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Background: The recovery from cardiac surgery involves resolving inflammation and remodeling with significant connective tissue turnover. Dynamics of smoldering inflammation and injury (white blood cells, platelets, CRP, IL-8, IL-6), vascular inflammation (IL-15, VEGF, RANTES), connective tissue remodeling (tenascin, MMP-9), cardiac injury and remodeling (YKL-40), and vascular remodeling (epiregulin, MCP-1, VEGF) were assessed up to 3 months after cardiac surgery. We hypothesize that at 3 months, studied markers will return to pre-surgical levels., Methods: Patients (n = 139) scheduled for non-emergent heart surgery were included, except for patients with pre-existing immunological aberrancies. Blood was collected before surgery(t baseline ), 24 h later(t 24h ) after the first sample, 7 days(t 7d ), and 3 months(t 3m ) after t baseline . Serum markers were measured via multiplex or ELISA. Electronic medical records (EMR) were used to extract demographical, pre-existing conditions and clinical data. Disposition (discharge home, discharge to facility, death, re-admission) was determined at 28 days and 3 months from admission., Results: Not all inflammatory markers returned to baseline (CRP↑↑, leukocytosis, thrombocytosis, IL-8↓, IL-6↓). Tenascin and YKL-40 levels remained elevated even at t 3m . YKL-40 serum levels were significantly elevated at t 24h and t 7d while normalized at t 3m . VEGF returned to the baseline, yet MCP-1 remained elevated at 3 months. CCL28 increased at 3 months, while RANTES and IL-15 declined at the same time. Disposition at discharge was determined by serum MMP-9, while YKL-40 correlated with duration of surgery and APACHE II 24h ., Conclusions: The data demonstrated an ongoing extracellular matrix turnover at 3 months, while acute inflammation and vascular remodeling resolved only partially., (© 2022. The Author(s).)

BACKGROUND Cardiac surgery triggers acute changes in serum leptin and fibroblast growth factor 21 (FGF-21). Considering their pleiotropic role in inflammation and abnormal glucose metabolism, perseverance of their abnormal serum level can have a long-term impact on recovery and end-organ failures. Long-term dynamics after cardiac surgery are unknown. MATERIAL AND METHODS Serum was collected from 123 patients before cardiac surgery (tbaseline) and 24 h (t24h), 7 days (t7d), and 3 months (t3m) later. Also, interleukin 6 (IL-6) and C-reactive protein (CRP) assessed nonspecific inflammatory responses. Neurodegeneration was gauged with serum amyloid ß1-40 and ß1-42. Demographic and clinical information, including disposition at 28 days and t3m from admission, were collected. RESULTS Serum leptin increased at t24h (leptinbaseline=613+747.9 vs leptin24h=768±718.1; P=0.0083) and decreased at t7d (leptin7d=499.5±540.2; P=0.043). FGF-21 levels increased at t24h and t7d. Cytokines normalized by t3m. Presurgical leptin levels were higher in Asians and were the primary determinant of postoperative leptin changes. Leptin levels were most elevated in patients undergoing aortic valve and arch surgery; the perioperative increase was significant only in patients with mitral valve surgery. Leptin and FGF-21 did not correlate with markers of general inflammation (CRP, IL-6), which partially resolved after t3m. Amyloid ß1-42 at t3m correlated with leptin peak at t24h. Low prehospital FGF-21 level correlated with the incidence of perioperative stroke; postoperative FGF-21 correlated with discharge to facility vs home. CONCLUSIONS Leptin and FGF-21 evolve independently from the inflammatory response in the aftermath of cardiac surgery and correlate with cardiac remodeling and neurodegeneration markers.

