Pakistan journal of pharmaceutical sciencesDaoman Xia, Jiana Zang
BACKGROUND: Adolescent diabetic kidney disease (DKD) represents an early-onset microvascular complication characterized by prolonged metabolic exposure and accelerated renal decline. Elevated serum creatinine and blood urea nitrogen (BUN) are key biochemical indicators of impaired renal function. OBJECTIVES: This scoping review aims to systematically map and evaluate pharmacological strategies for slowing the rise of creatinine and BUN in adolescents (aged 10-19 years) with DKD, with emphasis on renoprotective mechanisms, therapeutic sequencing and the potential applicability of these therapies to adolescent populations. METHODS: A scoping review was conducted in accordance with PRISMA-ScR guidelines. A comprehensive literature search was performed using PubMed, Scopus and Google Scholar for studies published between 2020 and 2025. Eligible studies included clinical trials, observational studies, clinical guidelines and relevant reviews focusing on pharmacological interventions in adolescents (10-19 years) with diabetic kidney disease. Study selection was based on predefined inclusion and exclusion criteria. RESULTS: A total of 35 studies and guideline-based references were included in the final synthesis. Intensive glycemic control (insulin for type 1 diabetes; metformin ± insulin for type 2 diabetes) was associated with improved metabolic control and favorable renal outcomes. Renin-angiotensin system blockers consistently reduced albuminuria and induced an acute hemodynamic reduction but stabilized the long-term decline in estimated glomerular filtration rate (eGFR). Sodium-glucose cotransporter-2 (SGLT2) inhibitors demonstrated additional renoprotective effects in type 2 diabetes; risks (euglycemic DKA) limit use in type 1. In adult studies, finerenone attenuated inflammatory and fibrotic pathways; no adolescent data exist. Glucagon-like peptide-1 receptor agonists improved metabolic control and reduced obesity-associated renal stress. However, pediatric-specific evidence remains limited, and much of the available evidence is derived from adult studies. CONCLUSION: Adult data suggest potential benefits of early multi-target pharmacotherapy, but adolescent-specific evidence is needed to confirm a critical role in delaying renal deterioration. Whether integration of conventional and novel agents improves long-term renal outcomes in adolescents requires direct investigation. Further pediatric-focused research is required to establish safety, efficacy and optimal therapeutic strategies.
Biomedical chromatography : BMCB Stojanovic, D Pecher, V Jeitler, S Portenschlager, T Geisendorfer, G Gmeiner
Analytical performance in anti-doping science continues to evolve through the identification of novel metabolites, improved detection sensitivity, and the use of alternative biological matrices. In recent years, dried blood spots (DBS) have gained increasing attention in doping control due to advantages such as improved analyte stability and simplified, cost-effective sample collection, shipment, and storage. However, DBS sampling is inherently limited by the small sample volume and the restricted number of spots available for analysis. Therefore, sensitive and comprehensive analytical strategies are required to maximize the information obtained from a single DBS or Tasso M20 devices. This study aimed to develop and validate a two-step analytical workflow enabling the detection of 91 target compounds, including selected non-threshold substances (NTS) and anabolic steroid esters (ASE), in two dried blood matrices: cellulose-based DBS cards and volumetric absorptive microsampling devices (Tasso M20 pebbles). The protocol comprises extraction with a methanol-acetonitrile mixture (4:1, v/v), followed by LC-MS/MS analysis for NTS. Subsequently, the extract is evaporated, derivatized with Girard P reagent, and analyzed by LC-MS/MS for ASE detection. The validated method proved suitable for qualitative detection of the selected prohibited substances.
Journal of medical primatologySarah M Kezar, Sarah J Neal, Gregory K Wilkerson
BACKGROUND: Owl monkeys (Aotus spp.) are a nocturnal nonhuman primate (NHP) native to central and South America that are used as infectious disease research models for human diseases, such as malaria and human immunodeficiency virus. Natural and infectious diseases may cause alterations in the hematology and serum biochemistry values, which necessitate the availability of reliable reference intervals for healthy animals. METHODS: In this study, hematology and serum chemistry reference intervals for Aotus nancymae were calculated from 191 healthy animals (95 female, 96 male) and were generated based on age class (juvenile, adult, geriatric), sex (adults only), and across the entire sample. RESULTS: Significant differences were observed in multiple parameters as a function of sex and age, some of which are inconsistent with existing data from Aotus spp. and other NHPs. CONCLUSIONS: The availability of age and sex specific reference intervals will be a valuable resource for monitoring the clinical health and effects of research interventions in owl monkeys.
