Search Results (54)

Obstructive sleep apnea (OSA) is a prevalent disorder linked to metabolic complications such as diabetes and cardiovascular disease. By fragmenting normal sleep architecture, OSA perturbs the growth hormone/insulin-like growth factor (GH/IGF) axis and alters circulating levels of IGF-binding proteins (IGFBPs). A prior clinical observation of elevated IGFBP4 in OSA patients motivated the present investigation in a controlled animal model. Building on the previously reported protocol, OSA was induced in male C57BL/6 mice (9–12 weeks old) through intralingual injection of polytetrafluoroethylene (PTFE), producing tongue hypertrophy, intermittent airway obstruction, and hypoxemia. After 8–10 weeks, the study assessed (1) hypoxia biomarkers—including HIF-1α and VEGF expression—and (2) neurobehavioral outcomes in anxiety and cognition using the open-field and novel object recognition tests. PTFE-treated mice exhibited a significant increase in circulating IGFBP4 versus both baseline and control groups. Hepatic Igfbp4 mRNA was also upregulated. Behaviorally, PTFE mice displayed heightened anxiety-like behavior and impaired novel object recognition, paralleling cognitive deficits reported in human OSA. These findings validate the PTFE-induced model as a tool for studying OSA-related hypoxia and neurocognitive dysfunction, and they underscore IGFBP4 as a promising biomarker and potential mediator of OSA’s systemic effects. Full article

Neurotrophins and inflammatory mediators are known to influence endometrial function, but their interplay in luminal epithelial cells remains poorly characterized. In this study, sheep endometrial luminal epithelial cells (SELECs) were treated with nerve growth factor (NGF), lipopolysaccharide (LPS), or both, and the effects on gene expression and prostaglandin secretion were evaluated. NGF stimulation alone induced a clear transcriptional activation of NGF, neurotrophic receptor tyrosine kinase 1 (NTRK1), p75 neurotrophin receptor (p75NTR), cyclooxygenase 2 (COX2), and steroidogenic acute regulatory protein (STAR). LPS treatment selectively increased Toll-like receptor 4 (TLR4), COX2, and insulin-like growth factor binding protein 6 (IGFBP6). Combined NGF and LPS treatment did not enhance the transcriptional response beyond that induced by NGF alone, except for STAR. However, co-treatment resulted in a modest increase in prostaglandin production, particularly prostaglandin F2α (PGF2α), but not prostaglandin E2 (PGE2), compared to single treatments, suggesting a possible post-transcriptional modulation rather than a transcriptional synergy. These findings indicate that NGF acts as the primary transcriptional driver in SELECs, while LPS contributes selectively and may enhance prostaglandin output. The observed increase in prostaglandin production may involve post-transcriptional mechanisms, although this remains to be confirmed. Full article

Insulin-like growth factor-binding protein-3 (IGFBP-3) plays a vital role in cellular growth, development, and survival. Incorporating IGFBP-3 into baseline prognostic evaluations may enhance the prediction of mortality in patients with sepsis. In this study, serum levels of IGFBP-3, C-reactive protein, procalcitonin, lactate, interleukin-6, and mid-regional pro-adrenomedullin were measured upon admission to the internal medicine unit (IMU) in 139 patients with microbiologically confirmed sepsis. The objectives were as follows: (1) to classify septic patient phenotypes based on optimal thresholds of independent prognostic biomarkers and (2) to evaluate whether these biomarkers improve the predictive accuracy of a clinical model (Model 1), which includes the clinical predictors of 1-year mortality. Age, sequential organ failure assessment (SOFA) score, multiple sources of infection, and IGFBP-3 levels independently predicted 1-year mortality. Patients with IGFBP-3 levels below 10.64 had significantly lower median body temperature (p = 0.008), reduced lymphocyte count (p = 0.001), and higher 1-year mortality (p < 0.001). Model 1 included age, SOFA score, and the presence of multiple sources of sepsis as predictor variables. Model 2 incorporated the same variables as Model 1, with the addition of IGFBP-3 levels. When comparing their prognostic performance, Model 2 demonstrated superior predictive accuracy for mortality at 60, 90, and 365 days following admission to the IMU. Low IGFBP-3 levels at IMU admission are strongly associated with worse outcomes in septic patients, supporting its potential use as a prognostic biomarker. Full article