Although several therapeutics are used to treat coronavirus disease 2019 (COVID-19) patients, there is still no definitive metabolic marker to evaluate disease severity and recovery or a quantitative test to end quarantine. Because severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infects human cells via the angiotensin-converting-enzyme 2 (ACE2) receptor and COVID-19 is associated with renin-angiotensin system dysregulation, we evaluated soluble ACE2 (sACE2) activity in the plasma/saliva of 80 hospitalized COVID-19 patients and 27 non-COVID-19 volunteers, and levels of ACE2/Ang (1-7) in plasma or membrane (mACE2) in lung autopsy samples. sACE2 activity was markedly reduced (p < 0.0001) in COVID-19 plasma (n = 59) compared with controls (n = 27). Nadir sACE2 activity in early hospitalization was restored during disease recovery, irrespective of patient age, demographic variations, or comorbidity; in convalescent plasma-administered patients (n = 45), restoration was statistically higher than matched controls (n = 22, p = 0.0021). ACE2 activity was also substantially reduced in the saliva of COVID-19 patients compared with controls (p = 0.0065). There is a strong inverse correlation between sACE2 concentration and sACE2 activity and Ang (1-7) levels in participant plasmas. However, there were no difference in membrane ACE2 levels in lungs of autopsy tissues of COVID-19 (n = 800) versus other conditions (n = 300). These clinical observations suggest sACE2 activity as a potential biomarker and therapeutic target for COVID-19., Competing Interests: Authors declare no competing interests., (© 2022 The Authors.)

Background: Despite clinical relevance of immunological activation due to histone leakage into the serum following cardiac surgery, long-term data describing their longitudinal dynamic are lacking. Therefore, this study examines the serum levels of histone 3 (tH3) and its modifications (H3K4me3 and H3K27ac) alongside immune system activation during the acute and convalescence phases of cardiac surgery., Methods: Blood samples from fifty-nine individuals were collected before non-emergent cardiac surgery (t pre-op ) and 24 h (t 24hr ), seven days (t 7d ), and three months (t 3m ) post-procedure to examine serum levels of tH3, H3K4me3, and H3K27ac. Serum heat shock protein-60 (HSP-60) was a surrogate of the cellular damage marker. Serum C-reactive protein (CRP) and interleukin 6 (IL-6) assessed smoldering inflammation. TNFα and IL-6 production by whole blood in response to lipopolysaccharide (LPS) evaluated immunological activation. Electronic medical records provided demographic, peri-operative, and clinical information. Paired longitudinal analyses were employed with data expressed as mean and standard deviation (X ± SD) or median and interquartile range (Me[IQ25; 75%]., Results: Compared to pre-operative levels (tH3 Pre-op  = 1.6[0.33;2.4]), post-operative serum tH3 significantly (p > 0.0001) increased after heart surgery (tH3 24hr  = 2.2[0.3;28]), remained elevated at 7 days (tH3 7d  = 2.4[0.37;5.3]), and at 3 months (tH3 3m  = 2.0[0.31;2.9]). Serum H3K27ac was elevated at 24 h (H3K27ac 24hr  = 0.66 ± 0.51; p = 0.025) and seven days (H3K27ac 7d  = 0.94 ± 0.95; p = 0.032) as compared to baseline hours (H3K27ac Pre-op  = 0.55 ± 0.54). Serum H3K4me3 was significantly diminished at three months (H3K4me3 Pre-op  = 0.94 ± 0.54 vs. H3K27ac 3m  = 0.59 ± 0.89; p = 0.008). tH3 correlated significantly with the duration of anesthesia (r 2  = 0.38). In contrast, HSP-60 normalized seven days after surgery. Peri-operative intake of acetaminophen, but no acetylsalicylic acid (ASA), acid, ketorolac or steroids, resulted in the significant depression of serum H3K4me3 at 24 h (H3K4me3 acetom-  = 1.26[0.71; 3.21] vs H3K4me3 acetom+  = 0.54[0.07;1.01]; W[50] = 2.26; p = 0.021). CRP, but not IL-6, remained elevated at 3 months compared to pre-surgical levels and correlated with tH3 24hrs (r 2  = 0.43), tH3 7d (r 2  = 0.71; p < 0.05), H3K4me3 7d (r 2  = 0.53), and H3K27ac 7d (r 2  = 0.49). Production of TNFα by whole blood in response to LPS was associated with serum tH3 24hrs (r 2  = 0.67). Diminished H3K4me3 24hrs, H3K27ac 24hrs , and H3K27ac 3m , accompanied the emergence of liver failure., Conclusions: We demonstrated a prolonged elevation in serum histone 3 three months after cardiac surgery. Furthermore, histone 3 modifications had a discrete time evolution indicating differential immune activation., (© 2022. The Author(s).)

