AIMS:The study aimed to investigate the following: (1) whether early-pregnancy serum polyunsaturated fatty acid (PUFA) species are associated with the risk of gestational diabetes mellitus (GDM); and (2) whether lysophosphatidylcholine (LPC)18:0 may statistically explain these associations in Chinese pregnant women. MATERIALS AND METHODS:We conducted a 1:1 age-matched case-control study of 486 pregnant women nested within a prospective cohort in Tianjin, China. Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression analysis was used to identify the PUFA species independently associated with GDM. Conditional logistic regression was conducted to obtain odds ratios (ORs) and their 95% confidence intervals (CIs). Sobel mediation analysis was used to assess the potential statistical role of LPC18:0. RESULTS:Among five PUFA species that differed significantly between cases and controls, arachidonic acid (AA, 20:4) and docosahexaenoic acid (DHA, 22:6) were selected and further analyzed. High AA (≥ 3.63 nmol/mL) and DHA (≥ 0.59 nmol/mL) were associated with increased GDM risk, with multivariable-adjusted ORs of 2.89 (95% CI: 1.84-4.54) and 2.90 (95% CI: 1.82-4.63), respectively. These associations were stronger among women with pre-pregnancy overweight/obesity (AA, OR: 5.32, 95% CI: 2.48-11.42; DHA, OR: 3.39, 95% CI: 1.65-6.99). Further adjustment for high LPC18:0 substantially attenuated the associations of AA (OR: 0.90, 95% CI: 0.45-1.80) and DHA (OR: 0.97, 95% CI: 0.51-1.85) with GDM risk, with Sobel test p values < 0.0001. CONCLUSIONS:Higher serum AA and DHA levels in early pregnancy were associated with increased GDM risk. LPC18:0 may statistically explain part of these observed associations.

Introduction and Objective: Gestational diabetes mellitus (GDM) and polygenetic risk scores (PRS) of body mass index (BMI) are both associated with childhood obesity. However, the interaction between GDM and PRS of BMI on childhood obesity is unclear. Methods: A total of 1,040 mother-child pairs were included from Tianjin GDM longitudinal observational study. Genome-Wide Association Study (GWAS) studies were performed using DNA extracted from whole blood collected during clinical visits. PRS of BMI was generated by associations between BMI at age of 3-9 and SNPs from GWAS and children were grouped into three PRS tiers. Odds ratios for childhood obesity according to PRS tertiles and GDM status were estimated by logistic regression. Results: Among 1,040 children (mean age 5.87 years, 52.2% male, 50.2% with maternal GDM), 13.3% developed childhood obesity. In interaction analyses stratified by GDM status and PRS categories, a clear dose-response relationship of childhood obesity risk across PRS tertiles was observed in both GDM and non-GDM groups. Across both non-GDM and GDM strata, higher PRS categories were associated with progressively higher odds of the outcome. Relative to the low risk PRS reference T1, Model 1 showed an OR of 1.70 (95% CI, 0.57 to 5.66) for T2 and 10.4 (4.33 to 30.9) for T3, and these estimates were similar after additional adjustment in Model 2 with ORs of 1.59 (0.50 to 5.56) for T2 and 10.7 (4.19 to 33.7) for T3. In the GDM group, compared with T1, Model 1 yielded ORs of 1.16 (0.34 to 4.13) for T2 and 17.0 7.21 to 50.2) for T3, while Model 2 produced ORs of 1.11 (0.31 to 4.18) for T2 and 13.8 (5.41 to 43.3) for T3. Conclusion: This study demonstrated a clear interaction between GDM and BMI-related PRS on childhood obesity, with increasing odds across PRS tertiles and stronger associations among children exposed to GDM. Notably, GDM exposure was not associated with increased obesity risk among children with low genetic risk. Disclosure G. Xu: None. Y. Shen: None. W. Cao: None. H. Sun: None. G. Hu: None.

