This systematic review and meta-analysis aimed to compare the efficacy and safety of tirzepatide versus semaglutide for weight reduction in adults with overweight or obesity. We included randomised controlled trials and observational studies comparing tirzepatide and semaglutide with ≥ 24 weeks of follow-up. The primary outcome was percentage weight change from baseline. Secondary outcomes included absolute weight change, weight-loss thresholds, HbA1c and safety outcomes. Ten studies including 41 381 participants were analysed. Tirzepatide was associated with greater percentage weight reduction than semaglutide (MD -4.28 percentage points; 95% CI -5.28 to -3.28; p < 0.00001) and greater absolute weight loss (MD -4.43 kg; 95% CI -5.56 to -3.30; p < 0.00001). Tirzepatide was also associated with a higher likelihood of achieving ≥ 10%, ≥ 15% and ≥ 20% weight loss, with no difference at ≥ 5%. HbA1c reduction was greater with tirzepatide (MD -0.29%; p = 0.0002). Subgroup analyses by study design and type 2 diabetes status yielded consistent findings. There was no significant difference in treatment discontinuation due to adverse events (RR 1.28; p = 0.54), whereas serious adverse events were more frequent with tirzepatide (RR 1.83; p = 0.007). Overall and gastrointestinal adverse events were similar between groups. Tirzepatide was associated with greater weight reduction, greater glycaemic benefit and a higher likelihood of achieving weight-loss thresholds than semaglutide, but with a higher risk of serious adverse events.
To investigate differences in cause-specific mortality risks between obesity classes stratified by age and sex, using a nationally representative sample of the US population. Differences in mortality risk by standard body mass index (BMI) categories with examination of Obesity Classes I-III, stratified by age (less or more than 65 years) and sex were examined using Cox proportional hazard ratios with data from NHANES Continuous (1999-2018) with mortality follow-up through 31 December 2019. Among younger adults (< 65 years), Obesity Class III was associated with higher all-cause, cardiovascular, non-cardiovascular/non-cancer and diabetes-related mortality compared to Class I. Among older adults (≥ 65 years), there were fewer significant associations with only cardiovascular and diabetes-related mortality risks being elevated in men with Obesity Class III and none in women. There were no differences in mortality risks between Obesity Classes I and II, except for diabetes-related mortality in younger adults and older men. Obesity Class III is strongly associated with higher mortality risk in younger adults (< 65 years) and to a lesser degree in older adults (≥ 65 years). Mortality risks were generally similar between obesity Classes I and II. Therefore, younger adults under 65 years of age with severe obesity may benefit more from aggressive obesity management.
Glucagon-like peptide-1 receptor agonists (GLP-1RAs), including semaglutide, are widely used for Type 2 diabetes mellitus (T2DM), obesity and related metabolic conditions. Evidence on potential neuropsychiatric effects remains inconsistent. This systematic review and meta-analysis evaluated depression risk among patients receiving semaglutide. Following PRISMA 2020 guidelines, major biomedical databases, trial registries, pharmacovigilance databases, conference abstracts and grey literature were searched from inception to January 2026. Eligible studies included randomised controlled trials, observational studies, large database analyses and pharmacovigilance disproportionality studies involving patients receiving semaglutide. Risk of bias was assessed using ROBINS-I and the Newcastle-Ottawa Scale. The pooled risk ratio for depression was 1.25 (95% CI: 0.95-1.65; I2 = 98%). For anxiety and suicidal ideation/attempt, pooled risk ratios were 1.22 (95% CI: 0.93-1.60; I2 = 99%) and 1.20 (95% CI: 0.90-1.62; I2 = 92%), respectively. No statistically significant differences were observed between semaglutide and comparator/placebo groups for outcomes. Pooled estimates did not show a statistically significant increase in depression, anxiety or suicidal ideation/attempt among patients receiving semaglutide compared with comparator groups. However, the certainty of evidence was limited by substantial heterogeneity, risk of bias and reliance on heterogeneous data sources, including spontaneous-reporting studies. These findings are reassuring but should be interpreted as the absence of a detected increased risk in the available evidence, rather than definitive proof of no psychiatric risk.
