• Advances in Islet Function Replacing Strategies After Total Pancreatectomy.
    3 months ago
    Total pancreatectomy is one of the radical treatments for various severe pancreatic conditions, including pancreatic cancer, chronic pancreatitis, and pancreatic trauma. However, the postoperative complication rate is higher compared to other surgical methods, and all patients inevitably develop insulin-dependent diabetes due to the loss of islet function. Previously, studies focused on pancreas/islet transplantation or stem cell therapy conducted in diabetic patients have achieved significant success, suggesting that adopting similar strategies to preserve or restore islet function after total pancreatectomy is feasible. To date, numerous preclinical and clinical studies have been conducted in this field, providing some basis for selecting islet function replacing strategies (IFRSs) after total pancreatectomy. This article will provide a review of the existing IFRSs after total pancreatectomy, as well as those in various stages of research. It will analyze the clinical evidence, advantages, and disadvantages of different strategies, thereby offering a reference for physicians in the relevant field.
    Diabetes
    Care/Management
  • Exploring vaccine safety and adverse events in major autoimmune diseases.
    3 months ago
    This study evaluates post-vaccination adverse events by analyzing a large dataset of patients with major autoimmune diseases, including Hashimoto's n=26,330; Rheumatoid Arthritis n=9,251; psoriasis n=5,589; Systemic Lupus Erythematosus n=4,208; Inflammatory Bowel Disease n=5,831; type 1 diabetes n=2,235; vasculitis n=466; Guillain-Barré Syndrome n=185; Immune Thrombocytopenic Purpura n=623; ankylosing spondylitis n=926; Sjögren's syndrome n=269; psoriatic arthritis n=2,355; polymyositis n=169; dermatomyositis n=130. Our objective is not to refute the importance of vaccines, but to raise awareness about potential risks observed in autoimmune patients by analyzing CDC (Centers for Disease Control and Prevention) data. The sex distribution analysis in vaccine adverse events highlights a consistent female predominance across most autoimmune conditions. We designed machine learning predictive classification models by identifying key predictors to predict severe adverse events (hospitalization or death) following vaccination based on clinical and demographic predictors including age, sex, vaccine type, dose series, and vaccine route. Our models identified distinct risk profiles for severe events across diseases. Example AUC values ranged from 0.90 for dermatomyositis and GBS to 0.98 for Psoriatic Arthritis with accuracy 96% observed for ankylosing spondylitis. Vasculitis and Sjögren's showed peak precision scores, while polymyositis showed peak recall (97%). Moreover, the reported adverse events in the first week and after the 6th week of vaccine administration are one order of magnitude larger than reported incidents in other time intervals for all diseases. Understanding these differences can inform safer vaccination strategies. We recognize the essential public health role of vaccines and underscore the importance of vigilant post-vaccination monitoring in autoimmune populations.
    Diabetes
    Diabetes type 1
    Care/Management
  • Glycated albumin is not applicable to differentiate gestational diabetes mellitus in Chinese pregnant women.
    3 months ago
    Some studies have suggested that Glycated albumin (GA) may represent a useful biomarker in pregnant women for diagnosing and monitoring gestational diabetes mellitus (GDM). However, whether GA is a sufficiently accurate marker to screen GDM in a general population of pregnant women remains unclear. The current study aimed to investigate the role of GA in screening GDM in Chinese pregnant women.

    In this study, 298 Chinese women between 24-28 weeks of gestation were included. A total number of 247 women with normal glucose tolerance and 51 with GDM were identified according to the glucose levels detection. GA concentrations (GA%) were measured using three different kits, all of which utilized the ketoamine oxidase method for analysis.

    Firstly, we found the GA% levels of the GDM group were significantly higher than those of healthy control. Specifically, the GA% level of the healthy control using Lucica, Maccura, Gcell was respectively 12.86 ± 0.8458, 13.40 ± 0.9344 or 10.98 ± 1.009, while that of the GDM patients was respectively 13.21 ± 1.101, 13.78 ± 1.219 and 11.44 ± 1.449. Then, the Receiving operator characteristic (ROC) curve analysis revealed that the areas under the curve (AUC) of all kits were less than 0.7 (Lucica, AUC = 0.6149; Maccura, AUC = 0.6140; Gcell, AUC = 0.6078), which do not provide support for the utilization of GA as a screening tool for GDM.

