The Teamwork, Targets, and Technology for Tight Glycemia (4T) Program has demonstrated effectiveness in early continuous glucose monitor use with remote patient monitoring among three diverse cohorts of youth with new onset type 1 diabetes (T1D, n = 451). Based on promising single center experience, we examine the potential for program scaling to the T1D Exchange Quality Improvement (T1DX-QI) Collaborative using an implementation science approach. We used the Simplified Implementation Logic Model to identify contextual determinants of implementation success. Then, we described the connections between the implementation support strategies used in 4T to address the contextual determinants and barriers to program reach to youth with T1D and provider adoption. We hypothesized mechanisms linking barriers and strategies to effectiveness and implementation outcomes. Limited clinician time was identified as a major barrier to program success. Several targeted strategies were used to address this, including the creation of the Timely Interventions for Diabetes Excellence (TIDE) clinical decision support tool early in the program and ongoing refinement of the tool. After clinical effectiveness of the 4T Program was established, the next phase focused on further allocating clinician monitoring to participants who would benefit the most. Additionally, cost to the family participants, cost to the clinic, and interest-holder engagement were other determinants addressed by the program strategies. This implementation evaluation informed connections between determinants, support strategies, mechanisms, and outcomes of the 4T Program. This enabled a more precise design in preparation to scale the program across a national network of pediatric diabetes clinics in the T1DX-QI.
Background and aims:Rodent studies suggest that endurance training may promote the browning of white adipose tissue and enhances adipose tissue thermogenesis during cold exposure. However, it remains unclear whether endurance training leads to similar adaptations in humans. The aim of this study was therefore to find out whether six weeks of intensive, fartlek-style cycle endurance training alters responses to cold exposure, specifically cold-induced changes of oxygen uptake, plasma noradrenaline concentrations and the effect of conditioned serum on markers of adipocyte browning in culture. Methods and results:Twenty-four healthy, untrained participants completed a six-week fartlek-style cycling intervention (3 sessions/week) or control period. We estimated cold-induced adaptive thermogenesis before and after the intervention by indirect calorimetry during 60 min of mild cold exposure at 18 °C. Endurance training increased on average the V˙O₂max by 5 ml/kg/min (95% CI 1 to 8; p = 0.010), maximal power output by 19 W (95% CI 5 to 33; p = 0.011), and power at the 4 mmol/l lactate threshold by 30 W (95% CI 18 to 43; p < 0.001). However, training did not alter cold-induced oxygen uptake, carbon dioxide production, energy expenditure, supraclavicular skin temperature, or mean skin temperature compared with controls. In an exploratory analysis, the cold-induced increase in plasma noradrenaline was attenuated after endurance training (-176 pg/ml, 95% CI -337 to -14; p = 0.035), whereas the exercise-induced noradrenaline response not altered significantly. Cold- or exercise-conditioned serum did not alter UCP1 mRNA expression in human beige adipocytes. Conclusion:Six weeks of fartlek-style endurance training increased cardiorespiratory and metabolic fitness but had little effect on the response to cold exposure with no evidence for adipose tissue browning based on the conducted serum incubation experiment.
Purpose To determine whether gender-affirming hormone therapy (GAHT) influences tear system health in transgender individuals. Methods This retrospective cohort observational study analyzed data from transgender men and women ages ≥18-years between 2004 and 2024 via electronic medical record (EMR) data. Following propensity score matching, subjects on hormone therapy included 23,623 transgender men, 15,933 transgender women, and an equal number in each matched control group. Results Among transgender men and women, respectively, tear system disorders occurred in 0.90% and 0.94% of those using GAHT and 0.90% and 1.17% of those not using GAHT (p = 0.211, p = 0.072). There was no significant difference in those with documented utilization of GAHT versus no GAHT, for both transgender men and women, respectively, in lacrimal system disorder (p = 0.427, p = 0.292), meibomian gland dysfunction (p = 0.687, p = 0.255), keratoconjunctivitis sicca (p = 0.685, p = 0.576), and combined tear disorders (p = 0.527, p = 0.168). Conclusions In this cohort, EMR-documented masculinizing or feminizing GAHT was not associated with an increased incidence of recorded tear-system disorders.