Background/Objectives: Patients with peripheral artery disease (PAD) have a heightened risk of major adverse cardiovascular events (MACE), including myocardial infarction, stroke, and death. Despite this, limited progress has been made in identifying reliable biomarkers to prognosticate such outcomes. Circulating growth factors, known to influence endothelial function and the progression of atherosclerosis, may hold prognostic value in this context. The objective of this research was to evaluate a broad range of blood-based growth factors to investigate their potential as predictors of MACE in patients diagnosed with PAD. Methods: A total of 465 patients with PAD were enrolled in a prospective cohort study. Baseline plasma levels of five different growth factors were measured, and participants were monitored over a two-year period. The primary outcome was the occurrence of MACE within those two years. Comparative analysis of protein levels between patients who did and did not experience MACE was performed using the Mann–Whitney U test. To assess the individual prognostic significance of each protein for predicting MACE within two years, Cox proportional hazards regression was performed, adjusting for clinical and demographic factors including a history of coronary and cerebrovascular disease. Subgroup analysis was performed to assess the prognostic value of these proteins in females, who may be at higher risk of PAD-related adverse events. Net reclassification improvement (NRI), integrated discrimination improvement (IDI), and area under the receiver operating characteristic curve (AUROC) were calculated to assess the added value of significant biomarkers to model performance for predicting 2-year MACE when compared to using demographic/clinical features alone. Kaplan–Meier curves stratified by IGFBP-1 tertiles compared using log-rank tests and Cox proportional hazards analysis were used to assess 2-year MACE risk trajectory based on plasma protein levels. Results: The average participant age was 71 years (SD 10); 31.1% were female and 47.2% had diabetes. By the end of the two-year follow-up, 18.1% (n = 84) had experienced MACE. Of all proteins studied, only insulin-like growth factor-binding protein 1 (IGFBP-1) showed a significant elevation among patients who suffered MACE versus those who remained event-free (20.66 [SD 3.91] vs. 13.94 [SD 3.80] pg/mL; p = 0.012). IGFBP-1 remained a significant independent predictor of 2-year MACE occurrence in the multivariable Cox analysis (adjusted hazard ratio [HR] 1.57, 95% CI 1.21–1.97; p = 0.012). Subgroup analyses revealed that IGFBP-1 was significantly associated with 2-year MACE occurrence in both females (adjusted HR 1.52, 95% CI 1.16–1.97; p = 0.015) and males (adjusted HR 1.04, 95% CI 1.02–1.22; p = 0.045). Incorporating IGFBP-1 into the clinical risk prediction model significantly enhanced its predictive performance, with an increase in the AUROC from 0.73 (95% CI 0.71–0.75) to 0.79 (95% CI 0.77–0.81; p = 0.01), an NRI of 0.21 (95% CI 0.07–0.36; p = 0.014), and an IDI of 0.041 (95% CI 0.015–0.066; p = 0.008), highlighting the prognostic value of IGFBP-1. Kaplan–Meier analysis showed an increase in the cumulative incidence of 2-year MACE across IGFBP-1 tertiles. Patients in the highest IGFBP-1 tertile experienced a significantly higher event rate compared to those in the lowest tertile (log-rank p = 0.008). In the Cox proportional hazards analysis, the highest tertile of IGFBP-1 was associated with increased 2-year MACE risk compared to the lowest tertile (adjusted HR 1.81; 95% CI: 1.31–2.65; p = 0.001). Conclusions: Among the growth factors analyzed, IGFBP-1 emerged as the sole biomarker independently linked to the development of MACE over a two-year span in both female and male PAD patients. The addition of IGFBP-1 to clinical features significantly improved model predictive performance for 2-year MACE. Measuring IGFBP-1 levels may enhance risk stratification and guide the intensity of therapeutic interventions and referrals to cardiovascular specialists, ultimately supporting more personalized and effective management strategies for patients with PAD to reduce systemic vascular risk. Full article

