Plasma Proteomic Signature of Endometrial Cancer in Patients with Diabetes.

The incidence and mortality of endometrial cancer (EC) have increased in recent years. There is mounting evidence that diabetes may play a role in the greater incidence of EC. The molecular mechanisms of the interaction between type 2 diabetes and EC are not yet clearly understood yet. The present study was undertaken to investigate the plasma proteomics of EC patients with diabetes in comparison to those of EC patients without diabetes. Plasma samples were obtained from age-matched patients (EC diabetic and EC nondiabetic). Untargeted proteomic analysis was carried out using a two-dimensional differential gel electrophoresis coupled with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Of the 33 proteins identified, which significantly differed in the plasma abundance between groups, 17 were upregulated and 16 were downregulated. The majority of the altered proteins are involved in the acute phase reaction, cholesterol metabolism, scavenging of heme from plasma, and plasma lipoprotein assembly and mobilization. α-2-macroglobulin, Ras association domain-containing protein 3, apolipoprotein A-I, α-1B-glycoprotein, and zinc-α-2-glycoprotein were significantly upregulated. The significantly downregulated proteins included haptoglobin, apolipoprotein A-IV, hemopexin, and α-1-antichymotrypsin. The differential expression of proteins found in patients who had EC and diabetes indicated severe disease and a poor prognosis. The protein interaction analysis showed dysregulation of cholesterol metabolism and heme scavenging pathways in these patients.

Metabolomic Profiling of Blood Plasma in Females with Hyperplasia and Endometrial Cancer.

Uterine cancer is the most prevalent gynecologic malignancy in women worldwide. Endometrial cancer (EC) has an 81% five-year survival rate, depending on disease stage and time of diagnosis. While endometrial cancer is largely treatable when detected early, no established screening techniques are available in clinical practice. As a result, one of the most significant issues in the medical field is the development of novel ways for early cancer identification, which could boost treatment success rates. Liquid chromatography-high-resolution mass spectrometry (LC-HRMS)-based metabolomics was employed to explore the metabolomic markers and pathways unique to this cancer type and link them to the benign endometrial hyperplasia that may progress to cancer in 5% to 25% of patients. The study involved 59 postmenopausal participants, 20 with EC type 1, 20 with benign hyperplasia, and 19 healthy participants. Metabolite distribution changes were analyzed, and 338 of these features were dysregulated and significant. The first two main components, PC1 and PC2, were responsible for 11.5% and 12.2% of the total metabolites, respectively. Compared with the control group (CO), EC samples had 203 differentially expressed metabolites (180 upregulated and 23 downregulated); in hyperplasia (HP), 157 metabolites were dysregulated (127 upregulated and 30 downregulated) compared to the CO group while 21 metabolites exhibited differential regulation (16 upregulated and 5 downregulated) in EC plasma samples compared to the HP group. Hyperplasia samples exhibited similar metabolic changes to those reported in cancer, except for alterations in triglyceride levels, 7a,12 b-dihydroxy-5b-Cholan-24-oic acid, and Hept-2-enedioyl carnitine levels. The metabolites N-heptanoyl glycine and -(Methylthio)-2,3-isopentyl phosphate and formimino glutamic acid can be specific markers for hyperplasia conditions and dimethyl phosphatidyl ethanolamine and 8-isoprostaglandin E2 can be specific markers for EC conditions. Metabolic activities rely on mitochondrial oxidative phosphorylation for energy generation. The changes in metabolites identified in our study indicate that endometrial cancer cells adopt alternative strategies to increase energy production to meet the energy demand, thereby supporting proliferation.

Analysis of Gremlin 1 Levels Following Sleeve Gastrectomy.

