AIMS:This study aims to systematically evaluate the efficacy of bimagrumab on body composition and glucose parameters in adults with obesity and metabolic dysfunction and its safety profile. METHODS:We searched MEDLINE, PubMed, Embase, and the Cochrane Library on April 20, 2026, for randomized controlled trials (RCTs) assessing bimagrumab treatment in adults with obesity, insulin resistance, or type 2 diabetes mellitus (T2DM). The risk of bias was assessed using the Cochrane Risk of Bias tool (RoB 2), and meta-analyses of efficacy and safety data were conducted using R software. The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system was used to assess the strength of evidence. The study was registered with PROSPERO (CRD420261377110). RESULTS:Of the 134 retrieved records, 4 RCTs (enrolling 268 participants) were included. The included population represented a broad spectrum of metabolic dysfunction, from obesity and nondiabetic insulin resistance to established T2DM. Compared with placebo, bimagrumab treatment significantly reduced total weight (mean difference [MD] -4.85 kg, 95% confidence interval [CI] -6.82 to -2.88), fat mass (-4.72 kg [-8.05 to -1.40]), and glycated haemoglobin (HbA1c) (-0.13% [-0.23 to -0.03]) and significantly increased total lean mass (1.66 kg [0.81 to 2.51]). However, bimagrumab led to an increase in low-density lipoprotein (LDL) concentrations of 0.47 mmol/L [0.03 to 0.91] and significantly increased incidences of discontinuation (risk ratio [RR] 5.75 [1.61 to 20.46]), muscle spasms (RR 10.44 [4.23 to 25.75]), and diarrhoea (RR 4.91 [2.38 to 10.11]). CONCLUSION:Bimagrumab effectively reversed adverse effects on body composition in obese individuals, resulting in significant fat reduction, increased skeletal muscle mass, and improved glycemic control, suggesting that bimagrumab is a promising new target for personalized metabolic therapy.

IntroductionThe global diabetes epidemic has brought gestational diabetes mellitus (GDM) and its long-term impacts on maternal-child health into sharp focus. Emerging evidence indicates that early-life metabolic programing, mediated significantly by gut microbiota, profoundly influences offspring glucose homeostasis. Notably, microbial-targeted nutritional interventions, including probiotic and prebiotic supplementation, have considerable potential as innovative therapeutic approaches. These strategies may effectively prevent intergenerational transmission of metabolic diseases by improving glucose metabolism in both mother and offspring.MethodsThis narrative review synthesizes evidence from clinical trials and animal studies investigating the effects of maternal probiotic and prebiotic supplementation on glucose metabolism. We searched and analyzed literature focusing on glycemic outcomes in pregnant women with or without GDM and their offspring, as well as studies exploring underlying mechanisms including gut microbiota modulation, metabolite production, inflammatory pathways, and epigenetic regulation.ResultsClinical and animal studies have shown that probiotics and prebiotics can significantly alleviate metabolic parameters such as elevated fasting glucose and insulin resistance in patients with GDM, but their preventive effect on the incidence of GDM is unclear. In addition, maternal supplementation with probiotics or prebiotics may positively affect glucose metabolism in offspring through multiple interconnected mechanisms, which include the modulation of intestinal microbial ecology, the increased generation of microbial- derived metabolites such as short-chain fatty acids (SCFAs), the mitigation of inflammatory responses, and epigenetic regulation (e.g., DNA methylation, lncRNA and miRNA modification).DiscussionDespite some heterogeneity in the results of existing studies, there is overall support for the therapeutic potential of probiotic and prebiotic interventions in optimizing metabolic outcomes for both maternal and pediatric populations. Future studies need to further define the optimal type, dose and timing of intervention for probiotics and prebiotics and explore precise intervention strategies on the basis of individual gut microbiota characteristics. In conclusion, probiotic and prebiotic supplementation during pregnancy and lactation may become an adjunctive tool to improve glucose metabolism in mothers and infants, resulting in innovative approaches for the primary prevention of metabolic diseases.

