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.

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).

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]).

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.

Diabetic kidney disease (DKD) remains a leading cause of chronic kidney disease worldwide despite current standard therapies. c-Kit⁺ renal progenitor cells have been implicated in kidney repair and regeneration. We investigated whether mesenchymal stem cells (MSCs) and the sodium-glucose cotransporter-2 inhibitor empagliflozin are associated with differential modulation of intrarenal c-Kit⁺ cell expression in a preclinical model of DKD using BTBR^ob/ob mice.

These BTBR^ob/ob mice were allocated into three groups: untreated DKD, MSC-treated DKD, and empagliflozin-treated DKD, and were compared with BTBR wild-type (WT) controls. BTBR^ob/ob mice received empagliflozin formulated inchow ad libitum at 25 mg/kg (Jardiance®, Boehringer Ingelheim, Ingelheim am Rhein, RP, Germany) starting at 4-5 weeks of age. MSCs (1 × 10⁶ cells per dose) were administered intraperitoneally at 8 and 10 weeks of age. Animals were evaluated at 10, 14-15, and 18-20 weeks. Renal c-Kit gene expression was quantified by quantitative real-time PCR (qPCR), and protein expression was assessed by immunohistochemistry in the cortex, medulla, and glomeruli. Statistical analyses included mixed-effects models and two-way analysis of variance (ANOVA).

c-Kit expression was significantly influenced by time and treatment in both cortex and medulla. In the renal cortex, MSC therapy was associated with a transient increase in c-Kit gene expression at 14-15 weeks, followed by a reduction at 18-20 weeks. Empagliflozin predominantly modulated cortical c-Kit expression at later time points. Immunohistochemistry demonstrated higher cortical c-Kit protein expression in MSC-treated animals compared with untreated DKD mice. In the medulla, MSC-treated mice exhibited increased c-Kit expression at 14-15 weeks, which declined at 18-20 weeks. Empagliflozin had a modest effect on c-Kit expression and was associated with infrequent glomerular immunoreactivity at 14-15 weeks.

MSC therapy and empagliflozin are associated with distinct temporal patterns of c-Kit expression in DKD. MSC treatment showed early modulation of c-Kit expression, whereas empagliflozin exhibited more delayed effects. These findings suggest that c-Kit⁺ cells are dynamically regulated during DKD progression. Given the absence of functional and mechanistic analyses, these results should be considered hypothesis-generating and warrant further investigation.

Glucagon-like peptide-1 (GLP-1) receptor agonists have revolutionized weight management and are becoming essential for the treatment of obesity-related medical conditions. This study aimed to determine the pharmacokinetics, preliminary pharmacodynamics, safety, and tolerability of a long-acting GLP-1 receptor agonist, TE-8105, in overweight or obese adults without T2DM. An open-label study of four single ascending dose cohorts (A1-A4, 0.5, 0.75, 1.5, and 3.0 mg TE-8105, respectively) and two multiple dose cohorts (B1 flat dosing, 1.0 mg TE-8105 Q2W SC for 5 doses, and B2 titration dosing, sequence 2 × 1.5, 2 × 2.0, 2 × 2.5, and 3 × 3.0 mg Q2W SC) was conducted using a combination of in-patient and out-patient assessments. The half-life of TE-8105 was about 120 h. There was no accumulation after flat dosing, but mean (SD) accumulation ratios were 3.75 (0.86) for C_max and 3.00 (0.65) for AUC following titration dosing. The mean % decrease in body weight from baseline to the end of study visit for titration dosing was 2.06%, with 4/8 participants maintaining weight loss of ≥5%. Treatment-related treatment emergent adverse effects (TEAEs) were consistent with the mechanism of action of TE-8105 and dose-dependent, including nausea (Part A: 16.7%; Part B: 21.4%), abdominal pain (Part A: 4.2%), constipation (Part A: 4.2%; Part B: 7.1%), and vomiting (Part A: 4.2%; Part B: 7.1%). Overall, TE-8105 was safe and well tolerated with pharmacokinetics potentially allowing for less frequent SC dosing than currently available GLP-1 receptor agonists.