BACKGROUND: In the current study, we aimed to assess the levels of Gremlin 1, an adipokine with a rich repertoire of metabolic effects, in association with the glycemic and lipid parameters after sleeve gastrectomy. MATERIAL AND METHODS: This study was conducted on 31 males with obesity aged 25 to 50 years who underwent sleeve gastrectomy. Plasma Gremlin 1 levels were evaluated using enzyme-linked immunosorbent assay (ELISA) at baseline and 6-12 months after the operation, along with body mass index, insulin, glucose, and lipid profile. RESULTS: Plasma Gremlin 1 levels were elevated (148.19±17.43 vs. 193.29±19.82 ng/mL, p < 0.05) after sleeve gastrectomy. This was accompanied by a decrease in body mass index (from 51.47±1.71 to 39.23±1.56 kg/m2, p < 0.05). Insulin and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) also exhibited a significant decrease (19.69±1.81 vs. 8.98±1.09 mIU/L and 6.52±0.98 vs. 2.57±0.036 p < 0.05, respectively) in the postoperative period. Total cholesterol levels were significantly increased after surgery (4.29±0.16 to 5.10±0.16, p < 0.05). Pearson correlation analysis showed that Gremlin 1 was positively correlated with insulin before surgery, but there was no significant correlation after surgery. CONCLUSION: The circulating Gremlin 1 levels were elevated postoperatively among our participants. The improvement in insulin sensitivity appears to be independent of the reported antagonistic effects of Gremlin 1.

Comparison of the Protective Effects of Nebivolol and Metoprolol against LPS-Induced Injury in H9c2 Cardiomyoblasts.

Here, we, for the first time, compared the cardioprotective effects of third-generation vasodilating beta-blocker nebivolol (Neb) and conventional beta-blocker metoprolol (Met) on LPS-induced injury in H9c2 cardiomyoblasts. Our findings denoted that Neb and Met pretreatment diminish LPS-mediated cytotoxicity and oxidative stress. Concomitantly, LPS-triggered inflammatory cytokines activation was significantly suppressed by Neb but not by Met. Pretreatment with either Neb or Met alleviated LPS-mediated mitochondrial impairment by enhancing the expression of genes related to its biogenesis such as PGC-1α, NRF1, and TFAM. On the contrary, Neb but not Met-upregulated mitochondrial fusion-related genes such as OPA, and MFN2. In summary, our findings suggest that Neb and Met treatment significantly ameliorated the LPS-induced cytotoxicity and oxidative stress. Additionally, these findings suggest that Neb but not Met significantly down-regulates LPS-induced proinflammatory factors, probably by enhancing mitochondrial biogenesis and fusion.

Proteomic Profiling Identifies Distinct Regulation of Proteins in Obese Diabetic Patients Treated with Metformin.

Background: Obesity and type 2 diabetes mellitus (T2DM) are characterized by underlying low-grade chronic inflammation. Metformin has been used as the first line of therapy in T2DM as it decreases hepatic glucose production and glucose intestinal absorption, enhances insulin sensitivity and weight loss, and is known to ameliorate inflammation. The mechanisms through which metformin exerts its effect remain unclear. Proteomics has emerged as a unique approach to explore the biological changes associated with diseases, including T2DM. It provides insight into the circulating biomarkers/mediators which could be utilized for disease screening, diagnosis, and prognosis. Methods: This study evaluated the proteomic changes in obese (Ob), obese diabetics (OD), and obese diabetic patients on metformin (ODM) using a 2D DIGE MALDI-TOF mass spectrometric approach. Results: Significant changes in sixteen plasma proteins (15 up and 1 down, ANOVA, p ≤ 0.05; fold change ≥ 1.5) were observed in the ODM group when compared to the Ob and OD groups. Bioinformatic network pathway analysis revealed that the majority of these altered plasma proteins are involved in distinct pathways involving acute-phase response, inflammation, and oxidative response and were centered around HNF4A, ERK, JNK, and insulin signaling pathways. Conclusions: Our study provides important information about the possible biomarkers altered by metformin treatment in obese patients with and without T2DM. These altered plasma proteins are involved in distinct pathways involving acute-phase response, inflammation, and oxidative response and were centered around HNF4A, ERK, JNK, and insulin signaling pathways. The presented proteomic profiling approach may help in identifying potential biomarkers/mediators affected by metformin treatment in T2DM and inform the understanding of metformin's mechanisms of action.

Proteomics Investigation of the Impact of the Enterococcus faecalis Secretome on MCF-7 Tumor Cells.

