Endocrinology, diabetes & metabolismAjmina Hasan Flabe, Bedowra Zabeen, Shatil Amirat, Jing Luo
OBJECTIVES: To characterise the magnitude of glycaemic variability and to examine the factors associated with it, with particular attention to residual beta-cell function measured by fasting C-peptide, in children, adolescents, and young adults with diabetes in Bangladesh. DESIGN AND SETTING: Prospective observational study at the BADAS Paediatric Diabetes Care and Research Centre, BIRDEM, Dhaka, using 14 days of blinded professional continuous glucose monitoring (CGM). Participants were enrolled between March and November 2024. PARTICIPANTS: Ninety-seven participants aged 1-25 years (68 with Type 1 and 29 with Type 2 diabetes) had at least seven valid CGM days and a paired HbA1c within 2 weeks of CGM initiation. Fasting C-peptide was available for 46 participants. MAIN OUTCOME MEASURES: The coefficient of variation (CV) of glucose as the primary metric of variability; time in range, time above range, and time below range as secondary metrics; and independent predictors of CV on multivariable regression. RESULTS: Mean CV was 39.4% (SD 9.2), and 59 of 97 participants (60.8%) were at or above the recommended target of 36%. CV was higher in Type 1 than Type 2 diabetes (41.9% vs. 33.3%). Lower fasting C-peptide was independently associated with higher CV after adjustment for diabetes type, age, and insulin dose (-1.94 percentage points per ng/mL, 95% CI -3.35 to -0.53; model R-squared 0.52), with a graded relationship across pre-specified C-peptide categories for CV, time in range, and time below range. CONCLUSIONS: Glycaemic variability substantially exceeds international targets in this setting. Fasting C-peptide, available for fewer than half of the cohort, showed a graded association with variability that is best regarded as hypothesis-generating; if confirmed in larger studies, it could offer a low-cost means of identifying children at highest variability risk where CGM access is limited.
European journal of nutritionStephany G Duarte, Carlos M Donado-Pestana, Larissa Rodrigues, Marcos Yoshinaga, Adriano B Chaves-Filho, Sayuri Miyamoto, Jarlei Fiamoncini
PURPOSE: The postprandial period provides a dynamic window to assess metabolic function, as nutrient intake elicits measurable shifts in metabolism, that can be used to assess health status. Traditional venipuncture, though standard for blood sampling, poses practical limitations for postprandial studies that require repeated collections. This study evaluated the feasibility of using dry blood spots (DBS) as a minimally invasive alternative for monitoring postprandial lipemia, which can vary significantly after the intake of high-fat meals. METHODS: Ten young women (26.1 ± 4.5 years) participated in a controlled clinical trial designed to evaluate lipidomic responses to a standardized, energy-dense meal using both DBS and capillary plasma samples. An analytical method based on ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-ESI-TOFMS) was employed for the quantitative profiling of lipid species. RESULTS: The postprandial lipidome derived from DBS and plasma samples exhibited high concordance, with triglycerides (TG) and free fatty acids (FFA) standing out among 18 identified lipid classes as the most responsive to food intake in both matrices. Postprandial TG concentrations increased by 64% in plasma and 34% in DBS, while FFAs decreased by 36% and 14%, respectively. In addition, DBS-specific postprandial lipidomic signatures were observed, including alterations in the levels of glycerophospholipids and sphingolipids, along with a peculiar kinetic pattern of phosphatidylethanolamines levels following food intake. CONCLUSION: These findings highlight the suitability of DBS for capturing postprandial lipidomic changes in circulation, particularly in TG and FFA levels, and support its utility as a practical and scalable tool for metabolic phenotyping in nutritional research, population studies, and clinical monitoring.
Journal of visualized experiments : JoVEDaniel Marques de Sá E Silva, Marlene Thaitumu, Georgios Theodoridis, Helen Gika
Blood microsampling (BµS) has emerged as a robust, minimally invasive alternative to traditional venipuncture, enabling the collection of low-volume specimens outside conventional clinical settings. By supporting decentralized sampling and improving patient adherence, these devices can be integrated with advanced omics technologies to facilitate large-scale and longitudinal study designs. However, successful implementation requires optimization of multiple critical steps, from sample collection and storage to extraction and analytical preparation. In this work, we propose a comprehensive end-to-end untargeted metabolomics workflow for BµS, with an emphasis on key parameters governing sample preparation and analytical performance. Volumetric absorptive microsampling (VAMS) devices were evaluated using two complementary platforms: reversed-phase liquid chromatography coupled to mass spectrometry and gas chromatography coupled to mass spectrometry. Application of the optimized workflow demonstrated broad metabolomic coverage across diverse chemical classes, highlighting the potential of VAMS-based sampling to support scalable, decentralized metabolomics studies while maintaining analytical robustness, reproducibility, and biological relevance.
INTRODUCTION: High intake of ultra-processed foods (UPFs) is associated with an increased risk of type 2 diabetes. However, evidence from randomised controlled trials evaluating the effect of UPF reduction on postprandial glucose responses and glycaemic variability in young adults is limited. The Ultra-Processed Food Reduction Intervention and Continuous Glucose Monitoring (ULTRA-CGM) trial aims to evaluate the effects of a UPF-reducing dietary intervention on postprandial glucose responses and glycaemic variability in healthy Korean young adults. METHODS AND ANALYSIS: This is a parallel, two-arm randomised controlled trial enrolling 50 participants (aged 20-39 years) with UPF intake ≥25% of daily energy. Following a 10-day baseline monitoring period using CGM and lifestyle diaries, participants are randomised 1:1 to a 40-minute one-on-one UPF-reducing dietary intervention or a 40-minute one-on-one standard dietary counselling based on national dietary guidelines (control). The intervention focuses on reducing UPF consumption, with participants counselled to maintain their usual total energy intake and lifestyle behaviours. After the intervention, participants undergo a 10-day CGM monitoring period and lifestyle diaries. The primary outcome is the change in postprandial glucose responses, quantified as 2-hour incremental area under the curve following meals, from baseline to postintervention. Secondary outcomes include changes in glycaemic variability metrics (coefficient of variation, SD, mean amplitude of glycaemic excursions, glucose spike frequency), time-in-range metrics, body weight, waist circumference, body composition, blood pressure and handgrip strength. For the analyses, between-group differences will be evaluated using analysis of covariance adjusting for baseline values, with daily CGM data analysed using linear mixed-effects models. This trial will provide evidence on whether targeted reduction of UPFs improves postprandial glucose control and glycaemic variability in healthy young adults. ETHICS AND DISSEMINATION: This study is approved by the Korea University Institutional Review Board (KUIRB-2025-0600-05). It will be conducted in accordance with the principles of the Declaration of Helsinki and the principles of the International Conference on Harmonisation Good Clinical Practice guidelines. Results will be disseminated through publications, academic conferences, PhD dissertation and social and lay media. TRIAL REGISTRATION NUMBER: NCT07175701.
PloS oneYuanzhi Yu, Margaret Banker, Jennifer Sherr, Denise M Scholtens
INTRODUCTION: Continuous glucose monitoring (CGM) produces rich time series data. Standard metrics such as time-in-range summarize glycemia but miss the sequence of changes. We aimed to characterize glucose dynamics using empirical transition probability techniques. MATERIALS AND METHODS: Using publicly available data for 244 participants who enrolled in the Insulin-Only Bionic Pancreas (IOBP2) randomized clinical trial, we mapped each CGM reading to one of five states: < 54, 54-69, 70-180, 181-250, or >250 mg/dL. We counted state changes between consecutive readings collected every 5 minutes. For each participant, we built a 5 × 5 transition probability matrix and averaged matrices within comparator groups. Statistical inference using estimated transition probability matrices was compared to inferences based on standard metrics including mean glucose, standard deviation, coefficient of variation, time-in-range metrics, Glycemia Risk Index (GRI), Mean of Daily Differences (MODD), and Mean Amplitude of Glycemic Excursions (MAGE). RESULTS: Transition probability analysis showed more frequent moves from hyperglycemia (181-250 or >250 mg/dL) to the in-range (70-180 mg/dL) state for the bionic pancreas that was evaluated in the IOBP2 trial compared to control. This pattern appeared in both adults and in children and persisted through the trial. Conventional CGM metrics also showed treatment differences in mean glucose, GRI, and time in range; MODD, MAGE, and coefficient of variation showed less consistent differences between treatment groups. CONCLUSION: Transition probability matrices provide an informative summary of glucose dynamics that complements established CGM metrics. In IOBP2, this approach highlighted improved patterns of recovery from hyperglycemia with the bionic pancreas compared with control. Future studies should determine whether transition-based summaries are associated with clinically meaningful outcomes.