Purpose Grip strength has been increasingly recognized as a predictor of chronic disease risk and mortality. The aim of our study was to investigate the association of grip strength and the trajectories of preclinical obesity progression.Methods Data were collected from 93 275 participants in the UK Biobank. Preclinical obesity was diagnosed based on an excess of anthropometric parameters, defined as elevated body mass index combined with at least 1 abnormal measure among waist circumference, waist-to-hip ratio, waist-to-height ratio, or percentage body fat, in the absence of obesity-induced dysfunctions. Three models captured different trajectories from baseline to dysfunctions and death, with or without intermediate progression. A multistate model was used to investigate the association between grip strength and the preclinical obesity progression and multiple-cause mortality risk. Sensitivity analyses were performed using free muscle volume, total lean mass, and muscle-to-weight ratio as exposures.Results Among 8163 death events over a mean follow-up of 13.4 years, each SD increase in grip strength was associated with a significantly reduced risk of preclinical obesity progression at each stage, with the strongest inverse association observed in baseline to first dysfunction [fully adjusted hazard ratio (HR): 0.86, 95% confidence interval (CI): 0.85-0.88]. Compared to the lowest tertile, the highest grip strength significantly showed protective effects across all trajectory models, with double dysfunctions to all-cause death yielding the most pronounced associations (fully adjusted HR: 0.77, 95% CI: 0.70-0.84). Further subgroup and sensitivity analysis showed consistent results.Conclusion Increased grip strength was significantly associated with a decreased risk of obesity-induced dysfunctions progression and multiple-cause mortality. These findings underscore the importance of improving muscle mass and strength in preclinical obesity.

OBJECTIVE:This study investigated the longitudinal impact of intensive medical intervention (IMI) and bariatric surgery procedures on indirect measures of pancreatic β-cell death and function. METHODS:Eighty-four participants (28 non-type 2 diabetes [T2D], 56 T2D) from the HEADS UP study were assessed at baseline and 1-year post-intervention. Circulating unmethylated and methylated insulin gene [INS] DNA were quantified from blood samples via droplet digital polymerase chain reaction (PCR). Metabolic biomarkers, including fasting plasma glucose, HbA1c, proinsulin-to-insulin ratio, insulin, and C-peptide, were analyzed. RESULTS:At baseline, participants with T2D had significantly higher levels of unmethylated INS DNA and higher unmethylated-to-methylated INS DNA ratios than individuals without T2D. After 1-year, significant reductions in these biomarkers were observed primarily in the T2D group. Bariatric surgeries yielded greater improvements in metabolic profiles and reductions in unmethylated INS DNA than IMI. Despite substantial metabolic improvement, participants with T2D maintained elevated proinsulin-to-insulin ratios, indicating alterations to β-cell function. CONCLUSIONS:Circulating unmethylated INS DNA is a non-invasive index of β-cell death and responds to weight-loss interventions. Metabolic surgeries are more effective than IMI in preserving β-cell mass and function, highlighting their potential in diabetes management. Long-term studies are necessary to confirm these initial findings.

IMPORTANCE:Suboptimal weight loss affects 20%-35% of patients after metabolic bariatric surgery (MBS). Randomised evidence on glucagon-like peptide-1 receptor agonist (GLP-1 RA) pharmacotherapy in this population is limited to small, single-center Western trials. No data exist from Chinese populations. OBJECTIVE:To emulate a target trial comparing GLP-1 RA initiation with standard care among suboptimal responders to MBS in a Chinese multicenter cohort. DESIGN, SETTING, AND PARTICIPANTS:Target trial emulation using electronic health record (EHR) data from two Tertiary A teaching hospitals in China (March 2019 to June 2024). Eligible adults aged 18-65 years had undergone sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB), were 12-36 months post-surgery with body mass index (BMI) ≥ 28 kg/m2 and suboptimal weight loss. The clone-censor-weight approach handled the 30-day grace period. 1:5 propensity score matching yielded 624 patients (104 GLP-1 RA, 520 standard care). INTERVENTIONS:Strategy A: GLP-1 RA initiated within 30 days. Strategy B: standard post-MBS care without GLP-1 RA. MAIN OUTCOME:Percentage of total body weight loss (%TBWL) at 12 months. RESULTS:Mean age was 36.4 years; 66% were female; mean BMI was 33.7 kg/m2. At 12 months, mean %TBWL was 7.5% in the GLP-1 RA group versus 1.2% in the standard care group (difference, 6.28 percentage points; 95% CI, 5.50 to 7.07; p < 0.001). The ≥ 5% TBWL responder rate was 75% versus 7%. The per-protocol effect was 6.44 percentage points (95% CI, 5.65 to 7.23). Results were consistent across surgery types, BMI thresholds, diabetes status, and all sensitivity analyses. CONCLUSIONS AND RELEVANCE:In this target trial emulation, GLP-1 RA initiation was associated with clinically meaningful weight loss among Chinese suboptimal responders to MBS. These findings extend Western randomised trial evidence to a Chinese multicenter real-world setting and support the integration of GLP-1 RA pharmacotherapy into post-bariatric care pathways in China.