Breast cancer is the most prevalent form of cancer among women. The microenvironment of a cancer tumor is surrounded by various cells, including the microbiota. An imbalance between microbes and their host may contribute to the development and spread of breast cancer. Therefore, the objective of this study is to investigate the influence of Enterococcus faecalis on a breast cancer cell line (MCF-7) to mimic the luminal A subtype of breast cancer, using an untargeted proteomics approach to analyze the proteomic profiles of breast cancer cells after their treatment with E. faecalis in order to understand the microbiome and its role in the development of cancer. The breast cancer cell line MCF-7 was cultured and then treated with a 10% bacterial supernatant at two time points (24 h and 48 h) at 37 °C in a humidified incubator with 5% CO2. Proteins were then extracted and separated using two-dimensional difference (2D-DIGE) gel electrophoresis, and the statistically significant proteins (p-value < 0.05, fold change > 1.5) were identified via matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF-MS). The protein fingerprints showed a differential protein expression pattern in the cells treated with E. faecalis for 24 and 48 h compared with the control. We found 58 statistically significant proteins changes in the MCF-7 breast cancer cells affected by E. faecalis. Kilin and transgelin were upregulated after 24 h of treatment and could be used as diagnostic and prognostic markers for breast cancer. In addition, another protein involved in the inhibition of cell proliferation was coiled-coil domain-containing protein 154. The protein markers identified in this study may serve as possible biomarkers for breast cancer progression. This promotes their future uses as important therapeutic goals in the treatment and diagnosis of cancer and increases our understanding of the breast microbiome and its role in the development of cancer.

Transcriptomic and Proteomic Analysis Reveals the Potential Role of RBMS1 in Adipogenesis and Adipocyte Metabolism.

Adipocytes play a critical role in maintaining a healthy systemic metabolism by storing and releasing energy in the form of fat and helping to regulate glucose and lipid levels in the body. Adipogenesis is the process through which pre-adipocytes are differentiated into mature adipocytes. It is a complex process involving various transcription factors and signaling pathways. The dysregulation of adipogenesis has been implicated in the development of obesity and metabolic disorders. Therefore, understanding the mechanisms that regulate adipogenesis and the factors that contribute to its dysregulation may provide insights into the prevention and treatment of these conditions. RNA-binding motif single-stranded interacting protein 1 (RBMS1) is a protein that binds to RNA and plays a critical role in various cellular processes such as alternative splicing, mRNA stability, and translation. RBMS1 polymorphism has been shown to be associated with obesity and type 2 diabetes, but the role of RBMS1 in adipose metabolism and adipogenesis is not known. We show that RBMS1 is highly expressed during the early phase of the differentiation of the murine adipocyte cell line 3T3-L1 and is significantly upregulated in the adipose tissue depots and adipocytes of high-fat-fed mice, implying a possible role in adipogenesis and adipose metabolism. Knockdown of RBMS1 in pre-adipocytes impacted the differentiation process and reduced the expression of some of the key adipogenic markers. Transcriptomic and proteomic analysis indicated that RBMS1 depletion affected the expression of several genes involved in major metabolic processes, including carbohydrate and lipid metabolism. Our findings imply that RBMS1 plays an important role in adipocyte metabolism and may offer novel therapeutic opportunity for metabolic disorders such as obesity and type 2 diabetes.

Early Cytokine Signatures of Hospitalized Mild and Severe COVID-19 Patients: A Prospective Observational Study.

Background: The severe manifestation of coronavirus disease 2019 (COVID-19) is known to be mediated by several cytokines and chemokines. The study aimed to compare the early cytokine profile of mild and severe COVID-19 patients to that with COVID-19-like symptoms and tested negative for Severe Acute Respiratory Syndrome Coronavirus-2 in the Reverse-Transcriptase Polymerase Chain Reaction (RT-PCR) test. Methods: This was a prospective, observational study on COVID-19 patients admitted to King Khalid University Hospital, King Saud University Medical City from June to November 2020. Clinical and biochemical data were collected from hospital charts. Blood samples were collected at the time of hospital admission to measure cytokines. A Cytokine and Growth Factor High-Sensitivity Array was used to quantitatively measure cytokines. Results: The study included 202 RT-PCR-positive individuals and 61 RT-PCR-negative individuals. C-Reactive protein (CRP) and Interleukin-10 (IL-10) levels were found significantly elevated in the RT-PCR positive group compared to the RT-PCR negative group (p=0.001). Patients with severe COVID-19 had significantly longer median hospital stays than those with mild COVID-19 cases (7 vs 6 days). They also had higher CRP and Vascular Endothelial Growth Factor (VEGF) levels and lower Interleukin-4 (IL-4) levels compared to the mild cases. CRP, interleukin-6, IL-10, VEGF, and Monocyte Chemoattractant Protein-1 (MCP-1) levels were significantly elevated in men and IL-10 was significantly higher and interleukin-8 was significantly lower in women compared to negative controls. Elevated Interferon-É£ (IFN-γ) and IL-10 levels were seen in mild COVID-19 cases and elevated level of MCP-1 was seen in severe COVID-19 cases when categorized according to the length of stay in the hospital. Conclusion: CRP and IL-10 levels were elevated in the RT-PCR positive group. People with severe COVID-19 had higher CRP and VEGF levels and lower IL-4 levels. Elevated IFN-γ and IL-10 levels were seen in mild COVID-19 cases and elevated level of MCP-1 was seen in severe COVID-19 cases when categorized according to the length of stay in the hospital.