    GA is not a good indicator for screening GDM initially.
    Diabetes
    Care/Management
  • First-trimester prediction of early-onset preeclampsia using PAPP-A and mean arterial pressure.
    3 months ago
    Predicting early-onset preeclampsia (EOP) during the initial stages of pregnancy is essential for effective clinical management and enhancing maternal-fetal outcomes. Current methodologies, which include clinical and demographic risk factors, biophysical parameters, and serum biomarkers, exhibit limited efficacy in predicting EOP. This study aimed to evaluate whether the incorporation of pregnancy-associated plasma protein-A (PAPP-A) and mean arterial pressure (MAP) significantly enhances EOP detection. We conducted a retrospective case-control study involving 518 gravidas, of whom 202 developed EOP and 316 experienced normal pregnancies. Logistic regression models were employed to assess EOP predictions, and the predictive accuracy of these statistical models was evaluated using receiver-operating characteristic curve analysis. Our findings indicate that lower PAPP-A levels, higher MAP, and increased body mass index (BMI) are associated with EOP. Notably, in pregnant women between 11+0 and 13+6 weeks of gestation, a 1-point decrease in PAPP-A corresponds to an 84% increase in the likelihood of developing EOP. The predictive performance of PAPP-A improves significantly when combined with other factors such as BMI, MAP, and a history of diabetes mellitus (DM). The risk of EOP is substantially heightened (20.410 times, 95% CI: 11.104-37.515) in patients exhibiting low PAPP-A levels (<0.88) and high BMI (≥35 kg/m²). Additionally, low PAPP-A combined with elevated MAP levels significantly increases EOP risk (adjusted odds ratio [OR]: 114.83). However, after adjustment, the association between low PAPP-A and a history of DM was not statistically significant (adjusted OR: 2.30, p = 0.202). In conclusion, employing a combination of multiple variables for predicting EOP yields a significant improvement over traditional methods that rely solely on individual factors.
    Diabetes
    Care/Management
  • Dual α-amylase and α-glucosidase inhibitors: recent progress from natural and synthetic resources.
    3 months ago
    Diabetes mellitus (DM) is a chronic metabolic disorder characterised by elevated blood glucose levels resulting from insufficient insulin production or insulin resistance. Its global prevalence has surged, particularly in low- and middle-income countries, with over 830 million affected. In recent years, dual inhibition of α-amylase and α-glucosidase, the enzymes involved in the metabolism of complex polysaccharides, has gained visibility in anti-diabetic medication research. The inhibition of these enzymes is responsible for reducing postprandial hyperglycemia. FDA-approved drugs, acarbose, voglibose, and miglitol, are effective but have serious side effects. Many research papers from various research groups have appeared in different databases, from natural to synthetic resources, describing the dual inhibition of α-amylase and α-glucosidase. However, none of the molecules have advanced to clinical development. The current review focuses on compiling an exhaustive report of novel molecules derived from synthetic and natural resources that act as dual α-amylase and α-glucosidase inhibitors. The review also highlights their biological activity, selectivity, structure-activity relationship, molecular docking, and mechanistic studies. A special emphasis on drug-designing strategies has also been given in the manuscript. The comprehensive compilation of research work in the field will provide an inevitable scope for designing and developing novel adenosine inhibitors with improved selectivity and efficacy.
    Diabetes
    Care/Management
  • Prevalence of diabetic kidney disease in Indian type 2 diabetes mellitus patients: A meta-analysis.
    3 months ago
    Diabetic Kidney Disease (DKD) is a major complication of Type 2 Diabetes Mellitus (T2DM) that contribute to end-stage renal disease (ESRD) globally, posing a major public health challenge. T2DM that poses a substantial burden on the Indian healthcare system. Therefore, the present study aimed to estimate the pooled prevalence of DKD among patients with T2DM in India.

    A comprehensive search of PubMed and Embase databases was conducted from inception to August 2024. Two independent reviewers performed screening and selection of studies reporting DKD prevalence. DKD was defined as the presence of albuminuria, reduced estimated Glomerular Filtration Rate (eGFR), or both. This study adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Quality assessment of all included studies was performed using the Joanna Briggs Institute (JBI) critical appraisal checklist. Subgroup and sensitivity analyses were also performed. Statistical analyses were conducted using Stata software.