Cardiometabolic risk encompasses the interconnected conditions of cardiovascular diseases (CVDs), type 2 diabetes (T2D), and other metabolic diseases, which are leading global health challenges. The American Heart Association (AHA) has introduced "Life’s Essential 8" (LE8), a framework emphasizing eight key lifestyle and health factors, including diet, physical activity, smoking, sleep health, body weight, blood glucose, blood lipids, and blood pressure to optimize cardiovascular health and reduce the burden of cardiometabolic risk. This review examined the associations between individual and combined lifestyle factors and the development and progression of cardiometabolic risk, using CVD and T2D as representative conditions. Evidence highlighted that adherence to healthy lifestyle behaviors, such as maintaining a balanced diet, engaging in physical activity, avoiding smoking, and achieving a healthy weight, significantly reduced the risks of CVD, T2D, and hypertension. Studies showed that adherence to 3–4 healthy lifestyle factors lowers the risk of transition from baseline to diabetes, complications, and mortality. Despite the proven benefits, barriers such as limited access to healthy food and safe environments for physical activity hinder widespread adoption. Addressing these challenges requires innovative public health interventions and personalized strategies targeting high-risk populations. This review underscored the importance of promoting and adhering to LE8 principles to reduce the global burden of cardiometabolic risk and improve overall health outcomes.

To estimate the short-term effect of rosuvastatin versus atorvastatin on the corrected QT interval (QTc) by emulating a published randomized controlled trial (RCT) using electronic health record (EHR) data, and to assess whether target trial emulation (TTE) can replicate RCT findings for a pharmacological safety outcome at substantially greater scale. Retrospective cohort study emulating a target trial, reported according to the Transparent Reporting of Observational Studies Emulating a Target Trial (TARGET) guideline. Single tertiary A teaching hospital in China, March 2012 to September 2024. Of 619,216 cardiology hospitalizations, 165,460 new statin users with suspected coronary artery disease met all eligibility criteria. After 1:1 propensity score matching, 98,860 patients (49,430 per group) constituted the analytic cohort. All standardized mean differences were below 0.013 after matching. The primary outcome was the change in Fridericia-corrected QT interval (ΔQTcF) from baseline to first follow-up electrocardiogram (24–72 h). Secondary outcomes included newly emerged QTc prolongation, any QTc increase, clinically significant increase (> 30 ms), severe QTc prolongation, and a composite cardiac safety endpoint. Both intention-to-treat and per-protocol effects were estimated. The mean ΔQTcF in the rosuvastatin group was + 7.71 ms (SD 20.41) versus + 0.31 ms (SD 22.30) in the atorvastatin group, yielding a between-group difference of 7.40 ms (95