Incorporating the advanced practice provider (APP) in the delivery of tele critical care medicine (teleCCM) addresses the critical care provider shortage. However, the current literature lacks details of potential workflows, deployment difficulties and implementation outcomes while suggesting that expanding teleCCM service may be difficult. Here, we demonstrate the implementation of a telemedicine APP (eAPP) pilot service within an existing teleCCM program with the objective of determining the feasibility and ease of deployment. The goal is to augment an existing tele-ICU system with a balanced APP service to assess the feasibility and potential impact on the ICU performance in several hospitals affiliated within a large academic center. A REDCap survey was used to assess eAPP workflows, expediency of interventions, duration of tasks, and types of assignments within different service locations. Between 02/01/2021 and 08/31/2021, 204 interventions (across 133 12-h shift) were recorded by eAPP (n routine  = 109 (53.4%); n urgent  = 82 (40.2%); n emergent  = 13 (6.4%). The average task duration was 10.9 ± 6.22 min, but there was a significant difference based on the expediency of the task (F [2; 202] = 3.89; p < 0.022) and type of tasks (F [7; 220] = 6.69; p < 0.001). Furthermore, the eAPP task type and expediency varied depending upon the unit engaged and timeframe since implementation. The eAPP interventions were effectively communicated with bedside staff with only 0.5% of suggestions rejected. Only in 2% cases did the eAPP report distress. In summary, the eAPP can be rapidly deployed in existing teleCCM settings, providing adaptable and valuable care that addresses the specific needs of different ICUs while simultaneously enhancing the delivery of ICU care. Further studies are needed to quantify the input more robustly., (© 2022. The Author(s).)

Identification of novel immune biomarkers to gauge the underlying pathology and severity of COVID-19 has been difficult due to the lack of longitudinal studies. Here, we analyzed serum collected upon COVID-19 admission (t1), 48 hours (t2), and seven days later (t3) using Olink proteomics and correlated to clinical, demographics, and therapeutic data. Older age positively correlated with decorin, pleiotrophin, and TNFRS21 but inversely correlated with chemokine (both C-C and C-X-C type) ligands, monocyte attractant proteins (MCP) and TNFRS14. The burden of pre-existing conditions was positively correlated with MCP-4, CAIX, TWEAK, TNFRS12A, and PD-L2 levels. Individuals with COVID-19 demonstrated increased expression of several chemokines, most notably from the C-C and C-X-C family, as well as MCP-1 and MCP-3 early in the course of the disease. Similarly, deceased individuals had elevated MCP-1 and MCP-3 as well as Gal-9 serum levels. LAMP3, GZMB, and LAG3 at admission correlated with mortality. Only CX3CL13 and MCP-4 correlated positively with APACHE score and length of stay, while decorin, MUC-16 and TNFRSF21 with being admitted to the ICU. We also identified several organ-failure-specific immunological markers, including those for respiratory (IL-18, IL-15, Gal-9) or kidney failure (CD28, VEGF). Treatment with hydroxychloroquine, remdesivir, convalescent plasma, and steroids had a very limited effect on the serum variation of biomarkers. Our study identified several potential targets related to COVID-19 heterogeneity (MCP-1, MCP-3, MCP-4, TNFR superfamily members, and programmed death-ligand), suggesting a potential role of these molecules in the pathology of COVID-19., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Laudanski, Jihane, Antalosky, Ghani, Phan, Hernandez, Okeke, Wu, Rader and Susztak.)