Abnormal oxygenation may influence thrombosis, but evidence in catheterized critically ill patients remains limited. We examined whether the first arterial partial pressure of oxygen (PaO2) measured within 24 hours after qualifying invasive venous catheter insertion was associated with documented acute upper-body deep or central venous thrombosis during hospitalization. This retrospective observational cohort study used the Medical Information Mart for Intensive Care IV database, version 2.2 (MIMIC-IV v2.2) (2008-2019). Adult intensive care unit admissions were included when a qualifying invasive venous catheter was present and an arterial PaO2 measurement was obtained after insertion, within 24 hours, and while the catheter remained in situ. PaO2 was analyzed continuously and categorically (≤80, 81-100, and >100 mmHg). Logistic regression models sequentially adjusted for patient characteristics, laboratory measurements, catheter characteristics, measurement timing, inspired oxygen concentration, respiratory support, and non-respiratory organ dysfunction. Multiple imputation addressed missing covariate data, and patient-clustered robust standard errors accounted for repeated admissions. The cohort included 11,277 hospital admissions from 10,789 patients; 195 admissions (1.73%) had the primary outcome. In the unadjusted model, higher PaO2 was associated with lower odds of the outcome (odds ratio [OR] per 10-mmHg increase, 0.970; 95% confidence interval [CI], 0.952-0.987), but this association attenuated after adjustment. In the fully adjusted model, PaO2 was not associated with the outcome (OR, 1.008; 95% CI, 0.989-1.027; P = 0.430). Most secondary analyses supported the primary result, although the 60-minute sensitivity analysis yielded adjustment-dependent estimates. In the complete cohort, a single early post-insertion PaO2 measurement was not independently associated with documented acute upper-body deep or central venous thrombosis. These findings do not support PaO2-based thrombosis risk stratification or modification of oxygen therapy for thrombosis prevention. Future studies should incorporate repeated oxygenation measurements and accurately timed, imaging-confirmed thrombotic outcomes.
Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and GynaecologyXufeng Gong, Qian Zhu, Linlin Wang
BACKGROUND: Gestational diabetes mellitus (GDM) is a common pregnancy complication. Although lipid parameters, the triglyceride-glucose (TyG) index, and TyG-body mass index (TyG-BMI) have been associated with GDM, their relative value within an integrated lipid-glycaemic prediction framework remains unclear. This study developed and internally validated an interpretable model for GDM risk estimation. METHODS: This single-centre retrospective study included 287 pregnant women who underwent 75 g oral glucose tolerance testing and fasting lipid assessment at 24-28 gestational weeks, including 72 with GDM and 215 without GDM. Candidate predictors comprised maternal characteristics, fasting plasma glucose (FPG), routine lipid fractions, apolipoproteins, the TyG index, and TyG-BMI. Forward stepwise likelihood-ratio logistic regression was used to develop the original combined model. A structured alternative model replaced pre-pregnancy BMI, FPG, and triglycerides with TyG-BMI. Model performance was evaluated using receiver operating characteristic analysis, calibration measures, threshold-dependent diagnostic metrics, 1,000-resample bootstrap internal validation, paired DeLong testing, a nomogram, and decision curve analysis. RESULTS: Eight variables were retained in the original combined model: maternal age, pre-pregnancy BMI, FPG, total cholesterol, triglycerides, non-high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B. Its apparent and optimism-corrected AUCs were 0.848 (95% CI: 0.786-0.909) and 0.830, respectively; the bootstrap-corrected calibration intercept was -0.03, calibration slope was 0.86, and Brier score was 0.147. The TyG-BMI alternative model had apparent and optimism-corrected AUCs of 0.831 (95% CI: 0.765-0.897) and 0.817. The AUC difference was 0.017 (95% CI: -0.011 to 0.045; P = 0.235). Decision curve analysis indicated potential net benefit for both models across clinically relevant thresholds. CONCLUSION: Both models showed good internally validated discrimination and acceptable calibration for GDM risk estimation at routine screening. The original model had a numerically higher AUC, but discrimination did not differ significantly between models. External validation is required before clinical implementation.
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal ObstetriciansMuyi Yang, Jiahui Qi, Lei Lei, Shuli Zhao
OBJECTIVE: Group B Streptococcus (GBS) colonization during pregnancy is associated with adverse outcomes. The associations between GBS colonization status and clinical parameters measured at different antenatal time points, and whether these differ by maternal age, remain unclear. This study aimed to explore age-stratified associations between GBS colonization and clinical parameters. METHODS: A retrospective case-control study was conducted at a single center. Cases were GBS-positive women (n = 110), and controls were GBS-negative women (n = 155) selected from the same cohort and matched on key characteristics. Participants were stratified by maternal age (<35 [GBS-positive: n = 90; GBS-negative: n = 96] vs. ≥35 years [GBS-positive: n = 20; GBS-negative: n = 59]). GBS colonization was determined by standard culture of vaginal and perianal swabs at 35-37 weeks. Oral glucose tolerance test (OGTT) was performed at 24-28 weeks. Hemoglobin (Hb) levels and other biomarkers were compared between cases and controls within each age group. RESULTS: Among women aged < 35 years, GBS colonization was not associated with second-trimester OGTT results but was associated with lower third-trimester hemoglobin levels (116.98 ± 9.89 g/L vs. 120.49 ± 10.19 g/L in controls, p < 0.05) and a statistically significant but clinically negligible earlier gestational age at delivery (39.11 ± 1.05 vs. 39.41 ± 0.98 weeks, p = 0.04). In women aged ≥ 35 years, GBS colonization was associated with significantly higher fasting and 2-hour OGTT glucose levels (p < 0.05) and a higher second-trimester neutrophil percentage (76.27% ± 5.43% vs. 73.90% ± 4.08%, p = 0.04) compared to controls. The 1-hour OGTT value showed a non-significant trend (p = 0.06). No significant differences were observed in birth weight, infant sex, or mode of delivery. CONCLUSIONS: This exploratory study suggests that maternal age may modify the associations between late-pregnancy GBS colonization status and clinical parameters measured earlier in gestation. The observed patterns highlight the potential importance of considering maternal age when evaluating prenatal laboratory findings in GBS-colonized women and generate hypotheses for future research. However, given the study's retrospective design and the small sample size in subgroups, these findings should be interpreted with caution as hypothesis-generating rather than as evidence to guide clinical practice.
Diabetes mellitus (DM) is known to impair the quality of life. Natural products with high antidiabetic potential and fewer side effects have attracted considerable interest. Recently, investigations into plant materials for their antidiabetic properties have received greater attention. Therefore, in the current study, the dried pulp of custard apple (Annona squamosa) (AS) was investigated for its effects on Streptozotocin and nicotinamide (STZ-NA)-induced DM. The antidiabetic activity of AS was evaluated by measuring body weight, plasma glucose, plasma lipid levels, and liver glycogen content. The results show no alteration in glucose levels in normoglycemic rats. In contrast, the OGTT reduced glucose levels to 85.16 ± 3.19 mg/dL. There was a decrease in plasma total cholesterol, triglycerides (TGs), low-density lipoprotein, and very low-density lipoprotein (mg/dL) of 95.29 ± 4.07, 72.05 ± 1.20, 56.90 ± 3.26, 24.87 ± 4.26, and 11.38 ± 2.11, respectively, in diabetic rats. The AS treatment increased the high-density lipoprotein (35.80 ± 1.51 mg/dL), liver glycogen (21.65 ± 3.61 mg/g), and body weight (178.10 ± 5.81 g) in diabetic rats. AS also increased pancreatic enzyme levels while decreasing TBA-reactive substances in diabetic rats. Annona squamosa treatment reduced liver enzyme levels in diabetic rats. These findings suggest that dried AS pulp may improve diabetes by improving glucose, lipids, antioxidants, and liver enzymes.
Clinical reviews in allergy & immunologyGabriel Kc Leung, Andy Kc Kan, Philip H Li
Hereditary angioedema (HAE) is a genetic disorder characterised by recurrent cutaneous or submucosal oedema. Most cases are caused by pathogenic SERPING1 variants (types I and II), while a smaller subset presents with normal C1-inhibitor (C1-INH) levels and function (HAE-nC1INH). Despite its potentially life-threatening attacks, HAE remains under-diagnosed owing to inconsistent screening practices, low clinical awareness, poor patient acceptance, and resource limitations, resulting in diagnostic delays and preventable morbidity. Although international guidelines recommend family screening to identify at-risk relatives, no standardised protocol exists for its systematic implementation. Cascade family screening offers a structured approach to trace and test all known at-risk relatives across generations. Complementing this strategy, dried blood spot (DBS) assays provide a less invasive, cost-effective alternative to conventional serological testing, with particular utility in resource-limited settings. In this review, we critically appraise current screening methodologies, synthesise emerging evidence on cascade family screening and DBS-based diagnostics, and propose an actionable clinical flowchart to standardise identification, testing, and patient education from index case detection through multi-generational family screening.
