Search Results (364)

Objectives: To evaluate the efficacy of a fixed-dose combination of berberine, white mulberry leaf extract, and chromium picolinate on body weight, body composition, and insulin sensitivity in Greek adults with obesity. Research Methodology/Design: This was a 12-week, randomized, double-blind, placebo-controlled trial. Adults with obesity and no diagnosed chronic disease were randomly assigned to receive either berberine (1000 milligrams), white mulberry leaf extract (400 milligrams standardized to 5% 1-deoxynojirimycin), and chromium picolinate (0.644 milligrams) or a matching placebo, administered in two daily doses before the main meals. Setting: The study was conducted in Greece among community-dwelling adults with obesity. Main Outcome Measures: The primary outcome was insulin sensitivity, assessed using the Matsuda Composite Insulin Sensitivity Index derived from a 75-g oral glucose tolerance test. Secondary outcomes included body mass index, total body fat mass, and visceral fat rating. Results: Ninety-three participants were randomized, with 46 assigned to the active intervention and 47 to placebo. Compared with placebo, the active intervention produced significantly greater reductions in body mass index (adjusted mean difference −1.24 kg per square meter; 95% confidence interval −2.15 to −0.33), total body fat mass (−2.35 kg; 95% confidence interval −4.12 to −0.58), and visceral fat rating (−0.92 units; 95% confidence interval −1.74 to −0.10). Insulin sensitivity improved significantly, with a 28% greater improvement in the active group than in the placebo group (adjusted geometric mean ratio 1.28; 95% confidence interval 1.14 to 1.44). Conclusions: The fixed-dose combination improved BIA-derived body-composition measures and OGTT-derived insulin sensitivity over 12 weeks compared with placebo. Because no single-agent arms were included, individual component contributions and synergy remain undetermined; confirmatory trials using direct metabolic and imaging methods are warranted. Full article

Crinum amoenum Roxb. ex Ker Gawl. (C. amoenum) is traditionally used in Nepal, but its antidiabetic potential remains insufficiently validated. This study characterized the 80% (v/v) ethanol bulb extract of C. amoenum and evaluated its antioxidant, α-amylase inhibitory, hypoglycemic, molecular docking, molecular dynamics (MD) simulation, and ADMET profiles. The ethanolic bulb extract was evaluated through phytochemical screening, thin-layer chromatography, total phenolic content (TPC), total flavonoid content (TFC) estimation, LC-MS analysis, antioxidant assays, α-amylase inhibition assays, acute toxicity testing, and hypoglycemic/oral glucose tolerance test (OGTT) studies in Wistar rats. Lycorine, pratorinine, and palmatine were docked against α-amylase (PDB ID: 5U3A) and GLP-1R (PDB ID: 6GB1), followed by 200 ns MD simulations and ADMET prediction. Qualitative analysis of the extract was positive for flavonoids, phenolic compounds, tannins, saponins, alkaloids, and carbohydrates, and a positive Salkowski reaction indicated the presence of constituents occurring in glycosidic form. The TPC was 173.38 ± 1.22 mg GAE/g, and the TFC was 314.58 ± 0.09 mg QE/g. LC-MS tentatively annotated lycorine, pratorinine, and palmatine based on retention time, m/z values in positive-mode electrospray ionization, and comparison with previously reported spectral information. The extract showed DPPH scavenging activity (IC₅₀: 90.98 μg/mL) and strong α-amylase inhibition (IC₅₀: 49.31 μg/mL) compared with acarbose (IC₅₀: 51.51 μg/mL). No deaths were observed following oral administration at 5000 mg/kg to rats. The 500 mg/kg dose produced the greatest hypoglycemic response, reducing blood glucose by 35.78% at 120 min in non-diabetic Wistar rats and by 19.21% at 60 min in glucose-loaded rats. Among all the compounds tested, pratorinine demonstrated the highest docking affinity with α-amylase (−8.2 kcal/mol; ASP300) and GLP-1R (−7.0 kcal/mol; GLY132). MD simulation supported greater stability of the α-amylase complex, and ADMET prediction identified pratorinine as a comparatively favorable predicted lead candidate (LD₅₀: 1000 mg/kg; Class 4 toxicity category). Pratorinine was identified as the most promising in silico antidiabetic candidate from the C. amoenum extract, primarily due to stable α-amylase interactions and favorable ADMET properties. Full article

