier encapsulating insulin was developed to achieve improved glucose accessibility and a rapid pH response using polyhedral oligomeric silsesquioxane (POSS) as a sterically stabilizing structure. Highly sensitive poly(acrylic acid) (PAA)-POSS-aminophenylboronic acid (APBA)@insulin (386 ± 69 nm), a spherical drug delivery carrier encapsulating insulin, was synthesized using POSS, a hydrophobic material, and PAA and APBA, which respond to pH and glucose, respectively. The drug carrier has dual reactivity with pH and glucose, and the synthesis of the carrier was confirmed through Fourier transform infrared (FT-IR) spectroscopy, which verified that the particles were stable at each pH through the zeta-potential data. In particular, PAA-POSS-APBA@insulin exhibited highly sensitive drug delivery characteristics, in which the backbone of PAA was expanded under acidic conditions (around pH 5.0) and insulin bound to the boronic acid inside could rapidly and selectively react with trace amounts of glucose. PAA-POSS-APBA@insulin nanoparticles exhibited no HeLa cell cytotoxicity up to a high concentration of 640 μg/mL, and the cell growth rate increased with the concentration, indicating biocompatibility. The average blood glucose level of diabetic mice treated with POSS-APBA@insulin (4.0 IU/kg) decreased for >6 h and remained stable. Thus, PAA-POSS-APBA@insulin can function as a stimulatory-responsive drug carrier targeting hyperglycemic environments.

To investigate the changes in fetal cardiac function in pregnant women with well-controlled gestational diabetes mellitus (GDM) using a novel ultrasound technology named HOLO-PW. Secondly, we aim to evaluate the predictive ability of cardiac function parameters for adverse perinatal outcomes and establish an individualized nomogram. This study included 122 pregnant women with well-controlled GDM and 256 pregnant women with normal blood glucose. Fetal cardiac function parameters were extracted based on the HOLO-PW technology. The differences between the 2 groups were analyzed. Subgroup analysis was performed in the GDM group according to the pregnancy outcome and fetal growth status. The effectiveness of cardiac function parameters in predicting adverse pregnancy outcomes in GDM was evaluated by receiver operating characteristic (ROC) curves. Independent predictors were identified through logistic regression with LASSO variable selection, and a nomogram was developed. The model's performance was evaluated with ROC analysis, calibration curves, and decision curve analysis (DCA). Compared with the control cohort, the myocardial performance index (MPI), K index (KI), isovolumic contraction time (ICT), and isovolumic relaxation time (IRT) of left and right ventricles were increased in the fetuses of GDM cohort (p < .05). Compared with the appropriate for gestational age (AGA), the fetuses with abnormal growth in the GDM cohort presented significant differences in the cardiac function parameters (p < .05). The incidence of adverse pregnancy outcomes in the GDM cohort was higher than that in the control cohort. The cardiac function parameters of fetuses with adverse and normal perinatal outcomes significantly differed in the GDM cohort (p < .05). We also evaluated the predictive capacity of each heart function parameter for adverse pregnancy outcomes in GDM. The LMPI showed the strongest ability to predict adverse pregnancy outcomes with an AUC of 0.951 (95% CI: 0.909-0.993). A nomogram constructed with the 3 key predictors selected by LASSO regression (LMPI, LKI, and RIRT) demonstrated excellent discrimination, with an AUC of 0.960 (95% CI: 0.924-0.996). The model was well calibrated, and DCA indicated clinical utility. Even under well-controlled glycemic conditions, fetal cardiac function is altered in GDM pregnancies. In this cohort, a model based on fetal cardiac function parameters showed good predictive performance for composite adverse perinatal outcomes. However, external validation is required before clinical implementation.

Background: The measures and interventions which contribute to the control of diabetes may play an important role in the disease prognosis. This study was conducted with the aim of evaluating the effect of medical and nutritional care in the control of type 2 diabetes. Methods: This work as retrospective cohort, was conducted on 200 patients diagnosed with type 2 diabetes, utilizing medical records of those receiving medical care. The participants completed the Diabetes Self-Management Questionnaire (DSMQ), which assesses self-care activities pertaining to glycemic control. Additionally, demographic information, disease history, treatment monitoring, self-monitoring of blood sugar, diet data, physical activity, and biochemical tests were obtained for analysis. Results: Out of the 200 patients with type 2 diabetes studied, 45% were male and 55% were female. The majority of patients (90%) lived in urban areas. The study found that patients who received nutritional education, including information on portion sizes, glycemic index, and adherence to weight loss diets, and who were followed up by a nutritionist, had better control of their diabetes. Patients who were aware of normal blood glucose levels and the consequences of uncontrolled diabetes also showed a significant relationship with better control of the disease. Conclusion: Overall, these findings highlight the importance of incorporating nutritional education into the management plan for patients with type 2 diabetes, as it can have a significant impact on both short-term and long-term health outcomes.

