AIMS/HYPOTHESIS: Nearly 40% of African adults with type 2 diabetes are lean (BMI <25 kg/m). Emerging evidence suggests that type 2 diabetes in African individuals who are lean may represent a distinct phenotype driven by impaired insulin secretion rather than insulin resistance, raising concerns about treatment mismatch and divergent disease outcomes. We examined complication profiles in Africans with type 2 diabetes who are lean vs overweight/obese. METHODS: We analysed harmonised, individual-level cross-sectional data from two large, well-characterised African cohorts (Africa America Diabetes Mellitus study, n=2790; Research on Obesity and Diabetes among African Migrants study, n=541; total n=3331) of adults with type 2 diabetes from Ghana, Nigeria and Kenya. Participants were classified as lean (BMI <25 kg/m) or overweight/obese (BMI ≥25 kg/m). Robust Poisson regression, adjusted for age, sex, education and treatment, assessed associations with retinopathy, chronic kidney disease, stroke, hypertension and 10-year cardiovascular disease risk. Cohort-specific estimates were pooled using random effects, followed by mediation analysis examining contributions of lifestyle and metabolic markers to observed differences. RESULTS: Type 2 diabetes in Africans who are lean was characterised by lower beta cell function and low insulin levels. Compared with individuals who are overweight/obese, adults who are lean showed a higher prevalence of retinopathy (pooled prevalence ratio [pPR] 1.36 [95% CI 1.13, 1.63]) and stroke (pPR 1.41 [95% CI 1.01, 1.99]), but lower hypertension (pPR 0.77 [95% CI 0.71, 0.85]) and 10-year cardiovascular disease risk (pPR 0.85 [95% CI 0.74, 0.97]). Chronic kidney disease prevalence did not differ between groups. Body fat percentage accounted for most differences (up to 92%). CONCLUSIONS/INTERPRETATION: Complication patterns in Africans with type 2 diabetes who are lean vs overweight/obese follow divergent paths. In Africa, where nearly 24 million people have type 2 diabetes, two-fifths of whom are lean, our findings add to growing evidence that lean type 2 diabetes may be a distinct phenotype, underscoring the urgent need for investigation into better-targeted management for this large, potentially mistreated, population.

AIMS/INTRODUCTION: While maternal obesity is a well-established risk factor for large-for-gestational-age (LGA) infants, the impact of maternal underweight on LGA in women with gestational diabetes mellitus (GDM) remains inconsistent. This issue is particularly relevant in Japan, given the high prevalence of underweight women. We investigated the association between maternal weight and body mass index (BMI) at age 20 and pre-pregnancy and the risk of LGA in Japanese women with GDM. MATERIALS AND METHODS: This retrospective study analyzed 537 Japanese women with GDM. Participants were categorized by BMI (underweight <18.5 kg/m, normal, and obesity ≥25.0 kg/m) and by weight quartiles at age 20 and pre-pregnancy. Multivariable logistic regression analyses were performed to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the association between underweight at age 20 and pre-pregnancy and LGA. RESULTS: The prevalence of underweight at age 20, underweight pre-pregnancy, and LGA was 30.4%, 13.4%, and 9.7%, respectively. After adjustment for confounders, underweight based on BMI at age 20 (adjusted OR 0.22, 95% CI: 0.06-0.75) and pre-pregnancy (adjusted OR 0.17, 95% CI: 0.03-0.64) was significantly and inversely associated with LGA compared with obesity. Similarly, the lowest weight quartiles at both time points were independently associated with a low risk of LGA. CONCLUSIONS: Maternal underweight at age 20 and pre-pregnancy was significantly associated with a lower risk of LGA in Japanese women with GDM. These findings suggest that weight status from early adulthood may play a crucial role in fetal growth outcomes.

OBJECTIVES: Hyperglycemia during pregnancy is related to adverse obstetric, neonatal, and long-term health outcomes for both mothers and the offspring. This study aimed to conduct a systematic review and meta-analysis of the global literature evaluating the association between maternal diabetes (DM) during pregnancy and the incidence of schizophrenia in the offspring. METHODS: Following PRISMA guidelines and registered in PROSPERO (CRD42024545505), a comprehensive search was conducted across major databases up to November 2024. Three retrospective cohort studies, including 2,603,889 individuals, met the inclusion criteria. RESULTS: Three studies were included in the quantitative synthesis. Meta-analysis of hazard ratios showed that maternal DM during pregnancy was associated with an increased risk of schizophrenia in the offspring (HR = 1.58; 95% CI: 1.22-2.03; P = 0.0004), with no heterogeneity (I² = 0%). Analysis based on odds ratios showed a similar trend but did not reach statistical significance (OR = 2.15; 95% CI: 0.13-34.69; P = 0.59). CONCLUSION: Maternal DM during pregnancy may be associated with an increased risk of schizophrenia in the offspring. Although maternal hyperglycemia may influence fetal neurodevelopment through inflammatory and metabolic mechanisms, the observational nature and limited number of included studies preclude causal inference, and these findings should be interpreted with caution.

