Endocrine Regulations Feed

Correlation of triglyceride-glucose index, complement C5, and lipoprotein(a) with carotid intima-media thickness in thyroid dysfunction: A cross-sectional study

Tue, 24 Mar 2026 00:00:00 GMT

Objective. Thyroid dysfunction is associated with metabolic disturbances and an increased risk of atherosclerosis. This cross-sectional study investigated the relationships between the triglyceride-glucose index (TyG index), complement C5, lipoprotein(a) (Lp(a)), and carotid intima-media thickness (cIMT). Methods. Clinical data were collected, blood samples analyzed, and cIMT measured using high-resolution ultrasound in 54 participants with thyroid dysfunction (27 with hypothyroidism and 27 with hyperthyroidism). Results. The study found a significant positive correlation between the TyG index and cIMT in both hypothyroid and hyperthyroid patients. Complement C5 levels were also positively correlated with cIMT. No significant association was found between Lp(a) and cIMT. Discussion. These findings highlight the complex interplay between thyroid dysfunction, metabolic dysregulation, and vascular health emphasizing the need for comprehensive cardiovascular risk assessment and management in patients with thyroid disorders.

ERN1-dependent regulation of BAG cochaperone 1 expression and the sensitivity to glutamine deprivation in U87MG glioblastoma cells

Tue, 24 Mar 2026 00:00:00 GMT

Objective. The BAG cochaperone 1 (BAG1) binds to oncogene BCL2 and markedly enhances its anti-apoptotic effects. This cochaperone represents a link between growth factor receptors and anti-apoptotic mechanisms mediated by endoplasmic reticulum stress. BAG1 interacts with the glucocorticoid receptor and modulates its transcription activity. As a cochaperone for several HSP70 proteins, it participates in control of protein folding. The present study aims to investigate the regulation of the BAG1 mRNA expression in U87MG glioblastoma cells by hypoxia and glucose or glutamine deprivation, depending on the inhibition of ERN1 (endoplasmic reticulum to nucleus signaling 1) with the intent to reveal the role of ERN1 signaling in the regulation of this gene expression and function in oncogenesis. Methods. The U87MG glioblastoma cells (transfected by an empty vector; control) and cells with inhibited ERN1 endoribonuclease and protein kinase (dnERN1) or only ERN1 endoribonuclease (dnrERN1) were used. Silencing of ERN1 and XBP1 mRNAs for suppression of ERN1 function was also used. A hypoxic condition was created by dimethyloxalylglycine (4 h). DMEM medium without glucose or glutamine was used for glucose and glutamine deprivation (16 h). The expression level of the BAG1 mRNA was studied by real-time qPCR and normalized to the beta-actin mRNA. Results. Inhibition of the endoribonuclease activity of ERN1 significantly decreased BAG1 mRNA expression. However, a lesser suppression of this mRNA expression was observed in dnERN1 cells (with inhibited ERN1 endoribonuclease and protein kinase) indicating the involvement of protein kinase in controlling BAG1 expression. The silencing of ERN1 and XBP1 mRNAs also reduced the expression of BAG1 mRNA demonstrating the involvement of XBP1s in this regulation. The expression of the BAG1 gene was resistant to glutamine deprivation and upregulated in response to glucose deprivation in control glioblastoma cells. However, the inhibition of ERN1 increased the sensitivity of BAG1 gene expression to both glucose and glutamine deprivation. Furthermore, the expression of the BAG1 gene was increased under hypoxia in control U87MG cells; however, a greater induction was observed in dnERN1 cells. Conclusion. The results of this study demonstrated that ERN1 inhibition reduces BAG1 mRNA expression through the endoribonuclease activity of ERN1 and that protein kinase activity counteracts endoribonuclease in regulating the expression of BAG1 mRNA. Moreover, ERN1 inhibition also enhances the sensitivity of BAG1 mRNA expression to nutrient supply and hypoxia resulting in reduced resistance of glioblastoma cells.