Metabolomic profile of patients on levothyroxine treatment for hypothyroidism.

Background: Hypothyroidism is clinically characterized by a decrease in levels of the circulating thyroid hormones namely thyroxine and triiodothyronine. The main treatment for hypothyroidism is thyroid hormone replacement using levothyroxine to normalize serum thyroid hormone levels. Objectives: In this study, we explored the metabolic changes in the plasma of patients with hypothyroidism after reaching a euthyroid state with levothyroxine treatment. Methods: Plasma samples from 18 patients diagnosed as overt hypothyroidism were collected before and after levothyroxine treatment upon reaching a euthyroid state and were analyzed by high-resolution mass spectrometry-based metabolomics. Multivariate and univariate analyses evaluated data to highlight potential metabolic biomarkers. Results: Liquid chromatography-mass spectrometry-based metabolomics revealed a significant decrease in the levels of ceramide, phosphatidylcholine, triglycerides, acylcarnitine, and peptides after levothyroxine treatment; this could indicate a change in the fatty acid transportation system and an enhanced ß-oxidation, compared with a hypothyroid state. At the same time, the decrease in the peptides suggested a shift in protein synthesis. In addition, there was a considerable rise in glycocholic acid following therapy, suggesting the involvement of thyroid hormones in stimulating bile acid production and secretion. Conclusions: A metabolomic analysis of patients with hypothyroidism revealed significant changes in several metabolites and lipids after treatment. This study showed the value of the metabolomics technique in providing a complementary understanding of the pathophysiology of hypothyroidism and as a crucial tool for examining the molecular impact of levothyroxine treatment on hypothyroidism. It was an important tool for investigating the therapeutic effects of levothyroxine on hypothyroidism at the molecular level.

Islet Autoantibodies to Pancreatic Insulin-Producing Beta Cells in Adolescent and Adults with Type 1 Diabetes Mellitus: A Cross-Sectional Study.

(1) Background: Type 1 diabetes mellitus (T1D) is a chronic autoimmune disease caused by the destruction of pancreatic insulin-producing beta cells. T1D is one of the most common endocrine and metabolic disorders occurring in children. Autoantibodies against pancreatic insulin-producing beta cells are important immunological and serological markers of T1D. Zinc transporter 8 autoantibody (ZnT8) is a recently identified autoantibody in T1D; however, no data on ZnT8 autoantibody in the Saudi Arabian population have been reported. Thus, we aimed to investigate the prevalence of islet autoantibodies (IA-2 and ZnT8) in adolescents and adults with T1D according to age and disease duration. (2) Methods: In total, 270 patients were enrolled in this cross-sectional study. After meeting the study's inclusion and exclusion criteria, 108 patients with T1D (50 men and 58 women) were assessed for T1D autoantibody levels. Serum ZnT8 and IA-2 autoantibodies were measured using commercial enzyme-linked immunosorbent assay kits. (3) Results: IA-2 and ZnT8 autoantibodies were present in 67.6% and 54.6% of patients with T1D, respectively. Autoantibody positivity was found in 79.6% of the patients with T1D. Both the IA-2 and ZnT8 autoantibodies were frequently observed in adolescents. The prevalence of IA-2 and ZnT8 autoantibodies in patients with a disease duration < 1 year was 100% and 62.5%, respectively, which declined with an increase in disease duration (p < 0.020). Logistic regression analysis revealed a significant relationship between age and autoantibodies (p < 0.004). (4) Conclusions: The prevalence of IA-2 and ZnT8 autoantibodies in the Saudi Arabian T1D population appears to be higher in adolescents. The current study also showed that the prevalence of autoantibodies decreased with disease duration and age. IA-2 and ZnT8 autoantibodies are important immunological and serological markers for T1D diagnosis in the Saudi Arabian population.