Environmental factors, such as nutrition, hormones, and metabolites, which are present in early stages of life, have long-lasting effects throughout an organism’s lifespan, and an abnormal nutritional environment throughout gestation and lactation may significantly increase the possibility that offspring will develop chronic metabolic disorders. The important nutrients docosahexaenoic acid (C22:6n-3, DHA) and eicosapentaenoic acid (C20:5n-3, EPA), which are essential long-chain omega-3 polyunsaturated fatty acids, contribute to proper neurological and retinal development and exhibit both anti-inflammatory properties and lipid-reducing capabilities. Recent research has demonstrated that maternal diets supplemented with EPA and DHA may regulate lipid metabolism-related genes in the liver and adipose tissues and alter the intestinal microbial composition in offspring. These changes influence the progression of lipid metabolic disorders, including dyslipidemia, obesity, and MAFLD in the next generation. This narrative review illustrates the effects of maternal EPA and DHA intervention during the prenatal and breastfeeding period on lipid metabolism in the offspring and the underlying mechanisms. We also explore the directions for future research.

Background Abnormal birth weights are associated with adverse pregnancy outcomes and future metabolic consequences. We aimed to examine cord blood lipidomes from low, normal and high birth weight (LBW, NBW, HBW) infants to identify core lipid signatures associated with non-optimum birth weight, and to derive biological insights through trans-omics data integration with placental proteome, maternal plasma lipidome and clinical phenome. Methods We conducted quantitative lipidomics of cord blood samples from two independent cohorts: a retrospective discovery cohort (n = 147) and a prospective validation cohort (n = 73). Integration with placental proteomics, maternal plasma lipidomics and clinical phenomics was conducted to elucidate potential biological implications. Findings We identified substantial reductions in cord blood polyunsaturated phospholipids (PUFA-PLs) (FDR <0.05) associated with placental vesicle trafficking and formation in LBW, and altered neutrophil degranulation in HBW. Combinatorial analyses of paired maternal plasma and cord blood samples indicated that cord blood PUFA-PL reductions were not attributable to deficient maternal supply, but rather to impeded assimilation (LBW) and increased utilisation (HBW). Interpretation Our findings provide biological insights that may inform targetable, lipid-oriented nutritional and/or pharmacological strategies to modulate foetal growth and development, with the goal of optimising clinical outcomes for both mother and child. Funding This work was supported by the National Natural Science Foundation of China (82170854, 81870579, 81870545, 82571043, 2357308); National High Level Hospital Clinical Research Funding (2022-PUMCH-C-019); Noncommunicable Chronic Diseases-National Science and Technology Major Project (2024ZD0530200 and 2024ZD0530204); Beijing Municipal Science & Technology Commission (Z201100005520011); Peking University Clinical Scientist Training Program (No. BMU2023PYJH022); Beijing Municipal Natural Science Foundation (7202163, 7184252).

Placenta-derived extracellular vesicles (EVs), particularly exosomes, serve as key mediators that influence metabolic programming in offspring under adverse early nutritional conditions, such as maternal obesity or gestational diabetes. They respond to maternal nutritional disturbances-such as obesity or gestational diabetes-by altering the composition of the miRNAs and proteins they carry. Evidence from in vivo and in vitro studies suggests that these modified EVs influence offspring metabolic programming through multiple putative pathways: regulating fetal pancreatic β-cell development and function, modulating lipogenesis via PPARγ signaling, affecting placental angiogenesis, and promoting inflammation and epigenetic alterations. By transmitting maternal environmental signals to the fetus, placental EVs are hypothesized to contribute to long-term metabolic phenotypes and disease susceptibility. This review critically examines the current evidence positioning placental EVs as key messengers in maternal-fetal communication, evaluates the strength of evidence supporting their role in shaping offspring metabolic health, identifies major knowledge gaps (e.g., limited direct evidence in human offspring, lack of standardized isolation methods), and suggests their potential as early intervention biomarkers or therapeutic targets for preventing metabolic disorders in offspring. We also highlight the need for prospective cohort studies and mechanistic validation in appropriate animal models to establish causality.