Modulation of appetite- and metabolism-regulating hormones after bariatric embolization, sleeve gastrectomy, and gastric plication

Tue, 24 Mar 2026 00:00:00 GMT

Objective. The obesity is associated with profound disturbances in appetite-regulating and metabolic hormones including ghrelin, leptin, adiponectin, resistin, and insulin. Bariatric arterial embolization (BEA) has recently emerged as a minimally invasive alternative to established bariatric procedures. However, comparative endocrine evidence remains limited. The aim of the study was to assess postoperative changes in key metabolic and appetite-regulating hormones following laparoscopic sleeve gastrectomy (LSG), laparoscopic gastric plication (LGP), and bariatric embolization of the gastric arteries (BEA). Methods. A total of 76 patients with obesity (BMI >35 kg/m²) were assigned to LSG (n=32), LGP (n=37), or BEA (n=7). Serum concentrations of total ghrelin, leptin, adiponectin, resistin, insulin, and HbA1c were measured preoperatively 3 and 6 months after intervention using standardized ELISA assays. Statistical significance was set at p<0.05. Results. All procedures resulted in significant improvements in hormonal and metabolic profiles within 6 months. Total ghrelin decreased by 55.6% after LGP, 69.7% after LSG, and 74.5% after BEA at 6 months (all p<0.001). Leptin significantly declined, while adiponectin increased in all groups with the most pronounced early (3-month) rise after BEA (+36.1%, p=0.033). Resistin, insulin, and HbA1c progressively decreased across all interventions indicating improved insulin sensitivity. Overall, BEA demonstrated the strongest early hormonal response, whereas long-term (6-month) effects were comparable across procedures. Conclusion. Laparoscopic gastric plication, sleeve gastrectomy, and bariatric embolization provide substantial improvements in appetite-regulating and metabolic hormones in patients with obesity. BEA shows a particularly favorable early endocrine profile supporting its potential as a minimally invasive metabolic intervention.

Circulating CXCL1 in newly diagnosed type 2 diabetes: context-dependent association with inflammatory load and metabolic indices

Tue, 24 Mar 2026 00:00:00 GMT

Objective. Metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM) share a chronic low-grade inflammatory milieu driven by adiposity. C-X-C motif chemokine ligand 1 (CXCL1) has been linked to insulin resistance and endothelial dysfunction, but its diagnostic relevance remains unclear. Methods. Our study employed a cross-sectional design and enrolled 104 adults: 52 newly diagnosed treatment-naive T2DM patients and 52 normoglycemic controls matched for age and sex. Serum CXCL1, high-sensitivity C-reactive protein (hs-CRP), and metabolic parameters were measured. Logistic regression models to discriminate MS and T2DM status were constructed (base model: age, sex, BMI) and then expanded by adding hs-CRP, CXCL1, or both. Model performance was assessed for discrimination (AUC), calibration (Integrated Calibration Index [ICI], Expected Calibration Error [ECE]), and clinical utility (decision curve analysis, DCA) in accordance with TRIPOD 2024. Results. CXCL1 correlated with BMI (r=0.33, q=0.004) and hs-CRP (r=0.29, q=0.021), but not glycemic indices. For MS, CXCL1 marginally improved the base model (ΔAUC=+0.003, p=0.81); for T2DM, ΔAUC=+0.007 (p=0.60). hs-CRP performed better (AUC=0.744 for T2DM; 0.743 for MS) and the combined panel achieved the highest discrimination (AUC=0.769 and 0.745, respectively). Conclusions. CXCL1 reflects adiposity-related inflammation but provides only minimal incremental discrimination for metabolic syndrome and T2DM beyond conventional markers such as age, sex, BMI, and hs-CRP. The combined hs-CRP+CXCL1 panel achieved the best overall statistical performance, although its clinical utility remains limited. These findings emphasize the need for integrated multi-marker approaches rather than single-biomarker screening in metabolic risk assessment.

One genotype with a myriad of phenotypes: A family with multiple endocrine neoplasia

Tue, 24 Mar 2026 00:00:00 GMT

Objective. Multiple endocrine neoplasia type 1 (MEN1) is a very rare genetic disorder characterized by an autosomal dominant inheritance. We aim through this case series to delineate the wide spectrum of its clinical features. Methods. In the present study, we report the clinical and genetic findings of four siblings affected by this disorder. DNA was extracted from patients’ blood leukocytes using a phenol-chloroform method and assessed for purity with a NanoDrop spectrophotometer. Ten exons of the MEN1 gene were amplified by PCR, verified by gel electrophoresis, and sequenced using Big Dye Terminator chemistry followed by capillary electrophoresis. The sequences were than analyzed with CHROMAS and compared to reference sequences. As for the variant, interpretation and pathogenicity were assessed using Ensembl, ClinVar, dbSNP, gnomAD, Alamut Visual, and VARSOME. Results. We highlight the wide range of phenotypes encompassing primary hyperparathyroidism, macroprolactinoma, lipomas, papillary thyroid carcinoma, ectopic thyroid, multinodular goiter, and bilateral adrenal nodules observed in this family contrasting with the same pathogenic frameshift mutation. We also pinpoint to a second mutation detected in two of the siblings while discussing its pathogenicity. Finally, we provide an overview of the clinical manifestations of MEN1 and its genetic background. Conclusion. This research sets the stage to further investigate the molecular mechanisms underlying the novel nonsense mutation. Additionally, it incites other research to explore the frequency of this mutation in other populations and finally to conduct functional studies.