Biomedical chromatography : BMCAbhishek Dixit, Arunava Das
Tucatinib (Irbinitinib, ARRY-380), a potent oral, selective HER2 kinase inhibitor that the FDA, has approved for the treatment of HER2-positive metastatic breast cancer and colorectal cancer. Tucatinib provides a powerful, targeted therapy for HER2-positive cancers, showing substantial benefits in survival and disease control, especially for patients with difficult-to-treat brain metastases, extending options beyond standard chemotherapy. This research aimed to create and validate a new rapid, sensitive, and specific LC-MS/MS technique for measuring tucatinib in dried blood spots (DBS) from mice, with afatinib serving as an internal standard (IS) following regulatory guidelines in the linearity range from 0.178 to 1009 ng/mL (r > 0.990). The chromatographic separation of tucatinib and IS was achieved using the Acquity BEH C18 column with an isocratic mobile phase at a flow rate of 0.6 mL/min within 1.15 min total run time and 2 μL injection volume. Detection and quantification of tucatinib and the IS was done by using a triple quadrupole mass spectrometer in multiple reaction monitoring (MRM) mode. Tucatinib remained stable under various storage conditions. Comparison of DBS versus plasma samples concentrations showed a strong correlation, suggesting that DBS can serve as a valid alternative to plasma for pharmacokinetic evaluation.
Tropical animal health and productionDiannett Benito López, Laura B Gualdrón-Duarte, Rassiel Macedo Sucari, Guadalupe Orellana Ligas, Yemi Sanca Uscamayta, Feliciano Rivera Pachiño, Nancy F Huanca…
This study evaluated the effects of alpaca variety (Huacaya vs. Suri) and period on physiological parameters and stress indicators in late pregnancy, grazed on high-altitude cultivated pastures in Cusco, Peru (4,141 m.a.s.l). Eight Huacaya and six Suri alpacas were monitored in two experimental periods Transition (gestation months 8‒9) and Wet (gestation months 10-11), this last coinciding with the beginning of the rainy season. Data were analysed using a repeated measures model and Pearson correlations were established among selected variables. Regardless of variety, alpacas lost liveweight during the Transition period despite increased feed intake. Suri females displayed lower body temperatures (36.1 vs. 37.5 °C), and heart rates (60 vs. 65 beats/min) compared to Huacaya. No differences were associated either with variety or period in adrenocorticotropic hormone (ACTH) or cortisol in blood serum. The albumin-to-globulin ratio was lower in Suris and increased in Wet period. Differences in pasture crude protein contents between periods may explain increases blood urea nitrogen (BUN; + 1.25 mg/dL) in Wet period, whereas creatinine (CREA) was responsive to both variety and period. Distinct stress responses in Huacaya and Suri alpacas were evidenced by cortisol-ACTH correlations. Huacaya exhibit a stable hormonal feedback loop, whereas Suri are more influenced by period. Both alpaca varieties displayed unexpected negative cortisol-glucose correlations and differed in cortisol-protein metabolism associations. Despite physiological differences, kidney function remained consistent for both varieties. These findings highlight unique metabolic adaptations in alpacas and underscore the need for further research.
Acute gastroenteritis (AGE) is a common cause of pediatric emergency department (ED) visits and is frequently associated with dehydration and metabolic disturbances. Rapid assessment of electrolytes and glucose is essential in clinical management. Although venous blood gas analysis provides faster results, its agreement with standard serum biochemistry in pediatric AGE remains unclear. This retrospective observational study included children aged 1 month to 18 years who presented to the pediatric ED with AGE between January 1, 2024, and December 31, 2025, and underwent paired venous BGA and serum biochemical testing during the same visit. A total of 1853 paired measurements were obtained from 1191 patients, as some children contributed multiple paired measurements during repeated testing. Method comparison was performed according to Clinical and Laboratory Standards Institute (CLSI) EP09-A3 guidelines using intraclass correlation coefficients (ICC), paired comparisons, Pearson correlation, and Bland-Altman analysis. Both analyzers demonstrated acceptable intra-device reliability (ICC > 0.70). However, agreement between venous blood gas and serum biochemistry was poor for sodium, potassium, chloride, and glucose, with all inter-method ICC values below 0.70. Mean values differed significantly between methods for all parameters (P < .01). Bland-Altman analysis demonstrated wide limits of agreement (LOA) between the 2 methods; for example, glucose measurements showed a mean difference of 2.1 mg/dL with LOA ranging from -64.3 to 68.5 mg/dL. Venous blood gas electrolyte and glucose measurements are not interchangeable with serum biochemistry in children with acute gastroenteritis. While blood gas analysis may be useful for rapid screening or trend monitoring in urgent settings, confirmatory serum biochemical testing remains necessary for clinical decision-making in pediatric AGE.