A distinct "South Asian phenotype" and unhealthy dietary patterns contribute to the high burden of type 2 diabetes mellitus (T2DM) in India, highlighting the need for context-specific nutritional management. Five regional advisory board meetings were conducted to gather expert perspectives on the unique epidemiology of T2DM and key aspects of nutritional management, including optimal dietary practices and the role of high-protein, high-fiber (HPHF) supplements or meal replacements. A total of 60 experts attended the meetings. During each meeting, an optional multiple-choice poll was administered as part of the discussion. Expert perspectives were derived from optional poll responses and discussions informed by scientific evidence and participants' clinical experience. High carbohydrate and low protein intake, insulin resistance, central obesity, suboptimal muscle mass, and genetic predisposition characterize Indian patients with diabetes. Recognizing this phenotype is essential for providing tailored nutritional interventions. Key assessments to facilitate nutritional interventions include anthropometry (weight, body mass index, and waist circumference), lipid profile, and 24-hour dietary recalls. Experts emphasized that customized nutrition plans should be developed based on individual nutritional status, clinical profile, and dietary preferences. Dietary strategies should emphasize increased consumption of complex carbohydrates, high-fiber foods, and protein. The high burden of "diabesity" underscores the need for nutritional interventions addressing both glycemic control and weight management, including the appropriate use of meal replacement strategies. Protein and fiber are key nutrients in diabetes management. While dietary sources should be prioritized, experts noted that low-glycemic index, HPHF supplements/replacements may be considered for patients with overweight/obesity, poor nutrition intake, weakness or fatigue, or uncontrolled hyperglycemia. However, their limited use in clinical practice highlights the need for further research to evaluate their indications for use, effectiveness, safety, implementation, cost considerations, and long-term outcomes. This expert opinion highlights the unique epidemiology of T2DM in India and provides context-specific, evidence-informed insights to support nutritional management strategies. These perspectives are derived from advisory board discussions and should be interpreted as expert opinion rather than systematic evidence synthesis or formal guideline recommendations.

Aceruloplasminemia (ACP) often presents with systemic, psychiatric, and neurological features. In this case, diabetes mellitus was diagnosed several years before psychiatric symptoms, which were then followed by neurological decline, which significantly delayed diagnosis. This case highlights the importance of considering metabolic and neurodegenerative causes in atypical psychiatric presentations and expands the genetic spectrum with a novel CP gene mutation.

BACKGROUND: Metabolic disease is accelerating across Low- and Middle-Income Countries (LMICs), where calorie-focused dietary prescriptions frequently fail due to cost and complexity. Time-Restricted Eating (TRE) is a distinct approach. It restructures when food is eaten rather than what or how much, limiting daily intake to a 6 to 10 hour window as a cost-free chronomedicine strategy. Its mechanisms and long-term glycemic effects in diverse LMIC populations remain incompletely synthesised. OBJECTIVES: To systematically review TRE's clinical efficacy on glycemic control, insulin sensitivity, and anthropometric outcomes across LMIC cohorts, and to evaluate molecular evidence for AMPK/mTOR pathway activation. DATA SOURCES AND METHODS: A PRISMA 2020-compliant systematic review was conducted using PubMed, Scopus, and Web of Science. Eligible studies included randomised controlled trials and quasi-experimental designs involving adults in LMICs with metabolic conditions. TRE windows of 6 to 10 hours were required. Risk of bias was assessed using RoB 2.0 and ROBINS-I. The review was prospectively registered with PROSPERO (CRD420261352841). RESULTS: Twenty-six unique cohorts (28 reports) across India, China, Indonesia, Iran, Tunisia, and Brazil were included. TRE was associated with reductions in insulin resistance, fasting blood sugar, and body weight across most included studies. A persistent HbA1c reduction of -0.78% at 18 months in one longitudinal cohort suggested that glycemic benefits may compound with sustained adherence. Contradictions emerged between centres regarding TRE's superiority over caloric restriction. CONCLUSION: TRE may represent a feasible, low-cost dietary strategy for metabolic health management in resource-limited settings, though further evidence from larger and longer trials is needed.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease worldwide and includes a spectrum ranging from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH), advanced fibrosis, and cirrhosis. Given the heterogeneous nature of disease progression and the central role of fibrosis predicting local or systemic clinical outcomes (e.g. liver cirrhosis, hepatocarcinoma, cardiovascular diseases), early identification and longitudinal monitoring of individuals at risk is crucial. However, current diagnostic tools present important limitations, particularly across diverse metabolic profiles such as individuals living with obesity or type 2 diabetes. Therefore, this review provides a comprehensive overview of current diagnostic and monitoring strategies for MASLD and MASH, including routine biochemical markers, noninvasive steatosis and fibrosis scores, imaging modalities, and liver biopsy. Multimodal and individualized diagnostic approaches integrating clinical, metabolic, imaging, and molecular data appear essential to improve early detection, refine longitudinal monitoring, and support precision-based management of MASLD.