Inhibition of ERN1 suppresses the expression of phosphoenolpyruvate carboxykinase 2 in U87MG glioblastoma cells and increases its sensitivity to glucose and glutamine deprivation

Tue, 24 Mar 2026 00:00:00 GMT

Objective. Phosphoenolpyruvate carboxykinase (PCK) catalyzes the conversion of oxaloacetate to phosphoenolpyruvate and regulates pyruvate metabolism and gluconeogenesis in response to glucocorticoid and insulin stimuli. Mitochondrial isoform of this enzyme (PCK2) is overexpressed in glioblastoma cells and participates in metabolic reprogramming and cell proliferation. This study aims to examine the impact of ERN1 (endoplasmic reticulum to nucleus signaling 1) inhibition on PCK2 expression and sensitivity to glucose and glutamine deprivation to determine the role of ERN1 signaling in the regulating its expression in glioblastoma cells. Methods. The glioblastoma cell line U87MG and two genetically modified variants of these cells were used. These were glioblastoma cell sublines with suppressed endoribonuclease and protein kinase activities of ERN1 (dnERN1) or only ERN1 endoribonuclease (dnrERN1), and control cells transfected with an empty vector. The suppression of ERN1 function by silencing of ERN1 and XBP1 mRNAs was also used. Hypoxia was generated using the HIF1A prolyl hydroxylase inhibitor dimethyloxalylglycine. For glucose and glutamine deprivation, DMEM medium without glucose or glutamine was used. The expression level of the PCK2 mRNA was analyzed by real-time qPCR and normalized to the beta-actin mRNA. Results. It has been demonstrated that PCK2 mRNA expression is significantly decreased in dnERN1 glioblastoma cells. Similar suppression of this mRNA expression was also observed in cells with only the endoribonuclease activity of ERN1 inhibited, indicating that this enzymatic activity is involved in the regulation of PCK2 expression. The silencing of ERN1 and XBP1 mRNAs also induced similar changes in PCK2 mRNA expression, possibly mediated by XBP1s. The expression of PCK2 was enhanced under glutamine deprivation in control glioblastoma cells, but inhibition of ERN1 activity strongly increased this effect. Upregulated PCK2 expression was also observed in control glioblastoma cells under glucose deprivation. However, the inhibition of ERN1 activity strongly increased the sensitivity of this gene expression to glucose deprivation. Furthermore, PCK2 mRNA expression was resistant to hypoxic conditions in cells with native ERN1. At the same time, in glioblastoma cells with inhibited ERN1 activity, a strong induction of PCK2 expression was observed. Conclusion. The results of this study demonstrated that ERN1 inhibition reduces PCK2 mRNA expression through the ERN1 endoribonuclease activity. This mRNA expression is upregulated under glutamine and glucose deprivation. Moreover, ERN1 inhibition strongly enhanced the sensitivity of PCK2 mRNA expression to glucose and glutamine deprivation as well as to hypoxia.

Analysis of the risk factors impact on the life quality of patients with arterial hypertension

Tue, 24 Mar 2026 00:00:00 GMT

Objective. Recently, multicomponent quality-of-life indicators have become increasingly important in monitoring the health status of patients with hypertension and evaluating the effectiveness of treatment. Improving patient quality of life is considered one of the key objectives of the medical intervention. Methods. To assess the quality of life of patients with, we used the standardized SF-36 (Short Form-36 Health Survey) questionnaire, which allows to explicitly examine the respondent physical and psycho-emotional status. Results. We analyzed the association between polymorphisms of endothelial nitric oxide (NO) synthase (eNOS) (NOS3, T786C) and angiotensin II receptor type 1 (AGTR1, A1166C) genes and quality of life. Patients with polymorphisms associated with lower intravascular pressure had lower baseline QoL scores, particularly on the “physical functioning” and “general health” scales (p<0.05). Patients with heterozygous or homozygous “unfavorable” genotypes (AGTR1_CC, NOS3_CC) have significantly lower total indicators of both physical and psycho-emotional health compared to patients with “better” genotypes (AA, TT) and the control group. Conclusion. Patients with polymorphisms that cause reduced bioavailability of NO or excessive activation of AGRT1 show a significant deterioration in quality of life on all key SF-36 scales. This indicates the significant role of genetic factors in shaping the subjective perception of health in patients with arterial hypertension.