Euglycemic diabetic ketoacidosis (EDKA) is a distinct form of diabetic ketoacidosis characterized by severe metabolic acidosis in the presence of normal blood glucose levels. The increasing incidence of EDKA is associated with the widespread use of sodium-glucose cotransporter type 2 (SGLT2) inhibitors. This review summarizes current data on the pathogenesis, risk factors, diagnostic criteria, and therapeutic approaches to EDKA. Emphasis is placed on the importance of early recognition and timely correction of water–electrolyte imbalance to prevent complications. Special attention is given to the clinical features of EDKA in patients receiving SGLT2 inhibitors and to strategies for preventing recurrence. Systematization of existing knowledge may improve clinicians’ awareness and optimize the management of patients with this potentially life-threatening complication of diabetes mellitus.

Physiological condition and nutritional status are key factors influencing athletic performance, particularly in sports that demand speed and endurance such as basketball. Monitoring random blood glucose levels and nutritional status provides an overview of athletes’ metabolic readiness during training periods. This study aimed to describe the profile of random blood glucose, nutritional status, and speed among male adolescent basketball players aged 12–14 years during the training period at Sahabat Basketball Club Makassar. This research employed a qualitative observational method with a cross-sectional design, involving 36 male adolescent basketball athletes selected through purposive sampling. Data collected included height and weight to determine Body Mass Index (BMI), random blood glucose (mg/dL) measured using a glucometer, and 20-meter sprint speed (seconds). Descriptive analysis was performed using Microsoft Excel. The athletes’ mean BMI was 20.1 ± 4.0 kg/m², with most (61.1%) categorized as normal nutritional status. The mean random blood glucose level was 95.1 ± 12.8 mg/dL, and the mean 20-meter sprint time was 3.41 ± 0.16 seconds. Athletes with normal nutritional status showed faster sprint times compared to underweight or overweight peers. Most adolescent basketball athletes exhibited normal nutritional status and random blood glucose levels that supported optimal speed performance. Regular monitoring of nutritional and metabolic parameters is recommended to maintain physical readiness and enhance athletic performance during training.

An adaptive optimization model of integrated traditional Chinese and Western medicine based on reinforcement learning was proposed to solve the problems of dependence on experience in plan adjustment, insufficient description of individual difference response, and continuous optimization of combined intervention in the process of integrated traditional Chinese and Western medicine. In this model, western medicine clinical indicators, TCM syndrome characteristics, historical treatment trajectories and patient stage feedback are integrated into the state-action-reward framework, and the dynamic update of combined treatment strategy is realized by using deep Q network. Based on anonymized clinical records and time-series follow-up data, a continuous treatment decision sample was constructed, and the index improvement ability, syndrome adjustment effect, synergy gain, Q value convergence, patient satisfaction and treatment interruption of the model were comprehensively evaluated. The results showed that in the model group, the average fasting blood glucose decreased by 1.47 mmol/L, the average glycosylated hemoglobin decreased by 0.83%, the total syndrome score decreased by 9.2 points, the synergy gain index reached 0.34 in the sixth week, the average satisfaction score was 4.47, and the cumulative interruption rate in the sixth week was controlled at 14.4%. The research shows that reinforcement learning can provide computational support for continuous decision-making and joint strategy updating in integrated traditional Chinese and western medicine treatment, and provide new technical solutions for intelligent optimization of clinical intervention pathways.

Background/Objective: In recent years, epidemiological and clinical evidence has suggested an association between the use of second-generation antipsychotics (SGAs) and hyperglycemic complications: notably, diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS). However, the role of first-generation antipsychotics (FGAs) remains less well understood. To conduct a systematic review of evidence established in case reports (CRs) on adverse drug reactions, specifically DKA and HHS, associated with the use of both FGAs and SGAs in order to identify patterns that may inform clinical awareness and future research. Methods: Pertinent bibliographic databases (MEDLINE, EMBASE, PsycINFO and the Cochrane Central Register of Controlled Trials (CENTRAL)) were searched using index phrases and keywords up until 17 October 2025. Eligible CRs discussed exposure to at least one US FDA-approved antipsychotic drug (APD) and assessed either DKA or HHS. Results: A total of 151 CRs were included in the systematic review (DKA, n = 121; HHS, n = 28; both conditions, n = 2). Patients aged 30 to 39 years accounted for the highest number of emergencies (n = 49, 32.5%), which occurred mostly in males (n = 108, 71.5%). The most common mental health diagnosis was schizophrenia (n = 77, 51%), followed by bipolar disorder (n = 26, 17.2%). Olanzapine was associated with the highest number of DKA cases (n = 53, 43.1%), followed by clozapine (n = 24, 19.5%). The average blood glucose at presentation was 842.8 mg/dL for DKA patients and 1252.8 mg/dL for HHS patients. The average hemoglobin A1c levels (HbA1c) were 11.5% and 12%, respectively, for these two conditions. Of the 12 reported fatalities, treatment with olanzapine was noted in four DKA cases and in one HHS case. Conclusions: This analysis provides additional evidence of an association between the use of atypical APDs and DKA or HHS. Clinicians should continue to monitor metabolic risk factors for these conditions, as well as educating patients about the prevention of acute diabetic complications.