Purpose: Diabetes mellitus (DM) is a global health concern linked to various complications, including cardiovascular disease (CVD). However, long-term follow-up studies on the risk of DM and CVD using different blood glucose assessment methods in the general Korean population are lacking. This study aimed to assess the predictive abilities of fasting plasma glucose (FPG), 2-h oral glucose tolerance test (OGTT), and glycosylated hemoglobin (HbA1c) for new-onset DM and high CVD risk in a middle-aged and older Korean population., Methods: This study used data from the Korean Genome and Epidemiology Study, a population-based prospective cohort. Blood sugar measures (FPG, OGTT, and HbA1c) were examined. The primary endpoint was the development of new-onset DM, and CVD risk was evaluated using the Framingham risk score. The predictive abilities for new-onset DM based on glycemic values were evaluated using Harrell's Concordance index and 95% confidence intervals., Results: Among the 10,030 participants, data of 6813 participants without DM at baseline were analyzed. The study revealed that OGTT outperformed FPG and HbA1c in predicting new-onset DM. The combination of FPG and HbA1c did not significantly enhance predictions for DM compared with OGTT alone. OGTT also outperformed FPG and HbA1c in predicting high CVD risk, and this difference remained significant even after adjusting for additional confounders., Conclusion: OGTT has superior predictive capabilities in identifying new-onset DM and high CVD risk in the Korean population. This suggests that relying solely on individual blood sugar measures may be insufficient for assessing DM and CVD risks., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Gestational diabetes mellitus (GDM) has a strong genetic predisposition. Integrating metabolomics with Mendelian randomisation (MR) analysis offers a potent method to uncover the metabolic factors causally linked to GDM pathogenesis., Objectives: This study aims to identify specific metabolites and metabolic pathways causally associated with GDM susceptibility through a comprehensive MR analysis. Additionally, it seeks to explore the potential of these identified metabolites as circulating biomarkers for early GDM detection and risk assessment. Furthermore, it aims to evaluate the implicated metabolic pathways as potential therapeutic targets for preventive or interventional strategies against GDM., Methods: A two-sample MR study was conducted using summary statistics from a metabolite genome-wide association study (GWAS) of 8299 individuals and a GDM GWAS comprising 13,039 cases and 197,831 controls. Rigorous criteria were applied to select robust genetic instruments for 850 metabolites., Results: MR analysis revealed 47 metabolites exhibiting putative causal associations with GDM risk. Among these, five metabolites demonstrated statistically significant associations after multiple-testing correction: Beta-citrylglutamate, Isobutyrylcarnitine (c4), 1,2-dilinoleoyl-GPC (18:2/18:2), Alliin and Cis-3,4-methyleneheptanoylcarnitine. Importantly, all these metabolites exhibited protective effects against GDM development. Additionally, metabolic pathway enrichment analysis implicated the methionine metabolism and spermidine and spermine biosynthesis pathways in the pathogenesis of GDM., Conclusion: This comprehensive MR study has robustly identified specific metabolites and metabolic pathways with causal links to GDM susceptibility. These findings provide novel insights into the metabolic underpinnings of GDM aetiology and offer promising translational implications. The identified metabolites could serve as potential circulating biomarkers for early detection and risk stratification, while the implicated metabolic pathways may represent therapeutic targets for preventive or interventional strategies against GDM., (© 2024 John Wiley & Sons Ltd.)

Purpose: This paper is to offer insights for designing research utilizing Olink technology to identify biomarkers and potential therapeutic targets for disease treatment., Experimental Design: We discusses the application of Olink technology in oncology, cardiovascular, respiratory and immune-related diseases, and Outlines the advantages and limitations of Olink technology., Results: Olink technology simplifies the search for therapeutic targets, advances proteomics research, reveals the pathogenesis of diseases, and ultimately helps patients develop precision treatments., Conclusions: Although proteomics technology has been rapidly developed in recent years, each method has its own disadvantages, so in the future research, more methods should be selected for combined application to verify each other., (© 2024 Wiley‐VCH GmbH.)

In vitro studies have demonstrated that the differentiation of embryonic stem cells (ESCs) into cardiomyocytes requires activation of caspases through the mitochondrial pathway. These studies have relied on synthetic substrates for activity measurements, which can be misleading due to potential none-specific hydrolysis of these substrates by proteases other than caspases. Hence, caspase-9 and caspase-3 activation are investigated during the differentiation of human ESCs (hESCs) by directly assessing caspase-9 and -3 cleavage. Western blot reveals the presence of the cleaved caspase-9 prior to and during the differentiation of human ESCs (hESCs) into cardiomyocytes at early stages, which diminishes as the differentiation progresses, without cleavage and activation of endogenous procaspase-3. Activation of exogenous procaspase-3 by endogenous caspase-9 and subsequent cleavage of chromogenic caspase-3 substrate i.e. DEVD-pNA during the course of differentiation confirmes that endogenous caspase-9 has the potency to recognize and activate procaspase-3, but for reasons that are unknown to us fails to do so. These observations suggest the existence of distinct mechanisms of caspase regulation in differentiation as compared to apoptosis. Bioinformatics analysis suggests the presence of caspase-9 regulators, which may influence proteolytic function under specific conditions., (© 2024 Wiley‐VCH GmbH.)