Background: Neutrophil extracellular traps (NETs) have been known to be involved in the gestational diabetes mellitus (GDM), but the underlying role remains poorly understood. Methods: We conducted an integrated analysis of bulk RNA-seq data, single-cell transcriptomic sequencing (scRNA-seq) data, clinical laboratory findings, and cell models to identify hub genes linked to NET formation (NETosis) and to elucidate how NETs contribute to placental injury in GDM. Results: We found that circulating NET levels were increased in pregnant women with GDM both under fasting conditions and following an oral glucose tolerance test (OGTT). Primary neutrophils isolated from healthy pregnant women produced more NETs upon high-glucose stimulation in vitro. The mRNA expression of PADI4, a key regulator of NETosis, was upregulated and positively correlated with MMP8 mRNA in patients with GDM. Inhibition of MMP8 suppressed intracellular reactive oxygen species (ROS) generation and attenuated NETosis in neutrophils. scRNA-seq analysis of placental tissues from patients with GDM identified a neutrophil subset with higher PADI4 expression. In vitro stimulation with NETs induced functional impairment of HTR8/SVneo cells. Conclusions: We uncovered that MMP8, a novel NETosis-promoting molecule, is a promising target for GDM intervention. Full article

Background/Objectives: Depressive symptoms are more frequent following pregnancies complicated by gestational diabetes mellitus (GDM), prompting postpartum depression screening recommendations in the German S3 guideline. Although GDM is associated with increased postpartum depression risk, the relationships between postpartum metabolic parameters and the Edinburgh Postnatal Depression Scale (EPDS) scores remain unclear. We investigated whether metabolic markers measured during diabetes screening 6–12 weeks postpartum are associated with depressive symptoms. Methods: We retrospectively analyzed EPDS screenings conducted during postpartum testing at our inpatient clinic between 07/2021 and 02/2024. The EPDS is a validated 10-item tool (score range 0–30), with scores ≥10 indicating potential depression. Metabolic parameters included HbA1c, the 75 g oral glucose tolerance test (oGTT), insulin, and the Homeostasis Model Assessment index (HOMA index). Group comparisons were performed using non-parametric tests and receiver operating characteristic (ROC) analyses, with the Youden index identifying optimal cutoffs. Results: Among the 102 women presenting for postpartum testing, 43.1% had normal glucose tolerance, 54.9% prediabetes, and 2.0% diabetes. A total of 13.7% (n = 14) screened positive for potential depression, including two who reported suicidal ideations. Women with positive EPDS scores had significantly higher HbA1c [5.7% (38.3 mmol/mol) vs. 5.4% (35.5 mmol/mol), p = 0.013]. An HbA1c cutoff of 5.42% (35.75 mmol/mol) showed discriminatory ability for depressive symptoms with an Area Under the Curve (AUC) of 0.708 (CI 0.567–0.849). Other metabolic parameters showed no significant associations. Conclusions: Elevated postpartum HbA1c is associated with depressive symptoms after GDM pregnancies. An HbA1c threshold of 5.42% (35.75 mmol/mol) may help identify women at increased postpartum depression risk and prompt subsequent psychological assessment when depression screening is otherwise omitted. Full article

Background: Gestational diabetes mellitus (GDM) is one of the most common medical complications of pregnancy and has a high prevalence in Saudi Arabia. GDM increases the risk of adverse maternal and fetal outcomes and is associated with cardiovascular risk factors. Glycemic severity, represented by the continuous 1 h plasma glucose value from the diagnostic two-hour 75 g oral glucose tolerance test (OGTT), may provide additional insight into glycemic status among women with GDM. Physical activity (PA) plays a vital role in maternal health. Therefore, the aim of this study was to identify the associations between PA and glycemic severity among pregnant women with GDM in Saudi Arabia and to identify factors associated with glycemic severity. Methods: This cross-sectional study enrolled 96 pregnant women during routine second-trimester visits at a maternity clinic in Riyadh. PA was assessed using the Pregnancy Physical Activity Questionnaire (PPAQ). Glycemic severity was assessed using the continuous 1 h plasma glucose value obtained from the diagnostic two-hour 75 g OGTT. Results: One-way ANOVA demonstrated a significant association between PA levels and glycemic severity (F = 2.78; p < 0.04). Multiple linear regression identified low-intensity PA, non-employment, and smoking during pregnancy were significantly associated with higher glycemic severity (p < 0.05). Conclusions: The study identifies a significant association between PA and glycemic severity. Furthermore, employment status and smoking were also significantly associated with glycemic severity. These findings suggest that PA and other modifiable lifestyle factors play role in glucose regulation during pregnancy. However, the cross-sectional design precludes any inference of causality. Full article