ObjectiveTo report a novel GCK variant (c.263T>C) identified in a patient with glucokinase-maturity-onset diabetes of the young (GCK-MODY) and to evaluate its pathogenicity and potential structural impact using in silico analyses. The proband had a paternal history of type 2 diabetes mellitus (T2DM) and was overweight with marked insulin resistance, presenting with clinical features suggestive of T2DM. She also exhibited transient glutamic acid decarboxylase antibody (GADA) positivity. Clinical characteristics were further evaluated to facilitate the differential diagnosis.Case presentationA novel GCK missense variant was identified in a Chinese family, with the daughter as the proband. At 6 years of age, she presented with mild fasting hyperglycemia and initial GADA positivity and was misdiagnosed with type 1 diabetes mellitus (T1DM). However, her clinical features and family history were suggestive of MODY. Whole-exome sequencing revealed a heterozygous GCK c.263T>C variant, confirmed by Sanger sequencing in her mother, maternal grandmother, and maternal grandaunt. The variant was classified as likely pathogenic, establishing a diagnosis of GCK-MODY. Notably, she also exhibited obesity and a paternal family history of T2DM. During follow-up, GADA seroconverted to negative, with no evidence of persistent autoimmune diabetes.ConclusionThis case identifies a novel likely pathogenic GCK variant (c.263T>C) in a Chinese family and highlights the coexistence of GCK-MODY with insulin resistance within the same pedigree. The proband’s severe insulin resistance may be attributable to the combined effects of obesity and a paternal history of T2DM, contributing to a complex clinical phenotype. Transient GADA positivity was not associated with persistent autoimmune diabetes, suggesting it may reflect metabolic stress rather than true autoimmune pathogenesis.

Background/Objectives: The developmental origins of health and disease (DOHaD) theory suggests that intrauterine and early postnatal life represents a critical window for programming lifelong health trajectories and disease susceptibility in offspring. Maternal nutritional imbalance during this period is closely associated with obstetric complications and an elevated risk of metabolic disorders in children. As central metabolic hubs, mitochondria constitute a critical axis linking adverse in utero exposure to metabolic defects in offspring across generations. Methods: In this narrative review, we searched PubMed and Web of Science (up to 8 July 2026) for English-language literature linking maternal metabolic conditions and mitochondrial dysfunction. We included in vivo, in vitro, and clinical studies, explicitly excluding primary inherited mtDNA mutations and nonnutritional toxicant exposures to isolate nutritional programming effects. Results: Maternal metabolic stress induces multifaceted, tissue-specific mitochondrial alterations in the developing offspring. Rather than a uniform systemic decline, mitochondrial reprogramming exhibits profound spatial and cellular heterogeneity across critical metabolic organs, including the placenta, liver, skeletal muscle, heart, and hypothalamus. These developmental adaptations often manifest as molecular compensations, such as altered mitochondrial dynamics, perturbed biogenesis, and shifted OXPHOS capacity, ultimately leading to functional bioenergetic failure, oxidative stress, and the establishment of insulin resistance. Discussion: Organ-specific mitochondrial dysfunction drives the maternal transmission of metabolic syndrome. Targeting these mechanisms via dietary modifications, exercise, pharmacological agents, and mitochondrial transplantation offers promising strategies to rescue bioenergetics and prevent metabolic diseases in offspring.

Aim Monogenic diabetes is a group of disorders arising from single gene mutations with a clear pathophysiology, most of which present with impaired beta cell function rather than insulin resistance. This study aims to evaluate the ability of TyG index and polygenetic risk score (PRS) to identify multi-type beta cell monogenetic diabetes (beta-cell-MgD) in Chinese early-onset type 2 diabetes (EOD) population. Methods A prediction model for beta-cell-MgD was established by logistic regression analysis in Cohort 1 (92 beta-cell-MgD, 512 EOD). Model performance was evaluated by receiver operating characteristic curves (ROC) and validated in an independent case-control sample (Cohort 2, 35 beta-cell-MgD, 50 EOD) and a newly diagnosed drug-naive EOD cohort (Cohort 3, 7 beta-cell-MgD, 176 EOD). PRS was constructed based on Genome-wide genotyping data from participants in Cohort 3. The ability of PRS to identify beta-cell-MgD was tested by ROC. Results The TyG-MgD score based on age at diagnosis, BMI and TyG presented a good performance to distinguish beta-cell-MgD (AUC=0.769), and achieving AUCs of 0.966 and 0.754 respectively in validation cohorts. At the optimal cutoff point -16.19, the model achieved a sensitivity of 66.3% and a specificity of 75.39%, allowing one case of beta-cell-MgD identified among every three patients. -16.85 could be used as the screening threshold prioritizing 80% sensitivity (with 59% specificity). Models combining TyG-MgD with East Asian PRS and beta-cell dysfunction-high proinsulin partitioned polygenetic score showed AUCs of 0.842 and 0.834 respectively for indentifying beta-cell-MgD. Conclusion We developed a clinical prediction model as a simple screening tool for multi-type beta-cell-MgD, identifying who are most likely to benefit from next genetic sequencing in Chinese population. PRS might be helpful for further screening of MgD.