As the amount and complexity of biomedical data continue to increase, machine learning methods are becoming a popular tool in creating prediction models for the underlying biomedical processes. Although all machine learning methods aim to fit models to data, the methodologies used can vary greatly and may seem daunting at first. A comprehensive review of various machine learning algorithms per biomedical applications is presented. The key concepts of machine learning are supervised and unsupervised learning, feature selection, and evaluation metrics. Technical insights on the major machine learning methods such as decision trees, random forests, support vector machines, and k-nearest neighbors are analyzed. Next, the dimensionality reduction methods like principal component analysis and t-distributed stochastic neighbor embedding methods, and their applications in biomedical data analysis were reviewed. Moreover, in biomedical applications predominantly feedforward neural networks, convolutional neural networks, and recurrent neural networks are utilized. In addition, the identification of emerging directions in machine learning methodology will serve as a useful reference for individuals involved in biomedical research, clinical practice, and related professions who are interested in understanding and applying machine learning algorithms in their research or practice., (© 2024. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Detergents are amphiphilic molecules that serve as enabling steps for today's world applications. The increasing diversity of the detergentome is key to applications enabled by detergent science. Regardless of the application, the optimal design of detergents is determined empirically, which leads to failed preparations, and raising costs. To facilitate project planning, here we review synthesis strategies that drive the diversification of the detergentome. Synthesis strategies relevant for industrial and academic applications include linear, modular, combinatorial, bio-based, and metric-assisted detergent synthesis. Scopes and limitations of individual synthesis strategies in context with industrial product development and academic research are discussed. Furthermore, when designing detergents, the selection of molecular building blocks, i. e., head, linker, tail, is as important as the employed synthesis strategy. To facilitate the design of safe-to-use and tailor-made detergents, we provide an overview of established head, linker, and tail groups and highlight selected scopes and limitations for applications. It becomes apparent that most recent contributions to the increasing chemical diversity of detergent building blocks originate from the development of detergents for membrane protein studies. The overview of synthesis strategies and molecular blocks will bring us closer to the ability to predictably design and synthesize optimal detergents for challenging future applications., (© 2023 The Authors. ChemPlusChem published by Wiley-VCH GmbH.)

Bimetallic Nanoalloy catalysts have diverse uses in clean energy, sensing, catalysis, biomedicine, and energy storage, with some supported and unsupported catalysts. Conventional synthetic methods for producing bimetallic alloy nanoparticles often produce unalloyed and bulky particles that do not exhibit desired characteristics. Alloys, when prepared with advanced nanoscale methods, give higher surface area, activity, and selectivity than individual metals due to changes in their electronic properties and reduced size. This review demonstrates the synthesis methods and principles to produce and characterize highly dispersed, well-alloyed bimetallic nanoalloy particles in relatively simple, effective, and generalized approaches and the overall existence of conventional synthetic methods with modifications to prepare bimetallic alloy catalysts. The basic concepts and mechanistic understanding are represented with purposely selected examples. Herein, the enthralling properties with widespread applications of nanoalloy catalysts in heterogeneous catalysis are also presented, especially for Hydrogen Evolution Reaction (HER), Oxidation Reduction Reaction (ORR), Oxygen Evolution Reaction (OER), and alcohol oxidation with a particular focus on Pt and Pd-based bimetallic nanoalloys and their numerous fields of applications. The high entropy alloy is described as a complicated subject with an emphasis on laser-based green synthesis of nanoparticles and, in conclusion, the forecasts and contemporary challenges for the controlled synthesis of nanoalloys are addressed., (© 2023 Wiley-VCH GmbH.)

Detergents have been major contributors to membrane-protein structural study for decades. However, membrane proteins solubilized in conventional detergents tend to aggregate or denature over time. Stability of large eukaryotic membrane proteins with complex structures tends to be particularly poor, necessitating development of novel detergents with improved properties. Here, we prepared a novel class of detergents, designated 3,4-bis(hydroxymethyl)hexane-1,6-diol-based maltosides (HDMs). When tested on three membrane proteins, including two G-protein-coupled receptors (GPCRs), the new detergents displayed significantly better behaviors compared with DDM. Moreover, the HDMs were superior or comparable to LMNG, an amphiphile widely used for GPCR structural study. An optimal balance of detergent rigidity vs. flexibility of the HDMs is likely responsible for their favorable behaviors toward membrane-protein stability. Thus, the current study not only introduces the HDMs, with significant potential for membrane-protein structural study, but also suggests a useful guideline for designing novel detergents for membrane-protein research., (© 2022 Wiley-VCH GmbH.)