To assess the variability in the population attributable fraction (PAF) of GDM to overweight/obesity and the relationship of BMI and GDM across three diagnostic criteria: IADPSG, NICE and Diabetes in Pregnancy Study Group India (DIPSI). The PAF of GDM to overweight/obesity and the relationship of GDM and BMI were estimated using Poisson regression models in a retrospective cohort of 4317 women who underwent GDM screening during the 2013-2017 period. Multiple linear regression models were applied to associate BMI with fasting, 1-h and 2-h plasma glucose values. The PAF of GDM to overweight/obesity for IADPSG, NICE and DIPSI criteria was 34.84%, 28.17% and 18.44%, respectively. There was a quadratic relationship between BMI and GDM for all criteria, and the peak BMI values for IADPSG, NICE and DIPSI criteria were 34.26, 33.28 and 32.01 kg/m2, respectively. The relationship between BMI and PG values was also quadratic, with peaks in FPG, 1-h and 2-h PG at BMI values of 40.91, 35.50 and 33.04 kg/m2, respectively. PAF of GDM to overweight/obesity among South Asian women varies by the GDM diagnostic criteria. The quadratic relationship between BMI and GDM probability and between BMI and plasma glucose values is a novel observation.
Clinically relevant weight loss (≥ 5%) is a key treatment goal in dietetic care for patients with overweight or obesity. While clinical trials often demonstrate successful weight loss, less is known about success rates in routine dietetic practice, timing of weight loss and maintenance. This study examined when patients achieve and maintain ≥ 5% weight loss during 12 months of dietetic treatment in Dutch primary care, and how this relates to treatment intensity and patient characteristics. In this retrospective cohort study, routinely collected data from dietetic electronic health records (EHRs) was used. Follow-up duration was 12 months. Weight change was analysed at 3, 6, 9 and 12 months. The study included 4503 adults (≥ 18 years) with overweight or obesity (BMI ≥ 25 kg/m2) receiving dietetic treatment between 2016 and 2020 in over 70 primary care dietetic practices in the Netherlands. The primary outcome was achieving and maintaining ≥ 5% weight loss from baseline at 3, 6, 9 and 12 months. Multivariable logistic regression assessed associations of ≥ 5% weight loss with visit frequency, visit time, sex, age, BMI and comorbidity. Overall, 33% of patients achieved ≥ 5% weight loss. Of these, 60% did so within 3 months. Each additional visit in the first 3 months was associated with threefold higher odds of success (OR = 3.0). In months 3-6, each additional visit was associated with 61% higher odds of success. Early dietetic treatment intensity is strongly associated with weight loss success. Structuring care around the early treatment phase warrants prospective evaluation in routine dietetic practice.
Metabolic and bariatric surgery achieves durable weight loss and meaningful improvement in obesity-related comorbidities yet carries a risk of neurological complications that remains under-recognised in routine clinical practice. This systematic review, registered with PROSPERO (CRD42024591611) and conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines, searched MEDLINE, Embase, Emcare, CINAHL and Cochrane databases through September 2023 to evaluate the incidence, spectrum, timing, pathophysiology and management of post-operative neurological complications. Twelve studies comprising over 5000 patients were included. Reported incidence ranged from 1.4% to 16%, with peripheral neuropathy the most frequent manifestation. Mononeuropathies, particularly carpal tunnel syndrome, were prominent in several cohorts, while central complications including Wernicke encephalopathy occurred less commonly but with considerably greater severity. Thiamine deficiency was the predominant aetiological factor. Onset varied from days to several years postoperatively, with early presentations typically compression-related and later ones nutritionally mediated. Outcomes were generally favourable with early intervention, though severe or delayed cases were associated with persistent neurological deficits and occasional mortality. Neurological complications after bariatric surgery are heterogeneous and largely preventable, and structured post-operative follow-up with consistent adherence to nutritional supplementation remains central to reducing long-term harm.