Protective Effects of Nanoceria against Mitochondrial Dysfunction and Angiotensin II-Induced Hypertrophy in H9c2 Cardiomyoblasts.

Mitochondrial dysfunction triggered by increased reactive oxygen species (ROS) generation is involved in the pathogenesis and development of cardiac hypertrophy. Nanoceria (cerium oxide nanoparticle) has powerful ROS-scavenging properties and is considered a potential therapeutic option for curbing ROS-related disorders. Here, we explored the signaling mechanism underlying the protective effects of nanoceria against angiotensin (Ang) II-stimulated pathological response in H9c2 cardiomyoblasts. Our data revealed that pretreatment of H9c2 cardiomyoblasts with nanoceria significantly prevented Ang II-stimulated generation of intracellular ROS, aberrant expression of pro-inflammatory cytokines, and hypertrophy markers. Nanoceria pretreatment increased the mRNA levels of genes regulating the cellular antioxidant defense system (SOD2, MnSOD, CAT) in Ang II-treated cells. Furthermore, nanoceria restored mitochondrial function by decreasing mitochondrial ROS, increasing mitochondrial membrane potential (MMP), and promoting the mRNA expression of genes associated with mitochondrial biogenesis (PGC-1α, TFAM, NRF1, and SIRT3) and mitochondrial fusion (MFN2, OPA1). Collectively, these findings demonstrate the protective effects of nanoceria against Ang II-mediated mitochondrial dysfunction and pathological hypertrophy in H9c2 cells.

Proteomic Profiling Reveals Cytotoxic Mechanisms of Action and Adaptive Mechanisms of Resistance in Porphyromonas gingivalis: Treatment with Juglans regia and Melaleuca alternifolia.

The increasing trend in the rise of antibiotic-resistant bacteria pushes research to discover new efficacious antibacterial agents from natural and synthetic sources. Porphyromonas gingivalis is a well-known bacterium commonly known for causing periodontal disease, and it is associated with the pathogenesis of life-changing systemic conditions such as Alzheimer's. Proteomic research can be utilized to test new antibacterial drugs and understand the adaptive resistive mechanisms of bacteria; hence, it is important in the drug discovery process. The current study focuses on identifying the antibacterial effects of Juglans regia (JR) and Melaleuca alternifolia (MA) on P. gingivalis and uses proteomics to identify modes of action while exploring its adaptive mechanisms. JR and MA extracts were tested for antibacterial efficacy using the agar well diffusion assay. A proteomic study was conducted identifying upregulated and downregulated proteins compared to control by 2D-DIGE analysis, and proteins were identified using MADLI-TOF/MS. The bacterial inhibition for JR was 20.14 ± 0.2, and that for MA was 19.72 ± 0.5 mm. Out of 88 differentially expressed proteins, there were 17 common differentially expressed proteins: 10 were upregulated and 7 were downregulated in both treatments. Among the upregulated proteins were Arginine-tRNA ligase, ATP-dependent Clp protease proteolytic, and flavodoxins. In contrast, down-regulated proteins were ATP synthase subunit alpha and quinone, among others, which are known antibacterial targets. STRING analysis indicated a strong network of interactions between differentially expressed proteins, mainly involved in protein translation, post-translational modification, energy production, metabolic pathways, and protein repair and degradation. Both extracts were equi-efficacious at inhibiting P. gingivalis and displayed some overlapping proteomic profiles. However, the MR extract had a greater fold change in its profile than the JA extract. Downregulated proteins indicated similarity in the mode of action, and upregulated proteins appear to be related to adaptive mechanisms important in promoting repair, growth, survival, virulence, and resistance. Hence, both extracts may be useful in preventing P. gingivalis-associated conditions. Furthermore, our results may be helpful to researchers in identifying new antibiotics which may offset these mechanisms of resistance.

Alterations in circulating lipidomic profile in patients with type 2 diabetes with or without non-alcoholic fatty liver disease.