Detergents are widely used for membrane protein structural study. Many recently developed detergents contain multiple tail and head groups, which are typically connected via a small and branched linker. Due to their inherent compact structures, with small inter-alkyl chain distances, these detergents form micelles with high alkyl chain density in the interiors, a feature favorably associated with membrane-protein stability. A recent study on tandem triazine maltosides (TZMs) revealed a distinct trend; despite possession of an apparently large inter-alkyl chain distance, the TZM-Es were highly effective at stabilizing membrane proteins. Thanks to the incorporation of a flexible spacer between the two triazine rings in the linker region, these detergents are prone to folding into a compact architecture in micellar environments instead of adopting an extended conformation. Detergent foldability represents a new concept of novel detergent design with significant potential for future detergent development., (© 2022 Wiley-VCH GmbH.)

Detergents are the most frequently applied reagents in membrane protein (MP) studies. The limited diversity of one-head-one-tailed traditional detergents, however, is far from sufficient for structurally distinct MPs. Expansion of detergent repertoire has a continuous momentum. In line with the speculation that detergent pre-assembly exerts superiority, herein we report for the first time cross-conjugation of two series of monomeric detergents for constructing a two-dimensional library of dimeric detergents. Optimum detergents stood out with unique preferences in the systematic evaluation of individual MPs. Furthermore, unprecedented hybrid detergents 14M8G and 14M9G enabled high-quality EM study of transporter MsbA and NMR study of G protein-coupled receptor A 2A AR, respectively. Given the abundance of cross-coupling chemistries, comprehensive diversity could be readily covered that would facilitate the finding of new detergents for the manipulation of thorny MPs and innovation of the functional and structural study in future., (© 2022 Wiley-VCH GmbH.)

Dry reforming of CH 4 /CO 2 provides an attractive route to convert greenhouse gas into syngas; however, the resistance to sintering and coking of catalyst remains a fundamental challenge at high operation temperatures. Here we create active and durable metal-oxide interfaces in porous single-crystalline (PSC) CeO 2 monoliths with in situ exsolved single-crystalline (SC) Ni particles and show efficient dry reforming of CH 4 /CO 2 at temperatures as low as 450 °C. We show the excellent and durable performance with ≈20 % of CH 4 conversion and ≈30 % of CO 2 conversion even in a continuous operation of 240 hours. The well-defined active metal-oxide interfaces, created by exsolving SC Ni nanoparticles from PSC Ni x Ce 1-x O 2 to anchor them on PSC CeO 2 scaffolds, prevent nanoparticle sintering and enhance the coking resistance due to the stronger metal-support interactions. Our work would enable an industrially and economically viable path for carbon reclamation, and the technique of creating active and durable metal-oxide interfaces in PSC monoliths could lead to stable catalyst designs for many challenging reactions., (© 2021 Wiley-VCH GmbH.)

Purpose: To identify the specific glucose metrics derived from maternal continuous glucose monitoring (CGM) data, which were associated with a higher percentile of offspring birth weight., Methods: In this cohort study, we recruited singleton pregnant women with GDM who underwent CGM for 5-14 days at a mean of 28.8 gestational weeks between Jan 2017 and Nov 2018. Commonly used single summary glucose metrics of glucose exposure (including mean 24-h, daytime, and nighttime glucose level) and variability (including J-index and mean amplitude of glycaemic excursions) were derived from CGM data. A novel comprehensive glucose metric-hours per-day spent in a severe variability glucose mode (HSSV)-was identified using the spectral clustering method, which reflects both glucose level and variability. Multiple linear regression models were used to estimate the associations of sex- and gestational age-adjusted birth weight percentile with CGM parameters., Results: Ninety-seven women comprising 127,279 glucose measurements were included. Each 1-SD increase in maternal nighttime mean glucose level and HSSV was associated with 6.0 (95% CI 0.4, 11.5) and 6.3 (95% CI 0.4, 12.2) percentage points increase in birth weight percentile, respectively. No associations were found between other glucose metrics and birth weight percentile., Conclusion: Nighttime mean glucose level has a comparable effect size to HSSV in association with fetal growth, suggesting that endogenous hyperglycemia might drive the association between maternal hyperglycemia and birth weight. Further studies need to examine the effect of lowering nighttime glucose level and/or HSSV on preventing fetal overgrowth in GDM women., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)