There is a lack of knowledge on the registration of body mass index (BMI) and prevalence of obesity-related complications in the Belgian healthcare system. We therefore evaluated these in Belgians living with overweight or obesity. BMI registration and obesity-related complication prevalences were determined using cross-sectional data from a Belgian general practitioners' morbidity registry (Intego) with 208 891 personal records and from 3605 visitors to an obesity clinic. Two Intego data subsets were used: 53 555 individuals with and 84 017 individuals without registered BMI. Groups were compared using chi-square tests (p-value of < 0.05). For Intego data, BMI was registered in 25.6% of cases. Individuals with registered BMI (mean BMI 27.1 ± 5.5 kg/m2) had a higher prevalence of hypertension (30.1% vs. 17.0%), dyslipidemia (26.9% vs. 14.7%), prediabetes (17.0% vs. 7.9%), type 2 diabetes (12.7% vs. 4.4%) and sleep apnea (3.8% vs. 1.5%) compared to people without registered BMI. People assessed at the obesity clinic (mean BMI 39.0 ± 6.5 kg/m2) had higher prevalences of hypertension (43.1% vs. 37.5%), dyslipidemia (44.4% vs. 32.9%) and sleep apnea (37.9% vs. 5.5%) compared to Intego individuals with BMI ≥ 25 kg/m2(mean BMI 30.3 ± 4.3 kg/m2). BMI is registered only in 25% of patient files in general practice, and people with a registered BMI in general practice have a substantially higher prevalence of the five obesity-related complications than people without registered BMI. When registered, mean BMI is substantially lower than in the obesity clinic, but the prevalence of complications is already substantial, though lower than in the obesity clinic.
The prevalence of obesity is increasing worldwide, with approximately nine million people affected in Canada. Obesity is associated with high rates of morbidity and mortality as well as significant healthcare costs and economic burden. The primary therapeutic options for weight maintenance and treatment of weight regain include behaviour modification, lifestyle intervention and pharmacotherapy. This randomised, double-blind, placebo-controlled, crossover trial aimed to determine the effect of a fixed-dose, extended-release combination of naltrexone and bupropion (NB-ER) (commonly known as Contrave) on weight maintenance and further weight loss following the intensive portion of a behaviour modification program. The results from this study demonstrate that after an intensive lifestyle intervention program, treatment with NB-ER for six months prevented weight regain compared to placebo. Additionally, a greater proportion of subjects experienced weight maintenance and less absolute weight regain on NB-ER compared to placebo, supporting the use of NB-ER as an effective option for weight maintenance in patients with significant prior weight loss.
The aim of this study was to evaluate the association between indices of adiposity and 20-year cumulative incidence of type 2 diabetes (T2D) among apparently healthy adults participating in the ATTICA cohort study (2002-2022). The present analysis included data from 2000 individuals free of atherosclerotic cardiovascular disease (ASCVD) and T2D at baseline (age 43 ± 13 years; 51% women). Sociodemographic, anthropometric, lifestyle, clinical, and biochemical parameters were collected at baseline and follow-up examinations. Obesity-related anthropometric indices, in terms of total and central adiposity, along with dysfunctional adipose tissue-related indices, were measured. The 20-year cumulative incidence of T2D was 26.3% (95% CI [24.4%, 28.3%]). All indices were independently associated with the 20-year incidence of T2D, with an overall predictive accuracy of approximately 75%. With the exception of LAP (lipid accumulation product), all indices reflecting adipose tissue dysfunction demonstrated moderate discriminative accuracy for incident T2D (C-statistic varied between 0.70 and 0.80) over the 20-year follow-up period, in line with obesity-related anthropometric indices assessing total and central adiposity (C-statistic 0.70-0.80). Obesity-related anthropometric indices as well as dysfunctional adipose tissue-related indices were moderately predictive of long-term T2D onset, highlighting the complex role of increased body weight on glucose metabolism.
Obesity is a key risk factor for chronic disease and multimorbidity, yet variation in how obesity is defined may influence risk estimation in clinical practise. Waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR) are better at capturing fat distribution than body mass index (BMI) and may have a role in obesity related multimorbidity prediction. To examine multimorbidity risk across obesity groups classified using BMI in combination with WHR/WHtR. A UK Biobank cohort free of comorbidity at baseline (n = 179 876) was followed for incident first long-term condition and multimorbidity (≥ 2 of 38 conditions) over a mean of 9.9 years. Six adiposity categories combining BMI with WHR/WHtR were analysed using Cox proportional hazards models. Subgroup analyses evaluated whether high central obesity (WHtR ≥ 0.6) provided additional risk stratification within BMI groups. Combined general with central obesity showed highest risk for the first condition (HR 1.11; 95% CI 1.087-1.138) and multimorbidity (HR 1.13; 95% CI 1.093-1.172). However, BMI-stratified subgroup analyses, central obesity provided additional risk discrimination only among individuals in the overweight category (BMI 25-29.9 kg/m2), but not among those with BMI ≥ 30 kg/m2. Waist-based measures improved risk identification in adults with overweight BMI, supporting the potential role of combined BMI-waist approaches for earlier multimorbidity prevention.