MedicineHongsheng Deng, Kun Chen, Xinyong Liu, Jirun Chen
Although pulse oximetry (SpO2) is useful for real-time monitoring of oxygen saturation, it may not predict which patients will subsequently develop hypoxemia and require oxygen therapy. Laboratory biomarkers collected at admission may therefore facilitate earlier risk stratification and guide clinical decision-making. This study aimed to evaluate the association between the lactate dehydrogenase-to-albumin ratio (LAR) and oxygen therapy requirement in hospitalized patients with COVID-19. This retrospective study included hospitalized patients with COVID-19 admitted to the ICU of the Cancer Center of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, between February and March 2020. Patients were categorized into a non-oxygen therapy group (n = 40) and a group requiring oxygen therapy (n = 21) according to the requirement for supplemental oxygen therapy (SpO2 < 93%). Univariate and multivariate logistic regression analyses were performed to identify factors associated with oxygen therapy requirement. Receiver operating characteristic (ROC) curves were used to assess the predictive performance of the identified factors. Sixty-one hospitalized patients with COVID-19 (mean age 63.18 ± 11.01 years; 22 males [36.07%]) were included, among whom 21 required oxygen therapy. Multivariable logistic regression analysis showed that the lactate dehydrogenase-to-albumin ratio (LAR; OR = 2.06, 95% CI: 1.00-4.21, P = .049) was independently associated with oxygen therapy requirement. ROC analysis demonstrated that LAR had an area under the curve (AUC) of 0.762 with 81.0% sensitivity and 72.5% specificity at an optimal cutoff value of 5.240. A combined model incorporating LAR, lymphocyte count, cough, d-dimer, bilateral lung involvement, chest tightness, and shortness of breath achieved an AUC of 0.818 with 76.2% sensitivity and 80.0% specificity. LAR was independently associated with oxygen therapy requirement in hospitalized patients with COVID-19 and may help clinicians identify patients at higher risk of requiring oxygen therapy, thereby supporting early triage and optimal allocation of medical resources.
Journal of infection and chemotherapy : official journal of the Japan Society of ChemotherapyEiki Ogawa, Yuto Fukuda, Eiji Hisamatsu, Kenta Ito
INTRODUCTION: Urinalysis is commonly used to diagnose urinary tract infections (UTIs), but its accuracy is reduced in children undergoing clean intermittent catheterization (CIC) because of asymptomatic pyuria. This study aimed to determine the optimal urinary leukocyte cutoff value for diagnosing UTIs using a hemocytometer. METHODS: This retrospective observational study included children (<16 years) on CIC at a tertiary children's hospital between April 2020 and March 2025. Quantitative urinalysis was performed using a UF-1500 hemocytometer. UTI was defined as bacteriuria ≥104 CFU/mL accompanied by antimicrobial treatment. Receiver operating characteristic (ROC) curve analysis was used to identify the optimal cutoff for urinary white blood cell (WBC) count. RESULTS: Among 134 patients (2871 specimens), 101 specimens were classified as infection cases (3.5%). Median urinary WBC counts were markedly higher during infection (1514.6/mm3) than during non-infectious periods (21.2/mm3; p < 0.001). ROC analysis yielded an area under the curve of 0.950 (95% CI, 0.935-0.964). The optimal cutoff value was 220.8/mm3, corresponding to 94.1% sensitivity, 84.7% specificity, and 99.7% negative predictive value. WBC counts did not significantly differ among infections caused by different uropathogens. CONCLUSIONS: Hemocytometer-based quantification of pyuria provided high diagnostic accuracy and may be particularly useful as a rule-out test for UTIs in children undergoing CIC.
