Search Results (406)

Objectives: The objective of this study was to investigate the relationship between the simultaneous 75 g Oral glucose tolerance test (OGTT), gestational diabetes mellitus (GDM), and fetal pancreatic circumference at 24–28 weeks of gestation. Methods: This prospective case–control study was conducted between September 2024 and February 2025 at our perinatology clinic, which provides tertiary health care services. The correlation between the 75 g OGTT, GDM, and pancreatic circumference was assessed by comparing fetal pancreatic circumference between the groups with and without GDM at the time of diagnosis. Results: A total of 130 pregnant patients were recruited for this` study, with 64 patients forming the GDM group and 66 patients forming the control group. Fetal pancreas circumference (7.0 cm vs. 6.4 cm, p < 0.001), fetal pancreas circumference percentile (88.5 vs. 52, p < 0.001), and the rate of fetal pancreas size >90th percentile (15.6% vs. 3%, p < 0.001) were significantly higher in the GDM group compared to the control group. Conclusions: Although our findings demonstrate a statistically significant correlation between fetal pancreatic circumference and GDM, diagnostic performance remains modest. Therefore, fetal pancreatic circumference should be interpreted as a supportive marker, such as family history, rather than a definitive marker for identifying individuals at risk for GDM. Full article

Background: BDE-47, a pervasive environmental pollutant detected in >90% of human serum samples, is increasingly linked to metabolic disorders. This study investigates the specific impact of BDE-47 exposure on the gut microbiota in prediabetic mice and evaluates the efficacy of therapeutic interventions in mitigating these effects. Objectives: To determine whether BDE-47 exposure induces diabetogenic dysbiosis in prediabetic mice and to assess whether dietary interventions, such as grape exosomes and an antioxidant cocktail, can restore a healthy microbiota composition and mitigate diabetes risk. Methods: In this study, a prediabetic mouse model was established in 54 male SPF-grade C57BL/6J mice through a combination of high-sugar and high-fat diet feeding with streptozotocin injection. Oral glucose tolerance tests (OGTT) were conducted on day 7 and day 21 post-modeling to assess the establishment of the model. The criteria for successful model induction were defined as fasting blood glucose levels below 7.8 mmol/L and 2 h postprandial glucose levels between 7.8 and 11.1 mmol/L. Following confirmation of model success, a 3 × 3 factorial design was applied to allocate the experimental animals into groups based on two independent factors: BDE-47 exposure and exosome intervention. The BDE-47 exposure factor consisted of three dose levels—none, high-dose, and medium-dose—while the exosome intervention factor included three modalities—none, Antioxidant Nutrients Intervention, and Grape Exosomes Intervention. Fresh fecal samples were collected from mice two days prior to sacrifice. Cecal contents and segments of the small intestine were collected and transferred into 1.5 mL cryotubes. All sequences were clustered into operational taxonomic units (OTUs) based on defined similarity thresholds. To compare means across multiple groups, a two-way analysis of variance (ANOVA) was employed. The significance level was predefined at α = 0.05, and p-values < 0.05 were considered statistically significant. Bar charts and line graphs were generated using GraphPad Prism version 9.0 software, while statistical analyses were performed using SPSS version 20.0 software. Results: The results of 16S rDNA sequencing analysis of the microbiome showed that there was no difference in the α diversity of the intestinal microbiota in each group of mice (p > 0.05), but there was a difference in the Beta diversity (p < 0.05). At the gate level, the abundances of Proteobacteria, Campylobacterota, Desulfobacterota, and Fusobacteriota in the medium-dose BDE-7 group were higher than those in the model control group (p < 0.05). The abundance of Patellar bacteria was lower than that of the model control group (p < 0.05). The abundances of Proteobacteria and Campylobacterota in the high-dose BDE-7 group were higher than those in the model control group (p < 0.05). The abundance of Planctomycetota and Patescibacteria was lower than that of the model control group (p < 0.05), while the abundance of Campylobacterota in the grape exosome group was higher than that of the model control group (p < 0.05). The abundance of Patescibacteria was lower than that of the model control group (p < 0.05), while the abundance of Firmicutes and Fusobacteriota in the antioxidant nutrient group was higher than that of the model control group (p < 0.05). However, the abundance of Verrucomicrobiota and Patescibacteria was lower than that of the model control group (p < 0.05). At the genus level, the abundances of Bacteroides and unclassified Lachnospiraceae in the high-dose BDE-7 group were higher than those in the model control group (p < 0.05). The abundance of Lachnospiraceae NK4A136_group and Lactobacillus was lower than that of the model control group (p < 0.05). The abundance of Veillonella and Helicobacter in the medium-dose BDE-7 group was higher than that in the model control group (p < 0.05), while the abundance of Lactobacillus was lower (p < 0.05). The abundance of genera such as Lentilactobacillus and Faecalibacterium in the grape exosome group was higher than that in the model control group (p < 0.05). The abundance of Alloprevotella and Bacteroides was lower than that of the model control group (p < 0.05). In the antioxidant nutrient group, the abundance of Lachnospiraceae and Hydrogenophaga was higher than that in the model control group (p < 0.05). However, the abundance of Akkermansia and Coriobacteriaceae UCG-002 was significantly lower than that of the model control group (p < 0.05). Conclusions: BDE-47 induces diabetogenic dysbiosis in prediabetic mice, which is reversible by dietary interventions. These findings suggest that microbiota-targeted strategies may effectively mitigate the diabetes risk associated with environmental pollutant exposure. Future studies should further explore the mechanisms underlying these microbiota changes and the long-term health benefits of such interventions. Full article