BACKGROUND:Women with a history of gestational diabetes mellitus (GDM) are at increased risk of developing type 2 diabetes later in life. This study evaluated whether lifestyle intervention can reduce the risk of type 2 diabetes in women with previous GDM. METHODS:This was a two-arm randomized controlled study conducted at the Tianjin Women and Children's Health Center. Women in six urban districts of Tianjin with previous GDM were randomly assigned in a 1: 1 ratio to either a 4-year lifestyle intervention group or a standard care control group between August 1, 2009 and July 31, 2011. Random allocation sequences were generated in patients but not in study coordinators. Each participant in the intervention group received individualized counseling aimed at reducing body weight in overweight women, increasing physical activity, and maintaining appropriate intakes of fat and carbohydrates especially fiber. Major components included six face-to-face meetings with a dietitian in the first year and two additional sessions in each subsequent year. The primary outcome was the development of type 2 diabetes, assessed using an oral glucose-tolerance test (OGTT). Participants were followed until the date of the diagnosis of diabetes, the last date of an OGTT, or death, whichever occurred first, up to December 2020. For participants who missed any OGTTs, self-reported physician-diagnosed diabetes data were collected. RESULTS:A total of 1180 women with a recent history of GDM were randomized to either an intensive lifestyle intervention ( n = 586) or usual care ( n = 594) 1-5 years postpartum (mean: 2.26 years). The mean follow-up was 4.5 years. During the trial, women in the intervention group, compared with the control group, lost more weight, increased physical activity and consumed more fiber. The incidence of diabetes after four years or more of follow-up was 9.0 and 15.3 cases per 1000 person-years in the lifestyle intervention and control groups, respectively. The lifestyle intervention reduced the incidence of diabetes by 46% (95% confidence interval: 10-67%) using the OGTT to diagnose diabetes, and by 40% (95% confidence interval: 11-59%) using either the OGTT or self-reported physician-diagnosed diabetes. CONCLUSIONS:Healthy lifestyle management significantly reduced the incidence of diabetes among young women with previous GDM. TRIAL REGISTRATION:ClinicalTrials.gov , NCT01554358.

The purpose of this survey study was to comprehensively examine if various types of screen time differed between children with overweight or obesity (OWOB; ≥ 85th BMI percentile) vs. normal weight (NW: < 85th BMI percentile) in a largely socioeconomically disadvantaged population. 739 parent proxies of children aged 5-11 years (M = 9.27, SD = 1.49) mostly enrolled in Medicaid (83.9%) in a United States (US) southern state responded to an online questionnaire called the Movement Behavior Questionnaire - Child (MBQ-C; open version). Eight items of the MBQ-C separately measured passive and interactive screen time on weekdays and weekend days. The survey also gathered parent-reported child weight and height, along with their sociodemographic characteristics. Compared to children with NW (M = 294.5 ± 7.2 min/day), children with OWOB (M = 364.3 ± 10.6 min/day) reported greater amount of total screen time (MDiff = 69.8 min/day, 95% CI = [45.0-94.6], p < 0.001). Of the sample, 24.9% met the sedentary screen time guidelines of no more than 2 hours/day favoring children with NW (OR = 0.59, 95% CI [0.39, 0.86], p = 0.008). The difference of screen time between weight-status groups was greatest in passive screen time, particularly on weekdays (MDiff = 63.2 min/day, 95% CI = 47.6-78.7, p < 0.001). Demographic factors did not significantly moderate the relationship between screen time and weight status. Most of the disadvantaged children failed to meet the screen time guidelines. Children with OWOB reported higher screen time, particularly passive screen time on weekdays. These findings suggest the need for tailored interventions to not only curb overall screen time but also mitigate specific types of screen time behaviors on specific days for children with OWOB (i.e., passive screen use on weekdays).

Women with a history of gestational diabetes mellitus (GDM) have a substantial 20–50

Hepatic steatosis index (HSI) and triglyceride glucose (TyG) index are emerging markers associated with metabolic health and cardiovascular risk. Their combined effects on cardio-renal outcomes remain poorly understood. This study evaluated the joint effect of HSI and TyG index on cardio-renal outcomes in a real-world population. We analyzed 16,109 participants, stratified by tertiles of TyG index and HSI groups (≤ 36 vs. >36). Cardio-renal outcomes included composite major adverse cardiovascular events (MACE: cerebrovascular events, coronary artery disease, heart failure, myocardial infarction) and renal events (eGFR decline ≥ 50