JAMA network openAndrew J Karter, Melissa M Parker, Holly Finertie, Joshua R Nugent, Lisa K Gilliam, Ajit Mahapatra
IMPORTANCE: Real-time continuous glucose monitoring (rtCGM) improves short-term glycemic control in diabetes. However, scant evidence exists regarding rtCGM's longer-term benefits for glycemia or kidney health. OBJECTIVE: To evaluate whether rtCGM initiation and sustained use is associated with improved glycemic control and kidney markers in high-risk adults with type 2 diabetes (T2D). DESIGN, SETTING, AND PARTICIPANTS: This comparative effectiveness research study compared glycemic control and kidney markers among high-risk adults with T2D initiating and sustaining use of rtCGM (rtCGM arm) vs no initiation (controls) using inverse probability-weighted marginal structural models to estimate per-protocol outcomes of an emulated target trial. Target trial eligibility criteria were as follows: age of 19 years or older, T2D, no prior CGM use, and poor glycemic control (hemoglobin A1c [HbA1c] >8%) or emergency department or inpatient treatment for hypoglycemia. Baseline was defined by the rtCGM initiation date and applied to temporally matched CGM-naive controls who met the eligibility criteria, sampled monthly from risk sets from January 1, 2015, to June 30, 2023. Data were censored at nonadherence to the target trial protocol (eg, rtCGM arm discontinued use or controls initiated CGM), coverage gaps, death, or after 36 months of follow-up. Data analysis was performed July 2025 to March 2026. EXPOSURE: rtCGM use. MAIN OUTCOMES AND MEASURES: Cumulative differences for HbA1c, urinary albumin-creatinine ratio (UACR), and estimated glomerular filtration rate (eGFR). RESULTS: The study included 25 648 individuals (2771 in the rtCGM arm and 22 877 in the control arm) who were target trial eligible (mean [SD] age, 61.5 [13.1] years; 13 885 [54.7%] male). The mean (SD) baseline HbA1c level was 9.5% (1.5%). After 36 months of follow-up, the rtCGM arm had an approximately 0.8-percentage point lower HbA1c level than controls (7.83% [95% CI, 7.55%-8.11%] vs 8.58% [95% CI, 8.49%-8.66%], P < .001). There was substantial attrition during follow-up; 1228 (44.3%) in the rtCGM arm were censored due to discontinuation and 4284 (18.7%) in the control group were censored due to CGM initiation. There were no significant differences in UACR between arms initially; however, by the end of 36 months, rtCGM initiators had a UACR of 125.3 mg/g (95% CI, -196.6 to -54.0 mg/g; P = .001) lower than that of controls. There were no differences in eGFR during follow-up. CONCLUSIONS AND RELEVANCE: In this comparative effectiveness study using a target trial emulation, sustained, longer-term use of rtCGM was associated with durable improvements in glycemic control and later regression of UACR. By addressing glycemic deterioration, rtCGM may extend the time before pharmacologic escalation is required and potentially delay diabetic kidney disease progression.
Journal of managed care & specialty pharmacyShannon Gadd, Connor Willis, Ishfaq Rashid, Kyu Yun Park, Kayla Holland, Amy Beal, Carl Asche, Priyanka Ghule, Diana Brixner
BACKGROUND: Although continuous glucose monitoring (CGM) is well established for insulin-treated diabetes, its utility in non-insulin-treated type 2 diabetes (T2D) remains less studied. OBJECTIVE: To evaluate the short-term clinical and economic outcomes following personal use of CGM in patients with T2D. METHODS: This prospective pre-post study enrolled adults with poorly controlled non-insulin-treated T2D (hemoglobin A1c ≥8%; target N = 200) initiating G7 CGM and observed them for 6 months. Primary endpoints were changes in A1c and Audit of Diabetes-Dependent Quality of Life (ADDQoL) scores. Glycemic events, health care utilization, and medication use were evaluated in a subgroup with claims data. Baseline was defined as the 3 months before CGM initiation. Changes at 3 and 6 months were assessed using the Wilcoxon signed-rank test. Multivariable analysis of covariance models evaluated A1c change, adjusting for baseline A1c and clinical covariates. ADDQoL was analyzed using linear mixed-effects models with random intercepts and fixed effects for time, whereas Cuzick's test assessed quality-of-life trends. RESULTS: Of 217 enrolled patients, a subgroup of 76 had claims data. Most were White (75%) and male (58%), with mean age 58.3±11.5 years. Baseline median A1c was 8.60% (IQR = 8.20-9.10), and mean A1c was 8.96%±1.24%. Prevalent comorbidities included hyperlipidemia (73%), hypertension (70%), and obesity (44%). A1c significantly decreased at 3 and 6 months after CGM (median: -1.10%, -1.40%; mean: -1.28%, -1.42%; P < 0.001). In adjusted models, the adjusted mean change in A1c from baseline was -1.32 percentage points at 3 months (95% CI = -1.48 to -1.15; P < 0.001; n = 153) and -1.48 percentage points at 6 months (95% CI = -1.68 to -1.28; P < 0.001; n = 143). American Diabetes Association (ADA) (<7%) and Healthcare Effectiveness Data and Information Set (HEDIS) (<8%) target attainment improved from 0% at baseline to 26.4% and 50.9% at 6 months (both P < 0.001). Hyperglycemic events declined from 53.7% at baseline to 16.3% at 6 months, although not significantly. No significant changes were observed in health care utilization, medication adherence, or medication burden. Greater CGM use and higher time in range were associated with improved A1c and glucose management indicator outcomes. The proportion reporting good-to-excellent quality of life increased from 24.1% at baseline to 45.8% at 6 months, while weighted ADDQoL scores remained stable. CONCLUSIONS: CGM use in non-insulin-treated patients with T2D was associated with significant improvements in glycemic control and perceived quality of life, with stable health care utilization and medication therapy. These findings support expanded implementation and reimbursement of CGM in this population, but further research is required to assess the long-term sustainability of these improvements and the specific roles of diet, medication, and adherence.
Liver international : official journal of the International Association for the Study of the LiverNicolas Capelli, Amandine Pisoni, Fadi Meroueh, Anne-Marie Mondain, Patrick Pastor, Philippe Van de Perre, Ilka Engelmann, Edouard Tuaillon
BACKGROUND & AIMS: Achieving HCV elimination requires diagnostic strategies capable of reaching underserved populations who remain poorly accessed by conventional healthcare pathways. Dried blood spot (DBS) sampling enables decentralised testing, but concerns remain regarding its analytical sensitivity and the potential risk of missed diagnoses. METHODS: We conducted a 5 year real-world implementation study of DBS-based HCV screening in France (2020-2024). DBS samples were collected in harm reduction centers and other community-based facilities and sent to Montpellier University Hospital for centralised analysis. We evaluated the diagnostic yield of DBS in routine practice and estimated the potential number of missed cases by comparing the DBS detection threshold with the distribution of plasma HCV RNA levels observed at diagnosis in untreated individuals. RESULTS: The limit of detection (LOD) for HCV RNA on DBS was 1252 IU/mL, with a systematic underestimation compared with plasma measurements (mean bias -2.29 log10 IU/mL). Among 1552 individuals tested using DBS, 428 (27.6%) were HCV RNA positive, including five cases with no detectable HCV antibodies. DBS testing accounted for 56.4% of all HCV infections identified in our laboratory during the study period. Based on plasma viral load distributions at diagnosis, 2.7% of infections, corresponding to approximately 12 additional cases, were estimated to be missed due to low HCV RNA levels. CONCLUSION: Despite a modest reduction in analytical sensitivity compared with plasma-based testing, the substantial public health benefits associated with increased testing coverage strongly outweigh this limitation and support the integration of DBS into HCV elimination strategies.
European journal of sport scienceNaoya Takei, Ryuji Muraki, Olivier Girard, Hideo Hatta, Yumiko Takahashi
Repeated short sprints (≤ 10 s) in hypoxia are often used to enhance performance, but acute responses to longer sprints (> 10 s) performed in a repeated-sprint format with short recovery periods (∼30 s) remain unclear. We examined performance and physiological strain during repeated short (10-s) and long (15-s) sprints with identical recovery (30 s) comparing acute responses between sexes. Sixteen highly trained sprinters (7 females) performed 7 × 10-s (10:30) and 15-s (15:30) sprints with 30-s rest in normobaric hypoxia (FiO2: 0.15), using a randomized cross-over design. Average mean power output across the seven sprints was lower in 15:30 than 10:30 (6.30 ± 0.44 vs. 6.85 ± 0.82 W/kg; p < 0.001). Sprint decrement score (Sdec) was larger in 15:30 than 10:30 (-17.9 ± 4.8% vs. -13.1 ± 4.6%; p < 0.001). Average pulse oximetry-derived peripheral oxygen saturation (SpO2) across the seven sprints was lower in 15:30 than 10:30 (87.1 ± 4.2% vs. 89.7 ± 2.7%; p < 0.001), whereas the magnitude of change from sprint 1 to sprint 7 did not clearly differ between conditions. Heart rate increased across sprints (Δsprint1-7: +9.2 ± 5.3% and p < 0.001), independently of condition (p = 0.652). ΔSpO2 correlated with ΔSdec (r = 0.609 and p = 0.012). Female athletes experienced smaller performance declines than males in both conditions (p = 0.001). Longer repeated sprints with identical rest in hypoxia impair mechanical output while inducing greater physiological strain, with comparatively smaller performance reductions in females.
International wound journalMaegan Spiteri, Louise Savine, Peter R Worsley, Spyros Masouros
This study aimed to evaluate the physiological effectiveness of lateral pressure application in maintaining baseline transcutaneous oxygen (TcPO2) and carbon dioxide (TcPCO2) tensions in the buttocks during sitting, compared with a conventional static foam cushion. Secondary aims were to determine whether body mass index (BMI) influenced the physiological response when lateral pressure was applied and to investigate the relationship between transcutaneous oximetry and underbody interface pressure. A prospective, controlled, repeated-measures laboratory study was conducted with 30 healthy adults. Participants underwent two 20-min sitting conditions: sitting on static foam alone and sitting on static foam with lateral pressure applied by a prototype device. Transcutaneous gas tensions were measured at the right ischial tuberosity using an oximeter and normalised to unloaded standing baselines. Tissue responses were categorised according to the Chai and Bader tissue-response criteria, where changes in gas tensions of < 25% are Category 1, least risk, and changes of > 25% are Category 3, highest risk. Underbody interface pressures were recorded using a pressure-mapping array. Statistical comparisons between conditions were performed using paired parametric or non-parametric tests as appropriate. Mean and peak underbody interface pressures were significantly reduced (p < 0.0001) when lateral pressure was applied. Lateral pressure significantly reduced the mean change in TcPCO2 compared to static foam alone (11.9% ± 25.6% and 47.8% ± 72.9%, respectively, p < 0.0001) and reduced the change in TcPO2 to -29.5% ± 23.5% compared to -50.4% ± 34.8% with static foam alone (p < 0.0001). Eleven participants exhibited a Category 3 ischaemic response on static foam, compared with only two when lateral pressure was applied. Twenty-nine of 30 participants moved to a more favourable or unchanged tissue-response category when lateral pressure was applied. No correlation was found between interface pressure and changes in gas tensions. No significant differences were observed between BMI groups. Application of lateral pressure during sitting maintained tissue perfusion at the ischial tuberosity more effectively than static foam alone. These findings support the physiological rationale for applying lateral pressure as a novel strategy for pressure-ulcer prevention in seated patients.