Objective: Non-alcoholic fatty liver disease (NAFLD) and Type 2 diabetes mellitus (T2DM) often coexist and drive detrimental effects in a synergistic manner. This study was designed to understand the changes in circulating lipid and lipoprotein metabolism in patients with T2DM with or without NAFLD. Methods: Four hundred thirty-four T2DM patients aged 18-60 years were included in this study. Fatty liver was assessed by FibroScan. The comprehensive metabolic lipid profiling of serum samples was assessed by using high-throughput proton NMR metabolomics. Results: Our data revealed a significant association between steatosis and serum total lipids in VLDL and LDL lipoprotein subclasses, while total lipids in HDL subclasses were negatively associated. A significant positive association was found between steatosis and concentration of lipids, phospholipids, cholesterol, and triglycerides in VLDL and LDL subclasses, while HDL subclasses were negatively associated. Furthermore, a significant, association was observed between fibrosis and concentrations of lipids, phospholipids, cholesterol, and triglycerides in very small VLDL, large, and very large HDL subclasses. Subgroup analysis revealed a decrease in the concentrations of lipids, phospholipids, cholesterol, and other lipid biomolecules in patients using antilipemic medications. Conclusion: The metabolomics results provide evidence that patients with T2DM with higher steatosis grades have altered lipid metabolomics compared to patients without steatosis. Increased lipid, phospholipids, cholesterol, and triglycerides concentration of VLDL and LDL subclasses are associated with steatosis in patients with T2DM.

Prevalence of QT prolongation and its risk factors in patients with type 2 diabetes.

BACKGROUND: QT prolongation increases cardiovascular mortality in diabetes. The risk factors for QT prolongation vary across different studies. There is no data on the QT prolongation in patients with diabetes from the Arab region, where diabetes is highly prevalent. Here we aimed to assess the prevalence of QT prolongation and its associated risk factors in patients with type 2 diabetes from Saudi Arabia. METHOD: This was a retrospective, cross-sectional, hospital-based file review study. Data were collected from the medical records of patients with type 2 diabetes aged above 14 years and underwent ECG examination, and laboratory investigations were done within one month of ECG. RESULTS: The study included 782 patients with a prevalence of QTc prolongation of 13%. Patients with prolonged QTc interval were characterized by older age, higher BMI, longer diabetes duration, lower total cholesterol and LDL-C, and more diabetic nephropathy, hypertension, and CVD cases. They were also more in insulin treatment, antihypertensive medications, loop diuretics, and potassium-sparring diuretics. Logistic regression analysis revealed the odds of prolonged QTc interval increased significantly with CVD (OR = 1.761, 95% CI:1.021-3.036, p = 0.042), and usage of loop diuretics (OR = 2.245, 95% CI:1.023-4.923, p = 0.044) after adjusting for age, gender, and duration of diabetes. CONCLUSION: The risk factors associated with QTc prolongation in patients with type 2 diabetes are CVD, and loop diuretics. Age, BMI, and diabetes duration were more in people with QTc prolongation, whereas total cholesterol and LDL-C levels were lower. More patients had diabetic nephropathy, hypertension, and CVD with prolonged QTc.

Urinary Proteome Differences in Patients with Type 2 Diabetes Pre and Post Liraglutide Treatment.

Diabetes mellitus is a chronic multisystem disease with a high global prevalence. The glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide is known to lower glucose levels and reduce weight. However, the mechanisms underlying the benefits of liraglutide treatment in patients with type 2 diabetes mellitus (T2DM) remain unclear. Twelve male patients with T2DM (pre and post liraglutide treatment) and HbA1c between 8% and 11% were recruited. In the present study, a two-dimensional difference gel electrophoresis (2D-DIGE) matrix-assisted laser desorption/ionization-time of flight (MALDI TOF) mass spectrometric approach combined with bioinformatics and network pathway analysis was used to explore the urine proteomic profile. The mean age of the patients was 52.4 ± 7.5 years. After treatment with liraglutide, a statistically significant change (p < 0.006) was observed in HbA1c with no significant changes in body weight or markers of dyslipidemia. Two-dimensional difference gel electrophoresis identified significant changes (≥1.5-fold change, ANOVA, p ≤ 0.05) in 32 proteins (4 down- and 28 upregulated) in liraglutide post treatment compared to the pre-treatment state. Albumin, serotransferrin, metallothionein-2 (MT-2), and keratins K1 and K10 were found to be upregulated after liraglutide treatment. The patients showed significant improvement in glycemic control after the 12-week treatment with liraglutide. The renoprotective effect of liraglutide may be linked to the increased urinary abundance of MT-2 and the decreased abundance of zinc alpha 2-glycoprotein (ZAG) and Alpha-1 antitrypsin (α1-AT). More studies are needed to elucidate the molecular mechanisms behind the renoprotective effects of liraglutide.