    A total of 14 cross-sectional studies were included in the meta-analysis. The estimated overall prevalence of DKD among patients with T2DM in India was 44 % (95 % confidence interval (CI): 31 %-56 %). Subgroup analysis revealed a pooled DKD prevalence of 45 % (95 % CI: 29 %-62 %) in the southern region of India, while in the northern region, DKD prevalence was 42 % (95 % CI: 8 %-76 %).

    The findings from the current study showed a higher prevalence of DKD in patients with T2DM in India. Therefore, early preventive measures should be implemented to reduce the burden and complications associated with DKD among patients with T2DM in India.
    Diabetes
    Diabetes type 2
    Care/Management
  • FedGAN: Federated diabetic retinopathy image generation.
    3 months ago
    Deep learning models for diagnostic applications require large amounts of sensitive patient data, raising privacy concerns under centralized training paradigms. We propose FedGAN, a federated learning framework for synthetic medical image generation that combines Generative Adversarial Networks (GANs) with cross-silo federated learning. Our approach pretrains a DCGAN on abdominal CT scans and fine-tunes it collaboratively across clinical silos using diabetic retinopathy datasets. By federating the GAN's discriminator and generator via the Federated Averaging (FedAvg) algorithm, FedGAN generates high-quality synthetic retinal images while complying with HIPAA and GDPR. Experiments demonstrate that FedGAN achieves a realism score of 0.43 (measured by a centralized discriminator). This work bridges data scarcity and privacy challenges in medical AI, enabling secure collaboration across institutions.
    Diabetes
    Cardiovascular diseases
    Care/Management
  • Cardiovascular Events in Individuals Treated With Sulfonylureas or Dipeptidyl Peptidase 4 Inhibitors.
    3 months ago
    Sulfonylureas are commonly used to treat type 2 diabetes (T2D). Research findings on cardiovascular risk associated with sulfonylureas have been inconsistent.

    To emulate a target trial that compares the risk of cardiovascular events after initiation of treatment with individual sulfonylureas or dipeptidyl peptidase 4 inhibitors (DPP4is).

    This comparative effectiveness research study included individuals with T2D and moderate cardiovascular risk treated with metformin monotherapy who received care at 1 of 10 US health systems or were insured by 1 of 2 large health insurance plans between January 1, 2014, and January 1, 2023. Data were analyzed from July 2024 to March 2025.

    Initiation of treatment with a sulfonylurea (glimepiride, glipizide, or glyburide) or a DPP4i (reference category) as a second line therapy after metformin.

    The primary outcome was a 4-point composite of major adverse cardiovascular events (MACE-4): myocardial infarction, ischemic stroke, heart failure hospitalization, or cardiovascular death (from any of these conditions). The 5-year risks of each outcome were estimated.

    Among 48 165 eligible individuals (median [IQR] age, 61 [52-69] years; 22 674 female [47.1%]; median [IQR] hemoglobin A1C, 7.8% [7.3%-8.5%]; median [IQR] low-density lipoprotein cholesterol, 89 mg/dL [70-112 mg/dL]), 18 147 started glipizide, 14 282 started glimepiride, 1887 started glyburide, and 13 849 started a DPP4i. Over the median (IQR) follow-up of 37 (20-64) months, 3158 individuals (6.6%) experienced a MACE-4. The estimated 5-year risks of MACE-4 were 8.1% (95% CI, 7.5%-8.7%) for DPP4i, 8.4% (95% CI, 6.8%-9.9%) for glyburide, 8.6% (95% CI, 7.9%-9.2%) for glimepiride, and 9.1% (95% CI, 8.7%-9.7%) for glipizide. Compared with DPP4is, the 5-year risk ratio of MACE-4 was 1.13 (95% CI, 1.03-1.23) for glipizide, 1.07 (95% CI, 0.96-1.16) for glimepiride, and 1.04 (95% CI, 0.83-1.24) for glyburide.

