Polyendocrine metabolic ovarian syndrome (PMOS) (formerly known as polycystic ovary syndrome) is a metabolic-endocrine disorder that affects 8-13% of women globally and is associated with increased cardiovascular disease (CVD) across the lifespan. CVD develops in young women due to risk factors such as atherogenic dyslipidaemia, insulin resistance and elevated body weight. High-risk overweight-obese young women with PMOS often present with subclinical CVD including atherosclerotic CVD and cardiac hypertrophy. Metformin is prescribed as standard of care to treat insulin resistance and prevent development of diabetes; however, current guidelines and treatments inadequately address atherogenic dyslipidaemia and premature subclinical CVD, particularly in young women with PMOS. The aim of this trial is to evaluate the efficacy of fish oil as an adjunct therapy to standard-of-care metformin treatment in reducing plasma triglycerides and apoB-lipoproteins, thereby preventing the progression of premature atherosclerosis and cardiac remodelling-dysfunction in young high-risk women with PMOS.

Despite increasing evidence supporting the promising anti-diabetic potential of natural polysaccharides, studies on structurally well-defined polysaccharides and their systemic mechanisms of action in type 2 diabetes mellitus (T2DM) remain limited. Here, we characterize GFP-Z, a bioactive α-glucan (1760.0 kDa) isolated from Grifola frondosa, which features an α-1,4-linked backbone with α-1,6, α-1,3 and α-1,2 branches. Pharmacological evaluation in db/db mice showed that GFP-Z administration significantly alleviated hyperglycemia and diabetic symptoms, with glucose-lowering effects comparable to metformin under the tested conditions, without causing apparent hepatorenal toxicity. Integrated multi-omics analyses, biochemical assays, and a preliminary pharmacological attenuation experiment further suggest that GFP-Z may exert its effects, at least in part, through immunomodulation-associated metabolic regulation, as reflected by reduced hepatic M1-type macrophage infiltration, altered circulating cytokines and hepatic immunometabolites, activation of the hepatic JAK/STAT-PI3K/AKT signaling axis, and attenuation of GFP-Z-associated immune and glucose-lowering responses by tofacitinib. Taken together, our findings suggest that GFP-Z may represent a promising bioactive polysaccharide capable of improving metabolic disorders in T2DM, potentially through systemic immunomodulation-associated metabolic regulation.

A ZnO/CuO@amoxicillin nanocomposite was synthesized via a sol-gel route and characterized as a biphasic wurtzite ZnO-monoclinic CuO system with crystallite sizes of about 10-12 nm and an optical band gap of 3.30-3.36 eV, indicating defect-rich interfaces favorable for redox activity. In antidiabetic assays, the nanocomposite showed strong inhibitory effects on alpha-amylase (IC50 = 21.57 ± 1.68 mg/mL) and alpha-glucosidase (IC50 = 13.95 ± 0.76 mg/mL), with activities comparable to acarbose, while anti-inflammatory tests yielded low IC50 values of 0.22 ± 0.03 mg/mL for egg albumin denaturation and 0.34 ± 0.07 mg/mL for human serum albumin, approaching the performance of diclofenac. Antioxidant performance was outstanding, with total antioxidant capacity of 298.27 ± 4.70 mg ascorbic acid equivalents per gram and ferric reducing antioxidant power of 311.67 ± 2.53 mM Fe[2] [+]/g, both higher than ascorbic acid, alongside efficient hydrogen peroxide scavenging (IC50 = 0.16 ± 0.04 mg/mL) and protection against H2O2/FeCl3-induced hemolysis at an IC50 of 0.007 ± 0.00 mg/mL; together with moderate but significant acetylcholinesterase inhibition (IC50 = 33.16 ± 3.02 mg/mL vs. 21.80 ± 2.74 mg/mL for donepezil), these results support ZnO/CuO@amoxicillin as a multifunctional nano-platform for managing oxidative stress, inflammation, and metabolic disorders.