Background: Type 2 diabetes (T2D) has been placed among the risk factors for fragility (osteoporotic) fractures, particularly in menopausal women amid modern clinical practice. Objective: We aimed to analyze the bone status in terms of mineral metabolism assays, blood bone turnover markers (BTM), and bone mineral density (DXA-BMD), respectively, to assess the 10-year fracture probability of major osteoporotic fractures (MOF) and hip fracture (HF) upon using conventional FRAX without/with femoral neck BMD (MOF-FN/HF-FN and MOF+FN/HF+FN) and the novel model (FRAXplus) with adjustments for T2D (MOF+T2D/HF+T2D) and lumbar spine BMD (MOF+LS/HF+LS). Methods: This retrospective, cross-sectional, pilot study, from January 2023 until January 2024, in menopausal women (aged: 50–80 years) with/without T2D (group DM/nonDM). Inclusion criteria (group DM): prior T2D under diet ± oral medication or novel T2D (OGTT diagnostic). Exclusion criteria: previous anti-osteoporotic medication, prediabetes, insulin therapy, non-T2D. Results: The cohort (N = 136; mean age: 61.36 ± 8.2y) included T2D (22.06%). Groups DM vs. non-DM were age- and years since menopause (YSM)-matched; they had a similar osteoporosis rate (16.67% vs. 23.58%) and fracture prevalence (6.66% vs. 9.43%). In T2D, body mass index (BMI) was higher (31.80 ± 5.31 vs. 26.54 ± 4.87 kg/m²; p < 0.001), while osteocalcin and CrossLaps were lower (18.09 ± 8.35 vs. 25.62 ± 12.78 ng/mL, p = 0.002; 0.39 ± 0.18 vs. 0.48 ± 0.22 ng/mL, p = 0.048), as well as 25-hydroxyvitamin D (16.96 ± 6.76 vs. 21.29 ± 9.84, p = 0.013). FN-BMD and TH-BMD were increased in T2D (p = 0.007, p = 0.002). MOF+LS/HF+LS were statistically significant lower than MOF-FN/HF-FN, respectively, MOF+FN/HF+FN (N = 136). In T2D: MOF+T2D was higher (p < 0.05) than MOF-FN, respectively, MOF+FN [median(IQR) of 3.7(2.5, 5.6) vs. 3.4(2.1, 5.8), respectively, 3.1(2.3, 4.39)], but MOF+LS was lower [2.75(1.9, 3.25)]. HF+T2D was higher (p < 0.05) than HF-FN, respectively, HF+FN [0.8(0.2, 2.4) vs. 0.5(0.2, 1.5), respectively, 0.35(0.13, 0.8)] but HF+LS was lower [0.2(0.1, 0.45)]. Conclusion: Type 2 diabetic menopausal women when compared to age- and YSM-match controls had a lower 25OHD and BTM (osteocalcin, CrossLaps), increased TH-BMD and FN-BMD (with loss of significance upon BMI adjustment). When applying novel FRAX model, LS-BMD adjustment showed lower MOF and HF as estimated by the conventional FRAX (in either subgroup or entire cohort) or as found by T2D adjustment using FRAXplus (in diabetic subgroup). To date, all four types of 10-year fracture probabilities displayed a strong correlation, but taking into consideration the presence of T2D, statistically significant higher risks than calculated by the traditional FRAX were found, hence, the current model might underestimate the condition-related fracture risk. Addressing the practical aspects of fracture risk assessment in diabetic menopausal women might improve the bone health and further offers a prompt tailored strategy to reduce the fracture risk, thus, reducing the overall disease burden. Full article