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.
Scandinavian journal of medicine & science in sportsQingyang Li, Christian J Brakenridge, Jiawei Qin, Xiyun Li, Suvi Lamberg, Taija Finni, Neville Owen, Arto J Pesola, Ying Gao
Standing shows inconsistent associations with glycemic profiles. This study examined whether thigh muscle activity during standing modifies the association between standing time and glycemic profiles under free-living conditions. Thirty physically inactive young women contributed 52 participant-days while wearing a continuous glucose monitor, thigh-worn accelerometer, and textile electromyography (EMG) shorts. Waking behavior was classified into sitting, standing, and moving and expressed as a three-part compositional time-use variable. During standing, quadriceps and hamstring EMG were summarized as average normalized amplitude and active duration. Outcomes were mean glucose, coefficient of variation (CV), time in range (TIR), time above range (TAR), and time below range (TBR). Regression models tested whether standing-specific EMG metrics moderated associations between behavior composition and glycemic outcomes. Standing was not independently associated with glycemic outcomes. Hamstring EMG active duration moderated the association between standing and TIR (β = 0.473, 95% CI [0.277, 0.668], p < 0.001, Cohen's f2 = 0.15) and TBR (β = -0.467, 95% CI [-0.653, -0.282], p < 0.001, Cohen's f2 = 0.153), but not TAR, CV, or mean glucose after multiple testing correction. A higher standing proportion was associated with higher TIR when hamstring EMG active duration exceeded 38.8% and lower TBR when it exceeded 29.7%; below 16.8%, a higher standing proportion was associated with lower TIR. These findings suggest that the potential glycemic benefits of standing may depend on hamstring muscle engagement, highlighting EMG-derived muscle engagement as a marker for distinguishing physiologically heterogeneous forms of standing.
The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung DiseaseM A Habib, S S Efa, K Afrin, N Islam, M D Hossain
<sec><title>BACKGROUND</title>TB and diabetes mellitus (DM) frequently coexist, particularly in low- and middle-income countries. Evidence on their coexistence among the elderly in Bangladesh is limited. This study assessed prevalence of diabetes and associated factors with newly detected diabetes in elderly TB patients.</sec><sec><title>METHODS</title>This cross-sectional study was conducted in 2025 across eight tertiary care hospitals in Bangladesh. A total of 656 TB patients aged ≥60 years were included. Diabetes status was determined using prior diagnosis and oral glucose tolerance testing after 2 weeks of TB treatment initiation. Data were collected by face-to-face interview using semi-structured questionnaire. Informed written consent was taken and ethical issues were maintained. Data were analysed by IBM SPSS software. Multivariable logistic regression identified factors associated with newly detected diabetes.</sec><sec><title>RESULTS</title>Prevalence of diabetes was 30.3%, including 16.8% known and 16.3% newly detected. Newly detected diabetes was associated with age 65-69 years (adjusted odds ratio [AOR] = 3.81) and ≥70 years (AOR = 4.95), physical inactivity (AOR = 5.23), overweight/obesity (AOR = 7.73), family history of diabetes (AOR = 9.14), and pulmonary TB (AOR = 4.49). Dietary risk lost significance in adjusted analysis.</sec><sec><title>CONCLUSIONS</title>Due to high burden of diabetes in elderly TB patients, routine diabetes screening and TB-DM management, particularly targeting high-risk groups, are essential to improve outcomes.</sec>.
JMIR mHealth and uHealthFranziska Schmelter, Xinyu Huang, Annika Heidmann, Paul Beier, Friederike Miriam Rundfeldt, Christina Plöger, Artur Piet, Md Abid Hasan, Yuanheng Zhang, Lennar…
BACKGROUND: Continuous glucose monitoring (CGM) can facilitate weight management and lower the risk of metabolic diseases by providing real-time feedback on glycemic responses, thereby enabling more informed lifestyle decisions. However, current CGM systems remain constrained by invasiveness, cost, and short sensor lifespan, limiting their practicality for guiding individualized postprandial low-glycemic diets. OBJECTIVE: Extending earlier proof-of-concept findings, this study aimed to validate an interstitial glucose (IG) machine learning algorithm in real-world environments using multimodal, continuous data collected from wearable sensors and smartwatches. In the long term, we aim to embed a noninvasive, sensor-based algorithm for estimating tissue glucose within mobile health apps and postprandial low-glycemic diet frameworks to enable scalable, personalized prevention strategies. METHODS: We conducted a 2-week study phase during which participants continuously wore 2 noninvasive sensor devices: a scientific sensor wristband (Empatica EmbracePlus) and a commercially available smartwatch (Fitbit Sense 2). As a reference measurement, an invasive CGM sensor (Abbott FreeStyle Libre 3) measured IG levels. For metabolic characterization, 1-point fasting blood and urine samples were collected, and deep phenotyping using state-of-the-art nuclear magnetic resonance spectroscopy and bioelectrical impedance analysis was performed. For participants with overweight and obesity, clinical standard parameters focusing on glucose metabolism were analyzed. RESULTS: A total of 74 participants, 34 (46%) healthy controls and 40 (54%) metabolically at-risk (MR) individuals, simultaneously used an invasive CGM device together with 2 noninvasive wristbands over 2 weeks. Healthy controls were characterized by a mean age of 24.53 (SD 3.68) years and a mean BMI of 22.36 (SD 2.16) kg/m². In contrast, the MR cohort had a mean age of 55.38 (SD 15.08) years and a mean BMI of 35.38 (SD 4.91) kg/m². Furthermore, the MR cohort showed elevated fasting glucose levels (mean 107.56, SD 19.26 mg/dL), hemoglobin A1c levels (mean 5.67%, SD 0.63%), and an increased homeostatic model assessment of insulin resistance index (mean 4.34, SD 3.49), indicating a disturbed glucose metabolism. The proposed long short-term memory network based on feature vectors obtained the best IG prediction performance, with an average root-mean-squared error of 21.04 (SD 8.32) mg/dL and 98.3% of predictions in zones A and B of the Clarke error grid analysis, representing a high level of predictive accuracy. In addition, based on data from a smartwatch, we achieved a comparable average root-mean-squared error of 23.49 (SD 11.46) mg/dL for the overall cohort. CONCLUSIONS: This study demonstrates that IG levels can be predicted from multimodal, noninvasive wearable sensor data using a machine learning approach under real-world conditions. While further validation in larger and more diverse cohorts is warranted, this approach represents a promising step toward accessible, personalized glycemic monitoring and dietary guidance as a preventive tool in mobile health apps.
OBJECTIVE: To compare the effects of open suctioning (OS) versus closed suctioning (CS) on lung volume and oxygenation in acute respiratory distress syndrome (ARDS) patients receiving mechanical ventilation with positive end-expiratory pressure (PEEP) of 5-10 cmH2O. METHODS: This single-center, prospective randomized controlled trial enrolled 60 ARDS patients, who were randomly assigned to OS (n = 30) or CS (n = 30). All patients received lung-protective ventilation with volume-controlled mode. SpO2 was recorded before suctioning and at 1, 10, 20, and 30 minutes post-suctioning. Arterial blood gas analysis was performed at 30 minutes to calculate the oxygenation index (PaO2/FiO2). Changes in end-expiratory lung impedance (ΔEELI) were monitored using electrical impedance tomography (EIT) for the whole lung and four regions of interest (ROI). Secondary outcomes included extubation and survival, analyzed using Kaplan-Meier curves and Cox regression. RESULTS: The absolute values of global ΔEELI were significantly lower in the CS group than in the OS group at 1 minute (-0.54 ± 0.18 vs. -2.32 ± 1.34, P < .001) and 10 minutes (-0.31 ± 0.25 vs. -1.14 ± 0.80, P < .001) after suctioning, indicating that CS better preserved lung volume. However, lung volume recovered more rapidly in the OS group, returning to baseline by 20 minutes, whereas recovery in the CS group was not achieved until 30 minutes. Regional analysis showed that the protective effect of CS was primarily observed in non-dependent regions (ROI 1-3), with no significant difference in the gravity-dependent ROI 4 (P = .430). SpO2 was significantly lower in the OS group than in the CS group at 1 minute post-suctioning (98.07 ± 1.26% vs. 99.03 ± 0.93%, P = .007), and returned to baseline by 20 minutes in the OS group versus 10 minutes in the CS group. No significant difference in oxygenation index was observed at 30 minutes (P = .329). Secondary outcomes, including extubation and survival, did not differ significantly between the two groups (all P > .050). No adverse events were recorded. CONCLUSIONS: In ARDS patients receiving PEEP 5-10 cmH2O, CS reduces lung volume loss during suctioning and better preserves early oxygenation, but results in slower post-suctioning lung volume recovery compared with OS. These findings reveal a physiologically important trade-off between the two methods, though their clinical relevance warrants further investigation in larger, outcome-focused trials.