Background: The 75 g oral glucose tolerance test (OGTT) is the gold standard for diagnosing gestational diabetes mellitus (GDM) and, according to current guidelines, is recommended for postpartum testing. German guidelines recommend a two-step screening approach, which can delay treatment initiation. In order to prevent complications for mother and child, treatment of GDM should be started as early as possible. To expedite clinical decisions, point-of-care testing (POCT) is often used alongside venous laboratory analysis. For historical reasons, capillary blood was used for POCT at our competence center. This analysis evaluates the diagnostic accuracy of capillary POCT compared to the venous reference standard analyzed in our department of clinical chemistry. Methods: We retrospectively analyzed 401 OGTTs (260 during pregnancy, 141 postpartum) with simultaneous capillary POCT and venous laboratory glucose measurements and investigated the agreement between the two methods. Optimal capillary cut-offs were determined using ROC analysis. Results: In pregnant women (n = 260), capillary POCT showed 80.8% sensitivity and 73.4% specificity. Regarding the diagnostic classification, the initial agreement with the reference standard at fasting was 71.9% (8.9% false positives, 19.2% false negatives). Optimized capillary cut-offs—fasting ≥95 mg/dL (5.3 mmol/L), 1-h ≥203 mg/dL (11.3 mmol/L), and 2-h ≥174 mg/dL (9.7 mmol/L)—increased the proportion of correctly classified cases to 85.5% (fasting), 97.0% (1-h), and 94.4% (2-h), respectively, and effectively eliminated false negatives. Conclusions: While capillary POCT offers >80% sensitivity, its false-positive rate of more than 20% must be managed. Utilizing optimized cut-off values can mitigate this uncertainty. If at least one of these cut-offs is exceeded, capillary POCT via StatStrip^® (Nova Biomedical Corporation, Waltham, MA, USA) provides a sufficient basis for treatment initiation. Full article

Background: Gestational diabetes mellitus (GDM) affects between 1% and 14% of pregnancies worldwide. Major risk factors include advanced maternal age, excess adiposity, family history of type 2 diabetes, and unhealthy dietary habits. In Mexico, evidence on the association between dietary patterns and GDM remains scarce, particularly in socioeconomically vulnerable populations with limited access to specialized nutrition services. This study aimed to evaluate the association between dietary patterns and the presence of GDM in pregnant women attending the outpatient obstetrics clinic of a teaching public hospital in Guadalajara, México. Methods: We conducted a case–control study including 169 pregnant women: 71 with GDM confirmed by the ADA one-step 75 g oral glucose tolerance test OGTT criteria and 98 without GDM based on a negative OGTT, recruited consecutively from the same clinic during the same period. Dietary intake was assessed using a culturally adapted and validated Food Frequency Questionnaire. Dietary patterns were identified through Principal Component Analysis, and associations were examined using logistic regression adjusted for maternal age, pregestational BMI, and family history of type 2 diabetes. Results: Women with GDM had higher maternal age, greater pregestational BMI, and more frequent family history of type 2 diabetes compared with controls. Three dietary patterns were identified: Western, Healthy, and Dairy/Refined. High adherence to the Western pattern was inversely associated with GDM (aOR = 0.36; 95% CI: 0.16–0.78; p = 0.010); however, this finding most likely reflects post-diagnosis dietary modifications rather than a protective effect, while maternal age remained the strongest risk factor (OR = 1.09; 95% CI: 1.03–1.16; p = 0.002). The Healthy pattern (aOR = 1.25; 95% CI: 0.55–2.82; p = 0.593) and the Dairy/Refined pattern (aOR = 0.80; 95% CI: 0.39–1.66; p = 0.554) were not significantly associated with GDM in the adjusted model. Conclusions: GDM was associated with older maternal age, higher pregestational BMI, and family history of T2DM. The inverse association with the Western pattern may reflect post-diagnosis dietary changes rather than a protective effect. Due to the retrospective design, causal inference is not possible, highlighting the need for longitudinal studies. Full article