This service evaluation of a primary care-based specialist weight management service reports data from 1094 patients over 5 years (2014-2019), including weight data at 1-year post-discharge. The results show clinically and statistically significant improvements in weight, diet, physical activity, quality of life, blood pressure and blood glucose control (in people living with type 2 diabetes). Change in weight was statistically significant for all timepoints in all subgroups. At 1-year completers (n = 560) had lost a mean of 8.3 kg (SD 0.3) and 133 patients (23.8%) had lost ≥ 10% of their starting weight. Using baseline observation carried forward analysis on the whole cohort (n = 1094) the mean weight loss at the end of the 1-year programme was 4.5 kg (SD 0.2) and 144 (13.2%) had lost ≥ 10% of their starting weight. A year after discharge completers demonstrated a mean weight loss of 8.3% (SD 10.3 n = 303) and 35.6% (n = 108) of completers had maintained ≥ 10% change in body weight. Analysis showed a mean weight loss of 2.5% (SD 6.8 n = 1094) in the whole cohort using baseline observation carried forward, demonstrating maintenance of weight loss and suggesting that specialist weight management services in primary care may be effective in the longer-term.
To examine surgical experiences of diverse participants with obesity who underwent bariatric surgery and interacted with nurses and physicians in the prior 2-5 years. Qualitative analysis of a prospective longitudinal cohort study to understand adult experiences of people with obesity before and after bariatric surgery. Semi-structured interview data (n = 68) were analysed to identify patterns in supportive practices and unmet needs of participants with obesity. Two theme categories emerged describing supportive care and care gaps. Supportive themes were Appreciation, Support, Listening, and Understanding, Impact of Classes, and Importance of Information. Care gap themes included Stigma, Bias, and Judgement Lack of Decision Support, More Than Losing Weight, Weight Bias, Lack of Support/Communication, Lack of Follow-Up, Few Mental Health Supports, and Not Being Seen and Heard. Participants with obesity described experiences of bias, stigma, and concerns about knowledge and communication. Our study found stigma, bias, and judgement experienced by patients with obesity are barriers to bariatric care and successful outcomes. Gaps in communication, follow-up, and mental health contributed to feelings the participants expressed of "not being seen and heard." Active listening, transparent communication, and coordinated care were perceived by participants with obesity as essential for trust, respect, and belonging.
Post-bariatric hypoglycemia (PBH) is classically defined as venous glucose levels < 54 mg/dL accompanied by sympathetic or neuroglycopenic symptoms, with resolution after glucose correction (Whipple's triad), occurring in a typical post-surgical context (1-3 years after surgery, 2-4 h postprandially), after exclusion of other causes. Since 2015, studies using continuous glucose monitoring (CGM) have revealed a more complex glycemic profile following metabolic bariatric surgery (MBS) characterised by CGM-detected asymptomatic and nocturnal low interstitial glucose values, frequently occurring during prolonged intermeal periods, along with increased 24-h glycemic variability. Provocative tests are limited by non-physiological stimuli or poor standardisation. Meanwhile, although diagnostic workups for alternative etiologies not related to diabetes are recommended, these conditions are exceedingly rare compared with real-world CGM-detected events. Evidence from cohorts of individuals with diabetes links CGM metrics, such as nocturnal and prolonged intermeal low glucose exposure and glycemic variability, to adverse outcomes, including cardiovascular mortality, stroke, arrhythmias, next-day cognitive slowing, retinopathy, microalbuminuria, and arterial stiffness. These findings may support the potential prognostic relevance of similar phenotypes following MBS. We argue for: (1) a critical revision of diagnostic criteria, including standardised interstitial thresholds, event definitions, and the role of symptoms; and (2) prospective CGM cohorts of post-MBS patients without diabetes adequately sized to assess clinically meaningful endpoints, such as cardiovascular, microvascular, and cognitive outcomes. CGM has uncovered a likely blind spot in PBH, particularly asymptomatic and nocturnal hypoglycemia. Recognising this spectrum and aligning definitions, diagnostics, and care may improve outcomes.