BACKGROUND: The metabolic syndrome (MetS) is characterized by having three or more of these risk factors: increased blood glucose (Glc), serum triglycerides (TG), blood pressure (BP), waist circumference (WC), and reduced high-density lipoprotein (HDL). Mobile diagnostics using point-of-care (POC) blood analyzers could help identify individuals at risk. This pilot study assessed reliability and validity of MetS risk factor analysis using POC analyzers in a mobile examination unit. METHODS: Fifty participants (52 ± 7y; 170 ± 10 cm; 80 ± 19 kg, m/f: 21/29) were included for analysis. The mobile examination unit was equipped with different POC analyzers (Alere, LABGEO, CardioChek for Glc, HDL, TG; Quo-Test-A1C Testkit for HbA1c'). Agreement compared to a reference laboratory (RefLab) was analyzed by Bland-Altman (bias, Limits of Agreement (LoA)), ICC, SEM and McNemar's test. Test-retest analysis was assessed on two different days (max. two weeks apart) using Spearman's rho, ICC, test-retest variability (TRV%) and McNemar's test. RESULTS: Based on the smallest bias and low number of missing values (Glc: -5 [LoA - 25 to 6] mg/dl; TG: 8 [LoA - 58 to 30] mg/dl; HDL: -2 [LoA - 14 to 9] mg/dl), and the highest agreement in MetS diagnosis compared to the results of RefLab, the Alere POC device was chosen. Test-retest reliability (n = 16) for MetS risk factors and HbA1c measured in the mobile setup ranged from poor to excellent with low TRV (0.9-5.8%). Risk factor classification and MetS diagnosis did not differ between measurement days. CONCLUSIONS: A mobile setup using the Alere POC analyzer could be used as a valid mobile screening method for MetS to ensure early detection of risk factors.

A green, stability-indicating UV-spectrophotometric methods were designed and optimized for the quantitative determination of gliclazide (GLI), a second-generation sulfonylurea widely used in the management of type 2 diabetes mellitus (T2DM). The methods integrate first-derivative spectrophotometry (D) and Fourier Self-Deconvolution (FSD) to resolve the extensive spectral overlap between GLI and its alkaline degradation product (Gliclazide Impurity A) without prior separation. The assay demonstrated excellent linearity within 2.5-25 µg/mL for GLI and 2.5-15 µg/mL for its degradation product. LOD ranged from 0.31 to 0.43 µg/mL and LOQ from 0.94 to 1.31 µg/mL for both analytes. Using ethanol as a green, non-toxic solvent further enhanced the method's environmental sustainability. Method validation, performed according to ICH Q2(R1) guidelines, confirmed its selectivity, reproducibility, robustness, and accuracy with mean recoveries of 99.48 ± 0.83 and 100.87 ± 1.52 for GLI in the D and FSD methods, respectively. Comprehensive forced degradation studies under alkaline stress verified the procedure's stability-indicating capability, enabling reliable quantification of GLI in the presence of its degradation products. The greenness evaluation using Analytical Eco-Scale, GAPI, AGREE, NEMI tools, EPPI tool, AGSA tool, and MOGAPI method collectively affirmed the method's eco-friendly and sustainable nature. Furthermore, the analytical strategy was comprehensively assessed using multi-dimensional tools, including RAPI and AMRI for analytical performance and reliability, CaFRI for carbon-footprint reduction, CACI for analytical practicality, and the RGB 12 model for an integrated multi-colored analytical profile. In summary, the developed methods provide a highly efficient, environmentally friendly, and analytical alternative to conventional chromatographic techniques for the routine quality control and green pharmaceutical analysis of gliclazide in bulk and dosage forms.