Clinical biochemistryJason L Robinson, Veni Bharti
INTRODUCTION: Chemical urinalysis provides rapid analysis of multiple tests simultaneously including glucose, ketones, leukocyte esterase, nitrite, bilirubin, urobilinogen, pH, specific gravity, protein and hemoglobin. While highly coloured urines may impact readability of urine dipsticks there is no specific data on the effects of visible blood for dipstick analysis. We aimed to evaluate the effect of urinary hemoglobin on 10SG multistix and establish a process for handling visibly bloody urines received in our laboratories. METHODS: In vitro bloody urine pools were made using residual RBCs or leukoreduced RBCs and tested for interference patterns among tests included on the 10SG multistix. We further examined the effect of centrifugation and lysis on bloody urine samples both in vitro and among visibly bloody patient urine specimens. RESULTS: The presence of blood in urine samples caused profound interference for leukocyte esterase, nitrite, protein, glucose, ketones, and urobilinogen. Urine protein was most sensitive to hemoglobin interference at >0.2 g Hgb/L; and clinically significant interference was observed at >1 g Hgb/L with 10SG dipsticks. Bloody patient urines demonstrated similar interference patterns observed in vitro, although some clinical samples were positive for bilirubin. This phenomenon was replicated in vitro after RBC lysis. Centrifugation was not a viable strategy to eliminate interference due to blood. CONCLUSION: Visibly bloody urines are wholly unreliable for chemical urinalysis with 10SG multistix when hemoglobin is >1 g/L. An optimal process was established to withhold results of visibly bloody urines when dipstick hemoglobin is 3+ and protein is >1+ using 10SG multistix.
Ecotoxicology and environmental safetyTianjiao Lan, Weixin Liu, Sicheng Li, Shiqi Chen, Jiaxin Liu, Jian Zhang, Chi Heng, Gang Wang, Tao Zhou
Evidence on the association between maternal exposure to fine particulate matter (PM2.5) and gestational diabetes mellitus (GDM) remains inconsistent, and more robust evidence is lacking. We investigated the association between maternal PM2.5 exposure and GDM, identified susceptible exposure windows, and explored potential effect modification. Using data from the China Southwest Birth Cohort, daily PM2.5 exposure was estimated at residential addresses during the first trimester, the second trimester, and the first two trimesters combined. GDM was diagnosed using a 2-hour 75-g oral glucose tolerance test between 24 and 28 gestational weeks. To strengthen causal inference, we applied a two-stage residual inclusion instrumental variable approach using wind speed as the instrument. Among 15,266 participants, 2487 (16.3%) developed GDM. For each 10 μg/m3 increase in PM2.5, higher exposure during the first trimester (OR: 1.16, 95% CI: 1.04-1.30) and the first two trimesters (OR: 1.15, 95% CI: 1.01-1.31) were associated with increased GDM risk, whereas second-trimester exposure was not (OR: 1.08, 95% CI: 0.95-1.22). Attributable fraction analyses indicated that 7.9% and 30.6% of GDM cases for first-trimester exposure, and 6.9% and 29.8% for exposure during the first two trimesters, were attributable to PM2.5 above reference levels of 35 and 5 μg/m³ , respectively. For first-trimester exposure, the association appeared weaker among women with normal pre-pregnancy BMI and among those with regular physical activity. This study suggests that higher maternal PM2.5 exposure is associated with increased GDM risk, with early pregnancy as a susceptible exposure window. Abnormal pre-pregnancy BMI or lack of physical activity may increase susceptibility to PM2.5-related GDM.