Prostate cancer with bone metastasis exhibits significant heterogeneity, complicating prognosis, and treatment. This study explores the potential of plasma, serum, and urine biomarkers to stratify patients and evaluate their prognostic value. Using two-step clustering, we analyzed baseline levels of Platelet-derived growth factor-BB (PDGF-BB), Insulin-like growth factor-binding protein 1 (IGFBP-1), Bone Morphogenetic Protein 2 (BMP-2), Vascular endothelial growth factor (VEGF) (plasma and urine), prostate-specific antigen (PSA), neuron-specific enolase (NSE), chromogranin A (CgA) and bone-specific alkaline phosphatase (BAP) (serum) and creatinine (Cr), and type I collagen-cross-linked N telopeptide (NTx) (urine) in 29 patients with prostate cancer and bone metastasis. Longitudinal biomarker dynamics were assessed at baseline, 6 months, and 12 months. Clinical outcomes were evaluated using Kaplan–Meier and multivariate analyses. Three distinct groups (C1, C2, and C3) were identified. C1 exhibited elevated pPDGF-BB and pVEGF levels, C3 had increased pBAP and uNTx/Cr, and C2 showed lower biomarker levels. Prior treatments influenced biomarker levels, with bisphosphonates reducing bone turnover markers and radiotherapy correlating with long-term changes in growth factors. Longitudinal analysis revealed unique biomarker dynamics within each group, with a tendency for pPDGF-BB and pVEGF levels to decrease over time in C1, and distinct trends in uNTx/Cr between groups. Despite individual biomarkers failing to predict survival, C3 patients demonstrated significantly worse survival than C1 and C2. Molecular clustering of peripheral blood and urinary biomarkers identifies distinct subgroups with metastatic castration-resistant prostate cancer patients outperforming traditional models in outcome prediction and supporting its potential for personalized treatment and prognosis. Full article

Background: Glioblastoma is a highly aggressive brain tumour with poor survival outcomes, highlighting the need for reliable prognostic models. Developing robust and interpretable prognostic signatures is critical for improving patient stratification and guiding therapy. This study explored the integration of machine learning feature selection with regularised Cox regression to construct prognostic gene signatures for glioblastoma patients. Methods: We combined the Boruta algorithm and Random Survival Forests (RSFs) with regularised Cox regression, along with network-based regularisation techniques (HubCox and OrphanCox), to develop interpretable prognostic signatures for stratifying high- and low-risk glioblastoma patients. Using mRNA-seq and survival data from The Cancer Genome Atlas (TCGA), we developed predictive models following WHO-2021 glioma guidelines. Results: Integrating Boruta or RSF with regularised Cox regression improved the performance and interpretability. Boruta increased the concordance indexes (C-indexes) by 0.030 and 0.013 for LASSO and Elastic Net, respectively, while significantly reducing the feature numbers. RSF similarly enhanced the performance and feature reduction. The genes Lysyl Oxidase Like 1 (LOXL1) and Insulin Like Growth Factor Binding Protein 6 (IGFBP6) were consistently selected and linked to glioma survival, emphasising their clinical significance. The network-based methods demonstrated superior survival probability prediction (lower Integrated Brier Score), although with lower C-index values, highlighting limitations in ranking the survival times. To evaluate the generalisability, external validation using the Chinese Glioma Genome Atlas (CGGA) confirmed that a multigene signature derived from the most consistently selected genes significantly stratified the patients by risk. Conclusions: This study underscored the utility of combining machine learning feature selection with survival analysis to enhance prognostic modelling while balancing predictive performance and interpretability. Full article