INTRODUCTION: Few studies have investigated the relationship between metabolic syndrome (MetS) and muscle loss over a 10-year period in large working populations. This study aimed to investigate the influence of MetS-related and respiratory factors on changes in trunk muscles in the working population. MATERIALS AND METHODS: The cross-sectional areas (CSAs) of the psoas major (PM) and erector spinae (ES) were measured using abdominal low-dose CT imaging at baseline and at 10 years. Predictors of CSA loss were analyzed using multiple linear regression analysis. RESULTS: A total of 1504 males were included. The change in the CSA of the PM at 10 years decreased significantly with increasing age, BMI, abdominal circumference, visceral fat area (VFA), systolic blood pressure (sBP), and HbA1c. The change in the CSA of the ES at 10 years decreased significantly with increasing age, weight, BMI, abdominal circumference, VFA, sBP, HbA1c, and LDL level. Multiple linear regression analysis revealed that VFA and HbA1c were independently associated with PM loss, while a lower percentage vital capacity (%VC) was associated with ES loss. The ratio of forced expiratory volume in one second to forced vital capacity (FEV1.0%) at baseline was identified as a significant predictor of PM loss for individuals with MetS. CONCLUSION: Among MetS-related factors, VFA and HbA1c were associated with trunk muscle CSA loss over 10 years in the working population. Furthermore, in individuals with MetS, lower FEV1.0% was associated with PM loss.

BACKGROUND: Our goal was to evaluate the relationship between prenatal fluoride exposure and pregnancy outcomes. METHODS: We measured urinary fluoride collected during the second trimester among pregnant people recruited from California and Illinois from 2014 to 2020 (N = 949). We evaluated risk differences (RDs) of preterm birth (PTB), small-for-gestational age (SGA), large-for-gestational age (LGA), gestational diabetes, and differences in birthweight, birthweight-for-gestational age z-scores, and gestational age associated with a 0.1 mg/l increase in fluoride using linear regression to estimate effects on the additive scale. We also used modified treatment policies with machine learning to estimate the effects of hypothetical interventions to reduce urinary fluoride by 0.1 and 0.5 mg/l on pregnancy outcomes. In the Illinois cohort, we estimated effects by trimester. RESULTS: In our main analyses, we found no associations between urinary fluoride levels and pregnancy outcomes. For instance, for a 0.1 mg/l increase in fluoride, we saw no change in the risk of PTB, SGA, or gestational diabetes. We also found no differences associated with hypothetical reductions of prenatal fluoride by 0.1 mg/l or 0.5 mg/l for any outcomes. In the trimester-specific analyses for Illinois participants, we found increased LGA risk during the first (RD = 0.004, 95% CI -0.001, 0.009) and third trimesters (RD = 0.007, 95% CI 0.001, 0.012), and reduced LGA risk during the second trimester (RD = -0.006, 95% CI -0.011, 0.000), associated with 0.1 mg/l higher urinary fluoride. CONCLUSIONS: Prenatal fluoride exposure does not appear to affect pregnancy outcomes, but preliminary evidence suggests that higher fluoride levels may affect the risk of LGA depending on timing of exposure during pregnancy.

Mitochondrial protein homeostasis intersects with metabolic control, but the in vivo roles of specific mitochondrial co-chaperones remain unclear. The chaperone mtHSP70 plays a key role in import and folding of nuclear-encoded proteins targeted to mitochondrial matrix. Its protein folding cycle is regulated by the GrpE-like nucleotide exchange factor GRPEL1. Vertebrates also have a GRPEL2 paralog, postulated as the stress-sensitive counterpart, but its physiological relevance is not known. We show here that GRPEL2 is not essential for viability in mice, and its absence does not induce proteotoxic stress responses in stark contrast to GRPEL1. However, we find that GRPEL2 has a role in regulating body weight homeostasis. GRPEL2 knockout mice are protected from age- and diet-induced weight gain and maintain a better metabolic health and insulin sensitivity. Transcriptional profiling revealed minimal changes in liver and skeletal muscle, whereas white adipose tissue from Grpel2-deficient mice lacked the obesity-associated remodeling seen in controls. We propose that GRPEL2 fine-tunes metabolic setpoints without broadly perturbing mitochondrial protein import, thereby maintaining adipose tissue health during nutritional excess. These findings show that subtle alterations in mitochondrial chaperone systems reshape systemic metabolism and could suggest strategies to mitigate obesity and insulin resistance through targeted modulation of mitochondrial proteostasis.