Background: The most common female endocrinopathy is polycystic ovary syndrome (PCOS), affecting 10–20% of women of reproductive age. It is associated with a wide range of hormonal and biochemical abnormalities and long-term metabolic and cardiovascular risks. It is characterized by infertility due to chronic anovulation, hyperandrogenism, polycystic ovarian morphology, and is often associated with insulin resistance (IR) and obesity. Hyperinsulinemia further increases androgen production and reduces sex hormone-binding globulin (SHBG) levels, thereby aggravating symptoms. In addition, vitamin D deficiency is often present in PCOS patients, and increasing evidence suggests that it may also be associated with insulin resistance and hyperandrogenism. Objective: This study aimed to evaluate the relationships between insulin resistance, vitamin D deficiency, body mass index (BMI), and androgen levels in women with PCOS. Method: A cross-sectional study was conducted in which data from 195 women diagnosed with PCOS and not yet receiving therapy at a gynecologic endocrinology unit of a university-based tertiary clinical center, between 2019 and 2024, were analyzed. The parameters recorded were age, body mass index (BMI), 25(OH) vitamin D levels, androgen hormone levels (testosterone, androstenedione), glucose-insulin responses during a 3-point oral glucose tolerance test (OGTT). Statistical analyses, including linear regression, Pearson, and Spearman correlation tests were used to assess associations between variables. Results: The mean age of the patients was 24.8 years (18–42), and the mean BMI was 30.6 kg/m² (17–51). Vitamin D deficiency was observed in 84.1% of patients, hyperandrogenism in 45.8%, and insulin resistance in 44.5%. A significant inverse correlation was found between BMI and vitamin D levels (r = −0.31, p =< 0.01) indicating that higher BMI is associated with lower vitamin D status. Similarly, BMI also showed a significant negative correlation with SHBG levels (r = –0.45, p < 0.01), suggesting that increasing body weight is linked to reduced SHBG concentrations. In addition, BMI was significantly positively correlated with 2 h insulin levels (r = 0.43, p =< 0.01) and with testosterone levels (r = 0.21, p = 0.01). These findings suggest that increased adiposity intensifies insulin resistance and is linked to both vitamin D deficiency and elevated androgen levels. Moreover, the combination of hyperinsulinemia and low vitamin D further disrupts hormonal balance by promoting ovarian androgen production and decreasing SHBG levels, thereby increasing the bioavailability of testosterone. A significant inverse correlation was found between vitamin D levels and 2 h insulin levels (r = −0.28, p =< 0.01), indicating that lower vitamin D status is associated with increased insulin resistance. Furthermore, 2 h insulin levels showed a significant positive correlation with testosterone levels (r = 0.32, p =< 0.01), suggesting that greater insulin resistance is linked to higher androgen production. Additionally, vitamin D levels were inversely correlated with testosterone (r = −0.18, p = 0.02), demonstrating that a lower vitamin D status may further contribute to the hyperandrogenic environment. Vitamin D levels also showed a significant positive correlation with SHBG concentrations (r = 0.29, p < 0.01), indicating that a higher vitamin D status may be associated with increased SHBG levels. In contrast, 2 h insulin levels were inversely correlated with SHBG (r = −0.43, p < 0.01), reflecting the suppressive effect of hyperinsulinemia on SHBG production. Conclusions: Insulin resistance, BMI, and vitamin D deficiency are closely related to each other and to the severity of PCOS, which is confirmed by the correlations with androgen levels. The revealed relationships draw attention to the special importance of vitamin D supplementation and the correction of carbohydrate metabolism in alleviating the symptoms of the disease and reducing long-term health risks. Full article