Kidney function parameters including estimated glomerular filtration rate (eGFR) and urine albumin excretion are commonly used to diagnose chronic kidney disease (CKD). However, these parameters are relatively insensitive, limiting their utility for screening and early detection of kidney disease. Studies have suggested that urinary proteomic profiles differ by eGFR stage, offering potential insights into kidney disease pathogenesis alongside opportunities to increase the sensitivity of current testing strategies. In this study, we characterized and compared the urinary proteome across different eGFR stages in a Black African cohort from rural Mpumalanga Province, South Africa. We stratified 81 urine samples by eGFR stage (mL/min/1.73 m²): Stage G1 (eGFR ≥ 90; n = 36), Stage G2 (eGFR 60–89; n = 35), and Stage G3–G5 (eGFR < 60; n = 10). Urine proteomic analysis was performed using an Evosep One liquid chromatography system coupled to a Sciex 5600 TripleTOF in data-independent acquisition mode. Nonparametric multivariate analysis and receiver operating characteristic (ROC) curves were used to assess the performance of differentially abundant proteins (DAPs). Pathway analysis was performed on DAPs. Creatinine-based eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. In this study, thirty-eight urinary proteins were differentially abundant for eGFR Stages 3–5 when compared to Stages G1 (AUC = 0.95; CI: 0.86–1) and G2 (AUC = 0.84; CI: 0.64–0.98). Notably, only six urinary proteins (Cystatin M (CST6), glutathione hydrolase 6 (GGT6), sushi domain containing 2 (SUSD2), insulin-like growth factor binding protein 6 (IGFBP6), heat shock protein 90 beta family member 1 (HSP90B1), and mannosidase alpha class 1A member 1 (MAN1A1)) were differentially abundant when comparing Stage G1 and Stage G2 with a modest AUC = 0.81 (CI: 0.67–0.92). Pathway analysis indicated that DAPs were associated with haemostasis and fibrin clot formation. In a rural cohort from South Africa, the urinary proteome differed by eGFR stage, and we identified six differentially abundant proteins which, in combination, could help to differentiate earlier eGFR stages with higher predictive accuracy than the currently available tests. Full article

Matrix metalloproteinases (MMPs) are M2 macrophage markers that are modulated by inflammation. A disintegrin and metalloproteinases (ADAMS) and those with thrombospondin motifs (ADAMTS) regulate the shedding of membrane-bound proteins, growth factors, cytokines, ligands, and receptors; MMPs, ADAMS, and ADAMTS may be regulated by tissue inhibitors of metalloproteinases (TIMPs). This study aimed to determine whether these interacting proteins were dysregulated in PCOS. A Somascan proteomic analysis of 12 MMPs, three of their inhibitors (TIMP-1, 2, 3), two ADAMS (9, 12), five ADAMTS (1, 4, 5, 13, 15), insulin-like growth factor binding protein-1 (IGFBP-1), and insulin-like growth factor-1 (IGF-1) was undertaken in a well-validated PCOS database of 143 women with PCOS and 97 controls. Women with PCOS had significantly higher levels of MMP-9 and lower levels of MMP-2, MMP-14, TIMP-2, IGFBP-1, and IGF-1 compared to the controls (p < 0.0001, p < 0.005, p < 0.04, p < 0.05, p < 0.0001, and p < 0.0001, respectively). No differences were observed for any other MMPs. The ADAMS or ADAMTS levels did not differ between groups. Body mass index (BMI) was correlated with MMP-9 (p < 0.01), MMP-1 (p < 0.05), MMP-2 (p < 0.05), MMP-10 (p < 0.005), MMP-12 (p < 0.005), ADAM-9 (p < 0.05), and IGFBP-1 (p < 0.0001), but only MMP-9 still differed after accounting for BMI. MMP-9/TIMP-1, MMP-9/TIMP-2, and MMP-9/TIMP-3 ratios were higher in the PCOS group (p < 0.01), whilst MMP-17/TIMP-1 and MMP-17/TIMP-2 were lower (p = 0.01). MMP-2/TIMP ratios showed no difference between groups. TIMP-2 was positively correlated with CRP (p < 0.01). MMP changes in PCOS are largely driven by BMI, though increased MMP-9 is BMI-independent, suggesting that any deleterious effects of MMP-9 would be potentially exacerbated by a concomitantly increased BMI. The significant increases in the MMP-9/TIMP ratios suggests MMP-9 overactivity in PCOS. Full article