Prevalence and predictors of poor glycemic control in patients with type 2 diabetes mellitus attending Alexandria Main University Hospital

Tue, 24 Mar 2026 00:00:00 GMT

Objective. Despite the advances in diabetes management, there is still a high prevalence of poor glycemic control worldwide. This study aimed to determine the prevalence and predictors of poor glycemic control among patients with type 2 diabetes mellitus (T2DM) attending the outpatient clinic at Alexandria Main University Hospital (AMUH) Egypt. Methods. This cross-sectional study was conducted on 290 patients with T2DM. Data were collected on sociodemographic factors, medical history, comorbidities, lifestyle behaviors, medication adherence, and biochemical measures. Statistical analyses including correlation and regression models were used to explore the relationships between various factors and glycemic control. Results. The study revealed that 82.8% of participants had uncontrolled diabetes. Poor glycemic control was significantly associated with older age, lower education, rural residence, unemployment, and lower income. Additionally, patients with uncontrolled diabetes had higher rates of hypertension, dyslipidemia, ischemic heart disease, and diabetic peripheral neuropathy. Better physical activity and dietary adherence were linked to improved glycemic control, while medication adherence was significantly lower in the uncontrolled group. Among the significant predictors, physical activity (ORs=116.6–575.8) was the strongest predictor of improved diabetes control. Moreover, medication adherence (OR=4.098) and higher education (OR=8.354) were strongly associated with better diabetes control. Conclusions. Socioeconomic factors, lifestyle behaviors, and medication adherence are key predictors of glycemic control in T2DM patients. Physical activity, medication adherence, and higher education were the strongest predictors of better glycemic control. Addressing these factors through targeted interventions, particularly in rural areas, is crucial for improving diabetes management and reducing the related complications.

Effects of endocrine disruptor mixtures on functions of cultured porcine ovarian follicular cells

Wed, 31 Dec 2025 00:00:00 GMT

Objective. Involvement of various endocrine disruptors (EDs) in pathophysiology of reproductive system disorders has been suggested previously. The studies have shown adverse effects of the individual substances, however, in the real-life situation, numerous chemicals enter the organism on a daily basis. This points to the importance of examination of the combined effects of exogenous chemicals on biological systems, including reproductive system. The ovaries are a target of different EDs, which may impact the processes within the ovarian follicles. The aim of the present study was to examine the effects of binary or ternary mixtures combining selected nonpersistent disruptors: bisphenol A (BPA), BPA-dimethacrylate (BPADM), benzyl butyl phthalate (BBP), 4-chloro-3-methylphenol (CMP), or alkylphenols (4-octylphenol, OP; 4-nonylphenol, NP; and tert-octylphenol, TOP) on ovarian follicular cell functions. Methods. Porcine oocyte-cumulus complexes (OCCs) and granulosa cells (GCs) were treated with the tested ED mixtures (BPA+BBP, CMP+BBP, BPA+BPADM, BPA+BBP+CMP, and OP+NP+TOP) in a wide concentration range from 10–10 to 10–4 M. Follicle-stimulating hormone (FSH)-induced cumulus expansion was assessed after 24 h of culture according to a subjective scoring system. After 44-h treatment, oocyte nuclear maturation was evaluated. Basal and FSHstimulated progesterone production by OCCs and GCs was measured by commercial radioimmunoassay after 44 h and 72 h of the culture, respectively. One-way ANOVA and Bonferroni post-test were used for statistical analysis of data. Results. The results obtained showed that the lower concentrations of ED mixtures (10–10– 10–6 M) did not exert significant changes, while the highest concentration (10–4 M) significantly inhibited cumulus expansion, oocyte meiotic maturation, and progesterone production by OCCs and GCs. Moreover, the inhibitory effects of ED mixtures seem to be more profound than the effects caused by the individual substances. Conclusion. The experimental approach of testing mixtures should provide a more comprehensive view on the effects of the ubiquitous EDs on various cell types of the reproductive organs.