This systematic review investigates the mediating factors in the relationship between ambient air pollution exposure and cognitive aging. We identified 16 studies examining 72 unique exposure-mediator-outcome associations for six pollutants (PM2.5, PM10, NO2, NOX, black carbon, and PM1 components). The most studied pollutant was PM2.5 (65% of analyses). Cognitive outcomes included memory, cognitive processing speed, and clinically diagnosed conditions such as dementia incidence. Potential mediators spanned mental health outcomes (depression, anxiety, stress), lung function (FEV1, FVC, PEF), vascular diseases (stroke, hypertension), inflammation (CRP), metabolic factors (type 2 diabetes), sleep, and neuroanatomical changes. The quality of mediation analysis reporting was generally good, but most studies had some risk of bias, particularly in outcome assessment and confounding adjustment. Cardio and Cerebro-vascular diseases emerged as a potential key mediator. Mental health outcomes, sleep, and lung function also showed mediating potential, but further research is needed to confirm these findings. This review highlights the need for rigorous causal mediation analyses and standardized reporting to better understand the complex pathways linking air pollution to cognitive aging, in order to identify targeted preventive measures to reduce the negative impact of ambient air pollution on cognitive health.

AIMS: To identify BMI trajectories after type 2 diabetes (T2D) diagnosis and examine associations with laboratory measures, medication use, comorbidities, and healthcare utilization. METHODS: We analyzed BMI trajectories in 3,539 adults with T2D in North Karelia (2011-2014) and followed until 2024. BMI trajectory classes were estimated using growth mixture modeling. Regression models were used to assess differences in measurement activity, treatment intensity and diabetes medication use between the classes. RESULTS: Three BMI trajectories were identified: stable (77.7 %), increasing (14.6 %), and decreasing (7.7 %). HbA1c and LDL cholesterol measurement activity was lowest in the decreasing class. Use of glucagon-like peptide-1 agonists varied over time, peaking in the decreasing class in 2015 and in the increasing class in 2024. Comorbidities increased in all classes but differed in pattern: the increasing class accumulated more chronic kidney and urinary tract diseases, obesity related diagnoses, sleep disorders, and chronic lower respiratory diseases, whereas the decreasing class had higher prevalence of dementia and cardiovascular and pulmonary diseases. Healthcare utilization was highest in the decreasing class. CONCLUSIONS: These findings reveal considerable heterogeneity in long-term outcomes among people with T2D and highlight the need for continuous monitoring and targeted support to maintain metabolic control and manage comorbidity burden.

AIMS: Evidence on the independent and combined effects of low and delayed fertility on the risk of gestational diabetes mellitus (GDM) remains limited despite the increasing prevalence of these reproductive patterns in high-income populations. METHODS: We compared baseline and clinical characteristics of women with GDM and those with a normal oral glucose tolerance test who delivered at Abano Polyclinic, Italy, between January 2022 and August 2025. The independent and combined contributions of low parity and advanced maternal age to GDM risk were evaluated. RESULTS: Among 2,560 term women with low and delayed fertility, 231 (9.9%) developed GDM. Women with GDM were older than controls (36.0 [31.5-39.0] vs. 33.0 [30.0-37.0] years; P < 0.001), whereas parity was similar between groups. GDM prevalence increased progressively with maternal age, reaching 16.1% after 40 years. Kaplan-Meier analysis demonstrated a significant age-related increase in GDM probability (log-rank χ = 31.5, P < 0.001), with no age-parity interaction (P = 0.55). Women with GDM also had a higher BMI at delivery than controls (27.9 vs. 26.8 kg/m), which remained independently associated with GDM after adjustment for maternal age and parity. CONCLUSIONS: Advanced maternal age and higher BMI at delivery are independent predictors of GDM in women with low and delayed fertility, supporting their inclusion in risk assessment and prevention strategies.

Red blood cells are not passive oxygen carriers. In overt type 2 diabetes, they have been proposed as both victims and amplifiers of metabolic and vascular dysfunction. Whether these alterations begin earlier in the prediabetic state is only beginning to emerge. This is the first comprehensive mechanistic review to synthesize evidence on RBC dysfunction in prediabetes. We aim to answer three questions. First, what happens to RBCs in prediabetes? We synthesize evidence on altered redox status, membrane composition, morphology, rheology, RBC-indices and function. Second, do these changes follow a predictable pattern as glycemia worsens? Based on available evidence, we propose a hypothesis-generating conceptual framework of progressive, plateau, late, and non-linear (peak, trough, and biphasic) trajectories, that warrants systematic validation through prospective studies. Third, can RBC markers be clinically useful? We evaluate their diagnostic, therapeutic, and screening potential, and assess the confounders that may limit their clinical utility. In conclusion, RBCs in prediabetes and diabetes are not merely mirrors of glycemia but appear to be hubs where altered oxidative stress, metabolism, and vascular biology converge. However, realizing their clinical promise will require prospective studies that account for the biological complexity of the RBC.