Background/Objectives: Gestational diabetes mellitus (GDM) represents one of the most common pregnancy-related disorders and it is correlated to increased risks of adverse maternal and neonatal outcomes. The prognostic role of initial glycemic values in predicting neonatal hypoglycemia and other complications remains underexplored. Methods: This retrospective study analyzed 233 women diagnosed with GDM between 2018 and 2024. Participants were stratified into three risk groups based on diagnostic oral glucose tolerance test (OGTT) values: low-risk group (fasting plasma glucose [FPG] 92–100 mg/dL, 1 h < 180 mg/dL, 2 h < 153 mg/dL), intermediate-risk group (FPG 101–110 mg/dL or 1 h 180–190 mg/dL or 2 h 153–163 mg/dL), and high-risk group (FPG > 110 mg/dL or 1 h > 190 mg/dL or 2 h > 163 mg/dL). Neonatal hypoglycemia was defined as the primary outcome, whereas secondary outcomes comprised insulin requirements, continuous glucose monitoring (CGM) use, macrosomia, polyhydramnios, and perinatal complications. Results: Non-significant differences across groups were observed except for Caucasian predominance in the high-risk group. Hypoglycemia trended higher in intermediate- and high-risk groups (26% and 21% vs. 17%), as well as polyhydramnios (14.3% and 13.8% vs. 4.5%) without statistical significance. Overall metabolic control was excellent, with almost 70% of patients maintaining HbA1c values ≤ 5.5% throughout the pregnancy with early and limited use of insulin therapy (17.3%). Conclusions: Diagnostic OGTT stratification provides limited prognostic value in optimized GDM care with early CGM and insulin use. Although trends for hypoglycemia and polyhydramnios suggest potential utility, the excellent metabolic control likely flattened the differences between groups. Prospective trials with CGM metrics are needed to develop more refined risk models, potentially enabling a more personalized management. Full article

Objective: To evaluate the clinical significance of a flat oral glucose tolerance test (OGTT) pattern and its association with obstetric and perinatal outcomes, focusing on fetal growth. Methods: This retrospective cohort study was conducted at a tertiary referral center between January 2023 and November 2025. A total of 1198 women who underwent a two-step OGTT between 24 and 32 weeks of gestation were screened, and 685 eligible participants were included. A flat OGTT pattern was defined as fasting glucose < 95 mg/dL with all postprandial values < 100 mg/dL. The primary outcome was small-for-gestational-age (SGA); secondary outcomes included fetal growth restriction (FGR) and other obstetric outcomes. Logistic regression analyses were performed to assess independent associations. Results: Thirty-nine women (5.7%) exhibited a flat OGTT pattern. These pregnancies were characterized by a markedly attenuated postprandial glycemic response and lower fasting glucose levels. Most maternal and neonatal outcomes were similar between groups. However, SGA was significantly more frequent in the flat OGTT group (20.5% vs. 6.7%, p = 0.001). In multivariable analysis, a flat OGTT pattern remained independently associated with SGA (aOR 4.05, 95% CI 1.70–9.68, p = 0.002). Both SGA and FGR were more frequent among women with a flat OGTT pattern, although the association appeared stronger for SGA. Conclusions: A flat OGTT pattern appears to represent a distinct glycemic response characterized by an attenuated postprandial glucose response and lower fasting glucose levels. Although this pattern was not associated with a generalized increase in adverse obstetric or neonatal outcomes, it was associated with an increased risk of small-for-gestational-age infants. Full article

Introduction: Patients with psoriasis, a non-contagious, chronic, systemic inflammatory skin disease, often suffer from carbohydrate metabolism disorders, which can exacerbate systemic inflammation. Methods: This randomized, double-blind, placebo-controlled trial (RCT) evaluated the effects of chicory-derived inulin-type fructans (ITFs) on body composition, energy expenditure, and carbohydrate metabolism in patients with mild psoriasis (PS), using a healthy control (n = 32) group as a baseline reference. PS participants (n = 56) were randomized to receive 15 g/day of ITFs (n = 29) or a placebo (n = 27) for 8 weeks. Body composition using bioelectrical impedance analysis (BIA), carbohydrate metabolism (fasting glucose, insulin, glycated hemoglobin, Oral Glucose Tolerance Test (OGTT)) and resting energy expenditure (resting metabolic rate (RMR), oxygen consumption (VO₂), carbon dioxide production (VCO₂)) via indirect calorimetry were determined. Results: At baseline, patients with PS had significantly (p < 0.01) higher body mass index and visceral fat levels, and abnormal levels of selected parameters of carbohydrate metabolism, compared with healthy controls. Following the intervention, the ITFs group maintained stable fasting glucose levels, while the placebo group showed an undesirable increase (Δ_glucose = +5.7 mg/dL; p < 0.01). The energy expenditure analysis revealed a significant treatment effect on RMR and VO₂ parameters (p < 0.01), with a decrease in the placebo group (p < 0.01) while remaining stable in the prebiotic group. There was no significant effect of the intervention on body composition and anthropometric parameters. Conclusions: Patients with PS exhibit a higher metabolic risk than healthy controls. Although no significant changes were observed within the intervention groups, the deterioration of metabolic indices in the placebo group may indicate an unfavorable effect of the maltodextrin. Consequently, the stabilization of parameters in the prebiotic group should be interpreted with great caution. This RCT was registered at ClinicalTrials.gov (NCT05971992). Full article