Autoimmune type 1 diabetes mellitus (T1DM) has traditionally been associated with early onset disease and a lean phenotype; however, adult-onset disease increasingly presents with heterogeneous features that overlap with type 2 diabetes. We describe a 51-year-old obese man presenting with severe diabetic ketoacidosis (DKA). Laboratory evaluation demonstrated marked hyperglycemia (1297 mg/dL), metabolic acidosis (bicarbonate 7 mmol/L, anion gap 42), β-hydroxybutyrate >9 mmol/L, and hemoglobin A1c 13.3%. Autoimmune testing revealed strong glutamic acid decarboxylase antibody positivity with very low C-peptide, confirming profound insulin deficiency despite obesity. The patient improved with standard DKA management and was discharged on basal bolus insulin therapy. This case highlights the evolving phenotype of adult-onset autoimmune diabetes and emphasizes that obesity does not exclude T1DM. Early recognition using antibody testing and assessment of endogenous insulin secretion is essential to guide therapy and reduce recurrent metabolic decompensation.

Integrative genetic approaches can combine Mendelian randomization, variant annotation, pathway-level interpretation, and exploratory cellular measurements to investigate complex disease mechanisms. However, the relationship between genetic liability to insulin medication use and osteoarthritis (OA) remains incompletely characterized GWAS summary statistics for insulin medication use were obtained from the UK Biobank insulin medication-use dataset. Insulin therapy-associated SNPs were selected using a suggestive significance threshold (p < 5 × 10-6) and clumped (r2 < 0.001, 10,000 kb). Two-sample Mendelian randomization (MR) was performed using the inverse-variance weighted (IVW) method as the primary analysis, supplemented by MR-Egger, weighted median, simple mode, and weighted mode methods. Sensitivity analyses included Cochran's Q test, MR-Egger intercept, MR-PRESSO global test, and leave-one-out analysis. Insulin-associated genetic variants were functionally annotated using Ensembl VEP, ANNOVAR, FUMA, and Open Targets Genetics, and mapped genes were subjected to exploratory GO biological process and KEGG pathway enrichment analysis. A separate exploratory cellular experiment was performed in the immortalized human chondrocyte cell line TC28a2 using insulin treatment followed by Safranin O staining, RT-qPCR, western blotting, and ELISA. After SNP selection and harmonization, 56 instrument-outcome associations were retained, comprising 29 SNPs in the ukb-a-106 OA dataset and 27 SNPs in the ukb-b-14,486 OA dataset. IVW analysis suggested an association between genetic liability to insulin medication use and increased OA susceptibility (ukb-a-106: OR = 1.195, 95% CI = 1.062-1.344, p = 0.003; ukb-b-14,486: OR = 1.179, 95% CI = 1.066-1.305, p = 0.001). Sensitivity tests did not detect statistically significant heterogeneity or directional horizontal pleiotropy; however, indication-related genetic liability, correlated pleiotropy, and biologically plausible alternative pathways remain important concerns. Seven mapped genes were used for exploratory enrichment analysis. In a separate exploratory cellular experiment, insulin-treated TC28a2 cells under high-glucose conditions showed reduced proteoglycan staining, increased matrix-degrading and inflammatory markers, and reduced NRF2 protein expression. This study suggests an association between genetic liability to insulin medication use and OA susceptibility and provides exploratory functional-annotation and cellular observations for further investigation.

Hyperinsulinism-hyperammonemia (HI/HA) syndrome is a rare metabolic disorder caused by mutations in GLUD1, which encodes the mitochondrial enzyme glutamate dehydrogenase (GDH). This condition is characterized by recurrent hypoglycemia, elevated plasma ammonia, and potential neurological complications. We report the case of a 12-month-old male who presented with episodic hypoglycemia, hyperammonemia, and seizures. Family history was notable for childhood-onset hypoglycemia and seizures in the patient's mother and sister. The patient's laboratory findings during hospitalization were significant for markedly elevated C-peptide level of 4.9 ng/mL (SI: 1.63 nmol/L) (reference range; 1.1-4.4 ng/mL [SI: 0.36-1.46 nmol/L]). Insulin was inappropriately detectable at 20.2 µIU/mL (SI: 124.92 pmol/L) during hypoglycemia (reference range; 4.00-30.00 µIU/mL [SI: 24.0-180.0 pmol/L]). Genetic testing identified c.1491A>G (p.Ile497Met) in GLUD1. Following initiation of diazoxide therapy, he experienced symptomatic improvement with a marked reduction in hypoglycemic episodes. This case expands the literature on autosomal dominant HI/HA syndrome associated with an inherited GLUD1 p.Ile497Met mutation.