Genetic predisposition and unhealthy lifestyles are well-known contributors to disorders of glucose and lipid metabolism, including type 2 diabetes, obesity, and metabolic dysfunction-associated fatty liver disease. However, these factors alone cannot fully explain the rapidly rising prevalence of these conditions. Emerging evidence highlights the pivotal role of the intrauterine environment in gestational diabetes mellitus (GDM) in shaping epigenetic modifications and metabolic reprogramming, thereby predisposing offspring to long-term metabolic complications. Exosomes have recently been identified as key mediators of maternal-fetal communication. In GDM, both the quantity and cargo (e.g., proteins, miRNAs) of exosomes are altered. These altered exosomes not only contribute to maternal glucose and lipid metabolic abnormalities but also act as a critical vector for transmitting adverse metabolic signals to the offspring. This exosome-mediated communication disrupts placental function and the development of fetal metabolic organs, ultimately programming the offspring for long-term metabolic disorders. In this review, we summarize the characteristic changes of maternal exosomes in GDM and explore the potential mechanism by which exosomes regulate offspring metabolism during maternal-fetal crosstalk. We also propose the possible direction of exosomes in application, providing insights into early-life strategies for the prevention of metabolic diseases.

Ethnopharmacological relevance Mudan granules are Chinese patented medicines approved by the National Medical Product Administration, used to treat diabetic peripheral neuropathy (DPN) with Qi deficiency and collateral obstruction syndrome. However, placebo-controlled studies definitively establishing efficacy and safety are lacking. Aim of the study To evaluate the efficacy and safety of Mudan granules as an adjunct treatment for DPN with qi deficiency and collateral obstruction syndrome. Methods This multicenter, placebo-controlled, double-blind, randomized, controlled clinical trial recruited patients from 13 clinical centers in mainland China. 400 participants were randomly assigned in a 1:1 ratio to either the Mudan (Mudan granules + mecobalamin) or control group (placebo + mecobalamin), and were reassessed after the 24-week intervention. The primary outcome was the Michigan Diabetic Neuropathy Score (MDNS). Results The complete analysis set comprised 357 participants. The mean baseline MDNS of the Mudan and control groups were 9.69 and 9.43, respectively. The mean change in MDNS from baseline to week 24 was -4.80 in the Mudan and -2.66 in the control group. Using a covariate-adjusted analysis of covariance model, the least squares mean for the Mudan and control groups were -4.74 (-5.33 to -4.15) and -2.72 (-3.33 to -2.11), respectively. There was a statistically significant difference between the two groups. After 24 weeks of follow-up, the Mudan group showed a significant improvement in MDNS compared to the control group. Conclusion These findings suggest that Mudan granules may improve the clinical symptoms of DPN. Given this, Mudan granules may be helpful in the management of DPN.

Introduction and Objective: Metabolic dysfunction-associated steatotic liver disease (MASLD) is one of the most common complications of type 2 diabetes. Disease progression is closely linked to oxidative stress and ferroptosis, a novel form of regulated cell death. The effect and mechanism of miglitol, a classical anti-diabetic drug, on MASLD remain unclear. This study aimed to investigate the potential effect of miglitol on MASLD, thereby proposing a new therapeutic strategy for MASLD. Methods: Male C57BL/6N mice were randomly divided into six groups: control, high-fat diet (HFD), HFD with low-, medium-, high-dose miglitol, and HFD with acarbose. After 8 weeks of intervention, metabolic phenotypes and liver pathology were assessed. An in vitro model was established in AML-12 hepatocytes using palmitic acid/oleic acid (PA/OA), with or without miglitol co-treatment. Proteomics, biochemical assays, immunofluorescence, and Western blotting were employed to analyze its effects on lipid metabolism and ferroptosis. Results: In animal studies, miglitol significantly ameliorated HFD-induced weight gain, liver weight, and hepatic lipid accumulation. In PA/OA induced cell models, proteomic profiling revealed that miglitol potently modulated pathways related to lipid metabolism and ferroptosis. Immunofluorescence demonstrated that miglitol markedly attenuated intracellular lipid peroxide accumulation and labile iron pool. Western blotting further confirmed that miglitol counteracted the HFD-induced and PA/OA-induced upregulation of the pro-ferroptotic marker 4-HNE and restored the expression of key anti-ferroptotic proteins, GPX4 and FTH1. Conclusion: This study is the first to demonstrate that miglitol alleviates MASLD progression in vitro and in vivo by inhibiting ferroptosis, improving lipid metabolism, and reducing oxidative stress. These findings provide robust preclinical evidence for its repositioning as a potential therapeutic agent for MASLD. Disclosure J. Zhou: None. J. Liu: None. X. Xiao: None.