Gestational diabetes mellitus (GDM) is a common pregnancy complication with profound short- and long-term consequences for both mother and offspring. Beyond transient hyperglycemia, GDM represents a multifactorial metabolic condition shaped by the interplay of genetic predisposition, epigenetic regulation, and alterations in the maternal microbiome. Dysbiosis of the gut and reproductive tract microbiota contributes to inflammation, insulin resistance, and dyslipidemia during pregnancy, while microbial metabolites influence placental physiology and epigenetic remodeling of key metabolic and imprinted genes. These modifications, including changes in DNA methylation and non-coding RNA expression, link maternal hyperglycemia and microbial shifts to persistent alterations in gene expression that affect trophoblast activity, fetal growth trajectories, and long-term metabolic risk in offspring. Vertical transmission of maternal microbiota further imprints the neonatal microbiome, establishing an early-life foundation for reproductive and metabolic health. Although current diagnostic criteria and biomarkers remain inconsistent across populations, recent advances highlight the microbiome-epigenome axis as a promising source of predictive markers and therapeutic targets. Interventions such as probiotics, prebiotics, synbiotics, and dietary modulation show potential for improving maternal glycemic control, shaping placental function, and modulating fetal programming, although evidence for long-term efficacy is still emerging. Viewing GDM as both a metabolic stress test and a window of reproductive opportunity underscores the importance of early diagnosis and precision strategies. Integrating microbiome research and epigenetic insights into clinical practice offers new avenues to improve maternal outcomes, optimize fetal development, and reduce the intergenerational transmission of reproductive and metabolic disease risk.

This study aimed to evaluate the effects of cosupplementation with high-dose vitamin D3 and flaxseed oil on inflammatory markers, oxidative stress, and metabolic health in elderly patients with T2DM.

We conducted an 8-week, triple-blind, randomized, placebo-controlled clinical trial in Iran, enrolling 104 elderly patients with T2DM, of whom 102 completed the study. The intervention group received 500 mg of flaxseed oil three times daily and 50,000 IU of vitamin D3 orally every two weeks, while the control group received matching placebos.

The primary outcome, serum hs-CRP, was significantly reduced in the intervention group compared to controls (MD: -0.98 μg/mL, p = 0.034). Exploratory analyses of secondary outcomes suggested additional potential benefits: total antioxidant capacity improved (MD: +0.60 mmol/L, p < 0.05), and reductions were observed in weight (MD: -1.73 kg, p < 0.001), BMI (MD: -0.67 kg/m², p < 0.001), fasting blood glucose (MD: -22.83 mg/dL, p = 0.015), fasting insulin (MD: -0.94 μIU/mL, p = 0.008), homeostatic model assessment of insulin resistance (MD: -1.31, p = 0.001), triglycerides (MD: -15.00 mg/dL, p = 0.020), and total cholesterol (MD: -2.52 mg/dL, p = 0.028). Physical health-related quality of life, including pain scores and physical functioning, also improved significantly (p < 0.05). The intervention was well tolerated with minimal adverse events.

Cosupplementation with flaxseed oil and high-dose vitamin D₃ significantly reduced systemic inflammation in elderly patients with T2DM. Exploratory findings further suggest potential benefits for oxidative stress, glycemic control, lipid profile, and physical quality of life, warranting confirmation in future trials. Trial Registration: Iranian Clinical Trials Register: IRCT20161022030424N8.

Diabetic kidney disease (DKD) is a nutrition-related complication of type 2 diabetes mellitus (T2DM) characterized by complex disturbances in glucose, lipid, purine, and protein-related metabolism. This study aimed to investigate nutrient metabolic heterogeneity across renal stages in patients with T2DM and DKD, with particular focus on time in range (TIR), serum uric acid (SUA), TG/HDL-C ratio, and serum albumin (ALB).

This single-center cross-sectional study included 589 hospitalized patients with T2DM, including 128 patients without DKD and 461 patients with DKD. DKD patients were further stratified according to KDIGO eGFR categories. Continuous glucose monitoring-derived TIR, SUA, TG/HDL-C ratio, and ALB were evaluated as multidimensional nutrient metabolism indicators. Multivariable logistic regression analyses were performed to identify independent metabolic indicators associated with DKD. Renal-stage trend analyses and stratified analyses in G3 and G5 were further conducted to explore stage-specific metabolic patterns.