Dysphania ambrosioides L. (Amaranthaceae) is a medicinal plant widely used in traditional Moroccan medicine for the management of diabetes-related disorders. This study investigated the antidiabetic, antioxidant, and antibacterial activities of its hydroethanolic extract. Antidiabetic potential was evaluated through pancreatic α-amylase inhibition (in vitro and in vivo) and intestinal glucose absorption (in situ). Antioxidant and antibacterial activities were assessed using standard chemical assays and selected bacterial strains. The extract showed significant inhibition of pancreatic α-amylase in vitro (IC50 = 1.22 ± 0.18 mg/mL). In vivo, it markedly reduced starch-induced hyperglycemia in both normal and alloxan-induced diabetic rats (p < 0.001) and decreased intestinal glucose absorption in situ (p < 0.05). It also exhibited broad-spectrum antibacterial activity against Bacillus cereus, Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli, with MIC values ranging from 0.07 to 0.625 mg/mL and MBC values from 0.312 to 1.25 mg/mL. Moderate antioxidant activity was observed using the ABTS assay (IC50 = 293.98 ± 3.11 mg/mL), along with a high total antioxidant capacity. These results demonstrate that Dysphania ambrosioides exerts antidiabetic effects through inhibition of carbohydrate digestion and glucose absorption, alongside antioxidant and antibacterial activities. This study provides scientific evidence supporting its traditional use and highlights its potential as a natural source of bioactive compounds.

Hemoglobin A1c (HbA1c) remains a cornerstone of glycemic assessment in diabetes mellitus care, yet discordance between HbA1c and measured glucose values is common in clinical practice. Failure to recognize this discordance can lead to inappropriate treatment escalation, increased hypoglycemia risk, and patient distress. This article reviews the biological and clinical factors that contribute to HbA1c-glucose discordance and translates these findings into practical strategies for routine care. Common causes include iron deficiency, chronic kidney disease, altered red blood cell turnover, hemoglobin variants, and rapid changes in glycemia. A stepwise, practice-oriented framework is presented to guide clinicians in evaluating discordant glycemic data using targeted laboratory testing and continuous glucose monitoring metrics. Emphasis is placed on avoiding reflexive medication intensification and using glucose monitoring data to individualize treatment decisions. The role of interdisciplinary care and patient-centered communication is also highlighted.

To our knowledge, this is the first case reported in literature, regarding an increase in tumoral biomarkers during a treatment with Semaglutide. A 61-year-old patient was referred to our gynecological consultation due to suspected adnexal cysts following an MRI performed for a functional defecation disorder. The patient was on Semaglutide treatment. Gynecological examination and transvaginal ultrasound were normal, with no evidence of adnexal cysts. Tumor biomarker testing revealed a significant increase in CA 19-9 and a mild elevation in CA-125. In an asymptomatic patient, these findings raised suspicion of a possible neoplastic origin involving the pancreas or biliary tract. However, all further investigations yielded normal results. At a follow-up laboratory check one month later, CA 19-9 levels had decreased from 717 to 62 kU/L. A subsequent evaluation two months later confirmed the normalization of tumor biomarkers. Despite the elevation of CA19-9 during pancreatitis, which could be induced by Semaglutide, it is important to recognize that not all patients will experience this side effect. Moreover, an increase in tumor biomarkers can occur even in the absence of a clinically detectable disease, such as pancreatitis or cancer. Further research is needed to explore the potential relationship between Semaglutide and elevated CA 19-9 or CA-125 levels.