We investigated the feasibility and effects of using large language models (LLMs), particularly GPTs, to support the selection of anti-diabetic medications for T2DM management based on individual-level clinical information.

This retrospective study included adults diagnosed with T2DM who visited the Endocrine Department at Yongin Severance Hospital. ChatGPT 4.0 was used with zero-shot and few-shot learning approaches to recommend treatments based on clinical data. Concordance between ChatGPT's recommendations and clinician prescriptions for monotherapy, dual therapy, and triple therapy was categorised as agree, partially agree, and disagree.

Among the 85 individuals included, the overall concordance rate was highest for monotherapy and decreased as the treatment regimen became more complex. In treatment-naive individuals, agreement rates were 69.2% (1st), 69.2% (2nd), and 84.6% (3rd) for monotherapy; 12.5% (1st), 20.8% (2nd), and 0% (3rd) for dual therapy; and 0% at all three assessment points for triple therapy. The concordance rate was lower for individuals with prior treatment history. Few-shot prompting improved agreement compared with zero-shot, particularly for monotherapy and dual therapy.

ChatGPT shows potential as a decision-support tool for selecting anti-diabetic medications, particularly for treatment-naive individuals. Few-shot learning demonstrated improvements in recommendation accuracy, especially for simpler regimens. However, accuracy was notably limited in complex regimens such as triple therapy, highlighting the need for further refinement before clinical use.

Activation of neutrophil membrane receptors initiates intracellular signal transduction cascades that orchestrate the cell's effector functions, including phagocytosis, production of reactive oxygen and halogen species, degranulation, and NETosis (formation of neutrophil extracellular traps (NETs). NETs, which contain antimicrobial compounds such as myeloperoxidase (MPO), represent a strategy to combat infection. However, excessive production of NETs promotes thrombosis, diabetes mellitus, and other diseases. Therefore, investigations into the mechanisms of NETosis and the identification of modulators of this process are critical for developing strategies to address NETosis-related disorders. Here, we identified a novel NETosis inducer, human serum albumin (HSA) modified by the MPO product hypochlorous acid (HSA _HOCl), whose accumulation in vivo was correlated with inflammatory processes. Using human blood neutrophils, we investigated HSA _HOCl-induced NETosis and detected NET formation by flow cytometry. The results showed that the mechanism of HSA _HOCl-induced NETosis involved MPO, NADPH oxidase and phosphatidylinositol 3-kinases, and that HSA _HOCl activated a reactive oxygen species-dependent suicidal type of NETosis. Moreover, HSA _HOCl-induced NETosis was inhibited by an anti-HSA _HOCl monoclonal antibody. Thus, our findings may facilitate the development of strategies to modulate NETosis in inflammation correlated with elevated MPO activity.

Diabetes is one of the most prevalent chronic disorders globally and is linked to obesity. Research has shown that rhoifolin (ROF) can effectively treat metabolic illnesses. This study examines the impact of ROF on glucose and lipid metabolism in a rat model of Type 2 Diabetes Mellitus (T2DM) and investigates its underlying mechanisms.

T2DM was induced in adult male Wistar rats by administering a high-fat diet (HFD) along with a low dose of streptozotocin (STZ) (35 mg/kg, i. p.). All experiments were conducted over 8 weeks. Six rat groups (n = 7 per group) were administered either a vehicle or incremental doses of ROF (10, 20, 40 mg/kg) for the last 4 weeks.

ROF significantly improved body weight and protected against hepatic damage and steatosis. It notably reduced plasma glucose, insulin, hemoglobin A1c (HbA1c), and the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). Serum lipid profiles also improved, with decreases in triglycerides (TGs), cholesterol (CHOL), low-density lipoprotein cholesterol (LDL-c), and free fatty acids (FFAs), and an increase in high-density lipoprotein cholesterol (HDL-c). Hepatic dysfunction was alleviated, as evidenced by normalized levels of aspartate transaminase (AST), alanine transaminase (ALT), and gamma-glutamyl transferase (GGT). ROF reduced inflammation, demonstrated by lower tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) levels and decreased transcription and nuclear accumulation of nuclear factor kappa beta (NF-κB). It also mitigated oxidative stress, evidenced by reduced malondialdehyde (MDA) and increased glutathione (GSH), superoxide dismutase (SOD), and heme oxygenase-1 (HO-1) levels. ROF normalized hepatic peroxisome proliferator-activated receptor alpha (PPARα) and reduced sterol regulatory element-binding protein 1 (SREBP1) activity. Additionally, it modulated apoptosis by decreasing Bax and caspase-3 while increasing Bcl-2. The treatment of ROF improved hepatic glucokinase (GK) activity and lowered glucose-6-phosphatase (G6Pase) levels. These effects were dose-dependent.