The molecular drivers of thyroid cancer are predominantly involved in the MAP kinase pathway, especially the BRAF and RAS pathogenic variants. The DNA repair pathways are rarely implicated in thyroid tumorigenesis. The MRE11-RAD50-NBS1 (MRN) complex is a key mediator of homologous recombination mode of double-strand break repair, and its role in thyroid cancer is poorly understood. We describe a patient with radioactive iodine-refractory, metastatic oncocytic thyroid carcinoma with an NBN gene (c.2166_2167delGCinsAT) pathogenic variant, who developed progressive disease despite receiving systemic therapy with lenvatinib and pembrolizumab. A gene query analysis for the three MRN complex genes (MRE11, RAD50, and NBN) across three thyroid cancer repositories on the cBioPortal database showed a prevalence of pathogenic variants in one or more MRN complex genes in 35/762 (4.6%) patients, and all the 35 patients had anaplastic thyroid cancer (ATC). Upon filtering the dataset to include only ATCs, the pathogenic variant prevalence increased to 22.2% (35/158 patients). The overall survival in ATC patients with MRN complex gene alterations was similar to ATC patients without the altered MRN complex genes [HR: 1.42 (95% CI: 0.93-2.17)]. A mutual exclusivity analysis demonstrated a tendency for pathogenic variants in one MRN complex genes to co-occur with pathogenic variants in the other two MRN complex genes. In conclusion, the MRN complex pathogenic variants could be potentially oncogenic in TCs and may be linked to aggressive forms of TC.
Currently, no clinical early predictive biomarkers of GDM exist. A key challenge is that many candidate biomarkers fluctuate during pregnancy. Previous studies with a single time point identified several miRNAs in early pregnancy associated with insulin sensitivity between 24 and 29 weeks of gestation, suggesting they serve as potential predictive biomarkers for GDM. However, the lack of longitudinal data limits our understanding of how these miRNAs behave over time. We conducted a longitudinal pilot study to evaluate the patterns of ten miRNAs, previously identified as potential early predictors of GDM. Blood samples were collected from 18 GDM women and 18 healthy pregnancies at 4 time points (GDM diagnosis, 28 weeks, 32 weeks, and one day before delivery). The levels of four placenta-specific C19MC miRNAs (miRNA-519d-5p, miRNA-512-3p, miRNA-516a-5p, and miRNA-517-5p) and six non-C19MC miRNAs (miRNA-141-3p, miRNA-143-3p, miRNA-218-5p, miRNA-221-3p, miRNA-483-5p, and miRNA-489-3p) were measured. The relative expressions of four C19MC miRNAs were significantly increased in GDM women at diagnosis, at 28 weeks of gestation, and one day before delivery. The relative expression of non-C19MC miRNA-221-3p was significantly decreased across all time points. The expression of non-C19MC miRNA-143-3p increased significantly at diagnosis and 28 weeks, and then declined before delivery. In contrast, the levels of non-C19MC miRNA-483-5p, miRNA-218-5p, and miRNA-489-3p were significantly decreased across all time points. No changes in miRNA-141-3p level were observed. Our pilot longitudinal study supports the predictive potential of C19MC miRNAs (miRNA-512-3p, miRNA-516a-5p, miRNA-517-5p) and non-C19MC miRNA-221-3p, which were previously identified as having elevated levels in early gestation.
Background:Irisin is a metabolism-related myokine associated with lipid metabolism and insulin resistance. However, its changes during glucagon-like peptide-1 (GLP-1) receptor agonist therapy remain unclear. Methods:This exploratory analysis of a multicenter trial included 189 adults with T2DM inadequately controlled with metformin and/or insulin secretagogue. The participants received the GLP-1 receptor agonist exenatide as an add-on therapy for 16 weeks. Serum irisin and glycolipid metabolism were evaluated. Comparison was performed between two subgroups of the participants stratified by a median change from baseline in serum irisin level. Associations between change in irisin level and changes in metabolic parameters were assessed using Pearson or Spearman correlation analysis and multivariable linear regression analysis. Results:After the 16-week exenatide treatment, serum irisin level significantly declined from baseline (3.22 ± 0.53 ng/mL vs. 3.35 ± 0.64 ng/mL, P = 0.031). Change in irisin level was positively associated with change in high-density lipoprotein cholesterol (HDL-C) level (r = 0.154, P = 0.035), and negatively associated with changes in triglyceride (TG) level (r = -0.159, P = 0.029) and TG/HDL-C ratio (r = -0.172, P = 0.018). These associations for TG level and TG/HDL-C ratio remained significant after multivariable adjustment. No significant association was observed between change in irisin level and glycemic control parameters. Conclusions:Serum irisin level declines during the exenatide treatment in patients with T2DM, and this reduction is associated with change in lipid metabolism but not glycemic control, suggesting a potential link between dynamic change of irisin and lipid metabolism during the exenatide treatment.