    In this comparative effectiveness research study of sulfonylureas vs DPP4i in patients with T2D, the risk of MACE-4 events was highest for glipizide. These findings suggest that sulfonylureas, glipizide in particular, may not be the optimal agent in treatment of individuals with T2D at moderate cardiovascular risk.
    Diabetes
    Cardiovascular diseases
    Diabetes type 2
    Care/Management
  • Ergosterol from edible fungi: Enhancing fatty acid oxidation via CPT1A to protect against diabetic kidney disease.
    3 months ago
    Background: Diabetic kidney disease (DKD), a common microvascular complication of diabetes mellitus, is recognized as a leading cause of end-stage renal disease. Ergosterol, a natural sterol abundant in edible fungi, has shown pharmacological effects that may benefit DKD treatment. However, its precise mechanisms of action remain elusive. This study aimed to evaluate the therapeutic efficacy of ergosterol in DKD and to delineate the underlying mechanisms. Methods: Transcriptome microarray sequencing data from DKD patients retrieved from the public GEO database, as well as data from mouse DKD models, were analyzed to identify differentially expressed genes. Db/db mouse, high-glucose-induced HK-2 cells and conditioned THP-1 cells were employed to evaluate the impact of ergosterol on renal function, lipid metabolism, and macrophage phenotypic transformation. Results: Transcriptional profiling of DKD kidneys revealed alterations in fatty acid metabolism, which were corroborated in db/db mice. Ergosterol significantly improved renal function, reduced lipid accumulation, and mitigated inflammation. CPT1A, a key modulator of fatty acid metabolism, was identified as a target. The inhibition of CPT1A in renal tubular epithelial cells led to impaired fatty acid oxidation and lipid accumulation. Excessive renal lipids further stimulated macrophages to transform into pro-inflammatory phenotypes, leading to renal inflammation infiltration and exacerbating kidney damage. Ergosterol upregulated CPT1A expression through transcriptional regulation of FOXA1, thereby reducing lipid accumulation and subsequent renal inflammation. Conclusion: Ergosterol enhances renal fatty acid oxidation via the FOXA1/CPT1A pathway, reducing renal lipid accumulation and inflammation, potentially delaying DKD progression. This study elucidates the therapeutic potential of ergosterol in DKD therapy and provides new insights into the treatment of this disease.
    Diabetes
    Care/Management
    Policy
  • Statin therapy and neuropathy in type 1 diabetes: A cross-sectional study.
    3 months ago
    Dyslipidaemia contributes to the pathogenesis of diabetic peripheral neuropathy (DPN). While statins improve cardiovascular outcomes in diabetes, their potential neurotoxic effects remain debated. This study examined the impact of statin use on neuropathy in type 1 diabetes mellitus (T1DM).

    Participants with T1DM (n = 160) and healthy controls (n = 64) underwent symptom and clinical evaluation of DPN, cardiac autonomic neuropathy (CAN) and corneal confocal microscopy (CCM). T1DM participants were stratified by statin use (non-statin: n = 68; statin treated: n = 92).

    There were significant differences between the non-statin and statin patients with T1DM and healthy controls for the diabetic neuropathy symptom score (DNS) (0.49 ± 0.14 vs. 0.90 ± 0.13 vs. 0.15 ± 0.13, p < 0.001), neuropathy disability score (NDS) (2.55 ± 0.29 vs. 3.67 ± 0.26 vs. 0.44 ± 0.28, p < 0.001), vibration perception threshold (13.68 ± 1.16 vs. 16.03 ± 1.03 vs. 6.05 ± 1.08, p < 0.001), corneal nerve fibre density (19.61 ± 1.04 vs. 19.02 ± 0.92 vs. 28.48 ± 0.97, p < 0.001), branch density (20.40 ± 2.21 vs. 21.39 ± 1.94 vs. 37.31 ± 2.05, p < 0.001), fibre length (11.97 ± 0.51 vs. 11.51 ± 0.45 vs. 16.55 ± 0.47, p < 0.001), DB-HRV (26.27 ± 1.76 vs. 24.21 ± 1.51 vs. 30.18 ± 1.67, p = 0.033) and 30:15 ratio (1.32 ± 0.04 vs. 1.21 ± 0.03 vs. 1.15 ± 0.07, p = 0.033). Despite the statin group being significantly older (p < 0.001) with a higher BMI (p = 0.001) and longer duration of diabetes (p < 0.001), statin-treated patients showed no significant differences in most neuropathy measures, except DNS (p = 0.04), NDS (p = 0.009) and 30:15 ratio (p = 0.04).

    This study demonstrates that individuals with T1DM exhibit neuropathic symptoms and disability, increased vibration perception thresholds, corneal nerve fibre loss and evidence of CAN. However, statin therapy was associated with comparable measures of DPN and CAN, despite statin-treated patients having a longer duration of diabetes and a higher BMI.
    Diabetes
    Diabetes type 1
    Care/Management