Sleep medicineWissal Baghdad, Mohamed Yassine El Brouzi, Aboubaker El Hessni, Sara El Ghaffouli, Otmane El Harrati, Marouane El Arbaoui, Oumaima Abouyaala, Amal Dimaoui, Lei…
Sleep deprivation (SD) is a potential risk factor for the development of various metabolic disorders, including type 2 diabetes (T2D). In humans, SD has been associated with impaired glucose metabolism. To date, the link between chronic sleep deprivation (CSD) and glucose homeostasis remains unclear. To better understand the underlying mechanisms, we investigated the impact of chronic REM-SD on glucose homeostasis, insulin sensitivity, and physiological functions in Wistar rats, as well as on markers of oxidative stress and histopathological changes observed in organs. Eighteen adult male Wistar rats were randomly divided into three groups: CSD, WP, and control (CON). Rats in the CSD group (n = 6) were subjected to daily REM sleep deprivation for 18 h/day (16:00 to 10:00) for five weeks using the modified multi-platform method (MMPM). An intraperitoneal glucose tolerance test and an insulin tolerance test were performed after REM-SD and a 12-h fasting period, respectively. The changes induced by REM-SD were assessed by monitoring body weight, water and food consumption, and the measurement of regulatory hormones such as acetylcholinesterase and corticosterone, insulin, and the HOMA-IR score. Biochemical parameters such as glucose, TG, TC, LDL, HDL, ASAT, ALAT, TP, ALB, CPK, CREA, URE, and LDH were also measured. In addition, an oxidative stress and histopathological study was performed on various organs. After REM-SD, rats exhibited glucose intolerance and also developed increased insulin sensitivity. Elevated plasma glucose levels, plasma levels of CORT, LDH, markers of oxidative stress, and decreased plasma levels of BuChE, as well as impaired hepatic and pancreatic function, confirmed by significant histopathological changes, were observed. Ticking together, these modifications and alterations in physiologic mechanisms induced by CSD lead to hyperglycemia, glucose intolerance, and insulin resistance. Our funding suggests that oxidative stress and cytotoxicity are the key potent mechanisms responsible for the impact of chronic REM-SD on the development of T2D in rats.
BACKGROUND: Nocturnal hypoxic burden (HB) has been described using multiple algorithmic definitions, each based on different assumptions regarding signal segmentation and baseline reference, in obstructive sleep apnea (OSA). However, existing approaches share several methodological limitations and lack a standardization. These metrics have been applied almost exclusively in OSA and only on polysomnographic recordings, rendering the resulting indices non-comparable across methods. To address these gaps, we introduce the Dynamic Evaluation of Peripheral Hypoxia (DEPH), a method applicable to nocturnal pulse-oximetry and across heterogeneous respiratory diseases. METHODS: A retrospective analysis was conducted on 1000 consecutive nocturnal pulse-oximetry recordings from patients with heterogeneous chronic respiratory disorders referred for suspected nocturnal hypoxemia. DEPH was designed to express HB as a dimensionless measure through the ratio of two areas (desaturation area/global area). The performance of DEPH was compared with that of three other methods (HB100, fixed 100% SpO2 baseline; HB90, fixed 90% baseline; HBFA, fully automated) already used for HB determination, after standardizing the HB (sHB), so that the resulting indices were directly comparable. RESULTS: The cohort had a mean age of 65.9 ± 13.1 years (60% male) and a mean BMI of 34.6 ± 9.0 kg m-2. Mean SpO2 was 90.0 ± 4.7%, nadir 75.3 ± 10.6%, SpO2stDev 2.8 ± 1.8% and T90 34.4 ± 33.9%, reflecting marked variability in oximetric patterns across individuals. The estimation of sHB was statistically different between the four methods used (sHBDEPH 4.1 ± 2.8%, sHBFA 2.4 ± 1.6%, sHB100 9.8 ± 3.9%, sHB90 1.9 ± 3.0%, p < 0.001). CONCLUSIONS: DEPH appears to provide a more complete representation of desaturation areas and hypoxic burden applicable to nocturnal pulse-oximetry across heterogeneous chronic respiratory diseases, while its standardization (sHB) offers a common scale on which existing HB methods can be directly compared. As a methodological exploration rather than a clinical validation, the approach requires further study in larger, external cohorts to establish its clinical and prognostic value.