Transition from pediatric to adult care is a critical period for young adults with type 2 diabetes mellitus (T2DM). This study included a retrospective chart review of 139 patients aged 17-25 years with T2DM followed in pediatric endocrinology between 2021 and 2022. Patients were categorized as transitioned to adult care, remained in pediatric care, or lost to follow-up. Of the cohort, 33.8% transitioned to adult care, 27.3% remained in pediatric care, and 38.9% were lost to follow-up. Among those who transitioned to adult care, 48.9% established care with family medicine, 27.7% with adult endocrinology, and 23.4% with internal medicine. The mean time to transition to adult care was 19.9 ± 19.3 months, and mean HbA1c at first adult visit was 8.9 ± 3.1%. Nearly 40% of young adults were lost to follow-up, and transitions to adult care were characterized by prolonged gaps in care, suggesting the need for structured transition pathways.
Background:Overweight and obesity rates have increased drastically among people with cystic fibrosis (CF), in part due to advancements in care, including highly effective modulator therapies (HEMT). Ethnic differences in the prevalence of overweight/obesity in CF are unknown. Methods:To determine the prevalence of overweight/obesity by ethnicity, we performed a cross-sectional retrospective chart review of patients ≥ 2yrs old with CF at the University of Texas Health San Antonio CF Center. Logistic regression stratified by age group (children: 2-17 yr, adults: ≥18 yr) was used to evaluate factors associated with overweight/obesity among Hispanics and non-Hispanic whites after adjustment for confounders. Results:One hundred seventy-two patients (68 children/104 adults, 49% Hispanic, 47% female) were assessed. Overweight/obesity was prevalent in 35% of children and 42% of adults. Multivariable analysis revealed that the odds of overweight/obesity were lower in children (p = 0.032) and adults (p = 0.007) who used supplemental feeds, but higher among adults using HEMT (p = 0.037) and adults with higher FEV1pp (p = 0.016). Ethnic differences in overweight/obesity prevalence were not apparent in either age group. Conclusion:The odds of overweight/obesity were lower among children and adults using supplemental feeds, whereas HEMT use and having higher lung function were associated with increased odds among adults. Multi-center studies performed in diverse CF populations are essential to understand factors associated with overweight/obesity.
Background:Type 1 diabetes (T1D) results in the loss of endogenous production of insulin and C-peptide, which are co-secreted by pancreatic β cells. Serum C-peptide following mixed-meal tolerance tests is commonly used in T1D trials to assess residual insulin secretion. Urine C-peptide (UCP) offers a non-invasive alternative suitable for home collection. Here, we aimed to optimize urine handling practices to support remote urine C-peptide monitoring in clinical trial settings. Methods:Randomly-voided urine was collected from 18 non-diabetic participants (mean age: 46.6 years; 94.4% female). Samples were treated with no preservative (NP), boric acid (BA), or sodium carbonate (SC) and incubated at 4°C or room temperature (RT, 22°C) for up to 72 h. Use of cold packs after initial refrigeration was also tested. UCP was quantified using the TOSOH immunoenzymatic assay and normalized to urine creatinine (UCP:Cr). Stability was expressed as percent change from baseline (%UCP:Cr). Results:NP samples lost %UCP:Cr more rapidly at RT, with decreases at 48 h (-16%, P < 0.05) and 72 h (-21%, P = 0.02) compared to 4°C. BA-preserved samples had declined %UCP:Cr at 72 h (-16%; P = 0.04) compared to 4°C. SC maintained UCP:Cr stability, showing no significant change in %UCP:Cr between 4°C and RT. Samples kept on cold packs following initial refrigeration showed no significant loss in %UCP:Cr compared to samples continuously refrigerated for 72 h. Conclusions:Cold storage of urine slows UCP:Cr degradation, and SC stabilizes UCP:Cr at room temperature. Our findings suggest that UCP:Cr offers a practical option for at-home urine collection in clinical studies.