ROF shows significant therapeutic potential by enhancing metabolic parameters and modulating key pathways in T2DM, which can pave the way for future animal and clinical intervention studies to validate its therapeutic efficacy and safety.

Non-steroidal anti-inflammatory medicines (NSAIDs) help to lower inflammation and pain, but improper prescription can cause potential drug-drug interactions (pDDIs), affecting the therapeutic outcomes. Given the great frequency of polypharmacy and concomitant medication interactions, NSAID-related problems are especially pertinent in outpatient settings. This study aims to assess the prescription pattern of NSAIDs at the Outpatient Pharmacy Department of a Secondary Care Hospital in the Northern Emirates of the United Arab Emirates.

A prospective observational study based on data from electronic medical records of patients who received NSAID prescriptions from Jan-June 2023. Data collected were screened for prescription patterns of NSAIDs and polypharmacy, and the potential drug-drug interactions (pDDIs) were identified using the Portable Emergency Physician Information Database (PEPID). Data were extracted and analyzed using descriptive statistics and logistic regression analysis to study the association between treatment-related variables and the presence of pDDIs. Chi-square was used to test the association between the type of NSAID prescribed and co-prescribed gastro-protective agents. P < 0.05 was considered statistically significant.

In total, 1005 NSAID prescriptions were analyzed, with a majority (53.23%) being prescribed to female patients. Pain related to elbow/shoulder/joints/lower back (41.09%) was the most common diagnosis in the study populations. Celecoxib (49.7%) was the most commonly prescribed oral, and Ketoprofen (39.5%) was the predominant topical NSAID. A significant association was found between the prescribed NSAID and its co-prescription with gastroprotective agents, specifically ibuprofen, celecoxib, piroxicam, meloxicam (P < 0.001), diclofenac (P = 0.007), and aspirin (P = 0.001). Age and chronic illnesses such as diabetes mellitus (OR = 1.446; 95% CI: 1.018-2.054) and cardiovascular disease (OR = 1.818; 95% CI: 1.279-2.585) are significantly associated with polypharmacy. Multiple logistic regression analysis revealed that the pDDIs were significantly higher with an increasing number of prescribed drugs and co-morbidities (p < 0.001).

The study examines NSAID prescribing trends and emphasizes the potential for drug-related issues, particularly in light of polypharmacy, which calls for careful monitoring and prescribing practices. Healthcare providers should routinely conduct medication reviews and team up with clinical pharmacists to ensure rational NSAID use, reduce drug interactions, and enhance patient safety by thus mitigating this risks.

To assess the glycemic status of consecutive melanoma patients undergoing standardized capillary fasting blood glucose (cFBG) assessment prior to fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) examination.

This retrospective study included 336 consecutive melanoma patients at the University Hospital Zurich, Switzerland. Fasting cFBG levels were measured prior to FDG PET/CT and classified according to American Diabetes Association guidelines. Multivariable linear regression analysis was performed to identify independent predictors of cFBG levels. Sensitivity analyses were performed on patients examined before 11 AM and fasting for 8 h as well as patients without known diabetes.

The cohort included 336 melanoma patients with a median age of 67 years (IQR 57-76), 36 % female (122/336), and 12 % (40/336) with known diabetes mellitus. The median cFBG was 103 mg/dL (IQR 94-112; 5.7 mmol/L, IQR 5.2-6.2). Overall, 58 % (194/336) of patients had non-normal cFBG levels (≥100 mg/dL; ≥5.6 mmol/L), consistent with findings from a sensitivity analysis of patients presenting before 11 AM, where 58 % (115/198) exhibited non-normal levels. Excluding patients with known diabetes, 56 % (165/296) of patients had non-normal cFBG levels, with 7 % (20/210) having levels ≥126 mg/dL (≥7.0 mmol/L), indicative of possible undiagnosed diabetes mellitus. Multivariable linear regression analysis identified male gender, active disease, and subcutaneous fat as independent predictors of cFBG levels, whereas traditional risk factors such as BMI, visceral fat, hypertension or lack of exercise were not independent predictors.