JMIR formative researchYong Huang, Nitish Nagesh, Ajan Subramanian, Li Wang, Zhiyu Liu, Yichen Sun, Weiyi Hou, Iman Azimi, Amir M Rahmani, Randall S Stafford
BACKGROUND: Suboptimal glycemic control remains a significant public health challenge among adults with type 2 diabetes and prediabetes, with 47.4% of US adults with diagnosed diabetes having hemoglobin A1c (HbA1c) ≥7%. Remote glucose monitoring programs have shown promise for supporting self-management, but real-world evidence on the causal impact of varying patient engagement levels on glycemic outcomes remains limited. OBJECTIVE: This study aimed to estimate the causal dose-response relationship between patient engagement, operationalized as weekly glucose monitoring frequency, and glycemic control measured by HbA1c among adults enrolled in a comprehensive primary care-integrated remote monitoring program. METHODS: We conducted a retrospective cohort study of 1436 adults with type 2 diabetes or prediabetes enrolled in the Unika Health program between 2019 and 2024. The program integrated Bluetooth-connected glucose meters, a mobile app, structured lifestyle coaching, and primary care coordination across 74 physician practices. Engagement was defined as mean weekly glucose monitoring frequency during the first 6 months. The causal effect of monitoring frequency on 6-month HbA1c was estimated using marginal structural models (MSMs) with inverse probability weighting to address time-varying confounding. Covariates included age, sex, BMI, baseline HbA1c, comorbidities, medication status, and physical activity level. RESULTS: The cohort was predominantly older (95.4%, 1370/1436 aged ≥46 years), with 82.6% (1186/1436) having hypertension and 45.9% (659/1436) classified as obese. Overall, HbA1c decreased by a mean of 0.54 (SD 1.47; 95% CI 0.47-0.62) percentage points (P<.001) over 6 months. Cluster analysis identified 3 engagement tiers: low (n=835; mean 2.55, SD 1.35 measurements/week), medium (n=493; mean 6.19, SD 1.46 measurements/week), and high (n=108; mean 12.59, SD 3.03 measurements/week). A monotonic dose-response was observed, with mean HbA1c reductions of 0.38 (SD 1.40; 95% CI 0.29-0.48), 0.71 (SD 1.50; 95% CI 0.58-0.85), and 1.01 (SD 1.67; 95% CI 0.69-1.32) percentage points for the low, medium, and high tiers, respectively (all P<.001 by 2-tailed paired t test). In weighted MSMs, each additional weekly measurement was associated with a 0.05 (95% CI 0.03-0.07) percentage point greater HbA1c reduction (P<.001). Among patients with high baseline HbA1c (≥9%), the high-engagement group achieved a mean reduction of 3.12 (SD 1.97; 95% CI 2.29-3.94) percentage points. Findings were consistent in sensitivity analyses at 3 months (β=-0.04; P<.001) and 12 months (β=-0.03; P=.003) and across alternative weighting specifications. CONCLUSIONS: Higher engagement with a digitally enabled, primary care-integrated remote glucose monitoring program was causally associated with significantly greater HbA1c reductions in adults with type 2 diabetes and prediabetes. These findings support scalable remote patient monitoring strategies that actively foster sustained patient engagement as an effective approach to improving glycemic control and reducing the burden of diabetes-related complications at a population level.
Zhonghua yi xue za zhiChinese Society of Anesthesiology, National Alliance of Geriatric Anesthesia
Perioperative glycemic abnormalities, including hyperglycemia, hypoglycemia, and glycemic variability, are important determinants of postoperative outcomes. Conventional glucose monitoring has inherent temporal limitations and fails to capture dynamic glycemic fluctuations in a timely manner. Continuous glucose monitoring (CGM) enables real-time, continuous assessment of glucose levels and trends, thereby facilitating more precise glycemic management. To standardize its clinical application, the Chinese Society of Anesthesiology, in collaboration with the National Alliance of Geriatric Anesthesia, convened a multidisciplinary expert panel to develop the "Expert consensus on the clinical application of CGM in adult patients during the perioperative period (2026 edition)". Key clinical issues, including monitoring strategies across different perioperative phases, data interpretation, and management of special populations, were systematically reviewed and deliberated by the expert panel, resulting in 20 recommendations. This consensus applies primarily to adults with diabetes scheduled to undergo surgery and adults at high risk of perioperative glycemic variability. It covers risk assessment for perioperative dysglycemia, interpretation of CGM data, preoperative initiation and assessment, and intraoperative monitoring and confirmatory testing. It also addresses postoperative handover and continued management, together with the use of CGM in special populations and specific surgical settings. This consensus aims to guide the standardized perioperative use of CGM, optimize glycemic management and improve patient safety.
JMIR formative researchRachel C Greer, Cristian Roman, Mayue Shi, Benn Gooch, Bethany K Lawson, Christopher Biggs, Clare Edwards, Sarah Vollam, Peter Watkinson, Lionel Tarassenko, An…
BACKGROUND: Remote vital sign monitoring of acute hospital at home (aHAH) patients is recommended in policy without clear guidance on implementation. While such monitoring has the potential to improve patient care, there is limited evidence for its feasibility and acceptability. OBJECTIVE: This study aimed to evaluate the feasibility and acceptability of using a remote, community-based monitoring system using a vital sign wearable patch and pulse oximeter in aHAH patients. METHODS: In this nonrandomized feasibility study, we recruited patients from an aHAH service in Oxford, United Kingdom, between January and October 2024. Eligible patients were aged 18 years and older with an acute illness (lower respiratory tract infection, cellulitis, urinary tract infection, systemic evidence of acute infection, acute kidney injury, or heart failure with acute fluid overload) requiring aHAH care. Pregnant women and those with contraindications to monitoring were excluded. Participants were asked to wear a chest patch to estimate their heart rate and respiratory rate (passive monitoring), and to intermittently check their oxygen saturations, blood pressure, and temperature (active monitoring). Participants were asked to complete a Technology Acceptance Questionnaire. All aHAH patients were screened. Recruitment was nonconsecutive due to the availability of the research team. Participants were monitored for 7 days or until discharge from the aHAH service, whichever was shorter. Fixed time windows were used to assess real-time vital sign data coverage during each participant's monitoring period. The primary outcomes were the proportion of 4-hour monitoring windows with a recorded heart rate and 12-hour daytime windows with a recorded oxygen saturation level. Time-series analyses and descriptive statistics were used for quantitative data. Content analysis was used to analyze the open-ended comments in the questionnaire. RESULTS: In total, 29 participants were recruited and 3 immediately withdrew from the study. Participants were monitored for 4.8 (IQR 2.9-6.2) days on average. Overall, 89% (600/674) of the 4-hour monitoring windows had a heart rate and 75.4% (508/674) had a respiratory rate recorded in real-time. For the 12-hour daytime windows, 58.1% (75/129) had an oxygen saturation, 54.3% (70/129) had a blood pressure, and 51.2% (66/129) had a temperature recorded. Data coverage was higher for passive monitoring compared to active monitoring. Most participants who had capacity found the combined monitoring system easy to use and thought it was useful for their health care. CONCLUSIONS: Remote monitoring of vital signs in aHAH patients is feasible. Good data coverage was achieved for the passive monitoring, which did not require specific actions by the participants or their caregivers. Further work is required to ascertain which patients would benefit most from this monitoring.
MedicineHalime Seda Küçükerdem, Giray Bozkaya, İsmail Demir
We aimed to investigate serum levels of FAM19A5, a novel adipokine implicated in inflammation and metabolic regulation, and to examine its association with key metabolic and inflammatory markers in individuals newly diagnosed with type 2 diabetes mellitus (T2DM). This case-control study included 54 patients with newly diagnosed T2DM and 54 age- and sex-matched normoglycemic controls aged 35 to 65 years. Continuous variables were summarized according to their distributions and compared using the independent-samples t test or Mann-Whitney U test, as appropriate. Spearman rank correlation was used to examine associations in the pooled sample, with false discovery rate correction for multiple testing. Subgroup analyses were conducted by metabolic syndrome, insulin resistance, and body mass index (BMI) category. The incremental value of FAM19A5 beyond conventional markers was explored using multivariable logistic regression and DeLong comparisons of the areas under the curve (AUCs). Serum FAM19A5 was lower in the T2DM group than in controls (376.1 [312.1-577.6] vs 554.5 [365.6-1524.2] ng/L; P < .001). In the pooled sample, FAM19A5 was inversely correlated with fasting glucose (ρ = -0.266, P = .005), 2-hour oral glucose tolerance test (ρ = -0.308, P = .001), and HbA1c (ρ = -0.212, P = .028), but not with BMI, waist circumference, lipid parameters, homeostasis model assessment of insulin resistance (HOMA-IR), or high-sensitivity C-reactive protein (hs-CRP). After false discovery rate correction, the associations with fasting and 2-hour oral glucose tolerance test remained significant. Within the T2DM group, FAM19A5 was lower in patients with metabolic syndrome (P = .004), insulin resistance (HOMA-IR > 2.71; P = .023), or BMI ≥25 kg/m² (P = .021). FAM19A5 alone showed poor discrimination for T2DM (AUC: 0.684; sensitivity: 66.7%; specificity: 53.7%). Adding FAM19A5 to a model containing BMI, HOMA-IR, and hs-CRP improved model fit (likelihood-ratio χ² = 13.1, P < .001) but not discrimination (AUC: 0.920 vs 0.943; DeLong P = .154). Serum FAM19A5 levels were lower in newly diagnosed T2DM and remained independently associated with diabetes status after adjustment for BMI, HOMA-IR, and hs-CRP. Correlations with glycemic measures were weak, and FAM19A5 alone had poor discriminatory performance. These findings support further investigation of FAM19A5 as a molecule of potential mechanistic interest, but not as a clinically useful diagnostic biomarker. Larger longitudinal studies are needed.