Background:There has been increasing public interest in a functional medicine (FM) approach to the care of type 2 diabetes (T2D). However, it is unclear if this approach can further improve diabetes management beyond conventional diabetes care. This study compared the addition of a FM approach (intensive lifestyle modifications and tailored dietary supplements) plus usual care (FM) to conventional endocrinology management alone (usual care, UC). Methods:In a 24-month unblinded randomized trial, participants with type 2 diabetes (T2D) were randomized to receive either FM or UC. The primary endpoint was discontinuation of insulin with no increase in HbA1c or HbA1c < 7% at 12 months. Secondary endpoints included changes in HbA1c, insulin dosage by weight, cardiometabolic biomarkers, hypoglycemic episodes, total number of medications and quality-of-life scores. Results:A total of 107 individuals were screened - 34 were randomized into FM and 37 into UC. Participants were 46% female and median age was 62 years. Median baseline HbA1c was 7.75%. Of those randomized, 47 participants completed the study (FM: 20; UC: 27); 15.8% of patients in FM arm achieved the primary endpoint compared to 11.1% in the UC arm (p = 0.68). Secondary exploratory endpoints including change in HbA1c, insulin dosage by weight, hypoglycemia, BMI, weight and quality-of-life did not differ significantly between arms. Conclusion:The addition of FM did not lead to significant improvement in glycemic, metabolic or quality-of-life outcomes compared to usual care for individuals with type 2 diabetes.
Diabetic kidney disease (DKD) represents a prevalent and severe complication of diabetes mellitus, with growing evidence highlighting the critical role of lipid metabolic dysregulation in its pathogenesis. This review systematically examines the complex interplay between aberrant lipid metabolism and DKD progression, focusing on three major pathways: fatty acid metabolism disturbances, cholesterol homeostasis imbalance, and sphingolipid signaling alterations. We detail how these metabolic perturbations contribute to renal cell injury through multiple mechanisms, including in podocytes, tubular epithelial cells, and mesangial cells. Emerging therapeutic strategies targeting these metabolic pathways are comprehensively evaluated. Special emphasis is placed on recent advances in understanding cell-specific lipid metabolic reprogramming and its clinical implications. The review also discusses current challenges in translating these findings into clinical practice and proposes future research directions for developing personalized therapeutic approaches based on lipid metabolic profiling in DKD patients.
Introduction:Men generally have higher plasma uric acid (PUA) concentrations and are at greater risk for hyperuricemia-related diseases. Sex hormones may underlie this difference, though mechanisms remain unclear. Sex hormone therapy offers a unique opportunity to study these effects. Methods:Participants were included from two prospective observational cohorts: ENIGI (n = 544, 12 months of feminizing [n = 260] or masculinizing [n = 284] hormone therapy) and KNIGHT (n = 28, 3 months of feminizing [n = 15] or masculinizing [n = 13] hormone therapy). Outcomes included changes in PUA (ENIGI), uric acid clearance (UAC; KNIGHT), fractional excretion of uric acid (FE-UA; KNIGHT), fat distribution (ENIGI), and PUA-associated plasma proteomics (KNIGHT). Results:PUA decreased during feminizing hormone therapy (-86 μmol/L [95% CI, -95; -77]) and increased during masculinizing hormone therapy (+61 μmol/L [95% CI, 53; 70]). During feminizing therapy, UAC increased (+1.1 mL/min [95% CI, 0.1; 2.1]) without changing FE-UA. During masculinizing therapy UAC and FE-UA decreased (UAC: -1.0 mL/min [95% CI, -1.7; -0.3]; FE-UA: -0.8% [95% CI, -1.3; -0.4]). Android-to-gynoid and visceral-to-subcutaneous fat ratios decreased with feminizing and increased with masculinizing therapy (p < 0.05) and correlated positively with PUA changes (p < 0.001). Proteomics identified 126 PUA-associated proteins differentially expressed during sex hormone therapy. While proteins directly involved in uric acid production were unchanged, proteins related to fat distribution (adiponectin, leptin, SHBG) associated with PUA changes. Discussion:PUA significantly changes during sex hormone therapy, most likely through changes in UAC and fat distribution. These findings emphasize the role of sex hormones in uric acid metabolism and provide insight into sex differences in hyperuricemia-related conditions. Trial registration knight:Dutch Trial Register (ID: NL9517); ClinicalTrials.gov (ID: NCT04482920).