Overweight and obesity are global health concerns linked to impaired female fertility. Weight-lowering drugs are an alternative for achieving weight loss; however, their effect on natural female fertility is unclear. A systematic review and meta-analysis were conducted to summarise the literature on the effects of weight-lowering drugs on ovulation, conception, pregnancy and live birth rates. Inclusion criteria comprised interventional and observational studies involving women with overweight or obesity receiving weight-lowering drugs, compared with non-users, lifestyle modifications or other medications. MEDLINE, Embase, CINAHL, CENTRAL and ClinicalTrials.gov were searched, yielding 2731 records. After screening, seven clinical trials were included (n = 575), six of which were randomised. Sample sizes ranged from 40 to 120 women aged 25.9-29.7 years. Six trials evaluated orlistat, while one assessed semaglutide. In four trials, orlistat was associated with a higher ovulation rate than lifestyle modifications. A meta-analysis of ovulation rates comparing orlistat and metformin showed no significant difference (RR = 0.78, 95% CI: 0.41-1.49; p = 0.45). Two studies reported pregnancy rates: one found a higher rate with orlistat compared to lifestyle modifications (23.3% vs. 6.7%, p = 0.044), and another showed that adding semaglutide to metformin increased the pregnancy rate compared to metformin alone (35% vs. 15%, p < 0.05). Future studies should address current limitations and evaluate the effects of newer weight-lowering drugs on natural pregnancy and live birth rates in adequately powered studies.
The timing of obesity onset may influence long-term cardiovascular risk. Whether obesity beginning in early adulthood differs from obesity acquired later in life with respect to cardiometabolic and cardiovascular outcomes remains uncertain. We analysed adults with obesity (BMI ≥ 30 kg/m2) from the National Health and Nutrition Examination Survey (NHANES) 2017-2020. Participants were classified as having early-onset obesity (with obesity at approximately age 25) or adult-onset obesity (with obesity at study enrolment but not at age 25). Primary outcomes included measured hypertension and a composite of cardiovascular disease (CVD) (congestive heart failure [CHF], coronary heart disease, angina, myocardial infarction or stroke). The weighted population represented 19.4 million U.S. adults with obesity, including 2.56 million with early-onset obesity. Adjusted cardiometabolic measures did not differ. CHF was more common with early-onset obesity (13.5% vs. 6.6%), and adult-onset obesity was associated with lower odds of CHF (adjusted OR: 0.43, 95% CI: 0.23-0.82). No differences were observed for coronary heart disease, angina, myocardial infarction, stroke or hard CVD. Among U.S. adults with obesity, early-onset obesity is associated with a higher burden of CHF, suggesting a potential role of cumulative obesity exposure in heart failure development.
Excess adipose tissue has been extensively studied due to its role in the development of chronic diseases and inflammatory conditions. Obesity and visceral adipose tissue (VAT, fat stored within the abdominal cavity and around organs) are associated with increased susceptibility to respiratory infections and chronic low-grade systemic inflammation. This study investigates the relationship among VAT, epicardial adipose tissue (EAT, fat surrounding the heart), and mortality in critically ill patients diagnosed with COVID-19, aiming to identify which measure is more strongly associated with adverse outcomes. A retrospective observational cohort study was conducted with patients admitted to the Intensive Care Unit (ICU) who underwent chest computed tomography (CT). Measurements of VAT and EAT were obtained from contrast-free CT images. Statistical analysis included the Mann-Whitney U test and logistic regression. Individuals who died had a larger EAT area. In patients with BMI < 30 Kg/m2, an increase in EAT was associated with a higher risk of mortality (OR = 1.06, 95% CI 1.015-1.107, p < 0.01). EAT area measurement was associated with mortality risk in critically ill individuals without obesity (BMI < 30 kg/m2) diagnosed with COVID-19 and may serve as a prognostic marker for risk stratification in this population.
The aims of this study were to compare baseline Impact of Weight on Quality of Life-Lite Clinical Trials Version (IWQOL-Lite-CT) scores between adults with obesity participating in either observational or clinical studies and to conduct a psychometric evaluation of the IWQOL-Lite-CT in the context of observational research. Analyses of covariance were used to compare baseline IWQOL-Lite-CT Total, Physical, Physical Function, and Psychosocial composite scores between participants with a body mass index (BMI) ≥ 30 in a US longitudinal survey (an observational study) and a multinational phase 3a study of subcutaneous semaglutide 2.4 mg for weight management (STEP 1). Data from the longitudinal survey were also used to evaluate the psychometric properties of the IWQOL-Lite-CT composite scores. Adjusting for BMI, age, and sex, on average, participants in the longitudinal survey scored lower than STEP 1 participants at baseline by 23.4 points on the IWQOL-Lite-CT Total, 20.7 on the Physical composite, 20.3 on the Physical Function composite, and 24.8 on the Psychosocial composite. While the internal consistency, test-retest reliability, and construct validity of the IWQOL-Lite-CT composite scores were confirmed in the longitudinal survey, responsiveness analyses were limited by small changes in weight. The weight-related functioning of US individuals with obesity who participated in a longitudinal survey was more limited than that of participants in the STEP 1 clinical trial. Psychometric results support use of the IWQOL-Lite-CT in observational research in addition to the clinical trial setting.