Medical science monitor : international medical journal of experimental and clinical researchNing Zhang, Xingjie Zhou
BACKGROUND Respiratory distress syndrome (RDS) is defined as acute respiratory distress caused by surfactant deficiency-induced gas exchange disturbance in premature infants. We aimed to assess the effects of T-piece resuscitator combined with intubation-surfactant-extubation (INSURE) on short-term respiratory outcomes and complications in premature infants with RDS. MATERIAL AND METHODS This retrospective observational study included 100 premature infants with RDS who were treated between January 2019 and December 2023. The primary outcomes were blood gas and oxygenation indicators, including oxygenation index, partial pressure of carbon dioxide (PaCO₂), partial pressure of oxygen (PaO₂), and inhaled oxygen concentration. The infants were categorized into an INSURE group (n=50) and a combination group (n=50) based on treatment approaches. RESULTS Compared with the INSURE group, the combination group showed significantly lower oxygenation index, PaCO₂, and inhaled oxygen concentration, as well as significantly higher PaO₂ after intervention (P<0.05). In addition, the combination group had significantly increased blood oxygen saturation and shortened duration of nasal continuous positive airway pressure (nCPAP) ventilation compared with the INSURE group (P<0.05). Furthermore, the combination group exhibited significantly shorter length of hospital stay, duration of oxygen therapy, and duration of noninvasive ventilation, together with a lower incidence of complications (12% vs 30%, P<0.05). CONCLUSIONS T-piece resuscitator combined with INSURE technology may be associated with improved short-term blood gas and respiratory outcomes in premature infants with RDS, while potentially reducing the duration of respiratory support and incidence of complications. Nevertheless, further large-scale prospective studies are required to validate these findings.
BACKGROUND: Dysbiosis of gut microbiota plays a key role in type 1 diabetes mellitus (T1DM). Fecal microbiota transplantation represents a novel therapeutic avenue. We hypothesize that youth-derived fecal microbiota transplantation (yFMT) can remodel the gut microecosystem and improve clinical outcomes. This pilot trial aims to assess the feasibility, safety, and preliminary efficacy of yFMT in adults with T1DM. METHODS AND ANALYSIS: This single-center, randomized, double-blind, placebo-controlled pilot study will enroll adults with T1DM who have suboptimal glycemic outcomes (glycated hemoglobin [HbA1c] of 7.0-14.0% or time in range [TIR] <70%). Following a 17-day run-in period for insulin optimization, continuous glucose monitoring (CGM) wearing, baseline assessments and bowel preparation, participants will be randomly allocated (1:1) to take yFMT or placebo capsules for 6 consecutive days, alongside their standard insulin therapy, and then complete a 12-week follow-up. The primary efficacy endpoint is the change from baseline in the rate of achieving the composite target of TIR > 70% and time below range <4% at 12 weeks post-randomization. Secondary efficacy endpoints include: (1) the change from baseline in the same composite achievement rate at 4 weeks post-intervention; (2) changes from baseline at Weeks 4 and 12 in other glycemic metrics (including HbA1c, fasting plasma glucose, 2-hour postprandial glucose, and additional CGM metrics), C-peptide, immune responses, infection markers, and gut microbiota composition; and (3) changes from baseline at Week 12 in serum metabolomic profiles (bile acids, short-chain fatty acids, and other related metabolites). Feasibility will be assessed through recruitment rate, retention rate, intervention adherence, and acceptability. Safety endpoints include the incidence of adverse events and serious adverse events. DISCUSSION: Our findings will offer new insight into the feasibility and effects of oral yFMT capsules in adults with T1DM and provide the necessary evidence to power a subsequent multicenter large-scale study. Exploratory biomarker analyses conducted within this study may further pave the way for future individualized microbiome‑based therapeutics. TRIAL REGISTRATION: Chinese Clinical Trial Registry identifier: ChiCTR2500111955 (November 7, 2025).
Glucose transporter type 1 deficiency syndrome (Glut1DS) is a rare autosomal dominant genetic disorder caused by mutations in SLC2A1, which results in impaired glucose transport across the blood-brain barrier. Patients with Glut1DS present with various symptoms, including seizures, delayed development and movement disorders. The current first-line therapy - ketogenic diet - has shown variable efficacy, highlighting the need to explore alternative therapeutic strategies. This study aimed to investigate comprehensive phenotypic characteristics of the Glut1DS mouse model B6(D2)-Slc2a1<Rgsc200>/1Rbrc to establish foundational data for identifying novel therapeutic targets. The Slc2a1Rgsc200 mutant mouse was phenotypically characterized at the Japan Mouse Clinic of the RIKEN BioResource Research Center by using a phenotyping pipeline that included intraperitoneal glucose tolerance test (IPGTT) and clinical blood chemistry analyses. Heterozygous Glut1DS mutants exhibited no differences in basal plasma glucose or glycosylated hemoglobin A1c levels when compared to wild-type controls. However, female heterozygous mutants showed decreased glucose levels during IPGTT, accompanied by increased plasma insulin levels following glucose administration. These findings support recent evidence linking insulin signaling to seizure control in patients with Glut1DS, as demonstrated in human studies.
Hallmarks of aging are highly variable among individuals, and sexual dimorphism may contribute to these differences. However, the details are unclear.The gut-metabolism axisin naturally aging wild-type and Nrf2 knockout (KO) mouse models was investigated. In this study, intraperitoneal glucose tolerance tests were performed on 12- and 48-week-old wild-type and Nrf2 KO mice to assess glucose tolerance. Serum total cholesterol, triglyceride, low-density lipoprotein, and high-density lipoprotein levels were measured using biochemicaltest kits. The estradiol and testosterone levels in the serum were detected using enzyme-linked immunosorbent assays. Liver and adipose tissue morphology were examined using hematoxylin and eosin staining, and gut microbiota composition was analyzed using 16S rDNA sequencing of fecal samples.The results showed that glucose tolerance was significantly impaired in aging male Nrf2KO mice, and lipid accumulation in hepatic and adipose tissues increased in aging wild-type (WT) miceandaging Nrf2KO mice of both sexescompared with that in their young counterparts.Aged miceand Nrf2 KO mice exhibited divergent responses in their serum lipid profiles.Notably, female Nrf2 KO mice showed a significantly lowerα-diversity in gut bacterial composition, compared with both male Nrf2 KO mice and female WT controls.In conclusion, the resultsindicatethat aging and Nrf2 deficiency promoted weight gain and tissue lipid accumulation in both sexes but elicited sex-dimorphic differences in blood glucose stability, microbiota composition, and the magnitude of adiposity. Therefore, sex is an important factor contributing to age-related variations in gut microbiota and metabolism.
Background and Objectives: Continuous glucose monitoring (CGM) is increasingly used beyond diabetes care, but whether participant-visible feedback changes behavior or psychosocial outcomes in adults without diabetes remains uncertain. We evaluated dietary behavior/adherence, physical activity, psychosocial outcomes, and device burden. Materials and Methods: This PROSPERO-registered systematic review (CRD420261356163) searched seven bibliographic databases and two trial registries, followed by citation searching. Randomized and nonrandomized intervention studies and qualitative/mixed-methods evidence were eligible. RoB 2, ROBINS-I, MMAT 2018, and GRADE were applied. Clinical and methodological heterogeneity precluded meta-analysis. Results: Searches yielded 6265 database/registry records; 2627 unique records were screened. Citation searching added 431 new records and two eligible studies, giving 12 studies. Two randomized dietary comparisons suggested selected improvements; one 8-week trial comparing CGM plus low-glycemic-index/load education with education alone reported between-group reductions in carbohydrate intake (-15.2 g; 95% CI -20.9 to -9.5), glycemic index (-10.0; 95% CI -13.1 to -6.9), and glycemic load (-19.9; 95% CI -29.0 to -10.7). Physical activity showed no clear difference (-28.5 MET-min/week; 95% CI -171.9 to 114.8). Psychosocial evidence was insufficient to establish benefit or exclude harm; device burden evidence was sparse. Certainty was low for dietary outcomes and very low for the other domains. Conclusions: Participant-visible CGM may support selected dietary changes as a biofeedback adjunct within structured education or lifestyle interventions, but large, durable benefits and stand-alone efficacy are not established.
For the diagnosis of diabetes, glycemic control, treatment modification, and the avoidance of both acute and long-term consequences, accurate glucose monitoring is crucial. This study examines the development of glucose-monitoring systems, from traditional diagnostic tests and finger-prick electrochemical glucometers to wearable, continuous, minimally invasive, and non-invasive sensing platforms. Major invasive technologies, including enzymatic and non-enzymatic electrochemical sensors, microdialysis systems, hexokinase-based photometric assays, and field-effect transistor biosensors, are critically evaluated. The ability of minimally invasive methods to access interstitial fluid with less pain is discussed, including fluorescence probes, surface-enhanced Raman spectroscopy, and microneedle arrays. Emerging non-invasive approaches are also evaluated. These include reverse iontophoresis, optical coherence tomography, infrared and photoacoustic spectroscopy, microwave resonators, smart contact lenses, and AI-assisted wearable systems. Finally, the review identifies major barriers related to sensitivity, selectivity, calibration, biofouling, biocompatibility, physiological variability, and clinical translation. It also outlines opportunities for intelligent, painless, and patient-centered glucose monitoring.