The association of cell adhesion molecules and selectins (VCAM-1, ICAM-1, E-selectin, L-selectin, and P-selectin) with microvascular complications in patients with type 2 diabetes: A follow-up study.

Objective: Chronic hyperglycemia induces pathogenic changes in the vascular endothelium and leads to the development of microvascular complications in patients with type 2 diabetes mellitus. Early identification of markers of diabetes complications may help to minimize the risk of the development and progression of microvascular complications. Methods: This follow-up study was conducted in type 2 diabetic cohort aged between 30-70 years. Out of 160 eligible participants, 70 of them completed follow-up. Levels of cell adhesion molecules and selectins (VCAM-1, ICAM-1, E-selectin, L-selectin and P-selectin) at baseline and follow-up were measured using Randox Evidence biochip analyzer (UK). Development of microvascular complications (diabetic neuropathy, retinopathy and nephropathy) was evaluated. Results: During the follow-up (2 years, median), 31 (44.3%) developed diabetic neuropathy, 10 (14.3%) developed diabetic retinopathy and, 27 (38.6%) developed diabetic nephropathy. A significant difference in levels of cell adhesion molecules and selectins were found in type 2 diabetic patients with and without microvascular complications. Multiple logistic regression analysis reveals that baseline level of VCAM-1 is significantly associated with microvascular complications; diabetic neuropathy(p=0.028), retinopathy (p=0.007) and nephropathy(p=<0.001). Additionally, levels of P-selectin (p=0.05) and L-selectin (p=0.008) is associated with diabetic nephropathy while retinopathy associated with L-selectin (p=0.005) only. Conclusion: Cell adhesion molecules and selectins are indicators of microvascular complication among patients with type 2 diabetes (T2D). Association of these markers with the development of microvascular complications may provide additive information for developing strategies for diabetes management and prediction of microvascular complications.

Low Circulating Free Triiodothyronine Levels are Associated with the Progression of Diabetic Nephropathy in Patients with Type 2 Diabetes.

Background: Diabetic Nephropathy (DN) is one of the most typical causes of end-stage renal disease and thyroid hormone exerts effects on the kidney. There are few reports on the role of thyroid hormone in the progression of DN. We aimed to assess the relationship between thyroid hormone and DN. Methods: In this cross-sectional study, 400 patients with type 2 diabetes (T2D) (aged between 35 and 70 years) were divided into two groups T2D control and DN group according to albumin creatinine ratio (ACR). Clinical biochemistry parameters were measured using the Rx Daytona chemistry analyzer and thyroid hormone levels (TT4, TT3, TSH, FT4, and FT3) using the Evidence Biochip analyzer. To assess the relationship between thyroid hormone and DN, multiple logistic regression models were developed. Results: Serum FT4 and FT3 levels were significantly lower in DN compared to T2D controls (p<0.05). Thyroid hormone levels tend to decrease with the progression of DN. In unadjusted and adjusted logistic regression models, FT3 levels were negatively associated with odds of having DN (OR=0.28, CI=0.128-0.616, p=0.002). Conclusion: The free triiodothyronine level was negatively associated with the progression of DN. Further longitudinal studies are required to assess the cause of thyroid hormone differences.

Higher carbohydrate intake in relation to non-alcoholic fatty liver disease in patients with type 2 diabetes.

Background: Non-alcoholic fatty liver disease (NAFLD) is an overlooked complication of type 2 diabetes (T2D). Current recommendations for the management of NAFLD are mainly focused on weight reduction, overlooking the role of macronutrient composition. Although dietary carbohydrates play a major role in intrahepatic fat synthesis, their association with the progression of liver steatosis has not been fully investigated in patients with T2D. Aim: To investigate the association between higher carbohydrate intake and the presence of liver steatosis in patients with T2D. Methods: This cross-sectional study included men and women aged 18-60 years diagnosed with T2D. Anthropometric measurements, hepatic steatosis assessment using the controlled attenuation parameter (CAP), blood samples, and dietary data were analyzed. Participants were divided into two groups: NAFLD and NAFLD-free. A two-sample t-test was used to evaluate the differences between the two groups. Stepwise multiple linear regression models adjusted for potential confounders were used to determine the association between CAP values and higher carbohydrate intake. Results: In total, 358 participants were included. NAFLD was present in 79.3% of the participants. Body mass index, waist circumference, ALT, HbA1c, and triglycerides showed direct, while HDL-Cholesterol revealed inverse associations with CAP values. No significant relationship was found between carbohydrate intake and steatosis in the total study sample; however, multiple linear regression analysis revealed a significant relationship between carbohydrate intake and CAP values in patients aged ≤50 years. Conclusion: In patients with T2D, higher carbohydrate intake was associated with liver steatosis in those aged 50 years and below. Further studies are required to confirm the causality between carbohydrate intake and liver steatosis.