Although body mass index (BMI) is widely used to diagnose obesity, it is an imprecise measure of health. The Edmonton Obesity Staging System (EOSS) assesses the health impacts of elevated BMI based on medical, mental and functional complications and has been shown to predict mortality more accurately than BMI alone. This study aimed to develop a simple clinical support tool for structured assessment of the EOSS domains in routine clinical practice. An EOSS-based clinical support tool was developed through an iterative Delphi process with obesity-care experts, including pilot testing with patients and general practitioners, a test-retest reliability assessment and a final consensus meeting. The final instrument consists of 48 items across six domains: personal information, medical history, lifestyle, weight-reduction measures, psychosocial burden and functional limitations. Pilot testing indicated good feasibility and clarity, and the test-retest reliability assessment indicated good temporal stability; low-reliability items were revised. This clinical support tool, based on the EOSS domains, is designed to support the structured collection of information on obesity-related medical, functional and psychosocial aspects. Further research is needed to evaluate its validity, feasibility in routine practice and implementation across diverse primary care settings.
Obesity is a chronic non-communicable disease; that significantly impacts cardiovascular health via related conditions such as hypertension, diabetes, and coronary artery disease. Bariatric surgery provides effective weight loss, however exercise's cardiometabolic benefits post-surgery remain underexplored. To gain deeper insight, we conducted an overview of systematic reviews (SRs) to assess the impact of exercise on cardiovascular risk in post-bariatric surgery patients. The searches were accomplished by EMBASE, MEDLINE/PubMed (via National Library of Medicine), Scopus, and Web of Science databases. We included SRs of exercise and cardiovascular risk in post-bariatric surgery patients published up until March 9th 2026. PRISMA was enforced for reporting quality, AMSTAR 2 was required for methodological quality and GRADE was executed for quality of evidence analysis. Following the exclusion of 133 publications, four SRs were included, revealing significant exercise-induced improvements in VO2max-VO2peak/kg (absolute effect: 0.197 [0.287; 1.06]), HDL-cholesterol (absolute effect: 0.107 [0.009; 0.43]), and triglycerides (absolute effect: -17.56 [-34.14; -0.96]). None of the SRs fully obeyed the PRISMA guidelines, while AMSTAR 2 and GRADE assessments indicated low to very low quality. The SRs designated that exercise provides cardiovascular risk benefits for post-bariatric surgery patients. Yet, we recommend enhancing the evidence base, in addition to the methodological and reporting standards, in forthcoming SRs.
Obesity in pregnancy is a well-established risk factor for adverse maternal and neonatal outcomes, including gestational diabetes mellitus (GDM). This study aimed to examine the effects of lifestyle intervention during pregnancy on the cardio-metabolic protein profile and its association with maternal and neonatal health. The Lifestyle in Pregnancy (LiP) study was a randomised controlled trial conducted between 2007 and 2010 in Denmark. It included 360 pregnant women with obesity (BMI 30-45 kg/m2), aged 18-40 years, who were allocated to either a lifestyle intervention (dietary counselling, physical activity program, free fitness club membership) or standard care. Fasting serum samples from 303 women were collected at 12-15 and 28-30 weeks' gestation and analysed using a 26-plex cardio-metabolic proteomics assay. When comparing the cardio-metabolic protein profiles between the intervention and control groups before and after the intervention in pregnancy, we found that in late pregnancy the levels of two proteins, vitronectin and vitamin D-binding protein, were significantly lower in the intervention group. In the total cohort, elevated vitronectin was associated with a higher risk of GDM (adjusted odds ratio = 1.45 (95% CI: 1.06-1.98), p = 0.02) and neonatal intensive care unit (NICU) admissions (adjusted odds ratio = 1.68 (95% CI: 1.03-2.73), p = 0.037). Vitronectin may represent a modifiable biomarker linked to metabolic dysfunction in pregnant women with obesity, suggesting a potential underlying pathway by which lifestyle interventions could improve pregnancy outcomes.