More than half of melanoma patients have elevated cFBG levels, even in those without known diabetes, highlighting the need for improved glycemic screening and management.

The use of oral glucose tolerance test (OGTT) is limited by an inconvenient procedure and poor reproducibility. This study aimed to develop and evaluate prediction models for gestational diabetes mellitus (GDM) diagnosis based on clinical and biochemical parameters.

An observational cross-sectional study was conducted among pregnant women aged 20-40 years in their second trimester (14-28 weeks) in Puducherry, South India, from May 2018 to March 2023. GDM was diagnosed according to the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria.

The study included 234 normoglycemic women and 115 GDM women. Model 1 comprised the biomarkers: fasting plasma insulin, serum sex hormone binding globulin (SHBG), homeostatic model assessment of insulin resistance (HOMA IR), and triglyceride glycemic index (TyG index) (area under the curve (AUC): 0.8870; 95% confidence interval (CI): 0.8440-0.9299; sensitivity: 80.87%; specificity: 86.32%); Model 2 incorporated the following clinical parameters: age, body mass index (BMI), gravida, parity, waist circumference, hip circumference, systolic and diastolic blood pressure, family history of GDM, family history of type 2 diabetes mellitus (T2DM), and family history of hypertension (AUC: 0.6846; 95% CI: 0.6269-0.7422; sensitivity: 90.43%; specificity: 31.6%); and Model 3 combined Models 1 and 2 (AUC: 0.9194; 95% CI: 0.8855-0.9531; sensitivity: 80.8%; specificity: 89.74%).

The predictive models highlighted in the study serve as effective screening tools for GDM and may help overcome the limitations of OGTT, particularly in settings where procedural challenges exist.

Time in range (TIR) is a novel end point that assesses the time during which an outcome remains within a predetermined range. Because the range includes normal parameters, it is indicative of clinically meaningful benefit. The MEAD trial comprised two 3-year randomized, multicenter, sham-controlled, phase III clinical studies that evaluated the efficacy and safety of dexamethasone intravitreal implant (DEX-I) in patients with diabetic macular edema. Dexamethasone intravitreal implant significantly improved best-corrected visual acuity (BCVA) and central retinal thickness (CRT) compared with sham treatment. We present a post hoc analysis of the MEAD trial to investigate TIR benefit across various thresholds of BCVA and CRT with DEX-I versus sham.

Post hoc analysis of results from the randomized, multicenter, sham-controlled, phase III MEAD trial (NCT00168337 and NCT00168389).

Adults with type 1 or 2 diabetes mellitus and fovea-involved macular edema associated with diabetic retinopathy.

Intravitreal injection of DEX-I 0.7 mg or sham procedure.

Time in range during year 1 was evaluated using BCVA thresholds of ≥69, ≥51, ≥59, and ≥64 letters, and CRT thresholds of <300, <353, <446, and <551 μm (the latter cutoffs being quartile [Q] 1, Q2, and Q3 of pooled baseline BCVA and CRT, respectively).

Dexamethasone intravitreal implant 0.7 mg was associated with a statistically significant longer TIR versus sham at the BCVA ≥69-letter threshold (15.0 vs. 9.1 weeks, respectively; P < 0.001) and the CRT <300 μm threshold (18.5 vs. 8.3 weeks, respectively; P < 0.001). Dexamethasone intravitreal implant was also associated with longer TIR versus sham at thresholds of BCVA ≥59 (greater than or equal to Q2) and ≥64 letters (greater than or equal to Q3) and CRT <353 μm (less than Q1), <446 μm (less than Q2), and <551 μm (less than Q3) (all P < 0.001).

Patients receiving intravitreal DEX-I 0.7 mg had a longer time with BCVA above the driving threshold and below the normal limit of CRT during year 1 of the MEAD trial versus those who received sham. These results suggest that patients treated with dexamethasone experience a longer time with clinically meaningful outcomes than with sham, such as being able to drive or regaining normal structural retinal features.

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

This study investigates the clinical significance of ectopic fat and iron deposition in the liver and pancreas for glucose metabolism in elderly obese patients, with a focus on their potential for early diabetes screening and intervention.