BiosensorsJia-Yuan He, Ming-Shan Shuai, Hao Zhang, Dan-Ni Yang
Given the prevalent use of horseradish peroxidase (HRP) as an enzyme label in immunoassays, the practical importance of point-of-care testing for the portable identification of HRP-related biomarkers is evident. Accordingly, this study devised a portable immunoassay platform using a personal glucometer (PGM) to achieve rapid detection of HRP-related biomarkers. 3,3',5,5'-tetramethylbenzidine (TMB) and dopamine (DA) were used as signal-regulating substrates, and the assay principle was based on the HRP-mediated redox reaction. In the absence of HRP, TMB and DA directly reacted with [Fe(CN)6]3- on commercial glucose test strips, producing a strong PGM response. When HRP and H2O2 were present, HRP facilitated the oxidation of TMB to generate oxidized TMB, which further reacted with DA to produce oxidized products with weak reactivity toward [Fe(CN)6]3-, resulting in a decreased PGM signal. Conducting the quantitative assay involved measuring the HRP-dependent change in the PGM readout. Unlike many PGM immunoassays that rely on additional glucose-producing enzyme labels or amplified nanomaterial tags, the proposed method directly converts the signal of the conventional HRP label into a PGM-readable response. The sensing platform demonstrated a good linear response to HRP concentrations ranging from 156 to 625 ng/mL, with a low detection limit of 26 ng/mL. Interference experiments indicated good tolerance to the tested nonspecific proteins. The preliminary applicability of the platform was further evaluated by detecting cardiac troponin I (cTnI) and heparin-binding protein (HBP) in spiked serum samples, with recoveries ranging from 93.0% to 117.1% for cTnI and from 88.3% to 112.5% for HBP. In summary, the proposed platform provides a portable digital readout for HRP-linked immunoassays and reduces the dependence on dedicated readout instruments.
Background and Objectives: Gestational diabetes mellitus (GDM) is usually diagnosed at 24-28 gestational weeks, although metabolic and placental alterations may emerge considerably earlier. This study evaluated whether routinely available first-trimester placental biomarkers, metabolic indices, and insulin-like growth factor (IGF)-axis components are associated with GDM diagnosed later in pregnancy and whether these markers provide complementary information across distinct biological domains. Materials and Methods: Of 200 women completing the 75-g OGTT (34 with GDM and 166 normoglycemic), deferred IGF-1 and IGFBP-5 assays were performed in a complete-biomarker analytic cohort of 90 participants with complete clinical follow-up and available stored specimens (30 GDM and 60 controls). At 11+0-13+6 weeks, pregnancy-associated plasma protein-A (PAPP-A), free β-human chorionic gonadotropin (free β-hCG), IGF-1, IGF-binding protein-5 (IGFBP-5), fasting glucose, insulin, and lipid parameters were assessed. HOMA-IR, the triglyceride-glucose (TyG) index, TG/HDL-C, and LDL/HDL-C were calculated. GDM was diagnosed using a 75-g oral glucose tolerance test at 24-28 weeks. Group comparisons, correlation analyses, and logistic regression were performed. Results: Compared with controls, women who later developed GDM had higher first-trimester insulin, HOMA-IR, triglycerides, VLDL-C, TyG, and TG/HDL-C and lower HDL-C, free β-hCG, PAPP-A, PAPP-A MoM, and IGF-1 (all p < 0.05). Birth weight was also higher in the GDM group. Correlation patterns differed between groups, suggesting distinct relationships among placental, metabolic, and IGF-related markers. In the four-variable adjusted model, higher HOMA-IR (OR 2.123, 95% CI 1.089-4.137; p = 0.027) and TyG (OR 3.747, 95% CI 1.010-13.894; p = 0.048) were associated with increased GDM odds, whereas free β-hCG MoM (OR 0.325, 95% CI 0.115-0.920; p = 0.034) and IGF-1 (OR 0.856, 95% CI 0.748-0.980; p = 0.024) showed inverse associations. Conclusions: Pregnancies that subsequently developed GDM showed detectable first-trimester differences across metabolic, placental, and IGF-related pathways. The combined pattern supports further evaluation of multidomain early-risk assessment, although clinical predictive utility requires validation in larger independent cohorts.
BACKGROUND: Respiratory failure is the leading cause of death in amyotrophic lateral sclerosis (ALS). Early detection of CO2 retention is crucial for assessing respiratory failure severity and guiding noninvasive positive pressure ventilation (NPPV) management. However, arterial blood gas analysis is invasive and uncomfortable for routine monitoring. OBJECTIVE: We investigated whether the serum sodium-chloride difference (Na-Cl value), calculated from routine blood tests, could serve as a screening marker for CO2 retention in ALS patients. METHODS: This retrospective study included 88 ALS patients with 116 paired samples of arterial blood gas and serum electrolyte data. We analyzed correlations between Na-Cl value and blood gas parameters (HCO3-, PCO2), performed receiver operating characteristic (ROC) analysis for detecting CO2 retention (PCO2 ≥ 45 mmHg), and examined relationships with respiratory function (%FVC). RESULTS: Na-Cl value showed strong correlation with HCO3- (r = 0.78, p < 0.001) and PCO2 (r = 0.71, p < 0.001). Na-Cl ≥ 37 mEq/L demonstrated sensitivity of 85.11% and specificity of 69.57% for detecting PCO2 ≥ 45 mmHg, with negative predictive value of 87.27% (AUC = 0.842). Na-Cl ≥ 39 mEq/L achieved specificity of 92.75%. Patients with %FVC < 50% had significantly higher Na-Cl, PCO2, and HCO3- values. CONCLUSIONS: Serum Na-Cl value serves as a simple, noninvasive screening marker for CO2 retention in ALS. Na-Cl ≥ 37 mEq/L warrants blood gas analysis, while Na-Cl ≥ 39 mEq/L provides specificity >90%. This marker can be calculated from routine blood tests without additional cost, making it suitable for frequent monitoring and reducing the risk of missing intervention timing.
African journal of reproductive healthYanjuan Zhou, Li Li, Wei Zhang
This single-center retrospective study explored the predictive value of early pregnancy fasting plasma glucose (FPG) combined with pre-pregnancy body mass index (BMI) for gestational diabetes mellitus (GDM). Healthy singleton pregnant women with natural pregnancy who delivered at the Second People's Hospital of Wuhu City between January 2023 and January 2025 were included. Blood glucose indicators were measured at 11-13 weeks of gestation, and a 75 g oral glucose tolerance test was performed at 24-28 weeks. Participants were classified into GDM and non-GDM groups. After Z-score normalization, univariate and multivariate Logistic regression analyses identified pre-pregnancy BMI, gestational weight gain and FPG as independent risk factors for GDM. The established Logistic regression model showed moderate predictive efficiency, with an AUC of 0.75, an accuracy rate of 0.82, a sensitivity of 0.48, a specificity of 0.92, a PPV of 0.63 and a NPV of 0.86. Bootstrap internal validation and Hosmer-Lemeshow test indicated acceptable model calibration, while decision curve analysis showed clinical net benefit within a threshold probability range of 0.10-0.50. We conclude that early pregnancy FPG combined with pre-pregnancy BMI may help identify women at high risk of GDM and support personalized intervention strategies.
BMJ openNa Zeng, Mohamed Kadry Taher, Daniel J Corsi, Daniel Krewski, Donald R Mattison, Douglas McNair, Wenshan Li, Smita Pakhale, Shi Wu Wen
OBJECTIVE: To quantify the risk of type 2 diabetes mellitus (T2DM) among women based on the number of abnormal values on 100-gram oral glucose tolerance test (OGTT). DESIGN: A 1:5 matched case-control study nested to a cohort of pregnant women was conducted. Conditional logistic regression was employed to estimate the independent association between glucose levels and future risk of T2DM. SETTING: This study used a large multicentre electronic health records (EHRs) database-Cerner Real-World Data (CRWD) between 2000 and 2016, covering approximately 21.6% of US inpatient EHRs. PARTICIPANTS: We identified a cohort of 130 172 pregnant women registered in the CRWD between 2000 and 2016 and were followed up until the end of 2016. A nested case-control study was conducted within this cohort, comprising 1 390 cases and 6 950 matched controls. RESULTS: Adjusted Odds Ratios for the risk of T2DM among women with one abnormal value and at least two abnormal values on OGTT diagnosed by the National Diabetes Data Group criteria, as compared with those women with normal OGTT values, were 5.69 (95% CI 4.34 to 7.47) and 13.20 (95% CI 10.52 to 16.57), respectively. CONCLUSION: Women with one abnormal value on the 100-gram OGTT had a significantly higher risk of developing T2DM compared with women with normal glucose value.