Collagen barrier membranes are frequently used in guided tissue and bone regeneration. The aim of this study was to analyze the signature of human serum proteins adsorbed onto collagen membranes using a novel protein extraction method combined with mass spectrometry. Native porcine-derived collagen membranes (Geistlich Bio-Gide^®, Wolhusen, Switzerland) were exposed to pooled human serum in vitro and, after thorough washing, subjected to protein extraction either in conjunction with protein enrichment or via a conventional surfactant-based method. The extracted proteins were analyzed via liquid chromatography with tandem mass spectrometry. Bioinformatic analysis of global profiling, gene ontology, and functional enrichment of the identified proteins was performed. Overall, a total of 326 adsorbed serum proteins were identified. The enrichment and conventional methods yielded similar numbers of total (315 vs. 309), exclusive (17 vs. 11), and major bone-related proteins (18 vs. 14). Most of the adsorbed proteins (n = 298) were common to both extraction groups and included several growth factors, extracellular matrix (ECM) proteins, cell adhesion molecules, and angiogenesis mediators involved in bone regeneration. Functional analyses revealed significant enrichment of ECM, exosomes, immune response, and cell growth components. Key proteins [transforming growth factor-beta 1 (TGFβ1), insulin-like growth factor binding proteins (IGFBP-5, -6, -7)] were exclusively detected with the enrichment-based method. In summary, native collagen membranes exhibited a high protein adsorption capacity in vitro. While both extraction methods were effective, the enrichment-based method showed distinct advantages in detecting specific bone-related proteins. Therefore, the use of multiple extraction methods is advisable in studies investigating protein adsorption on biomaterials. Full article

The treatment of childhood cancer is challenged by toxic side effects mainly due to chemotherapy-induced organ damage and infections, which are accompanied by severe systemic inflammation. Insulin-like growth factor I (IGF-I) is a key regulating factor in tissue repair. This study investigated associations between the circulating IGF-I levels and chemotherapy-related toxicity in pediatric acute lymphoblastic leukemia (ALL). In this prospective study, we included 114 patients (age: 1–17 years) with newly diagnosed ALL treated according to The Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL2008 protocol between 2013 and 2018. The patients’ plasma levels of IGF-I, and the primary binding protein, IGFBP-3, were measured weekly during the first six weeks of treatment, including the induction therapy. The patients’ systemic inflammation was monitored by their C-reactive protein (CRP) and interleukin (IL)-6 levels and their intestinal epithelial damage by their plasma citrulline levels. IGF-I and IGFBP-3 were converted into sex-and age-adjusted standard deviation scores (SDS) using 1621 healthy children as reference. At ALL diagnosis, IGF-I levels were decreased (median (quartiles): −1.2 SDS (−1.9 to −0.5), p = 0.001), but increased significantly following the initiation of chemotherapy, peaking on day 8 (0.0 SDS (from −0.8 to 0.7), p < 0.001). This increase correlated with the levels of CRP (rho = 0.37, p < 0.001) and IL-6 (rho = 0.39, p = 0.03) on day 15, when these markers reached maximum levels. A larger IGF-I increase from day 1 to 15 correlated with a slower recovery rate of the intestinal damage marker citrulline from day 15 to 29 (rho = −0.28, p = 0.01). Likewise, IGFBP-3 was reduced at diagnosis, followed by an increase after treatment initiation, and was highly correlated with same-day IGF-I levels. This study demonstrates a chemotherapy-induced increase in IGF-I, with a response that appears to reflect the severity of tissue damage and systemic inflammation, preceding CRP and IL-6 increases. IGF-I may have potential as an early reactive biomarker for acute toxicity in patients with ALL. Full article