Hypokalemic metabolic alkalosis as a clinical clue to ectopic ACTH syndrome: two cases of neuroendocrine carcinoma

Wed, 31 Dec 2025 00:00:00 GMT

Objective. Ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) is a rare, but potentially life-threatening cause of Cushing’s syndrome. Its clinical recognition may be delayed, especially when classical features of hypercortisolism are absent. We present two cases, in which hypokalemic metabolic alkalosis was the initial and main clinical clue leading to the diagnosis of neuroendocrine carcinoma with ectopic ACTH production. Case 1. The first case was a 71-year-old woman admitted with progressive weakness, gait disturbance, and uncontrolled hypertension. Laboratory tests revealed severe hypokalemia and metabolic alkalosis. Endocrine evaluation showed markedly elevated urinary free cortisol and plasma ACTH, with absent suppression on low-dose dexamethasone testing. Colonoscopy for anemia revealed a rectal mass and histopathology confirmed poorly differentiated neuroendocrine carcinoma. Imaging demonstrated widespread metastases. Despite supportive treatment, she died of multi-organ failure during hospitalization. Case 2. The second case was a 67-year-old woman presenting with fatigue, weakness, and weight loss. Laboratory findings included hypokalemia, metabolic alkalosis, renal dysfunction, and elevated liver enzymes. Hormonal studies again confirmed ACTH-dependent Cushing’s syndrome without suppression on dexamethasone testing. Imaging revealed a right hilar lung mass and bronchoscopy with biopsy confirmed small-cell neuroendocrine carcinoma. PET-CT showed disseminated metastases. Although chemotherapy was initiated, she developed rapid progression and died shortly thereafter. Conclusion. These cases highlight that severe hypokalemic metabolic alkalosis may represent the primary manifestation of ectopic ACTH syndrome even in the absence of overt Cushingoid features. Recognition of this biochemical pattern should prompt consideration of neuroendocrine tumors allowing earlier diagnosis and timely therapeutic intervention in this aggressive condition.

Association between shift work and levels of thyroid hormones and interleukin-37

Fri, 12 Dec 2025 00:00:00 GMT

Objective. Symptoms of thyroid defects involve sleep disorders, gain or loss of weight, tremors of hand, constipation, dry skin, bradycardia, diarrhea, irregular menses, and hot or cold tolerance. Workers in different professions face different situations that can lead to stress. This study aimed to examine the association between shift work (office or irregular) and thyroid function indicators, interleukin-37 (IL-37) levels, and development of chronic diseases (cardiovascular, diabetes). Methods. The current study comprised three groups: 1) office staff, 2) irregular staff (comprising different jobs), and 3) controls (not working subjects). Eighty-five subjects, aged 30–55 years, were included in the study. Body mass index (BMI) was calculated for each participant. Venous blood was collected and serum levels of triiodothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH), and thyroid peroxidase (TPO) were determined by electrochemiluminescence (ECL) analysis using an automatic immunochemical analyzer Cobas E 411 (Roche Diagnostics, Germany). Serum IL-37 levels were measured using ELISA kit. Results. Serum T3 (p<0.01) and T4 (p<0.001) levels were significantly decreased in both office and irregular shift work groups compared to the controls. The mean T3 levels were higher in subjects with irregular shift work (1.162±0.11 ng/mL) compared to subjects with office shift work (1.14±0.12 ng/mL). Significantly increased TSH and TPO serum levels (p<0.01) were found in both the irregular shift work and office shift work groups compared to the control group. Similarly, IL37 levels were significantly increased in office shift work (294.8±21.05 ng/mL) and irregular shift work subjects (278.0±16.22 ng/mL) (p<0.001) compared to controls (56.5±0.28 ng/mL). Cardiac disease (p<0.01), hypertension (p<0.001), and diabetes (p<0.001) showed significant differences between subjects with office shift work, irregular shift work, and the control group. Conclusion. Elevated levels of IL-37 and TSH in shift workers may serve as biomarkers of the impact of shift work and the workplace on the immunological and hormonal status of employees.

Mitochondria-targeting compounds for management of metabolic and hemostatic abnormalities associated with heart dysfunctions in experimental type 2 diabetes