Background/Objectives: Gestational diabetes mellitus (GDM) represents an increased metabolic risk in future life for both mother and child. We hypothesize free fatty acids (FFAs) and amino acids (AAs) disturbances in plasma during second trimester might be indicating high risk of persisting glucose intolerance (PGI). The aim of study was to determine plasma FFAs and AAs during pregnancy in women with normal pregnancy and GDM and also in post-GDM women with PGI after delivery and to find potential association of altered FFAs and AAs profile with adverse peripartal outcomes and PGI after GDM. Material and Methods: A total of 54 pregnant women were included in the study. Of those 34 participants had GDM. PGI was diagnosed by oGTT up to one year after delivery. Plasma FFAs were determined using GC-FID and plasma AAs levels were determined using CE-MS method. Results: Decreased levels of tetradecanoic acid and several AAs were found in GDM group during pregnancy. Oleic and docosahexaenoic acid correlated positively while almost all AAs negatively correlated with oGTT values in the pregnancy (all p < 0.05, Spearman). Logistic regression model (using AAs, FFAs and BMI) identified higher citrulline and glutamate levels and lower tetradecenoic acid and choline as the best predictors for postpartum PGI. Some differences in AA levels were detected in women with macrosomic babies. Conclusions: Data support a possible link between GDM development and PGI after delivery and selected metabolite levels. The predictive potential of plasma FFAs and AAs levels on a diabetes risk in future life requires further validation. Full article

Background/Objectives: Hepatic steatosis, characterized by abnormal fat accumulation in the liver, is a major health concern with limited effective treatments. Goat milk whey proteins have demonstrated various therapeutic benefits. This study aimed to evaluate the hepatoprotective effects of goat whey protein hydrolysate (GWPH) on high-fructose corn syrup (HFCS)-induced hepatic steatosis in a murine model. Methods: The GWPH was prepared through enzymatic hydrolysis using Alcalase^® and divided into fractions: GWPH03 (<3 kDa), GWPH0310 (3–10 kDa), GWPH1030 (10–30 kDa), and GWPH30 (>30 kDa). These fractions were administered to respective GWPH treatment groups at 200 mg/kg b.w/day via intragastric gavage for 8 weeks, with HFCS provided to all groups except the Naïve group. After dietary intervention, an oral glucose tolerance test (OGTT) was performed, and the mice were then sacrificed for further analysis. Results: Our results demonstrate that GWPH mitigates HFCS-induced hepatic steatosis, reduces body weight gain, improves glucose homeostasis, alleviates liver injury, and regulates hepatic lipid metabolism. Notably, GWPH treatment significantly suppressed hepatic fatty acid synthase (FASN) expressions, indicating reduced de novo lipogenesis (DNL). Molecular docking of the identified peptides from GWPH—particularly PFNVYNVV, which showed strong binding affinity for KHK—suggests that it has potential as a competitive inhibitor of fructose metabolism. Conclusions: Collectively, our findings suggest that GWPH and its derived peptides could be promising candidates for managing hepatic steatosis and related metabolic abnormalities. Full article