(1) Colorectal cancer is a major cause of cancer-related death, with colorectal adenomas (CRAs) serving as precursors. Identifying risk factors such as vitamin D deficiency and the insulin-like growth factor (IGF) axis is crucial for prevention. (2) This case–control study included 85 participants (53 CRA patients and 32 controls) who underwent colonoscopy. We measured serum vitamin D3 (cholecalciferol), calcidiol (vitamin D metabolite), calcitriol (active vitamin D metabolite), insulin-like growth factor-1 (IGF-1), and insulin-like growth factor binding protein-3 (IGFBP-3) to explore their associations with CRA risk. (3) Results: We found that lower cholecalciferol levels were a significant risk factor for CRA (OR = 4.63, p = 0.004). Although no significant differences in calcidiol and calcitriol levels were observed between CRA patients and controls, calcidiol deficiency was common in the study population. IGF-1 levels inversely correlated with age, calcitriol, and IGFBP-3 in CRA patients. (4) This study highlights the potential of lower cholecalciferol levels to detect patients at risk of CRA when calcidiol values cannot, suggesting the importance of evaluating different vitamin D metabolites in cancer prevention research. Our findings underscore the need to further investigate the interactions between calcitriol, the active form of vitamin D, and the IGF axis in colorectal cancer development. Full article

Insulin-like growth factor 1 (IGF-1) regulates dairy cow reproduction, while the paracrine IGF system locally influences fertility. In both systems, IGF-1 bioactivity is regulated through binding proteins (IGFBPs) inhibiting IGF-1 binding to its receptor (IGF1R). This study aimed to investigate a possible transfer between this endocrine and paracrine system. Therefore, blood and follicular fluid (FF) from postpartum dairy cows were analysed for ß-hydroxybutyrate (BHB), IGF-1, IGFBP-2, -3, -4, -5, and an IGFBP fragment in two study parts. The mRNA expression of IGFBP-2, IGFBP-4, IGF1R, and the pregnancy-associated plasma protein A (PAPP-A) in granulosa cells was measured. The results showed correlations between plasma and FF for IGF-1 (r = 0.57, p < 0.001) and IGFBP-2 (r = −0.57, p < 0.05). Blood BHB negatively correlated with IGF-1 in blood and FF and IGFBP-3, -5 and total IGFBP in blood (IGF-1 plasma: r = −0.26, p < 0.05; FF: r = −0.35, p < 0.05; IGFBP-3: r = −0.64, p = 0.006; IGFBP-5: r = −0.49, p < 0.05; total IGFBP: r = −0.52, p < 0.05). A negative correlation was found between IGFBP-2 expression and IGF-1 concentration in FF (r = −0.97, p = 0.001), while an IGFBP fragment positively correlated with IGF1R-mRNA in FF (r = 0.82, p = 0.042). These findings suggest a transfer and local regulation between the somatotropic axis and the follicular IGF system, linking the metabolic status with local effects on dairy cow fertility. Full article