AIMS: To evaluate the independent and combined associations of gestational diabetes mellitus (GDM) and multifetal gestation with maternal morbidity, particularly hypertensive disorders of pregnancy (HDP). METHODS: We conducted a national multicenter retrospective cohort study from six university-affiliated medical centers (2010-2024) mapped to the OMOP Common Data Model. Pregnancies were categorized as singleton without GDM, singleton with GDM, multifetal without GDM, and multifetal with GDM. Outcomes included HDP, ICP, cesarean delivery, and placental abruption. Multivariable Firth logistic regression adjusted for maternal age, body mass index, parity, and fertility treatment. RESULTS: Among 134,517 pregnancies, HDP rates increased from 4.5% in singleton pregnancies without GDM to 10.2% in singleton pregnancies with GDM, 11.0% in multifetal pregnancies without GDM, and 16.4% in multifetal pregnancies with GDM. GDM was independently associated with HDP (aOR 1.7, 95% CI 1.6-1.8). Multifetal gestation showed stronger associations with HDP (aOR 2.2-2.5) and severe preeclampsia (aOR 3.6). ICP was most frequent in multifetal pregnancies with GDM (aOR 6.5,95% CI 3.5-10.9). No statistically significant interaction between GDM and multifetal gestation was detected for HDP(q = 0.088). CONCLUSION: Both GDM and multifetal gestation were independently associated with maternal morbidity. Multifetal gestation showed stronger associations with hypertensive outcomes, without evidence of interaction between the two exposures.

Gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (HDP), preterm birth, and intrauterine growth restriction represent major contributors to maternal and neonatal morbidity worldwide. Traditional screening methods relying on single biomarkers or linear models often demonstrate limited predictive accuracy. This review examines the transformative role of machine learning (ML) in shifting obstetric care toward predictive, preventive, and personalized approaches. Advanced computational models integrating multimodal data sources clinical records, biochemical markers, multi-omics profiles, medical imaging, and lifestyle factors show promising performance. Ensemble methods such as Random Forest and XGBoost, alongside deep learning architectures, frequently outperform conventional logistic regression, achieving AUC values above 0.90 in selected cohorts. Emphasis is placed on preprocessing techniques for class imbalance (e.g., SMOTE), model interpretability via Explainable AI (SHAP), and privacy-preserving strategies like federated learning. While technical and ethical challenges including bias, external validation, and data heterogeneity remain, robust ML frameworks offer substantial potential for early risk stratification and timely intervention in precision obstetrics. Prospective, multicenter validation is essential for clinical translation.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with disrupted iron homeostasis, lipid peroxidation, and ferroptosis-related liver injury. Although exercise is recommended for MASLD management, whether moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT) exert comparable effects on hepatic iron metabolism and ferroptosis-related changes remains unclear. This study compared the effects of MICT and HIIT on hepatic iron homeostasis, ferroptosis-related markers, and lipid metabolic remodeling in high-fat diet (HFD)-induced MASLD rats. Forty male Sprague-Dawley rats were assigned to a normal-fat diet group or an HFD group. After 8 weeks of HFD feeding, HFD-fed rats were further divided into HFD control, MICT, and HIIT groups and underwent an additional 8-week intervention. HFD feeding induced metabolic dysfunction, hepatic steatosis, liver injury, iron accumulation, increased activation-related markers of the IL-6/JAK2/STAT3-hepcidin pathway, and ferroptosis-related changes, including reduced GPX4 and increased PTGS2 and MDA. Both MICT and HIIT improved metabolic and histological outcomes, reduced hepatic Fe accumulation and lipid peroxidation, increased FPN1 expression, decreased DMT1 expression, reduced activation-related markers of IL-6/JAK2/STAT3-hepcidin signaling, and improved antioxidant defense. Untargeted lipidomics indicated partial remodeling of HFD-induced disturbances in glycerophospholipid, glycerolipid, sphingolipid, ether lipid, thermogenesis, insulin-resistance, and AMPK-related pathways. Most endpoint outcomes did not differ significantly between MICT and HIIT. Because no pathway-specific manipulation, iron-rescue experiment, or ferroptosis inhibitor was used, the present data do not establish that the IL-6/JAK2/STAT3-hepcidin-FPN1 axis causally mediates the exercise response. Instead, the findings indicate that MICT and HIIT exert broadly comparable protective effects that are associated with improved hepatic iron homeostasis, lower ferroptosis-related susceptibility, and hepatic lipid metabolic remodeling.