Obesity is a global health concern that elevates the risk of noncommunicable diseases (NCDs) such as type 2 diabetes, cardiovascular disease, and certain cancers. Phaseolus vulgaris (white bean) contains α-amylase inhibitors (αAIs) that can reduce carbohydrate digestion and absorption, potentially mitigating obesity and metabolic syndrome. This study investigated the impact of P. vulgaris extract (PVE) on obese rats. Male Wistar rats were fed either a standard diet (SD) or a cafeteria diet (CAF) for 17 weeks to induce obesity. Subsequently, rats in each dietary group were randomly assigned to receive a vehicle, low-dose PVE (200 mg/kg), high-dose PVE (300 mg/kg), or metformin (200 mg/kg) via an oral gavage for 6 weeks. The CAF group exhibited significantly greater weight gain compared to the SD group. In the CAF group, a low dose of PVE lowered postprandial glycemia during an oral glucose tolerance test (OGTT) at 60 and 120 min and decreased food and energy intake during weeks 17–20 and 18–19, respectively. In the SD group, a high dose of PVE reduced glycemia at 90 min in the OGTT, as well as body weight gain, food intake, and energy intake during week 17. However, the overall areas under the glucose curves in the OGTT were not significantly different across treatment groups (p > 0.05), and while individual time points showed changes, the overall glucose exposure (AUC) was not significantly altered. In conclusion, the αAIs present in P. vulgaris demonstrate the potential to reduce body weight, weight gain, glycemia, total cholesterol, and triglycerides in vivo, but in the CAF group, neither PVE dose significantly altered the TC or TG. This study provides strong support for further exploring Phaseolus vulgaris extract as a valuable functional ingredient in the food industry, particularly for developing products that aid in weight management and glycemic control. Full article

Background: Two changes to gestational diabetes mellitus (GDM) testing were implemented in the Australian Capital Territory in 2015 and 2017. Aims: We aimed to determine the associations between testing regimes and the prevalence of GDM and large-for-gestational-age (LGA) and small-for-gestational-age (SGA) infants and to compare the prevalence of LGA and SGA infants between women with and without GDM in each testing period. Methods: A total of 23,790 singleton live births with estimated GDM testing and birth dates between June 2012 and December 2019 were stratified into groups: pre-testing changes (June 2012–December 2014, group 1, n = 8069), revised diagnostic criteria (January 2015–May 2017, group 2, n = 8035) and changed pathology centrifugation protocol (June 2017-December 2019, group 3, n = 7686). Women were allocated to groups based on their estimated GDM testing date and stratified by their GDM status. A chi-square test, pairwise z-tests and logistic regression tested the associations. Results: The GDM prevalence significantly increased from 9.5% (group 1) to 19.4% (group 2) to 26.3% (group 3) (all: p < 0.001). The LGA infant prevalence significantly decreased in non-GDM women following revised diagnostic criteria implementation (11.6% vs. 9.7%, p = 0.001). Compared to group 1, women with GDM in groups 2 and 3 had significantly reduced odds of having LGA infants (aOR = 0.73, 95% CI of 0.56–0.95 and p = 0.021 and aOR = 0.75, 95% CI of 0.59–0.97 and p = 0.029, respectively). Compared to group 1, non-GDM women in groups 2 and 3 had significantly reduced odds of having LGA infants (aOR = 0.83, 95% CI of 0.74–0.92 and p < 0.001 and aOR = 0.88, 95% CI of 0.79–0.99 and p = 0.026, respectively). There were no significant associations for group 3 compared to group 2 nor for SGA infants. Conclusions: While significantly increasing the GDM prevalence, implementing the testing changes was associated with a reduced whole-population LGA infant prevalence without a change in the SGA infant prevalence. Full article