Overcoming gastrointestinal degradation, epithelial impermeability, and hepatic clearance has been the long-sought goal in oral insulin delivery. Xia et al.’s pioneering work in Science Advances achieves a paradigm shift using site-specific adaptive milk-derived nanovesicles (MiNVs). Engineered from bovine milk exosomes and biothiol-responsive liposomes, MiNVs exploit IgG-FcRn transcytosis for efficient intestinal uptake and glutathione-activated release in the liver. This dual-mechanism enables sustained glycemic control and high oral bioavailability in rodent and porcine diabetic models. More than an incremental advance, this represents a transformative leap toward physiological, injection-free insulin therapy.

Maternal diets during pregnancy and lactation are critical determinants that regulate the metabolic homeostasis in offspring. Our previous research demonstrated that maternal genistein (GEN) intervention ameliorated the dysregulation of glucolipid metabolism induced by intrauterine overnutrition in adult offspring, accompanied by changes in the composition of gut microbiota; however, the underlying mechanisms remain unclear. Here, we used a maternal overnutrition model induced by excess energy intake before and throughout pregnancy and lactation, with maternal GEN administered during the same period. The female offspring were raised on a standard chow diet until sacrificed at 24 weeks. The mRNA levels of browning markers were quantified in inguinal subcutaneous adipose tissues, followed by methylation analysis via the MassArray method. Cecal contents were collected for untargeted metabolomic analysis and a target quantitative analysis of methionine cycle metabolites. Spearman correlation analyses were used to assess whether cecal metabolites are involved in the methylation of browning-related genes and influence their expression. The results showed that maternal GEN supplementation reversed the downregulation of browning markers caused by perinatal high-fat diets in adult female offspring, consistent with a reduction in their methylation levels. Subsequently, we also found that maternal GEN consumption altered cecal metabolite profiles in offspring, promoting the production of bile acids, potent regulators of glucolipid metabolism, and reducing metabolites involved in the methionine cycle, key methyl donors for the methylation process. Furthermore, the abundances of these metabolites were significantly correlated with the methylation and expression levels of browning markers. Overall, this discovery suggested that maternal GEN intake decreased the methylation level of browning markers and induced browning in white adipose tissue of offspring, which correlated with alterations in cecal metabolites. We provide a novel theoretical basis for GEN as a promising nutritional supplement to break the vicious cycle of maternal metabolic disturbances being transmitted to offspring.

Lipid metabolism is essential for maintaining cellular homeostasis and human health, and its dysregulation can contribute to metabolic disorders such as obesity and diabetes. As one of the most prevalent RNA modifications, the N6-methyladenosine (m6A) modification plays a pivotal role in regulating gene expression and metabolic pathways. The gut microbiota influences lipid metabolism by modulating the host's m6A modification patterns. Research has shown that the gut microbiota can regulate the levels of the m6A modification in host tissues, while the m6A modification also impacts the composition and functionality of the gut microbiota. This review comprehensively examines the interaction between the m6A modification and the gut microbiota, elucidating its underlying mechanisms in lipid metabolism and highlighting the potential applications of this crosstalk in addressing metabolic diseases. Future investigations should aim to further elucidate the precise molecular mechanisms governing the interplay between the m6A modification and the gut microbiota, thereby providing novel therapeutic targets and strategies for metabolic disease management.

Type 2 diabetes mellitus (T2DM) is a progressive disease involving multiple pathophysiologic defects, and combination therapy is often required to achieve and sustain glycaemic control. Triple oral therapy with metformin, dipeptidyl peptidase-4 inhibitors (DPP-4i), and sodium-glucose cotransporter-2 inhibitors (SGLT2i) has demonstrated high and durable glycaemic-lowering efficacy, favourable safety and tolerability, and additional metabolic benefits in T2DM patients with diverse background therapies, including those who are treatment-naïve and those with inadequate control on monotherapy or dual therapy. In light of the increasing clinical use of this triple regimen and the absence of established consensus to guide its use, the Diabetes Committee of the Chinese Research Hospital Association convened an expert panel comprising endocrinologists and evidence-based experts. Through a systematic literature review and a Delphi process, the panel formulated 11 consensus recommendations (8 strong and 3 weak recommendations) on the clinical use of metformin + DPP-4i + SGLT2i, including fixed-dose combination formulations. Safety considerations regarding its use were also described. This consensus aimed to provide clinicians with practical guidance to optimize the effective and safe use of metformin + DPP-4i + SGLT2i in T2DM management.