Evidence from repeated early-childhood BMI measurements in Chinese children remains limited. This study aimed to examine associations between body mass index (BMI) trajectories from ages 1 to 7 years and cardiometabolic risk at age 8 in this population, and to further distinguish cumulative and timing-specific effects of early BMI development. We followed 1072 mother–child pairs from Tianjin, China for 8 years. Height and weight were measured annually between ages 1 and 7 years; blood pressure, fasting glucose, and lipid concentrations were assessed at age 8. Group-based trajectory modeling was used to identify BMI trajectories. Excess BMI-years, adiposity rebound (AR) age, and interval-specific conditional BMI Z-score gain at ages 1–3, 3–5, and 5–7 years were further assessed. Generalized linear and logistic regression models were used to estimate associations with a modified continuous cardiometabolic risk score (modified cMetS) and cardiometabolic risk traits (CRTs) at age 8. Two adverse BMI trajectories were identified: late obesity growth pattern (LOGP) and persistent obesity growth pattern (POGP). Compared with control trajectory, LOGP and POGP were associated with higher modified cMetS in fully adjusted models [LOGP: regression coefficient (β) = 0.88, 95

OBJECTIVE:To examine how race, income and food insecurity (FI) interact during pregnancy and whether FI contributes to disparities in maternal and infant health outcomes. DESIGN:Observational cohort study employed sequential explanatory a mixed-methods design, with a survey phase (including Household Food Security Survey Module [HFSSM] six-item) and medical record abstraction followed by semi-structured interviews. SETTING:Online survey, virtual interviews. PARTICIPANTS:The participants were individuals who gave birth in Louisiana, USA, between June 2020 and June 2021. The quantitative phase comprised 1691 individuals who completed the survey. A nested cohort of forty individuals (evenly split by race (Black v. White) and income (low v. high)) subsequently completed semi-structured interviews. RESULTS:Race and income were independently associated with both FI and maternal and infant health outcomes. When considering both income and FI, low-income individuals with FI were 1·73 times more likely to deliver low birthweight (LBW) infants (adjusted Odds Ratio [aOR] 95 % CI: 1·07, 2·82) and 1·43 times more likely to experience adverse infant outcomes (aOR 95 % CI: 1·02, 2·00) than high-income individuals without FI. Black individuals with FI were 2·49 times more likely to deliver LBW infants (aOR 95 % CI: 1·45, 4·29) than White individuals without FI. Interview findings revealed low-income individuals faced disproportionate barriers to accessing healthy food and making dietary choices, which were further complicated by pregnancy-related conditions. CONCLUSIONS:The interplay between race, income and FI significantly increases the risk of adverse infant health outcomes, demonstrating a synergistic effect. Targeted efforts to address FI, particularly among low-income pregnant individuals, are essential to improving maternal and infant health outcomes.

BackgroundKnee osteoarthritis (OA) is a common cause of pain and disability without a cure. Glucosamine is widely used as a symptomatic treatment owing to its safety, yet its clinical efficacy remains uncertain amid mixed trial results and conflicting guidelines. This umbrella review synthesized evidence from published systematic reviews and meta-analyses on the effectiveness and safety of glucosamine in knee OA.MethodsWe searched MEDLINE (via PubMed), Embase, Web of Science, and the Cochrane Library up to November 2025. Eligible studies were systematic reviews or meta-analyses of randomized trials in adults with knee OA comparing glucosamine (any formulation) with placebo or other non-surgical comparators and reporting pain, physical function, or joint structure. Two reviewers independently screened, extracted data, and assessed quality (AMSTAR-2). Key outcomes were pain (visual analog scale [VAS] and WOMAC [Western Ontario and McMaster Universities Osteoarthritis Index]), functional measures, joint space narrowing (JSN), and adverse events. Overlap among shared primary trials was quantified using the corrected covered area, and the resulting dependence was addressed using robust variance estimation to pool standardized mean differences (SMDs), with p < 0.05 considered significant. Effect sizes were interpreted against minimal clinically important difference (MCID) thresholds.ResultsNineteen reviews were included (most low or critically low quality). Glucosamine produced a small but statistically significant reduction in VAS pain (SMD − 0.36, p = 0.02), whereas WOMAC pain showed no significant difference. Functional outcomes (WOMAC total and function) showed no significant improvement. Glucosamine was associated with significant slowing of JSN progression (SMD − 0.32, p = 0.01), though this signal derived mainly from long-duration sulfate trials. The magnitude of the significant effects was at or below accepted MCID thresholds. Adverse event rates did not differ from placebo.ConclusionGlucosamine demonstrated at most minimal-to-modest efficacy for knee OA, yielding a small pain reduction and possible slowing of radiographic progression but no clear functional benefit, with effects at or below the threshold of clinical importance. Given the low quality of evidence, extensive overlap among reviews, and the predominantly out-of-pocket nature of glucosamine use, these findings should be interpreted with caution and weighed against cost in shared decision-making.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier (CRD420251207513).