Fri, 12 Dec 2025 00:00:00 GMT

Objective. Cardiovascular complications are highly prevalent in type 2 diabetes mellitus (T2DM) driven by obesity, dyslipidemia, hypertension, and hypercoagulability associated with insulin resistance. The purpose of this study was to elucidate the effects of combined treatment with acetyl-L-carnitine (ALC), alpha-lipoic acid (ALA), and nicotinamide (NAm) on diabetes-induced metabolic, hemostatic, and heart abnormalities. Methods. Male non-linear Wistar rats were fed with a high-calorie diet for 2 months followed by a single low-dose streptozotocin injection to induce T2DM. Two weeks later, the diabetic rats received ALC (100 mg/kg), ALA (50 mg/kg), and NAm (100 mg/kg) for 2 weeks in separate daily injections. Fasting blood glucose, glycated hemoglobin (HbA1c), and hemostatic parameters: fibrinogen, protein C, factor X, plasminogen activator inhibitor-1 (PAI-1), were measured. The NAD+ content and NAD+/NADH ratio were assessed in the heart tissue. Results. After 12 weeks, blood glucose and HbA1c levels in diabetic rats were 1.8-fold and 2-fold higher, respectively. Diabetes increased fibrinogen (1.5-fold) and PAI-1 (1.7-fold) levels, caused the appearance of soluble fibrin monomers complexes, while protein C and factor X levels were decreased by 18% and 19%, respectively, indicating hypercoagulability and impaired fibrinolysis. In diabetic rats, the cardiac NAD+ level was reduced by 48%. The NAD+/NADH ratio decreased by 2-fold. Combined treatment lowered the glucose levels by 1.3-fold and HbA1c by 1.7-fold and improved the NAD+ metabolism and partially corrected the hemostatic abnormalities. Conclusion. Co-treatment with ALC, ALA, and NAm improved the glycemic control, partially restored the cardiac NAD+ metabolism and reduced the hemostatic abnormalities in T2DM suggesting their potential as a safe adjunct therapy for diabetes-associated cardiovascular complications.

Post-radiation hypothyroidism in patients with head and neck tumors: An overview assessment

Fri, 12 Dec 2025 00:00:00 GMT

Head and neck tumors are common in Slovakia. Although the number of tumors associated with smoking and alcohol is decreasing, the number of tumors associated with human papilloma-virus increases. Radiotherapy plays an important role in their treatment. The thyroid gland, due to its oneself location, is predisposed to the development of post-radiation dysfunction. Nowadays, there are methods able to reduce this risk and also available new options for treatment and dispensary care for these patients. The aim of this work is to analyze the incidence and pathophysiological mechanisms of post-radiation hypothyroidism in patients with head and neck tumors, to highlight the risk factors associated with radiotherapy and evaluation of prevention possibilities and treatments, and an overview of modern therapeutic approaches. Special attention is devoted to the importance of a multidisciplinary approach and the need for a long-term patient monitoring as well as the assessment of thyroid function as an integral part of a comprehensive oncological care.

Endogenous intoxication and morpho-functional changes in the liver during experimental acute generalized peritonitis in diabetic rats

Fri, 12 Dec 2025 00:00:00 GMT

Objective. The study aims to evaluate the severity of endogenous intoxication and characterize morpho-functional liver changes during experimental acute generalized peritonitis (AGP) in diabetic rats. Methods. Fifty-six adult male Wistar rats were used, including 8 controls and 48 males with experimental pathology. Diabetes mellitus was induced by an intraperitoneal (i.p.) injection of streptozotocin (60 mg/kg). On day 14, AGP was induced by i.p. injection of a 10% filtered fecal suspension. Endogenous intoxication was assessed by measuring hydrophilic and hydrophobic molecular products in the blood. Liver function was evaluated by serum aminotransferase activity, total protein, and protein fractions. Histological analysis of liver tissue was performed using standard hematoxylin-eosin staining. Results. A progressive increase in endogenous intoxication was observed peaking on day 7. This was marked by a significant elevation in middle molecular weight molecule (MMWM) concentrations at wavelengths of 254 nm and 280 nm by 103.0% (p<0.001) and 340.0% (p<0.001), respectively. The erythrocyte intoxication index (EII) increased by 148.8% (p<0.001) compared to controls. Concurrently, aminotransferase activity increased, while serum total protein and albumin levels decreased. Histologically, inflammatory infiltration and vascular congestion were evident on day 1 progressing to hepatocellular dystrophy and necrosis by day 3. By day 7, signs of hepatic failure were present including disruption of trabecular architecture, hydropic degeneration, intra-cellular cholestasis, and portal tract expansion due to vascular hyperemia. Conclusions. Experimental acute generalized peritonitis in diabetic rats resulted in a pronounced endogenous intoxication accompanied by progressive morpho-functional liver damage culminating in hepatic insufficiency by day 7.