Polycystic ovary syndrome (PCOS) is a complex endocrine disease. This study investigates the relationship between endothelial function, insulin resistance, and hormonal profiles in women with PCOS. Forty women with PCOS were included: metformin (n = 20), GLP1-RAs (n = 10), and oral contraceptive pills (n = 10). A 75 g oral glucose tolerance test (OGTT) was performed, and the 0, 60, and 120 min insulin, glucose, and endothelial functions were evaluated. The postprandial and fasting state Matsuda Index and HOMA Index were measured. All measurements were performed at baseline and at a 6-month follow-up. At baseline, the percentage change in the Perfused Boundary Region (PBR) was associated with the percentage change in glucose at 120 min of the OGTT (r = 0.42, p < 0.05). The Matsuda Index, Homa Index, and testosterone levels were associated with the PBR (2.91 ± 0.1 μm) at 120 min of the OGTT (r = 0.41, r = 0.38 and r = 0.28, respectively). MMP9 levels were associated with the Matsuda and Homa Index (r = 0.45, p < 0.05 and r = 0.41, p < 0.05, respectively). At the 6-month follow-up, all the participants presented improvements of the Matsuda Index (7 ± 0.31 vs. 9.1 ± 0.2), Homa Index (5.3 ± 0.8 vs. 2.91 ± 0.1), MMP9 (210 ± 30 vs. 178 ± 28 ng/mL), and testosterone levels (44.2 ± 5 vs. 39.1 ± 2 ng/dL) compared to the baseline (p < 0.05 for all the comparisons). Patients who received GLP1-RA agonists presented the greatest improvement in MMP9 levels. Postprandial hyperglycemia, insulin resistance, and testosterone levels are associated with an impaired glycocalyx thickness in women with PCOS. Full article

Background/Objectives: Previous studies have shown that unformulated extracts of Passiflora ligularis leaves exhibit promising antidiabetic activity. This research aimed to demonstrate that formulating the extract into a self-emulsifying drug delivery system (PLE-SEDDS) enhanced its antidiabetic activity in a high-fat-diet/streptozotocin-induced diabetic mouse model. Methods: Blood glucose levels (BGLs) of diabetic mice were monitored during 21 days of oral administration of P. ligularis extract (PLE) and PLE-SEDDS. Control groups included metformin (positive control), vehicle, and SEDDS vehicle (negative controls). The animals underwent an oral glucose tolerance test (OGTT). The oxidative stress markers superoxide dismutase (SOD), catalase (CAT), and lipid peroxidation quantified by malondialdehyde (MDA) levels were measured in the kidney, liver, and pancreas, complemented with histopathological analysis. Additionally, plasma lipid profile parameters were evaluated. Results: The PLE-SEDDS formulation demonstrated superior efficacy compared to the PLE extract in improving antidiabetic outcomes. Animals treated with PLE-SEDDS exhibited a minimal increase in blood glucose levels (11.5%) during the OGTT, compared to 27.4% with PLE and over 77% in the vehicle groups. PLE-SEDDS also showed greater enhancement of SOD and CAT activity, along with a more pronounced reduction in MDA levels, indicating stronger protection against oxidative stress. Histological analysis revealed significant preservation of pancreatic islets, and lipid profile analysis showed greater reductions in triglycerides, cholesterol, and LDL-C, alongside increased HDL-C levels. Conclusions: Altogether, these findings suggest that PLE-SEDDS exhibits superior antihyperglycemic, hypolipidemic, and antioxidant effects compared to the unformulated extract, making this novel formulation a promising option for treating type 2 diabetes mellitus. Full article