Background: Gestational diabetes mellitus (GDM) adversely affects offspring neurobehavioral outcomes, yet evidence regarding continuous markers of maternal glucose metabolism remains limited. Although polyunsaturated fatty acids (PUFAs) have been shown to affect associations between glucose metabolism and respiratory outcomes, their effects on children’s emotional and behavioral problems remain unclear. This study investigated the association between maternal glucose metabolism and emotional and behavioral problems in children and the potential modifying effect of maternal erythrocyte PUFAs. Methods: This prospective birth cohort included 481 mother–child pairs. Maternal glucose metabolism during pregnancy was assessed using GDM diagnosis via a 75 g oral glucose tolerance test (OGTT), fasting plasma glucose (FPG), 1 h and 2 h OGTT glucose, hemoglobin A1c (HbA1c), insulin, and insulin resistance (HOMA-IR). Maternal erythrocyte PUFAs were quantified by gas chromatography. Children’s emotional and behavioral problems at age 5 years were assessed using the Strengths and Difficulties Questionnaire (SDQ). Generalized linear models were used to evaluate associations, including multiplicative interaction terms between glucose metabolism indicators and PUFAs. Results: Maternal FPG (OR = 1.63; 95%CI: 1.08–2.47), OGTT-1h glucose (OR = 1.84; 95%CI: 1.08–3.12), and HOMA-IR (OR = 1.52; 95%CI: 1.01–2.27) were each positively associated with an increased risk of abnormal total difficulties scores in children. Maternal insulin levels were positively associated with abnormal total difficulties scores in girls (p for interaction < 0.05). Higher maternal n-3 PUFA levels and lower n-6 PUFA levels attenuated the risk of glucose metabolism-related emotional and behavioral problems in children. Conclusion: Maternal glucose metabolism was associated with increased risk of emotional and behavioral problems in children. PUFA biomarkers could modify glucose-related emotional and behavioral outcomes in children. Full article

Introduction: Hypertensive disorders in pregnancy (HDP) and gestational diabetes mellitus (GDM) represent two significant maternal cardiometabolic disorders closely related to each other. This study aims to identify predictive risk factors for gestational hypertension in patients with GDM within our population. Methods: This cohort study was conducted at the Department of Obstetrics and Gynecology, Policlinico “G. Martino” of Messina from January 2012 to December 2019. It included 684 pregnant women diagnosed with GDM by Oral Glucose Tolerance Test (OGTT) according to Italian guidelines. A detailed medical history was taken for each patient to identify potential predictive risk factors for HDP. Patients with pre-existing hypertension or diabetes were excluded. Results: Among 684 women with GDM, 69 (10.1%) developed hypertensive disorders of pregnancy (HDP). Women with HDP had a significantly higher pregestational BMI (30.1 ± 7.7 vs. 26.5 ± 5.6 kg/m², p = 0.001) and a higher prevalence of obesity (51% vs. 34%, p = 0.0001). Post-load glucose at 60 min was higher in the HDP group (178 ± 34 vs. 164 ± 32 mg/dL, p = 0.0001), with more women exceeding the diagnostic threshold (>180 mg/dL: 56% vs. 35%, p = 0.001). Multivariate analysis confirmed that pregestational obesity and higher 60-min glucose levels during OGTT were the strongest independent predictors of HDP. Conclusions: Obesity and glycemia above the cut-off after 1 h during OGTT are predictive risk factors for hypertensive disorders in patients with GDM. Full article