Background: Regular biochemical monitoring is essential for the safe and effective dietary treatment of inherited disorders of amino acid metabolism. However, conventional venous blood sampling may limit monitoring frequency and increase the burden on families. This study evaluated the feasibility and clinical usefulness of home-collected dried blood spot (DBS) samples analyzed using tandem mass spectrometry and additional chromatographic methods for dietary monitoring in inherited disorders of amino acid metabolism other than phenylketonuria. Methods: Between 2022 and 2025, children, adolescents, and young adults aged between 4 months and 20.5 years who were followed at a national metabolic center were monitored using DBS samples. The initial cohort included patients with maple syrup urine disease, tyrosinemia type III, homocystinuria, glutaric aciduria type 1, methylmalonic aciduria, isovaleric aciduria, argininosuccinic aciduria, methionine adenosyltransferase I/III deficiency, beta-ketothiolase deficiency, propionic aciduria, gyrate atrophy, and citrullinemia type 1. Disease-specific amino acids and metabolites were assessed to guide individualized dietary recommendations. Results: The number of monitored patients ranged from 24 to 40 per year. Overall annual completion rates of planned DBS measurements ranged from 56.7% to 73.0%, with additional clinically indicated samples collected in selected patients. DBS monitoring detected abnormal metabolite concentrations and supported dietary interventions, particularly in maple syrup urine disease, glutaric aciduria type 1, homocystinuria, tyrosinemia type III, and MAT I/III deficiency. In several other disorders, routine monthly DBS monitoring showed limited additional clinical value. Conclusions: DBS-based monitoring is a feasible approach that may support individualized dietary management in selected inherited disorders of amino acid metabolism, especially in early childhood and during periods of increased metabolic risk.
European journal of nutritionReza Bagheri, Hamid Ghobadi, Mehdi Kargarfard, Katsuhiko Suzuki
PURPOSE: To examine secondary lipid, kidney-related, and liver-enzyme responses to three protein intakes during resistance training (RT) alone or the same RT plus cycling (CT) in middle-aged to older women. METHODS: In this randomized 2×3 factorial trial, 108 women aged 40-77 years were assigned to RT or CT and 0.8, 1.6, or 2.2 g kg-1 d-1 protein for 12 weeks. This complete-case secondary analysis included 83 participants. Linear mixed-effects models tested Time × Training, Time × Protein, and Time × Training × Protein effects, with false-discovery-rate-adjusted omnibus tests and Holm-adjusted contrasts. RESULTS: Triglycerides, total cholesterol, LDL-C, and apolipoprotein B decreased and HDL-C increased in all conditions. Lipid changes differed by protein condition, and several were more favorable with CT; however, CT comprised RT plus additional cycling and greater exercise exposure. Urea, blood urea nitrogen, creatinine, the blood urea nitrogen-to-creatinine ratio, and cystatin C increased, whereas three eGFR estimates decreased. Responses differed mainly between 0.8 and the two higher protein conditions, with little evidence of differences between 1.6 and 2.2 g kg-1 d-1. ALT, AST, and GGT differed by protein condition; AST and GGT also showed training-dependent responses. CONCLUSIONS: The dietary and exercise interventions modified lipid and clinical-chemistry responses. Because energy and food composition were not fully matched and CT added cycling to RT, the findings do not isolate protein dose or exercise modality. Changes in eGFR estimates and liver enzymes do not establish organ injury or long-term safety.
BMJ openBusra Donat Ergin, Katharina Mattishent, Anne Marie Minihane, Richard Ian Gregory Holt, Helen Murphy, Ketan Dhatariya, Michael Hornberger
BACKGROUND: Type 2 diabetes (T2DM) and cognitive impairment are common long-term chronic conditions affecting older people in hospital. Cognitive impairment can complicate glucose monitoring and lead to diabetes-related emergencies in T2DM. Traditionally, point of care test measurements of capillary blood glucose are conducted in-hospital for T2DM while continuous glucose monitoring (CGM) is not widely used. AIM: To understand the feasibility, acceptability and tolerability of using CGM in older inpatients with T2DM and cognitive impairment. METHODS: 32 older people (mean age=78.7±6.7 years) with comorbid T2DM and cognitive impairment (Abbreviated Mini-Mental Test ≤8/10 and Mini-Addenbrooke's Cognitive Examination ≤22/30) were recruited within a tertiary care hospital in the UK. All participants were naive to CGM and were asked to wear blinded Dexcom G7 sensors for up to 10 days. Participants were asked about feasibility, acceptability and tolerability questions at the point of sensor removal. RESULTS: 29 participants (96%) reported no pain during CGM fitting. All participants (100%) agreed that they did not notice wearing the sensor, and it did not affect their day-to-day hospital activities. All participants (100%) found it 'very easy' or 'easy' to have the sensor fitted and wearing it for 10 days, with 27 participants (90%) finding CGM convenient. 17 participants (57%) reported favourable perceptions of the subcutaneous sensor sensation. CONCLUSION: CGM use in older inpatients with T2DM and cognitive impairment is highly feasible and acceptable for patients. Future studies and trials are now needed to evaluate the clinical use of CGM for glucose monitoring in hospitalised or community-dwelling older individuals with T2DM and cognitive impairment.
Frontiers in cellular and infection microbiologyJisong Ahn, Minhong Kim, Se Hee Min, Hyun-Gyeong Bae, Ji-Yun Bae, Jinhee Kwon, Hana Yi, Do Hyun Park
BACKGROUND: Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder characterized by impaired glucose homeostasis and β-cell dysfunction. Emerging evidence suggests that the gut microbiota-incretin axis may contribute to metabolic regulation. However, whether microbiota from duodenal light stimulation (DLS)-conditioned donors can influence metabolic phenotypes via fecal microbiota transplantation (FMT) remains unclear. METHODS: We evaluated whether FMT from DLS-conditioned donors was associated with metabolic and intestinal changes in diabetic GK (Goto-Kakizaki) rats. Recipients received FMT from week -2 to week 0 and were then followed for 7 weeks after the final FMT dose. Metabolic phenotyping, intestinal histology, short-chain fatty acid (SCFA) profiling, and shotgun metagenomic profiling of bacterial and viral communities were performed. RESULTS: FMT recipients showed within-group improvement in OGTT glucose profiles, without significant changes in fasting glucose levels. Total glucose AUC0-120 was significantly reduced within the FMT group in the within-group (period) comparison; however, the group × period interaction was not significant, indicating no statistically significant longitudinal between-group treatment effect. Early GLP-1 responses showed a modest increasing trend in FMT recipients, whereas total GLP-1 AUC0-120 was not significantly changed. HOMA-β (homeostatic model assessment of β-cell function) increased within the FMT group, and pancreatic insulin-positive area was greater in FMT recipients than in controls at the study endpoint. Intestinal remodeling was evident, including an increased villus:crypt ratio and increased colonic GLP-1-positive cells. FMT was associated with fecal bacteriome differences, including one FDR-significant taxon and several nominally associated taxa, such as Akkermansia muciniphila and Xylanibacter rodentium. No significant global shift in fecal virome composition was observed, although selected viral taxa showed nominal group-associated differences that did not remain significant after FDR correction. Exploratory network analysis suggested group-specific bacteriome-virome association patterns after FMT. CONCLUSION: FMT from DLS-conditioned donors was associated with improved glucose tolerance, intestinal incretin-related remodeling, increased pancreatic insulin-positive area, and fecal bacteriome differences in diabetic GK rats based on within-group longitudinal changes for the glucose- and β-cell-related outcomes, for which the group × period interactions were not significant, whereas the histological and microbiome differences reflect cross-sectional between-group comparisons at the study endpoint. These findings support a hypothesis-generating link between donor-conditioned FMT, intestinal remodeling, and microbiome-associated metabolic regulation, while further studies are required to define DLS-specific and donor-derived effects.
PLoS medicineKevin Y H Liang, Thomas M Zheng, Dandan Tan, Takayoshi Sasako, Yann Ilboudo, Yiheng Chen, Guillaume Butler-Laporte, Satoshi Yoshiji, J Brent Richards
BACKGROUND: Chronic kidney disease (CKD) occurs in 20-50% of the people living with Type 2 diabetes (T2D) and is the leading cause of kidney failure worldwide. The cause of CKD is not fully understood, and few interventions prevent CKD in individuals living with diabetes. Here, we use large-scale proteomics data to identify circulating proteins that mediate the relationship between T2D and kidney disorders. METHODS AND FINDINGS: First, we used two-sample mendelian randomization (MR) and identified 71 circulating proteins whose levels were altered by genetic predisposition to T2D based on circulating proteomic GWAS from deCODE with 35,559 individuals and T2D GWAS with 80,154 cases. Then, we used cis-genetic variants to proxy the causal effect of some of these T2D-influenced circulating proteins and found that, collectively, five proteins (INHBC, GNPTG, LPO, AGRN, and CTSD) affected three kidney traits (blood urea nitrogen [BUN], estimated glomerular filtration rate [eGFR] and CKD risk) based on GWAS with up to 1,004,040 participants. Notably, we found that higher levels of circulating INHBC protein were estimated to lead to a lower eGFR and higher BUN based on MR analyses. We then replicated this MR analysis with proteomic GWAS from four additional cohorts, namely, UKB-PPP, Fenland, ARIC, and EPIC-Norfolk. We observed a consistent direction of effect across all four proteomic GWAS datasets, supporting the robustness of our results against platform and cohort variation. In observational analyses, increased circulating INHBC levels were associated with increased hazard for kidney disease diagnosis in 37,854 UK Biobank participants. We estimated that circulating INHBC levels mediate 1.3% (95% confidence interval [0.85%, 1.9%]) of the association between T2D and kidney disease diagnosis. There are important limitations in this study. Firstly, although we observed limited evidence for violations to the MR assumptions, some are untestable. Secondly, our study was not based on individuals with diabetic kidney diseases, but rather independent population-based studies assessing diabetes and kidney function separately. Therefore, additional functional analyses in disease specific cohort are needed. CONCLUSIONS: Collectively, these findings suggest that T2D influences the risk of CKD, in part, through increased circulating INHBC levels.