Type 2 diabetes mellitus remains a critical global health challenge, driving the pursuit of novel therapeutic strategies. This study investigated the anti-diabetic efficacy of the peptide 1CBR, derived from sodium caseinate hydrolysate, administered orally at 25 mg/kg/day to db/db mice over a 4-week period. Glucose tolerance was evaluated via oral glucose tolerance tests (OGTT), while plasma dipeptidyl peptidase-IV (DPP-IV) activity, glucagon-like peptide-1 (GLP-1), and insulin concentrations were quantified using enzyme-linked immunosorbent assays (ELISA). Two bioactive peptides, GPFPLPD and APDSGNFR, were isolated and characterized, exhibiting half-maximal inhibitory concentrations (IC₅₀) of 99.12 µM and 73.07 µM for DPP-IV inhibition, respectively, and both significantly stimulated GLP-1 secretion in enteroendocrine cells in vitro. Pharmacokinetic analysis in Sprague–Dawley rats demonstrated oral bioavailability of 11.28% and 19.12% for these peptides, surpassing typical expectations for peptide-based agents. Collectively, these results provide compelling evidence that 1CBR-derived peptides exert glucose-lowering effects through the dual mechanisms of DPP-IV inhibition and GLP-1 stimulation, combined with favorable oral absorption profiles. These findings underscore the potential of 1CBR peptides as promising candidates for development into nutraceuticals or pharmaceutical agents for diabetes management. Full article

Background: An univocal definition for a lack of glucose peak during the oral glucose tolerance test in pregnancy (flat curve) has never been agreed upon. Thus, the aim of this study was to provide a definition for the flat 75 g oral glucose tolerance test (OGTT) and to assess its clinical significance. Methods: A retrospective cohort study, where 8.810 pregnant singleton women were evaluated at the time of a 75 g OGTT between 24⁰ and 28⁶ weeks for the universal screening of gestational diabetes (GDM). The 75 g OGTT was considered flat when the difference between peak and fasting glucose concentrations was ≤30 mg/dL. A total of 953 (10.8%) women were diagnosed as having GDM, while 7.857 (89.2%) had normal glucose tolerance (NGT); 2791 women with normal glucose tolerance (35.5%) had a FLAT curve and 5066 (64.5%) had a concentration difference > 30 mg/dL (NGT). In all groups, we evaluated maternal characteristics and perinatal outcome. Results: Women with a FLAT curve were younger, taller, thinner, and their pre-pregnancy body mass index was lower than the other groups (all p < 0.001). The rate of obesity was also lower (p < 0.01). The vaginal delivery rate was higher than in NGT (80.4% vs. 77.8%; p < 0.01) and women with GDM (73.0%; p < 0.001) and that of primary cesarean lower than in NGT (11.9% vs. 14.8%; p < 0.001) and women with GDM (18.2%; p < 0.001). Between women with a FLAT and NGT OGTT curve, there was no significant difference for birthweight < 10th percentile (6.9% vs. 6.2%; p = 0.2), though the proportion of birthweight > 90th was lower (8% vs. 10%; p < 0.01). Conclusions: A 75 g flat OGTT as defined does not represent an abnormal maternal phenotype nor portend an adverse perinatal outcome. Full article

Background: Camel milk is considered to be an important source of bioactive peptides with potential anti-diabetic effects. However, the mechanism by which these active peptides exert their anti-diabetic effects is not clear. The aim of this study was to systematically evaluate the in vivo anti-diabetic effects of Leucine-Leucine-Proline-Lysine (LLPK), a novel dipeptidyl peptidase-4 (DPP-4) inhibitory peptide identified from the in vitro gastrointestinal digestion product of camel milk. Methods: A db/db diabetic mouse model was used, and LLPK was administered to mice at doses of 50 mg/kg BW and 100 mg/kg BW as a daily oral gavage for 30 days. The effects of LLPK on fasting blood glucose (FBG), oral glucose tolerance test (OGTT), insulin tolerance test (ITT), and serum lipid levels were monitored, and possible mechanisms of action were elucidated using proteomics. Results: The results demonstrated that LLPK significantly improved diabetic symptoms, including FBG, OGTT, ITT, and serum lipid levels in db/db diabetic mice. Furthermore, significantly increased levels of serum glucagon-like peptide 1 (GLP-1) and reduced serum DPP-4 activity were observed in the LLPK-treated group compared to the control group. Hepatic proteomics indicated that LLPK improved glucose and lipid metabolism via the PPAR signaling pathway, where the key targets were Scd1, Acox1, Acaa1b, Slc27a1, Acsl1, and Ehhadh. Conclusions: In summary, this study provided new insights into the anti-diabetic mechanisms of camel milk and supported the development of camel milk-based anti-diabetic functional foods or nutraceuticals. Full article