Background: Several studies have investigated the association between maternal gestational diabetes mellitus (GDM) and the risk of elevated blood pressure in offspring, but findings have been inconsistent. Objective: This study aimed to examine the association between maternal GDM and offspring’s hypertension risk from 6 to 8 years of age. Methods: A total of 1,156 mother-child pairs (578 with GDM and 578 without GDM) were followed longitudinally at a mean of 5.9 ± 1.2 years postpartum. Of these, 912 pairs (486 GDM and 426 non-GDM) remained at a follow-up conducted at 8.3 ± 1.6 years postpartum. Childhood blood pressure was measured using standardized protocols. Results: At 5.9 years of age, children born to mothers with GDM had significantly higher mean value of systolic blood pressure Z scores compared to those born to mothers with normal glucose levels during pregnancy (0.05 vs. −0.21, P < 0.001). After adjusting for multiple variables, children of mothers with GDM had higher odds ratios of hypertension (OR 1.80, 95% confidence intervals [CI]: 1.73–1.86) and high blood pressure (OR 1.56, 95% CI: 1.06–2.31). At 8.3 years of age, the association between maternal GDM and childhood high blood pressure became stronger. Adjusted odds ratios were 2.89 (95% CI: 2.14–3.90) for hypertension and 2.16 (95% CI: 1.04–4.78) for high blood pressure. Conclusions: Maternal GDM was an independent risk factor for childhood hypertension at both 5.9 and 8.3 years of age. The strength of this association increased with the child’s age.

OBJECTIVE:To explore the association between maternal cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like 1 (CDKAL1) gene and adverse growth patterns in offspring aged 1-8 years, and whether gestational diabetes mellitus (GDM) mediates this association. METHODS:An 8-year follow-up was conducted on 345 mother-infant pairs in Tianjin, China. Growth patterns in offspring aged 1-8 years were identified by group-based trajectory modeling. Logistic regression and restricted cubic splines analyzed the association between CDKAL1 polygenic risk scores (PRS) and growth patterns in offspring aged 1-8 years. RESULTS:Four growth patterns were identified, including normal (n = 151), persistent lean (n = 128), and obesity (n = 66), which included both late and persistent obesity subtypes. In the adjusted model, the CDKAL1 PRS > 0.5 was associated with the persistent lean growth pattern (OR: 1.91, 95%CIs: 1.32-2.77) and the obesity growth pattern (OR: 2.07, 95% CIs: 1.65-2.60). After further adjustment for GDM, the associations remained significant for both the persistent lean growth pattern (OR: 1.97, 95% CI: 1.36-2.85) and the obesity growth pattern (OR: 2.19, 95% CI: 1.74-2.75). CONCLUSION:Maternal CDKAL1 gene was associated with adverse growth patterns in offspring, independently of GDM. IMPACT:Maternal CDKAL1 gene independently increases offspring's dual risk of persistent lean and obese growth patterns during childhood, independently of gestational diabetes (GDM). Challenges conventional understanding by revealing a direct effect of maternal genes on offspring growth beyond GDM-mediated pathways. Shifts research focus toward GDM-independent mechanisms, such as placental programming or direct metabolic set-point regulation. Enables early stratification of childhood growth risks and facilitates preemptive personalized nutritional interventions. Provides novel genetic perspectives and preventive opportunities for addressing the dual burden of childhood growth disparities.