Higher exposure to organophosphate flame retardants (OPFRs) may contribute to type 2 diabetes mellitus (T2DM), but prospective evidence, lifestyle modification, and biological plausibility remain insufficiently characterized. We conducted a nested case-control study within the Henan Rural Cohort to evaluate associations between OPFRs exposure and incident T2DM. Cox models, WQS, QGC, BKMR, and an adaptive elastic-net-based environmental risk score were used to assess single and mixed OPFRs exposure. Baseline and trajectory-based healthy lifestyle scores were applied to evaluate joint effects, and signed Wald χ² decomposition quantified contributions of OPFRs and lifestyle domains. Mechanistic evidence was integrated from in vitro experiments and toxicogenomic analyses, including RNA-sequencing, network toxicology, molecular docking, and GEO re-analysis, to evaluate EGFR-related signaling and build an integrative adverse outcome pathway. Higher urinary OPFRs, particularly TPHP, were associated with increased T2DM risk, and OPFRs mixtures showed a linear dose-response relationship with T2DM risk. High OPFRs exposure combined with unhealthy or deteriorating lifestyle trajectories conferred the greatest risk, with OPFRs plus lifestyle explaining 55.36% of total model χ². In HepG cells, TPHP impaired glucose consumption and downregulated EGFR, whereas EGFR overexpression alleviated the TPHP-associated abnormal glucose consumption. EGFR overexpression was confirmed at both mRNA and protein levels. The p-AKT/total AKT results provided supportive evidence of AKT-related signaling changes, whereas total GLUT2 protein abundance was not significantly altered. Molecular docking supported potential TPHP-EGFR binding affinity of -8.5 kcal/mol, and GEO analyses provided external supportive evidence that EGFR expression tended to be higher in healthier lifestyle-related conditions. These findings suggest that mixed OPFRs exposure, dominated by TPHP, was associated with higher incident T2DM risk, partly attenuated by healthier lifestyle trajectories, supporting combined exposure-reduction and lifestyle-based prevention strategies.

AIMS: To identify, appraise and synthesise the current evidence relating to symptoms, experiences, management and impact of menopause on QoL among women with type 1 diabetes (T1DM) or type 2 diabetes (T2DM) and to identify evidence gaps. METHODS: We conducted a scoping review guided by Arksey and O'Mally's framework by searching CINAHL, MEDLINE, EMBASE, PsychINFO and PubMed using an iterative approach to pre-specified eligibility criteria which were reviewed with increasing familiarity with the literature. Studies focusing on peri-menopausal and menopausal people assigned female at birth with a diagnosis of T1DM or T2DM were included. RESULTS: In total, 16,681 records were identified from which 77 papers were subjected to full review, with 22 eligible. Research focus and methodology varied: 16 observational studies, 2 expert consensus reviews, 2 interventional studies, 1 patient and public involvement paper and 1 qualitative grounded theory paper. PRISMA-ScR guidelines were followed for transparency of reporting. Findings indicate women with diabetes experience menopausal symptoms similar to those of women without diabetes; however, they may be at risk of increased severity of symptoms, HRT use was linked to lower HbA1c levels but is largely overlooked, limited research has been undertaken exploring women's experiences and awareness of support during the menopause; existing research evidence suggests they are ill-informed and lacking effective evidence based support. There is a particular dearth of evidence relating to women with T1DM. CONCLUSIONS: This review provides evidence that menopause has a negative influence upon quality of life for many women with diabetes. The impacts span managing diabetes and menopausal symptoms and seeking and receiving support. A hypothesised bidirectional relationship between diabetes and menopause may exist: whereby progression of one may be influenced by the other also resulting in a lower quality of life. While high-level evidence on this complex inter-relationship remains limited, particularly in T1DM populations, it suggests significant unmet need for those experiencing diabetes and menopause together.

OBJECTIVE: To evaluate early postoperative nutritional management with a diabetes-specific enhanced recovery after surgery (DS-ERAS) pathway in patients with lumbar spinal stenosis (LSS) and type 2 diabetes mellitus (T2DM). METHODS: This retrospective cohort study compared a DS-ERAS nutritional pathway with conventional perioperative care in LSS patients with T2DM. Outcomes included postoperative recovery, nutritional status, glycemic control, inflammation, complications, and hospital stay. Effect size metrics (relative risk reduction [RRR], absolute risk difference [ARD], number needed to treat [NNT]), subgroup analyses, and multivariable linear regression were performed. RESULTS: The DS-ERAS group demonstrated faster gastrointestinal recovery, improved nutritional status and glycemic control, reduced inflammatory and shorter hospital stay (p < 0.001). The complication rate was lower (10.0% vs. 23.3%;  = 0.016), with a relative risk reduction of 57.1% and absolute risk difference of 13.3%. Subgroup analyses demonstrated consistent benefits across age, sex, body mass index (BMI), diabetes duration, and surgical segments (all for interaction > 0.05). Multivariable regression show that DS-ERAS was associated with a mean reduction in hospital stay of 1.57 days. CONCLUSION: Early postoperative nutritional management within the DS-ERAS pathway was associated with improved perioperative recovery in LSS patients with T2DM, with favorable nutritional , metabolic, inflammatory, and clinical outcomes.