Mirtazapine for gastrointestinal side effects of glucagon-like peptide-1 receptor agonist therapy in older adults

Fri, 12 Dec 2025 00:00:00 GMT

Objective. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) play a role in management of type 2 diabetes (T2D) and obesity by promoting glycemic control and weight reduction. Beyond these benefits, GLP-1 RAs have demonstrated positive effects on cardiovascular, renal, and neurological health, with emerging evidence supporting their therapeutic potential in conditions such as chronic kidney disease, asthma, obstructive sleep apnea, Parkinson’s disease, and Alzheimer’s disease. However, their widespread clinical use is often hindered by gastrointestinal side effects including nausea, anorexia, vomiting, and diarrhea that limit adherence and dose titration. Effective management of these adverse effects is essential to optimize treatment outcomes and maintain long-term therapy. Case report. A 72-year-old woman with a history of cognitive impairment, T2D, atrial fibrillation, obesity, and mood disorders presented with persistent gastrointestinal symptoms while receiving semaglutide. Dose escalation was restricted due to severe nausea, vomiting, and diarrhea, which markedly affected her quality of life. To manage these symptoms, mirtazapine was initiated. Following its introduction, the patient reported significant improvement in gastrointestinal tolerance enabling continued semaglutide therapy and successful dose advancement. Additional benefits included enhanced mood, better sleep, and overall well-being. No adverse effects related to mirtazapine were observed throughout the treatment. Conclusion. This case suggests that mirtazapine may be beneficial in mitigating GLP-1 RA-induced gastrointestinal side effects, thereby improving adherence and therapeutic efficacy. Further research is needed to evaluate the safety, mechanism, and generalizability of this approach in broader clinical practice.

LDL/HDL ratio and HOMA-IR as markers of severity of peripheral neuropathy in diabetic population

Fri, 12 Dec 2025 00:00:00 GMT

Objective. Diabetic peripheral neuropathy (DPN) is a common complication of type 2 diabetes mellitus (T2DM) that substantially impairs quality of life. This study aimed to assess the relationship between metabolic parameters and DPN severity in T2DM patients. Methods. A prospective observational study was conducted at PSG Institute of Medical Sciences and Research (Peelamedu, Coimbatore, India) from August 2023 to August 2024, enrolling 90 adults with T2DM on oral hypoglycemic agents after ethical approval and informed consent. Blood samples were analyzed for fasting glucose, HbA1c, lipid profile, and plasma insulin. The LDL/HDL ratio and HOMA-IR were calculated to evaluate metabolic status. DPN severity was measured using a biothesiometer. Results. The higher HbA1c levels significantly correlated with increased neuropathy severity (severe: 12.1±1.3% vs. mild: 8.4±2.0%; p=0.002). LDL/HDL ratio was elevated in patients with severe DPN (3.6±1.8) compared to mild DPN cases (2.5±1.0), but this difference was not significant (p=0.12). Severe DPN cases also showed higher HOMA-IR (10.2±2.8) suggesting a possible link to insulin resistance though not statistically significant (p=0.23). Conclusion. HbA1c strongly associates with DPN severity, while LDL/HDL ratio and HOMAIR showed no significant correlation. Further research is needed to clarify these metabolic relationships and their clinical relevance.

Sarcopenia and sarcopenic obesity in type 2 diabetes mellitus and cardiovascular disease: current perspective and narrative review

Mon, 10 Nov 2025 00:00:00 GMT

Sarcopenia, initially described as a disease of the elderly and its coexistence with obesity, now termed as ‘sarcopenic obesity’ (SO), are now emerging to be important health problems worldwide. Their relatively recent recognition as distinct clinical entities with growing research has shown an increasing prevalence of both sarcopenia and SO. There is a strong independent association, which exists between sarcopenia/SO, type 2 diabetes mellitus (T2DM), and cardiovascular disease (CVD). Studies investigating prevalence of sarcopenia/SO indicate considerable heterogeneity, likely due to the lack of a universally accepted definition, differences in age groups, gender, ethnicity, and socio-demographic factors of the population studied, apart from use of distinct diagnostic criteria and methods of estimation based on either muscle mass or strength.

The role of circadian rhythm disruptions in the diabetes pathogenesis

Mon, 10 Nov 2025 00:00:00 GMT

Diabetes mellitus has become a major global health concern with increasing prevalence worldwide. Recent studies have highlighted the critical role of the circadian rhythm, the body’s internal biological clock, in the pathogenesis of diabetes. The circadian system regulates glucose metabolism, insulin secretion, and energy homeostasis. Modern lifestyle factors such as sleep disturbances shift work and irregular eating patterns disrupt circadian rhythms promoting insulin resistance and glucose intolerance. At the molecular level, mutations or altered expression of clock genes contribute to diabetes development. Clinical and experimental evidence suggests that maintaining the circadian integrity can reduce the diabetes risk and the chronotherapy time-based treatment approaches may enhance the therapeutic efficacy. The future advances including genetic profiling, AI-assisted monitoring and microbiota modulation hold promise for improved diabetes management. This review comprehensively examines the relationship between diabetes and circadian disruption emphasizing the importance of circadian biology in preventing and treating the metabolic diseases.