OBJECTIVE:To assess the effect of dapagliflozin plus calorie restriction on remission of type 2 diabetes. DESIGN:Multicentre, double blind, randomised, placebo controlled trial. SETTING:16 centres in mainland China from 12 June 2020 to 31 January 2023. PARTICIPANTS:328 patients with type 2 diabetes aged 20-70 years, with body mass index >25 and diabetes duration of <6 years. INTERVENTIONS:Calorie restriction with dapagliflozin 10 mg/day or placebo. MAIN OUTCOME MEASURES:Primary outcome: incidence of diabetes remission (defined as glycated haemoglobin <6.5% and fasting plasma glucose <126 mg/dL in the absence of all antidiabetic drugs for at least 2 months); secondary outcomes: changes in body weight, waist circumference, body fat, blood pressure, glucose homoeostasis parameters, and serum lipids over 12 months. RESULTS:Remission of diabetes was achieved in 44% (73/165) of patients in the dapagliflozin group and 28% (46/163) of patients in the placebo group (risk ratio 1.56, 95% confidence interval (CI) 1.17 to 2.09; P=0.002) over 12 months, meeting the predefined primary endpoint. Changes in body weight (difference -1.3 (95% CI -1.9 to -0.7) kg) and homoeostasis model assessment of insulin resistance (difference -0.8, -1.1 to -0.4) were significantly greater in the dapagliflozin group than in the placebo group. Likewise, body fat, systolic blood pressure, and metabolic risk factors were significantly more improved in the dapagliflozin group than in the placebo group. In addition, no significant differences were seen between the two groups in the occurrence of adverse events. CONCLUSION:The regimen of dapagliflozin plus regular calorie restriction achieved a much higher rate of remission of diabetes compared with calorie restriction alone in overweight or obese patients with type 2 diabetes. TRIAL REGISTRATION:ClinicalTrials.gov NCT04004793.

In recent years, more and more evidence has confirmed the “Developmental Origins of Health and Disease (DOHaD)” hypothesis, which states that adverse environments in early life can increase the risk of long-term metabolic diseases such as obesity and diabetes. Gestational diabetes mellitus (GDM) and subclinical hypothyroidism (SCH) during pregnancy are the most common endocrine diseases, which directly interfere with the intrauterine development environment of the fetus and thus are ideal research entry points for validating and extending the DOHaD theory. This study aims to deeply explore the early impact of maternal endocrine disorders during pregnancy (with a focus on GDM and SCH) on the healthy development of the fetus, using key indicators such as birth weight as measures of early health outcomes. The research objectives include: 1) To Identify potential biomarkers that can be used for early prediction of GDM and SCH; 2) To observe the extent to which GDM and SCH affect the pregnancy outcome. This will be a prospective cohort study involving 300 pregnant women. In addition to collecting general demographic information and clinical data of pregnant women, we also collect peripheral blood, urine, and fecal samples from pregnant women during the early, middle, and late stages of pregnancy. We also collect placental and umbilical cord blood samples during delivery. We conduct multi-omics analysis on the samples to comprehensively screen for differentially expressed molecules related to gestational endocrine diseases (GDM and SCH) and adverse outcomes. The main evaluation indicators are the birth weight of the offspring, including low birth weight, macrosomia, small for gestational age, and large for gestational age. The secondary outcome indicators include the following: 1) neonatal-related outcomes that include intrauterine growth restriction (IUGR), intrauterine fetal death (IUFD), preterm birth, low Apgar score, admission to the neonatal intensive care unit (NICU); and 2) maternal pregnancy outcomes that include gestational hypertension, preeclampsia, eclampsia, anemia, spontaneous abortion, type of delivery (vaginal, assisted vaginal delivery or cesarean section) and other complications. This study aims to establish a prospective Chinese pregnant cohort to investigate the effects of GDM and SCH on pregnancy outcomes. On this basis, this study will utilize multi-time-point collected biological samples and combine multi-omics technologies to identify high-risk phenotypic characteristics related to GDM and SCH, with the aim of achieving early identification, and hopefully, intervention in the future, thereby reducing adverse pregnancy outcomes and the risk of long-term chronic diseases in the offspring. ClinicalTrials.gov ID: NCT05952739. Study Registration Dates: July 19, 2023.