Metabolic syndrome (MetS) poses considerable toxicological risks due to its association with an increased likelihood of metabolic dysfunction-associated steatotic liver disease (MASLD), and is characterized by hypertension, hyperglycemia, dyslipidemia, and obesity. This study aimed to investigate the therapeutic potential of flavonoid-rich lotus seedpod extract (LSE) in alleviating MetS and MASLD-related hepatic disturbances. In vivo, mice subjected to a high-fat diet (HFD) and streptozotocin (STZ) injection were supplemented with LSE or simvastatin for 6 weeks. Obesity indicators included body weight and epididymal fat, while insulin resistance was measured by fasting serum glucose, serum insulin, homeostasis model assessment–insulin resistance index (HOMA-IR), and oral glucose tolerance (OGTT). Also, the levels of serum lipid profiles and blood pressure were evaluated. Adipokines, proinflammatory cytokines, liver fat droplets, and peri-portal fibrosis were analyzed to clarify the mechanism of MetS. LSE significantly reduced the HFD/STZ-induced MetS markers better than simvastatin, as demonstrated by hypoglycemic, hypolipidemic, antioxidant, and anti-inflammatory effects. In vitro, LSE improved oleic acid (OA)-triggered phenotypes of MASLD in hepatocyte HepG2 cells by reducing lipid accumulation and enhancing cell viability. This effect might be mediated through proteins involved in lipogenesis that are downregulated by adenosine monophosphate-activated protein kinase (AMPK). In addition, LSE reduced reactive oxygen species (ROS) generation and glycogen levels, as demonstrated by enhancing insulin signaling involving reducing insulin receptor substrate-1 (IRS-1) Ser307 phosphorylation and increasing glycogen synthase kinase 3 beta (GSK3β) and protein kinase B (PKB) expression. These benefits were dependent on AMPK activation, as confirmed by the AMPK inhibitor compound C. These results indicate that LSE exhibits protective effects against MetS-caused toxicological disturbances in hepatic carbohydrate and lipid metabolism, potentially contributing to its efficacy in preventing MASLD or MetS. Full article

Aim: Insulin resistance (IR) and hyperglycemia have been associated with increased risk of heart failure (HF) in patients with and without diabetes. Global longitudinel strain (GLS) has been shown to be superior in the detection of left ventricular (LV) systolic dysfunction when compared to ejection fraction (EF). In this study, we aimed to assess GLS in relation to IR and pre-diabetes. Method: All participants underwent an echocardiography to assess LV systolic function using GLS. IR was evaluated using homeostatic model assessment for IR (HOMA-IR), and the participants were divided into tertiles based on their HOMA-IR values. An oral glucose tolerance test (OGTT) was performed to divide participants into normal glucose tolerance (NGT) and pre-diabetes. A multivariable linear regression model was used to assess GLS in relation to IR and glycemic groups. Results: In total, 359 men without significant coronary artery disease (CAD) and without diabetes were enrolled. Participants in the higher HOMA-IR tertile had significantly reduced GLS when compared with participants in the lower HOMA-IR tertile (−17.9% vs. −18.7%, p < 0.01). A significant trend was observed towards reduced GLS with increasing HOMA-IR tertile (p-trend 0.005). However, in the multivariable regression model, only waist-to-height-ratio (WH) (β 7.1 [95% CI 3.1–11.1, p = 0.001) remained significantly associated with GLS, whereas HOMA-IR tertile and pre-diabetes were not. Conclusions: In asymptomatic elderly men with no diabetes or CAD, neither IR nor pre-diabetes was associated with GLS in the adjusted regression model. Increased WH seems to be associated with reduced systolic function by GLS measurement. Full article