Impact of GHRL (RS696217) and LEPR (RS1137101) gene polymorphisms on hormonal and anthropometric outcomes after bariatric surgery

Mon, 10 Nov 2025 00:00:00 GMT

Objective. The aim of the study was to evaluate the influence of GHRL (rs696217) and LEPR (rs1137101) gene polymorphisms on weight loss dynamics and endocrine marker changes following various bariatric procedures. Patients and Methods. A total of 76 patients undergoing laparoscopic sleeve gastrectomy (LSG), gastric plication (LGCP), and gastric artery embolization (GAE) were genotyped for GHRL (rs696217) and LEPR (rs1137101). Body mass index (BMI), total weight loss (TWL), excess weight loss (EWL), and hormonal markers (ghrelin, leptin, adiponectin, resistin, HbA1c) were assessed preoperatively and at 3, 6, and 12 months postoperatively. Results. Carriers of the T allele of GHRL (rs696217) experienced significantly greater reductions in BMI, TWL, and EWL, particularly following LSG and GAE (p<0.05). A notable reduction in total ghrelin levels was observed in T allele carriers (up to –46.75%, p<0.001) 6 months after surgery. Improvements in resistin (p=0.0002) and HbA1c (p=0.014) levels were also more pronounced in this group. LEPR (rs1137101) polymorphism showed limited impact on outcomes after LGCP, but it was associated with improved TWL and EWL in A allele carriers after LSG (p=0.006 and p=0.016, respectively). Conclusion. The T allele of GHRL (rs696217) appears to be a promising predictive marker for greater metabolic and hormonal improvement following bariatric procedures targeting the ghrelin-producing stomach zones. LEPR (rs1137101) may also influence postoperative outcomes in a procedure-specific manner. These findings support the potential role of genetic screening in optimizing patient selection and predicting surgical success.

Oral health-related behaviors and prevalence of thyroid diseases in Iranian patients

Mon, 10 Nov 2025 00:00:00 GMT

Objective. Thyroid disorders can affect the general health-related quality of life with complications such as fatigue, anxiety, depression, and systemic manifestations. The aim of this study was to investigate the relationship between the oral health-related behaviors, the prevalence of thyroid diseases, and the oral health-related quality of the life. Methods. This cross-sectional and descriptive-analytical study was conducted on 419 patients with a history of thyroid disease and 100 healthy subjects with no thyroid disease as a control group. Demographic information including age, gender, BMI, smoking, alcohol consumption, and medical history was collected through questionnaires and interviews. An assistant of oral diseases evaluated the oral health-related behaviors and objective conditions of oral health status. The objective periodontal evaluation was based on the community periodontal index (CPI) and probing by WHO. The plaque index was examined by giving dental plaque disclosing tablets and chewing them for 30 seconds. Thyroid disease was based on the endocrinologist’s opinion and triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone (TSH) criteria. In this study, to evaluate the oral health-related quality of life, the Oral Health Impact Profile (OHIP-14) questionnaire was used. The obtained results were analyzed using T-test, Multivariate logistic regression analysis, Chi-Square test, and SPSS-21 software. The significance level in data analysis was p<0.05. Results. Among the 419 patients with a history of thyroid disorders included in the study, 82 (15.8%) had hyperthyroidism (TSH <0.4 mIU/L), 261 (50.3%) had normal thyroid (TSH <5.0 mIU/L), and 76 (14.6%) had hypothyroidism (TSH >5.0 mIU/L). Regarding the observation of the oral and dental health status in the group of participants with no history of thyroid disorder, 64% of subjects with thyroid disorders observed their oral and dental health well, while in the group of subjects with no history of thyroid disorder, 46.9% observed oral health well (p<0.001). The results revealed a significant relationship between the presence of periodontitis and a history of thyroid disorder (p<0.021). During the study, 11% of hyperthyroid patients, 4.6% of participants with normal thyroid status, and 1.3% of hypothyroid patients suffered from periodontitis. The score of oral health-related quality of life in participants without a thyroid disorder history was significantly lower than that with a history of thyroid disorder indicating that their oral healthrelated quality of life is better (p=0.049). Conclusions. The results revealed a significant relationship between the presence of periodontitis and a history of thyroid disorder. However, there was no significant difference between two experimental groups regarding the presence of microbial plaque. The score of oral health-related quality of life in participants without a history of thyroid disorder was significantly lower than that with a history of thyroid disorder indicating that their oral healthrelated quality of life is better.