Compared with patients without DKD, patients with DKD were older, had longer diabetes duration, and showed greater use of glucose-lowering and lipid-lowering medications. Patients with DKD also showed paradoxically higher TIR levels. In the overall multivariable model, higher TIR was associated with lower odds of DKD (OR = 0.97, 95% CI: 0.95-0.99, p = 0.010), whereas higher SUA (OR = 1.21, 95% CI: 1.08-1.31, p < 0.001) and TG/HDL-C ratio (OR = 1.27, 95% CI: 1.08-1.40, p = 0.002) were associated with higher odds of DKD. Higher ALB was associated with lower odds of DKD (OR = 0.91, 95% CI: 0.87-0.96, p < 0.001). Across renal stages, TIR decreased from G1 to G4, whereas SUA and TG/HDL-C ratio increased progressively with worsening renal function. ALB showed the lowest level in G5. In stratified analyses, TIR, SUA, and TG/HDL-C ratio remained significantly associated with DKD in G3, while ALB was the only significant metabolic correlate in G5.

DKD in T2DM is characterized by stage-specific nutrient metabolic heterogeneity involving glucose, purine, lipid, and protein-related nutritional metabolism. G3 may represent a renal stage characterized by more prominent glucose, uric acid, and lipid metabolic abnormalities, whereas G5 may be characterized by more evident nutritional deterioration. These findings should be interpreted as stage-specific associations rather than causal progression pathways because of the cross-sectional design.

https://www.chictr.org.cn/bin/home, identifier ChiCTR2500111406.

Chronic hyperglycemia may impair tissue oxygen delivery by glycating hemoglobin, increasing oxygen affinity, shifting the oxyhemoglobin dissociation curve leftward, and reducing oxygen unloading, a state termed glycohypoxia. This study quantified HbA1c-dependent oxygen-release impairment and tested whether the modeled signal is supported by preliminary clinical validation in type 2 diabetes mellitus (T2DM).

Six human studies (1984-2012; N = 450) reporting HbA1c and oxygen-release metrics were synthesized using random-effects meta-regression. The pooled ΔP50 was translated into oxygen-unloading changes using the Hill equation across microvascular PO₂ values of 20-40 mmHg. In parallel, 90 T2DM patients were stratified by HbA1c into controlled, moderately uncontrolled, and poorly controlled groups for assessment of P50, 2,3-BPG, arterial oxygenation, SpO₂-SaO₂ bias, lactate, and modeled unloading.

Sensitivity-adjusted meta-regression showed ΔP50 = -0.19 mmHg per 1% HbA1c (95% CI: -0.26 to -0.11; P < 0.001; I2 = 45%), predicting 0.5-1.3% less oxygen unloading per 1% HbA1c and 1.5-3.9% cumulatively from HbA1c 6-9%. Clinically, higher HbA1c was associated with lower P50 (27.0 ± 0.5 to 26.2 ± 0.7 mmHg; P < 0.01), reduced 2,3-BPG (4.8 ± 0.4 to 4.2 ± 0.5 µmol/g Hb), increased SpO₂-SaO₂ bias (+0.2 ± 0.4% to +1.8 ± 0.6%; P < 0.01), and higher lactate (1.2 ± 0.3 to 1.9 ± 0.5 mmol/L), despite preserved PaO2.

Quantitative modeling and exploratory clinical validation converged to support glycohypoxia as a measurable oxygen-handling phenotype in T2DM. This pattern may indicate a chronic low-grade functional hypoxic burden that accumulates with glycemic exposure and contributes to T2DM diabetic complications.

Hepatitis B virus (HBV) infection is a significant chronic infection in pediatric patients. Vaccination induces production of anti-Hepatitis B surface antibodies, which serve as markers of protective immunity. Given the long-term risks of cirrhosis and hepatocellular carcinoma during adulthood, this study aimed to assess and compare seroprotection between children with type 1 diabetes mellitus (T1DM) and nondiabetic participants.

In this case-control study, 127 children with T1DM and 124 controls, all in a healthy immune state and fully vaccinated against HBV, were recruited from Shiraz University pediatric endocrinology clinics. Exclusion criteria included immunosuppression, incomplete vaccination, or hepatitis history in the child/family. Ethical approval was obtained from Shiraz University of Medical Sciences. Comparisons of sex, age, antibody titers, and diabetes indices used appropriate inferential tests; odds of inadequate antibody titers were assessed by logistic regression.