Veterinary parasitologySergio Villanueva-Saz, Antonio Fernández, Diana Marteles-Aragüés, Laura Garza-Moreno, Luis Martínez-Lostao, R Adam Harris, A Russell Moore
Canine leishmaniosis caused by Leishmania infantum commonly induces marked dysproteinemia, yet restricted or apparently monoclonal gammopathies may complicate interpretation of serum protein electrophoresis (SPE). This study characterized SPE and immunofixation findings in 38 clinically sick dogs with confirmed canine leishmaniosis and evaluated interobserver agreement in gammopathy classification. SPE and immunofixation using anti-human reagents was performed on serum from 38 sick dogs with confirmed clinical leishmaniosis and without evidence of plasma cell neoplasia. The SPE data alone and a combined SPE and immunofixation (IF) study were interpreted by 4 reviewers. Inter-observer agreement for presence of an acute phase response and gammopathy pattern by electrophoresis alone or with immunofixation was assessed using Gwet's AC1 and quadratic weighted AC2. Change in agreement with addition of immunofixation was assessed. All dogs demonstrated hypergammaglobulinemia and decreased albumin-to-globulin ratios. Hyperproteinemia and hypoalbuminemia were common, and hyperbetaglobulinemia was frequently observed. Immunofixation labeling was predominantly IgG with minimal IgA and IgM detection. Most cases had an IgG polyclonal or restricted polyclonal gammopathy. Interobserver agreement for gammopathy classification using SPE alone was high (AC2 = 0.902), but disagreements spanned the diagnostic spectrum in some cases. The addition of immunofixation significantly improved agreement (AC2 = 0.944; P = 0.034) and reduced extreme interpretive divergence. No case was unanimously classified as monoclonal, and incorporation of immunofixation reduced suspicion for monoclonality in cases initially considered equivocal. Dogs clinically affected for canine leishmaniosis exhibit predominantly IgG-driven polyclonal hypergammaglobulinemia. Together, SPE and IF provide a more complete characterization of gammopathy patterns in dogs with leishmaniosis, particularly when SPE reveals restricted or monoclonal-like abnormalities that could otherwise raise concern for plasma cell neoplasia.
Diabetic medicine : a journal of the British Diabetic AssociationTaoming Qian, Donghao Guo, Meijun Zhang, Yuhan Liu, Juan Jin
BACKGROUND: Traditional management of type 2 diabetes mellitus (T2DM) and pre-diabetes centres on HbA1c reduction, yet this single metric fails to capture glycaemic variability (GV)-an independent driver of β-cell dysfunction, endothelial damage, oxidative stress, inflammation and cardiovascular risk, even in the pre-diabetes stage. Unlike existing reviews that focus predominantly on T2DM or HbA1c-centric approaches, this perspective articulates a unified three-pillar closed-loop framework that integrates continuous glucose monitoring (CGM) across the entire pre-diabetes-to-remission continuum. PERSPECTIVE: We synthesize evidence from prospective cohorts, mechanistic studies, randomized controlled trials and real-world data to demonstrate that GV is a modifiable therapeutic target. CGM uniquely reveals dynamic glucose patterns invisible to HbA1c, enabling precise, real-time interventions that improve time in range (TIR), reduce GV and hypoglycaemia and support the achievement of clinical remission (HbA1c <48 mmol/mol (<6.5%) without glucose-lowering medication for ≥3 months) in subsets of patients. CONCLUSIONS: CGM-centred management of glycaemic stability offers a clinically actionable paradigm shift from static, average-glucose control to dynamic, precision-guided care. The proposed three-pillar framework-tiered personalized targets, data-driven intelligent decision support and empowered patient-clinician collaboration-provides a structured roadmap grounded in current evidence. Long-term outcomes in pre-diabetes, cost-effectiveness and global accessibility remain important areas for future investigation.
Diabetes research and clinical practiceGabriella Rákóczi, Dávid Csányi, Roland Molontay, Gergely Agócs, Boglárka Lilla Szentes, Jimin Lee, Anett Rancz, Péter Hegyi, Emese Sipter
AIMS: Prediabetes classification based on hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) shows substantial discordance, potentially limiting early identification of individuals at metabolic risk. We evaluated whether continuous glucose monitoring (CGM) metrics can classify prediabetes with performance approaching that of HbA1c and FPG. METHODS: We conducted a cross-sectional analysis of 1,883 participants from the Human Phenotype Project with concurrent CGM, HbA1c, and FPG data. Individual CGM metrics were evaluated across four ADA-based laboratory reference definitions, and a combined model incorporating six clinically selected CGM metrics was additionally assessed. Discrimination was quantified using the area under the receiver operating characteristic curve (AUC). RESULTS: HbA1c- and FPG-based classifications showed marked discordance, with only 9.5% of participants meeting both prediabetes criteria. Several CGM metrics demonstrated classification performance approaching that of laboratory markers (AUC range 0.645-0.677). Discrimination improved when prediabetes was defined by both criteria, but no single marker achieved high performance independently. CONCLUSIONS: CGM metrics achieve classification performance approaching conventional laboratory markers while capturing complementary aspects of glycemic regulation. These findings support CGM as a complementary rather than standalone tool alongside conventional markers, particularly when laboratory results are discordant. Prospective studies incorporating oral glucose tolerance testing and longitudinal outcomes are warranted.