Background Finerenone, a nonsteroidal mineralocorticoid receptor antagonist, improves renal and cardiovascular outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D). However, evidence on its use in clinical practice remains limited. Within the FOUNTAIN platform (NCT05526157; EUPAS48148), this study aimed to characterize the profiles and treatment patterns of patients initiating finerenone in the United States following its regulatory approval in 2021. Methods This observational study used Optum’s de-identified Clinformatics® Data Mart Database to identify adults with T2D and CKD who initiated finerenone between July 2021 and September 2023. Baseline demographic and clinical characteristics (e.g., estimated glomerular filtration rate, urine albumin-to-creatine ratio [uACR]) were assessed, and treatment utilization patterns were described. Results Among 3,591 new finerenone users, mean age was 72.2 years and 47.5% were female. Most (62.4%) had stage 3 CKD, and of those with recorded uACR, 86.5% had moderate/severe albuminuria (≥30 mg/g). Renin-angiotensin-aldosterone system inhibitors (RAASi; 80.0%), sodium-glucose cotransporter 2 inhibitors (SGLT2i; 41.4%), and glucagon-like peptide-1 receptor agonists (GLP-1 RA; 30.2%) usage was common in the 90 days preceding finerenone initiation. Finerenone was typically initiated as an add-on to RAASi (58.5%), SGLT2i (28.0%), or GLP-1 RA (21.1%); monotherapy usage was infrequent (8.5%). Among those with ≥ 12 months’ follow-up, 56.0% remained on finerenone at 12 months and 16.7% had titrated from 10 mg to 20 mg. Conclusions Finerenone was primarily prescribed as a pillar of therapy that is used in combination with complementary medications in patients with T2D and CKD, aligning with clinical guidelines and regulatory labeling.
Background:Familial glucocorticoid deficiency (FGD; MIM: 614736) is a genetic disease of glucocorticoid insufficiency, with autosomal recessive mode of inheritance. The FGD is genetically heterogeneous disorder that involves multiple genes related to the pathway that regulates the signaling from pituitary to the adrenal cortex, or the specific redox reactions in mitochondria. The phenotypic spectrum for FGD is also diverse with considerable variability in clinical features. Among the genetic determinants of this disease, pathogenic mutations in NNT gene results in Familial glucocorticoid deficiency type 4. Here we report three consanguineous families with single nucleotide variants in NNT that manifest as familial glucocorticoid deficiency in multiple family members. Method:Prospective cohort of three families from different tribes were identified with clinical diagnosis of familial glucocorticoid deficiency (FGD). Whole exome sequencing (WES) done for affected family members followed by validation of discovered variant by Sanger sequencing and subsequent functional studies including quantitative PCR analysis and protein Modelling. Results:The screening of entire coding region of the genomes of probands in each family revealed three distinct mutations, including one novel missense variant (c.1067 C > T; p.Thr356Ile), classified as variant of uncertain significance (VUS; Class-3) and two recurrent variants (c.1025 T > C; p.Val342Ala and c.98dup; p.Leu33Phefs*13), classified as pathogenic [Class-I]. Computational protein modelling of these mutations (c.98dup and c.1025 T > C) suggests atypical changes in the structure of the mutant proteins that likely disrupt the physiological role of NNT in mitochondria of adrenal cortex. Conclusion:The exome sequencing genetically characterized the autosomal recessive sub-type 4 of hereditary glucocorticoid deficiency in families showing the features of cortisol deficiency, including the development of hypoglycemia and adrenal crisis. This strongly supports the pathogenicity of these variants. In addition, this suggests importance of mitochondrial function in post developmental maintenance of cortisol significance in terms of cellular metabolism, carried out by NNT protein. Identifying individuals with hereditary glucocorticoid deficiency is essential to start life-saving glucocorticoid replacement.