Considering an antibody titer of 10 mIU/mL as adequate, the non-protection rate was 54.3% (95% CI: 45.3%-63.2%) in diabetic individuals and 28.2% (95% CI:20.5%-37.0%) in non-diabetics. In a multivariable model controlling for time from vaccination, time from vaccination (OR = 1.26, 95% CI: 1.06-1.49, p < 0.001), and diabetes status (OR = 2.34, 95% CI: 1.33-4.14, p = 0.002) contributed to inadequate antibody titers. Sex, glycemic control, and disease duration over 1 year had no significant effect.

Children with type 1 Diabetes Mellitus exhibited lower anti-HBs antibody titers compared to their nondiabetic counterparts, with no association found with sex or glycemic control. The timing of vaccination and diabetes status should be considered when evaluating immune responses to HBV vaccination in children.

Polycystic ovary syndrome (PCOS), the most prevalent endocrine disorder among women of reproductive age, is associated with adverse pregnancy outcomes. However, the dynamic trajectory of fetal growth in PCOS pregnancies remains inadequately characterized.

This study aimed to longitudinally assess fetal growth in PCOS pregnancies and evaluate whether assisted reproductive technology (ART) modifies associated fetal growth restriction.

In this prospective multicenter cohort study (UNIHOPE; NCT03220750), 12,189 advanced maternal age pregnancies (364 with Rotterdam-diagnosed PCOS) underwent longitudinal fetal biometry in the second and third trimesters following ISUOG guidelines. Z-scores were derived using the study's advanced-age reference, adjusting for gestational age and sex. Generalized linear models were adjusted for maternal demographics, lifestyle factors, and gestational diabetes mellitus, with subgroup analyses stratified by ART conception.

Among 12,189 advanced maternal age pregnancies (364 PCOS), PCOS fetuses showed reduced second-trimester Z-scores for femur length (MD: -0.13; 95% CI, -0.25 to -0.02) and head circumference (MD: -0.14; 95% CI, -0.23 to -0.04), with third-trimester deficits extending to biparietal diameter (MD: -0.18) and abdominal circumference (MD: -0.16). Birth length (MD: -0.16) and weight (MD: -0.13) Z-scores were lower in PCOS neonates. Growth restriction was evident only in spontaneous conceptions, with no significant differences in ART-conceived pregnancies. Findings were robust to GDM adjustment.

Fetal growth restriction in PCOS pregnancies is detectable from the second trimester and persists to delivery. ART conception appears to mitigate this restriction, yielding fetal growth parameters comparable to the reference population. These findings underscore the necessity of dynamic ultrasound surveillance in PCOS pregnancies and highlight a potential protective role of ART in perinatal outcomes.

https://clinicaltrials.gov, identifier NCT03220750.

Maternal diabetes, encompassing gestational diabetes mellitus and pre-existing type 1 and type 2 diabetes are associated with adverse perinatal outcomes. Emerging evidence suggests that maternal hyperglycemia and insulin resistance may be associated with long-term neurodevelopmental outcomes, particularly increasing the risk of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). This review synthesizes current epidemiological and mechanistic evidence linking maternal diabetes with the incidence of ASD and ADHD in offspring. Large population-based cohort studies consistently demonstrate an elevated risk of ASD and ADHD among children exposed to maternal diabetes in utero, with risk magnitude varying according to diabetes type, timing of diagnosis, and treatment modality. ADHD appears to show a stronger and more consistent association, particularly in offspring of mothers with type 1 diabetes. Proposed biological mechanisms include hyperglycemia-induced oxidative stress, epigenetic modifications, hormonal dysregulation involving estrogen, progesterone, and androgens, and an increased incidence of preterm birth. Maternal factors such as obesity, advanced age, and fertility treatments further modulate risk. Despite accumulating evidence, heterogeneity across studies and residual confounding limit causal inference. Future prospective studies integrating detailed glycemic profiling, hormonal assessments, and neurodevelopmental phenotyping are required to elucidate underlying mechanisms and inform preventive strategies for pregnancies complicated by diabetes.