Severe aortic valve stenosis (AS) and pulmonary hypertension (PH) are life-threatening cardiovascular conditions, necessitating early detection and intervention. Recent studies have explored the role of Insulin-like Growth Factor-Binding Protein 2 (IGF-BP2) in cardiovascular pathophysiology. Understanding its involvement may offer novel insights into disease mechanisms and therapeutic targets for these conditions. A total of 102 patients (46 female, 56 male) with severe AS undergoing a transcatheter aortic valve replacement (TAVR) in a single-center study were classified using echocardiography tests to determine systolic pulmonary artery pressure (sPAP) and the presence (sPAP ≥ 40 mmHg) or absence (sPAP < 40 mmHg) of PH. Additionally, serial laboratory determinations of IGF-BP2 before, and at 24 h, 96 h, and 3 months after intervention were conducted in all study participants. Considering the entire cohort, patients with PH had significant and continuously higher serum IGF-BP2 concentrations over time than patients without PH. After subdivision by sex, it could be demonstrated that the above-mentioned results were only verifiable in males, but not in females. In the male patients, baseline IGF-BP2 levels before the TAVR was an isolated risk factor for premature death after intervention and at 1, 3, and 5 years post-intervention. The same was valid for the combination of male and echocardiographically established PH patients. The predictive role of IGF-BP2 in severe AS and concurrent PH remains unknown. A more profound comprehension of IGF-BP2 mechanisms, particularly in males, could facilitate the earlier consideration of the TAVR as a more effective and successful treatment strategy. Full article

Sirtuin 1 (SIRT1) inhibits growth hormone (GH) intracellular signaling for the insulin-like growth factor 1 (IGF-1) synthesis via the janus kinase (JAK)/signal transducer and activator of transcription proteins (STATs) pathway. The aim of this study was to compare SIRT1 concentrations in children with GH deficiency (GHD) and so-called idiopathic short stature (ISS, non-GH deficient), in order to determine the possible impact of changes in serum SIRT1 concentrations on the GH-IGF-1 axis. The study group included 100 short-stature children: 38 with GHD and 62 with ISS (maxGH in two stimulation tests <10 and ≥10 ng/mL, respectively). The control group consisted of 47 healthy, normal-height children. For each child, the concentrations of SIRT1, IGF-1 and insulin-like growth factor-binding protein 3 (IGFBP-3) were determined and the IGF-1/IGFBP-3 molar ratio was calculated. The level of SIRT1 was significantly higher in both groups of short children than in the controls (p < 0.0001), but there were no differences between GHD and ISS (mean ± SD: 0.89 ± 0.45 for ISS; 1.24 ± 0, 86 for GHD; and 0.29 ± 0.21 for controls). A significant negative correlation was found between SIRT1 and height standard deviation score (SDS), IGF-1 and IGF-1/IGFBP-3, but not between SIRT1 and maxGH. Elevated SIRT1 levels may serve as one of the mechanisms through which the secretion of IGF-1 is reduced in children with short stature; however, further research is required to confirm this issue. Full article

Lifestyle interventions can prevent type 2 diabetes (T2DM). However, some individuals do not experience anticipated improvements despite weight loss. Biomarkers to identify such individuals at early stages are lacking. Insulin-like growth factor 1 (IGF- 1) and Insulin-like growth factor binding protein 1(IGFBP-1) were shown to predict T2DM onset in prediabetes. We assessed whether these markers also predict the success of lifestyle interventions, thereby possibly guiding personalized strategies. We analyzed the fasting serum levels of IGF-1, IGFBP-1, and Insulin-like growth factor binding protein 2 (IGFBP-2) in relation to changes in metabolic and anthropometric parameters, including intrahepatic lipids (IHLs) and visceral adipose tissue (VAT) volume, measured by magnetic resonance imaging (MRI), in 345 participants with a high risk for prediabetes (54% female; aged 36–80 years). Participants were enrolled in three randomized dietary intervention trials and assessed both at baseline and one year post-intervention. Statistical analyses were performed using IBM SPSS Statistics (version 28), and significance was set at p < 0.05. Within the 1-year intervention, overall significant improvements were observed. Stratifying individuals by baseline IGF-1 and IGFBP-1 percentiles revealed significant differences: higher IGF-1 levels were associated with more favorable changes compared to lower levels, especially in VAT and IHL. Lower baseline IGFBP-1 levels were associated with greater improvements, especially in IHL and 2 h glucose. Higher bioactive IGF-1 levels might predict better metabolic outcomes following lifestyle interventions in prediabetes, potentially serving as biomarkers for personalized interventions. Full article