Diabetes research and clinical practiceJumana Abuqwider, Edoardo Pasolli, Giuseppe Scidà, Alessandra Corrado, Marilena Vitale, Annalisa Giosuè, Francesca De Filippis, Danilo Ercolini, Giovanni Annuz…
AIMS: To examine the associations between ultra-processed food (UPF) intake, glycemic control, cardiovascular risk factors, and gut microbiome in adults with type 1 diabetes (T1D). METHODS: In 253 adults with T1D, diet was assessed using the EPIC food-frequency questionnaire, and UPFs classified according to NOVA. Evaluations included lipid profile, HbA1c, and continuous glucose monitoring metrics. In a subgroup (n = 103), gut microbiota composition/function was analyzed using shotgun metagenomic sequencing and beta-diversity assessed by PERMANOVA. Associations were examined using multivariable regression models adjusted for age and Mediterranean diet adherence. RESULTS: Mean UPF intake was 15.5 % of total food intake. Higher UPF intake was independently associated with higher triglycerides (β per 20 g/1000 kcal = 3.62 mg/dL; 95 %CI 1.16-6.08) and lower HDL-cholesterol (β = - 0.98 mg/dL; 95 %CI - 1.72 to - 0.24). Sugar/artificially sweetened beverages were positively associated with triglycerides and animal-based UPFs inversely associated with HDL cholesterol. In participants on multiple daily injections or open-loop systems, ready-to-eat mixed dishes were positively associated with HbA1c. Microbiome beta-diversity significantly differed according to UPF intake. Triglycerides positively associated with microbial pathways (ketogluconate, tetrapyrrole, and acetate metabolism). CONCLUSION: Higher UPF intake was associated with atherogenic dyslipidemia, poorer glycemic control in selected groups, and gut microbiome alterations in adults with T1D. The study was registered at ClinicalTrials.gov with the identifier NCT05936242.
Contemporary clinical trialsKallie Brown, Mike Ushakov, Eugene Molodkin, Samantha R Spierling Bagsic, Camille Bell, Athena Philis-Tsimikas
BACKGROUND: Mobile health apps have the potential to enhance education for glycemic management in individuals with type 2 diabetes (T2D). The growing desire to use diabetes-related mobile applications indicates the industry's broad effort in leveraging technology to improve health outcomes in diabetes patients. However, many available applications still lack evidence-based features, and applications that go through clinical validation often do not include an active control in their studies. The purpose of this in-progress trial is to evaluate the effectiveness of a novel photo-based food diary smartphone app (Undermyfork) that visually connects meals to glucose excursions to promote behavior change. METHODS: This is a randomized, controlled, prospective, parallel-group trial with an active comparator, enrolling N = 90 adults with T2D, elevated HbA1c, and continuous glucose monitoring (CGM) naivety in a real-world community-based health system. Participants complete a run-in/screening period, and if eligible, are randomized into the intervention to use CGM alone (Group 1) or to use the Undermyfork mobile app in addition to CGM (Group 2). The trial will examine comparative effectiveness in improving CGM metrics, HbA1c, and diabetes self-care behaviors over 4 months. DISCUSSION: We hypothesize that Group 2 will have more evident improvements in CGM metrics and HbA1c given Undermyfork's focus on utilizing CGM data to understand meal-related decisions that may allow participants to gain insights into the relationship between their dietary choices and glucose fluctuations throughout the day. This trial may have implications for improved glycemic management, reduced risk of diabetes-related complications, and enhanced well-being for individuals with T2D. CLINICAL TRIAL REGISTRATION: Clinicaltrials.govNCT06501612https://clinicaltrials.gov/study/NCT06501612.