We conducted a cross-sectional study of 140 elderly obese patients (aged 65-80 years, BMI ≥28 kg/m²) who underwent MRI quantification of hepatic and pancreatic fat (MRI-PDFF) and iron content (R2* values), along with measurements of visceral and subcutaneous fat via T2-weighted imaging. Glucose metabolism was assessed through oral glucose tolerance testing and related biomarkers.

Compared to normal glucose tolerance (NGT) and impaired glucose regulation (IGR) groups, elderly obese patients with type 2 diabetes mellitus (T2DM) showed significantly higher ectopic fat in the liver (16.6% vs 6.9-13.4%) and pancreas (13.5% vs 8.5-9.0%), as well as increased visceral fat area (198.0cm² vs 137.8-163.9cm²). Liver fat percentage >11.8% was identified as an independent risk factor for abnormal glucose metabolism (OR=2.05, 95% CI 1.22-3.14), with a 2.05-fold increased risk compared to lower levels. The optimal diagnostic thresholds were determined as 11.8% for liver fat (sensitivity 83.2%, specificity 56.1%; AUC = 0.823) and 6.9% for pancreatic fat (sensitivity 72.2%, specificity 50.2%; AUC = 0.688), highlighting their clinical utility for early risk stratification.

Ectopic fat deposition in the liver, particularly when exceeding 11.8%, is a significant independent risk factor for glucose metabolism abnormalities in elderly obese patients. Our findings demonstrate that MRI-based quantification of hepatic fat provides a valuable tool for early identification of diabetes risk, enabling targeted interventions to prevent disease progression. This study highlights the clinical importance of monitoring ectopic fat deposition in clinical practice for elderly obese populations.

Type 2 diabetes mellitus (T2DM) has a high prevalence worldwide; its cardiac, renal, and visual complications greatly affect patients' quality of life. This, together with the large patient base, makes clinical health management of T2DM a problem. Existing studies have shown that obesity and the onset of T2DM are highly correlated, which can start from the earliest lipid metabolism problems and ultimately develop into T2DM. Moreover, adipose tissue can also seriously affect patient treatment by affecting insulin secretion, promoting pancreatic β-cell proliferation, and increasing insulin resistance. Our study describes the association between obesity and T2DM, summarizes the role played by the adipose tissue in T2DM, and focuses on fatty acid esters of hydroxy fatty acids (FAHFA), whose role in improving insulin secretion and increasing insulin sensitivity shows greater potential in T2DM. In addition, we summarize the existing more mature clinical treatment strategies, such as life interventions, drugs, and surgery, which can help control blood glucose levels and reduce adipose-related insulin resistance by reducing the adipose tissue. Among these treatments, Chinese medicine is another factor worth exploring. However, due to the influence of geography, culture, and other factors, this method has only achieved some success in China and part of the East Asia region and has been applied clinically. Although there is no evidence of clinical benefit for obesity or adipose tissue, its clinical benefit for T2DM has been demonstrated; therefore, there is still a need to develop it, as well as considerable potential for development.

The relationship between folic acid (FA) levels and type 2 diabetes mellitus (T2DM) with overweight or obesity remains uncertain. This study aimed to further investigate the relationship between them.

A retrospective study was conducted on 149 patients, comprising 64 patients with T2DM and normal weight and 85 patients with T2DM and overweight or obese status.

Our findings revealed significantly lower levels of FA and neutrophil-to-lymphocyte ratio (NLR) in overweight/obese T2DM patients compared to their normal-BMI counterparts (P < 0.001). The overweight/obese cohort exhibited elevated metabolic parameters, including fasting C-peptide, serum uric acid, total cholesterol (TC), triglycerides (TG), and very low-density lipoprotein cholesterol (VLDL-C) levels (P < 0.05). Notably, correlation analysis demonstrated a significant positive association between FA levels and both age (r = 0.341, P < 0.001), diabetes duration (r = 0.278, P = 0.001), and NLR (r = 0.212, P = 0.009). Conversely, inverse correlations were observed between FA levels and C-peptide (r = -0.240, P = 0.004), TG (r = -0.254, P < 0.001), and VLDL-C (r = -0.271, P = 0.001).

This research found that FA levels were significantly associated with T2DM in individuals who were overweight or obese.