Interleukin-40 (IL-40), encoded by the C17orf99 gene, is a recently identified B cell-associated cytokine that bridges innate and adaptive immune responses. Since its discovery in 2017, IL-40 has emerged as a pleiotropic immunoregulatory factor with broad implications in human diseases. Elevated IL-40 levels are consistently reported across systemic and organ-specific autoimmune disorders, including rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, systemic sclerosis, and autoimmune thyroid diseases. In these conditions, IL-40 correlates with disease activity, inflammatory burden, and adverse outcomes. Mechanistically, beyond B-cell differentiation and IgA production, IL-40 induces neutrophil extracellular trap (NET) formation (NETosis), triggering extracellular release of peptidylarginine deiminase 4. PAD4 catalyzes citrullination of intracellular proteins, converting arginine to citrulline residues, generating neoepitopes that break immune tolerance and drive anti-citrullinated protein antibody (ACPA) production-a hallmark of rheumatoid arthritis and related autoimmunities. Beyond autoimmunity, dysregulated IL-40 is observed in viral infections (COVID-19, Epstein-Barr virus), sepsis, and pneumonia, suggesting roles in host defense, systemic inflammation, and immunopathology. IL-40 deficiency impairs IgA homeostasis and alters gut microbiota, implicating it in mucosal immunity and microbiome crosstalk. In oncology, aberrant IL-40 expression is reported in solid tumors (breast cancer, hepatocellular carcinoma) and hematologic malignancies (acute/chronic myeloid leukemias, Hodgkin lymphoma), indicating context-dependent functions in tumor biology. Elevated IL-40 in obesity, metabolic syndrome, type 2 diabetes, and allergic diseases further implicates this cytokine in low-grade chronic inflammation and hypersensitivity. Overall, IL-40 represents a promising immunoregulatory cytokine with diagnostic and therapeutic potential across immune-mediated diseases and cancer. However, current evidence remains largely observational and animal-based, while mechanistic and clinical investigations are scarce. Future research should prioritize identifying IL-40 receptor(s) and downstream signaling pathways through well-designed cellular and molecular studies, alongside large-scale multicenter trials, to fully elucidate its biological functions and clinical utility.

PURPOSE: The present study aimed to explore the impact of combining methotrexate (MTX) and insulin (INS) to mitigate diabetes-associated myocardial injury and investigate the potential underlying mechanisms. METHOD: Diabetes was induced in rats by a single low-dose streptozotocin (STZ) injection (35 mg/kg, i.p.) after a four-week period of administration of a high-fat diet (HFD) feeding and fructose administration in water. RESULTS: Our data revealed that the diabetic rats had elevated serum cardiac injury biomarkers and a disturbed lipid profile in parallel with marked inflammation and distortion of normal cardiomyocyte architecture. Moreover, diabetes was associated with reduced levels of adiponectin, insulin receptor substrate (IRS)-1, phosphatidylinositol-3-kinase (PI3K), phosphorylated protein kinase B (p-AKT), and phosphorylated glycogen synthase kinase (p-GSK)-3β. Our findings showed that combining low doses of MTX and INS exerted superior ameliorative effects on serum cardiac injury biomarkers and the lipid profile, as well as histopathological abnormalities. Moreover, MTX enhanced the stimulatory effect of INS on adiponectin levels and the IRS-1/PI3K/p-AKT/FOXO-1 signaling pathway in the heart. MTX combined with INS also demonstrated a superior suppressive effect on cardiac FOXO-1 levels and the autophagy-associated biomarkers microtubule-associated protein 1A/1B-light chain (LC3-B) and beclin-1. Interestingly, the enhancement of cardiac INS signaling by MTX was accompanied by the inhibition of biomarkers of oxidative stress and the apoptotic executor caspase-3. CONCLUSION: Low doses of MTX offer added therapeutic value against diabetic cardiac injury when combined with INS. This effect may be attributed, at least in part, to the modulation of the adiponectin/IRS-1/PI3K/p-AKT/FOXO-1 signaling cascade.