Background/Objectives: A 90-day randomized double-blind and placebo-controlled study was conducted to assess the effect of carob (Ceratonia siliqua L.) on glucose metabolism in subjects with confirmed prediabetes. Methods: The carob liquid concentrate containing inositols of the carob fruit (D-pinitol, myo-inositol, D-chiro inositol) was administered at a daily dose of 6.66 g, divided into two doses of 3.33 g each. Study variables included glucose- and insulin-related parameters obtained at fasting conditions and during a standard 2 h oral glucose tolerance test (OGTT) at baseline and after 45 and 90 days of administration of the study products. Results: The study population included 52 subjects (25 in the experimental group, 27 in the placebo group), 27 men and 25 women, with a mean age of 45.6 ± 13.9 years. Subjects who consumed the active product showed improvements in glycated hemoglobin (HbA1c) and glucose levels as compared with placebo (p < 0.001 of the time × group interaction). Fasting serum insulin showed within-group significant decreases in the experimental group, with insulin indexes (HOMA-IR and QUICKI) improving significantly in the experimental group only. In the OGTT, there were significant improvements in the AUC of glucose and insulin, as well as glucose peak in the experimental group only. The product was well tolerated and no adverse effects were recorded. Conclusions: The use of a specific carob-based liquid concentrate decreased HbA1c and glucose levels in subjects with prediabetes, which may suggest its potential clinical relevance in the prevention of the transition from prediabetes to overt type 2 diabetes. Full article

This study evaluated the protective effects of green coffee (Coffea arabica L.) extract (GCE) against metabolic and endocrine disturbances induced by fipronil (FIP) in male rats. Animals were randomly allocated into four groups (n = 6): control, GCE (100 mg/kg), FIP (4.85 mg/kg), and combined FIP + GCE, and treated orally for 90 days. FIP exposure significantly impaired glucose homeostasis, as indicated by a 14.8% increase in the oral glucose tolerance test (OGTT) response and a 2.4-fold increase in the homeostatic model assessment of insulin resistance (HOMA-IR). It also disrupted lipid metabolism, with marked elevations in triglycerides (74.10%) and total cholesterol (57.55%). Endocrine imbalance was evident, including increased resistin levels (113.86%) and reduced triiodothyronine (T3; −37.5%), adiponectin (−42.73%), and high-density lipoprotein (HDL; −9.31%). Oxidative stress and inflammation were significantly enhanced, as demonstrated by elevated malondialdehyde (MDA; +93.56%) and pro-inflammatory cytokines (IL-1β: +246.56%; IL-6: +275%), alongside a reduction in total antioxidant capacity (TAC; −45.24%). Additionally, serum albumin levels decreased markedly (−54%). Co-administration of GCE significantly improved metabolic, hormonal, and inflammatory parameters, including insulin resistance (HOMA-IR). Histopathological analysis further confirmed its protective effects on hepatic and renal tissues. Overall, GCE mitigates FIP-induced metabolic and endocrine dysfunction, likely through its antioxidant and anti-inflammatory properties. Full article

Background: Sex-related differences in insulin sensitivity during adolescence remain incompletely understood, particularly in the context of obesity. Whether these differences reflect variations in basal insulin resistance or dynamic insulin responses remains unclear. Objective: To investigate sex differences in glucose and insulin responses during the oral glucose tolerance test (OGTT) and to explore mechanisms underlying potential dissociation between glycemic and insulinemic profiles. Methods: A cross-sectional analysis of 753 adolescents with obesity who underwent a standard oral glucose tolerance test (OGTT). Plasma glucose and insulin were measured at fasting and at 30, 60, 90, and 120 min. Mixed-effects models were used to examine glucose and insulin trajectories over time, including sex-by-time interactions, and to adjust for body mass index standard deviation score (BMI_SDS), pubertal stage (Tanner), metabolic syndrome (MetS), and body composition (resistance index). Multiple linear regression models were fitted to assess associations of sex with HOMA-IR, HOMA-β, total area under the curve (AUC), and phase-specific insulin AUCs. Results: Glucose trajectories during OGTT were similar between sexes, with no significant sex or sex-by-time interaction effects after adjustment. In contrast, insulin trajectories differed significantly by sex (sex-by-time interaction β = −0.10, p < 0.001). Boys exhibited higher baseline insulin levels and greater total insulin exposure (β = −11.2, p < 0.001), independent of BMI_SDS, pubertal stage, MetS, and body composition. Sex differences were sustained across all OGTT phases. HOMA-IR did not differ by sex, whereas HOMA-β showed a sex-related difference. BMI was positively associated with both basal and dynamic insulin measures. Conclusions: In adolescents with obesity, sex differences are characterized by altered dynamic insulin responses rather than differences in glycemic control. Boys exhibit greater compensatory insulin exposure during glucose challenge, independent of BMI-based adiposity, BIA-derived body composition and pubertal development. Full article