Clinical and biochemical characteristics of people experiencing post-coronavirus disease 2019-related symptoms: A prospective follow-up investigation.

Background: Post-acute coronavirus disease 2019 (COVID-19) syndrome, also known as long COVID, is a prolonged illness after the acute phase of COVID-19. Hospitalized patients were known to have persisting symptoms of fatigue, headache, dyspnea, and anosmia. There is a need to describe the characteristics of individuals with post-COVID-19 symptoms in comparison to the baseline characteristics. Purpose: To investigate the clinical and biochemical characteristics of people who recovered from COVID-19 after 6 months of discharge from the hospital. Methods: This was a prospective follow-up investigation of hospitalized and discharged COVID-19 patients. Adult patients admitted to King Saud University Medical City, Riyadh, Saudi Arabia, with laboratory-confirmed COVID-19 and discharged were recruited. The baseline demographic information, comorbidities, vital signs and symptoms, laboratory parameters, COVID-19 therapy, and outcomes were collected from the medical records. Blood samples were collected for cytokines estimation. A detailed interview about signs and symptoms was undertaken during the follow-up. Results: Half of the followed-up people reported experiencing at least one of the COVID-19-related symptoms. The mean blood pressure was found higher in follow-up. People with the symptoms were characterized by low lymphocyte count, lower serum calcium levels, and hyperglycemia compared to people without any post-COVID-19 symptoms. Cytokines IL-8, VEGF, and MCP-1 were higher in people with the most frequent symptoms. Conclusion: People with post-COVID-19 symptoms were characterized by lower lymphocyte count, lower serum calcium levels, and hyperglycemia compared to people without symptoms. Individuals with the most frequent post-COVID-19 symptoms had higher baseline pro-inflammatory, chemotactic, and angiogenic cytokines.

Risk factors of chronic kidney disease among type 2 diabetic patients with longer duration of diabetes.

Background: Chronic kidney disease (CKD) in patients with type 2 diabetes mellitus (T2DM) is the major cause of end stage renal disease, characterized by proteinuria with a subsequent decline in glomerular filtration rate. Although hyperglycemia is the major risk factor for the development and progression of kidney disease among diabetic patients, many other risk factors also contribute to structural and functional changes in the kidneys. As recommended by Kidney Disease Improving Global Outcomes (KDIGO), CKD classification based on cause and severity, links to risk of adverse outcomes including mortality and kidney outcomes. Objective: The aim of this study is to investigate the involvement of risk factors associated with the severity of CKD among participants with longer duration of diabetes. This study also aims to find whether number of risk factors vary among risk of CKD progression categories based on KDIGO classification. Material and methods: This cross-sectional study retrospectively selected 424 participants from type 2 diabetic cohort and categorized them based on the classifications for the diagnosis of kidney diseases in patients with diabetes, according to the KDIGO guidelines. Odds ratios and 95% CI of each risk factors according to severity of renal disease were determined. Results: Based on KDIGO classification, participants with type 2 diabetes (T2D) were categorized in to low risk (n=174); moderately increased risk (n=98); and high/very high risk (n=152). Type 2 diabetic participants with risk factors such as, hyperlipidemia, hypertension, DM duration ≥15 years and diabetic retinopathy showed a high/very high risk of CKD progression when compared with low-risk category. While T2D participants with risk factors such as, lack of exercise, hypertension, and diabetic retinopathy showed a moderately increased risk of CKD progression. In addition, participants with highest number of risk factors were significantly distributed among high/very high risk of CKD progression category. Conclusion: This study findings conclude that patients with T2DM and duration of ≥15 years, hyperlipidemia, hypertension and diabetic retinopathy have an increased prevalence of advanced CKD. In addition to this, increased number of risk factors could be an indicator of the severity of CKD in T2D.