Diabetes research and clinical practiceAnne E Sumner, Anika J Shah, Ananya Bharadwaj, Grace G Smith, Kauthrah Ntabadde, Bella S Izere, Christopher W DuBose, Ram Jagannathan, David B Sacks
Diagnostic reproducibility of diabetes was substantial (ҝ-statistic = 0.74, 95%CI: 0.58-0.90) in 154 African descent individuals with 1 h-OGTTs performed 10 ± 7d (mean ± SD) apart. Diabetes was diagnosed in 34 individuals with 65%(22/34) detected at both visits (non-switchers) and 35%(12/34) at one visit (switchers). With insulin resistance greater in non-switchers, 1 h-OGTT reproducibility may be better if insulin resistance present.
Biochemical and biophysical research communicationsAkira Toda, Shinsuke Mohri, Kisara Ueda, Koki Daido, Daichi Fuchisawa, Futoshi Furuya, Eri Mukai
D-Serine (D-Ser), an enantiomer of L-Serine (L-Ser), has been reported to exert unique physiological effects distinct from those of L-Ser. Chronic oral administration of L-Ser has been reported to improve glucose tolerance in diabetic model mice. In this study, we compared the acute effects of oral administration of L-Ser and D-Ser on postprandial blood glucose regulation and the underlying mechanisms in healthy mice. Oral glucose tolerance tests were performed in C57BL/6J mice administered L-Ser or D-Ser (2.0 g/kg BW) simultaneously with glucose loading. Both L-Ser and D-Ser significantly suppressed postprandial hyperglycemia compared with the control group. However, neither L-Ser nor D-Ser significantly affected serum insulin levels after glucose loading or insulin sensitivity during insulin tolerance tests, suggesting that their glucose-lowering effects were independent of insulin secretion and insulin sensitivity. In addition, intraperitoneal glucose tolerance tests showed no significant changes in postprandial hyperglycemia after administration of either L-Ser or D-Ser. In intestinal glucose absorption assays using everted intestine, both L-Ser and D-Ser significantly suppressed glucose absorption. Furthermore, Western blotting analysis demonstrated that L-Ser reduced GLUT2 expression in the brush border membrane, whereas D-Ser reduced both SGLT1 and GLUT2 expression. These findings demonstrate that single oral administration of l-/D-Ser acutely suppresses postprandial hyperglycemia independently of insulin secretion and insulin sensitivity by inhibiting intestinal glucose absorption. In addition, the underlying mechanisms may differ between L-Ser and D-Ser, as reflected by their distinct effects on intestinal glucose transporters, suggesting stereospecific regulation of intestinal glucose metabolism.
Journal of pharmaceutical and biomedical analysisXiaoxue Liu, Fangfang Liu, Haiping Dai, Fang Tang, Linsheng Liu, Jie Gao, Jia Chen, Qi Qu, Mengxing Xue, Haixia Zhou, Wenzhi Cai, Yin Liu, Yan Xie, Chenrong Hu…
Invasive fungal diseases pose a significant threat to human health. Therapeutic drug monitoring (TDM) of isavuconazole, a new-generation triazole antifungal agent, is recommended; however, conventional cubital venous blood collection is invasive and requires large blood volumes as well as sample transportation and storage. Quantitative dried blood spot (qDBS) sampling can overcome these limitations and may provide better analytical accuracy than conventional dried blood spot assays. This study developed and validated an ultra-performance liquid chromatography-tandem mass spectrometry method to determine isavuconazole in qDBS. Samples were extracted using an acetonitrile-water solution (70:30, v/v). Chromatographic separation was achieved on an Acquity UPLC® BEH C18 column (100 × 2.1 mm, 1.7 µm). The mobile phase consisted of water (0.02% formic acid) and acetonitrile at a flow rate of 0.6 mL/min, with a total runtime of 2.5 min. The method was linear over 0.1-50 µg/mL and demonstrated good precision (maximum coefficient of variation, 9.9%) and accuracy. Mean recovery was 96.9%. Hematocrit values ranging from 0.2 to 0.65 did not significantly affect the analysis results. qDBS samples were stable for 17 days at room temperature and for 22 days at -20 °C. Reconstituted samples in the autosampler (4 °C) were stable for at least 24 h. Plasma and fingerprick qDBS concentrations from 20 patients were compared using Passing-Bablok regression and Bland-Altman analyses, confirming good agreement. Overall, these findings support qDBS sampling for isavuconazole TDM and suggest that it may replace or supplement conventional sampling in hematology patients (HCT range 0.15-0.40).