Aims:Type 2 diabetes mellitus and non-alcoholic fatty liver disease increase cardiometabolic risk. This randomized controlled trial assessed the effects of cyclic yoga, a structured asana sequence, on anthropometric, glycemic, lipid, and hepatic parameters in overweight women with both conditions. Methods:Forty overweight women (mean age 50.5 ± 5.5 years) with type 2 diabetes and non-alcoholic fatty liver disease were randomized to either an eight-week cyclic yoga intervention (three sessions/week) or a control group maintaining usual activities. Pre- and post-intervention, fasting blood glucose, glycated hemoglobin, insulin resistance, lipid profile, liver enzymes (alanine aminotransferase, aspartate aminotransferase), anthropometric parameters were measured and analyzed using repeated measures analysis of variance. Results:The cyclic yoga group showed significant reductions in fasting blood glucose, glycated hemoglobin, insulin resistance, triglycerides, low-density lipoprotein cholesterol, alanine aminotransferase, aspartate aminotransferase, weight, body mass index, hip circumference, waist circumference, with increased high-density lipoprotein cholesterol compared to control group. Conclusions:Cyclic yoga appears to improve glycemic control, lipid profiles, liver enzymes, and anthropometric indices in women with type 2 diabetes mellitus and non-alcoholic fatty liver disease. These findings suggest that cyclic yoga may be a safe, practical, and cost-effective complementary therapy to improve metabolic and hepatic health in this high-risk population, although larger and longer term studies are warranted.
Introduction:MOTS-c (mitochondrial open reading frame of the 12S rRNA type-c) is a mitochondrial-derived peptide and regulator of metabolic homeostasis. Although its role in glucose and lipid metabolism is emerging, changes in circulating MOTS-c with obesity remain unclear. We hypothesized that circulating MOTS-c concentrations would be altered in obese vs. lean adults in associations with altered metabolic and inflammatory markers. Methods:Circulating MOTS-c levels, metabolic parameters, and inflammatory markers were compared between 22 lean controls and 32 obese participants scheduled for bariatric surgery. Longitudinal changes in weight, MOTS-c levels, and metabolic markers were also analyzed in 10 of the obese patients before and 6 months after bariatric surgery. Additionally, adipose tissue MOTS-c expression was assessed by immunofluorescence in lean kidney donors (n = 6) and obese (n = 14) subjects. Results:Circulating MOTS-c levels were significantly higher in obese compared to lean individuals (273 ± 56 vs. 223 ± 50 pg/mL; P < 0.01). BMI and HOMA-IR independently predicted elevated MOTS-c levels (P = 0.035 and P = 0.032, respectively). MOTS-c showed a biphasic relationship with HOMA-IR, rising sharply above HOMA-IR of ∼ 6.6 mmol/L×µU/mL. Adipose tissue MOTS-c did not differ between the groups or correlate with circulating MOTS-c. Despite significant BMI improvements post-surgery (P < 0.001), circulating MOTS-c levels remained unchanged (P = 0.913). Conclusion:Circulating MOTS-c levels are elevated in obesity, exhibiting a nonlinear relationship with BMI and insulin resistance. MOTS-c may represent a compensatory metabolic response in obesity and insulin-resistant states, highlighting its potential as a clinical biomarker. This preliminary exploratory study warrants validation in larger and independent cohorts.
Background: Medication discrepancies and omissions at hospital discharge are a common, preventable source of harm for patients with diabetes. Ensuring accurate prescriptions for insulin and diabetes supplies is critical for safe transitions of care. We aimed to evaluate the impact of a Best Practice Advisory (BPA) integrated into the electronic medical record (EMR) on the accuracy of diabetes-related discharge prescriptions. Methods: This quality improvement initiative was implemented across seven hospitals within a large health system. The BPA was triggered in the EMR discharge navigator for patients evaluated by a Diabetes Care and Education Specialist (DCES), prompting providers to review and order recommended diabetes medications and supplies. BPA utilization data were collected from February to December 2022. A retrospective chart review of 100 consecutive eligible patients discharged in December 2022 seen by DCES was assessed for prescription accuracy and supply provision. Results: The BPA was triggered 6,714 times for 2,266 patient encounters over 11 months. Among 100 reviewed patients (mean age 57 years, 58 % male, 76 % type 2 diabetes), insulin prescription accuracy at discharge was 99 %, and 88 % received all recommended diabetes supplies. Only 1 % of patients contacted the hospital post discharge for additional supplies, suggesting most omissions were clinically appropriate. Conclusions: Integration of a BPA into the EMR significantly improved the accuracy and completeness of diabetesrelated discharge prescriptions. This low-cost, sustainable digital intervention enhances patient safety and care quality, and represents a scalable model for improving discharge practices in inpatient settings.
Background:Metabolic dysfunction-associated steatotic liver disease (MASLD) is driven by dyslipidemia and chronic inflammation. We proposed a novel biomarker, the Remnant Cholesterol Inflammatory Index (RCII), and evaluated its association with MASLD, considering mediation via insulin resistance (TyG index). Methods:In 3,232 U.S. adults from NHANES 2015-2020 (709 with MASLD), participants were divided into RCII tertiles. Multivariable logistic regression, restricted cubic splines, threshold analysis, subgroup interaction tests, ROC curves, XGBoost SHAP, and mediation analysis were used to assess relationships and mechanisms. Results:Compared with the lowest tertile, the highest RCII tertile had an OR of 9.578 (95 % CI 6.420-14.291; P < 0.001) for MASLD. A nonlinear association was identified, with a stronger slope below RCII = 3.640 (1-unit increase associated with 76.1 % higher odds). Significant interaction was observed by smoking status. In SHAP ranking, RCII was the sole lipid-class feature among the top five predictors. ROC showed AUC = 0.747 for RCII versus 0.732 for RC, both outperforming TC/LDL-C. TyG index mediated 32.4 % of RCII's total effect on MASLD (P < 0.001). Conclusions:RCII is a robust lipid-inflammation marker that outperforms conventional lipids in predicting MASLD. Its association is partly mediated by insulin resistance, supporting RCII's use in MASLD risk stratification and early prevention.
Aims Patients with pancreatic tumours are at increased risk of diabetes mellitus (DM) and hyperglycaemia and a subsequent higher risk of developing postoperative complications. Continuous glucose monitoring (CGM) can be used to assess the prevalence of hyperglycaemia in pancreatic surgery patients. Methods This single-centre observational pilot study (2023–2025) included 15 patients with DM type 2 or new onset DM (HbA1c ≥ 48 mmol/mol (6.5 %)) undergoing pancreatic surgery. Blinded CGM was performed for 2 weeks preoperatively and 2 weeks perioperatively. Primary outcome was time above range (TAR)(glucose > 10.0 mmol/l (180.2 mg/dl)) as a percentage of total CGM wear time. Secondary outcomes were time below and in range, glucose metrics, difference in preoperative HbA1c and patient satisfaction regarding CGM wear. Results In total, 5 patients had new-onset DM, 6 suboptimal controlled DM (HbA1c ≥ 53 mmol/mol (7.0 %)) and 4 optimal controlled DM (HbA1c < 53 mmol/mol (7.0 %)) at baseline. Median preoperative TAR (>10.0 mmol/L (180.2 mg/dl)) was highest in the suboptimal controlled DM group (59.7 % [35.1–68.6]), compared to 7.9 % [0.9–19.4] in the optimal controlled and 16.7 % [7.7–23.7] in the new-onset DM group. Perioperatively, the optimal controlled DM group had the highest TAR (26.7 % [11.3–49.0]) while the new-onset and suboptimal controlled DM group had TARs of 4.6 % [1.2–9.6] and 16.3 % [11.5–23.4], respectively. Conclusions Blinded CGM revealed frequent pre- and perioperative hyperglycaemia and high inter-individual variability in TAR among patients with (new-onset) DM undergoing pancreatic surgery. These findings support the need for stricter and more individualized glucose monitoring. This could optimize preoperative glucose management and thereby possibly reduce postoperative complications.
Non-alcoholic fatty pancreas disease (NAFPD), marked by ectopic triglyceride accumulation in the exocrine pancreas, is increasingly observed yet its recognition as a cancer-predisposing condition remains limited. We synthesize evidence supporting NAFPD as an early and modifiable niche for pancreatic ductal adenocarcinoma (PDAC), using a PRISMA-ScR-guided framework. The findings were synthesized into three domains: epidemiological risk, metabolic–inflammatory signaling, and immune–stromal remodeling. Mechanisms include palmitate-induced ER stress, ROS-driven NLRP3–IL-1β and STAT5 signaling, and KRAS^G12D-mediated lipotoxicity. Lipid-laden stellate cells promote fibrosis, immunosuppression, and epithelial–mesenchymal transition. NAFPD may represent an early, modifiable PDAC niche, warranting further imaging–omic studies and targeted prevention trials.
