Determination of HLA class II risk alleles and prediction of self/non-self-epitopes contributing Hashimoto's thyroiditis in a group of Iranian patients.

One of the probable hypotheses for the onset of autoimmunity is molecular mimicry. This study aimed to determine the HLA-II risk alleles for developing Hashimoto's thyroiditis (HT) in order to analyze the molecular homology between candidate pathogen-derived epitopes and potentially self-antigens (thyroid peroxidase, TPO) based on the presence of HLA risk alleles. HLA-DRB1/-DQB1 genotyping was performed in 100 HT patients and 330 ethnically matched healthy controls to determine the predisposing/protective alleles for HT disease. Then, in silico analysis was conducted to examine the sequence homology between epitopes derived from autoantigens and four potentially relevant pathogens and their binding capacities to HLA risk alleles based on peptide docking analysis. We identified HLA-DRB1*03:01, *04:02, *04:05, and *11:04 as predisposing alleles and DRB1*13:01 as a potentially predictive allele for HT disease. Also, DRB1*11:04 ~ DQB1*03:01 (Pc = 0.002; OR, 3.97) and DRB1*03:01 ~ DQB1*02:01 (Pc = 0.004; OR, 2.24) haplotypes conferred a predisposing role for HT. Based on logistic regression analysis, carrying risk alleles increased the risk of HT development 4.5 times in our population (P = 7.09E-10). Also, ROC curve analysis revealed a high predictive power of those risk alleles for discrimination of the susceptible from healthy individuals (AUC, 0.70; P = 6.6E-10). Analysis of peptide sequence homology between epitopes of TPO and epitopes derived from four candidate microorganisms revealed a homology between envelop glycoprotein D of herpes virus and sequence 151-199 of TPO with remarkable binding capacity to HLA-DRB1*03:01 allele. Our findings indicate the increased risk of developing HT in those individuals carrying HLA risk alleles which can also be related to herpes virus infection.

Impact of interleukin-32α on T helper cell-related cytokines, transcription factors, and proliferation in patients with type 2 diabetes mellitus.

OBJECTIVE: The ability of interleukin (IL)-32α to induce T helper (Th) 1, Th17, and Treg cytokines (interferon gamma [IFN-γ], IL-17, and IL-10, respectively), and transcription factors ([signal transducer and activator of transcription (STAT) 1 and T-box (T-bet) for Th1, STAT3 and retinoid-related orphan receptor (ROR)-γt for Th17, and STAT5 and forkhead box P3 (Foxp3) for Treg]) were investigated in type 2 diabetes mellitus (T2DM). IL-32α effects on Th cell proliferation and related factors including IL-2 and NF-κB were also explored. METHODS: Serum levels of IL-32α in 31 patients and 31 healthy controls (HCs) were determined by ELISA assay. CD4+ T cells cultured with polyclonal activators in the presence and absence of recombinant IL-32α (rIL-32α). Gene expressions in cultured Th cells were assessed with real-time PCR. Cytokines in supernatants were measured with ELISA. Proliferation experiments were assessed by flow cytometry. RESULTS: The patients showed significant increase in IL-32α levels compared with HCs and its levels were positively correlated with fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c). rIL-32α enhanced IL-17 and IL-2 production, increased ROR-γt and NF-κB expression, and enhanced Th proliferation in both patients and HCs. In patients, IL-17, ROR-γt, NF-κB, and proliferation levels were higher than those in HCs, in cultures with and without rIL-32α (rIL-32α+ and rIL-32α-). IL-2 levels in rIL-32α+cultures of patients were significantly higher than the HCs, and it was positively correlated with proliferation rate and NF-κB expression. CONCLUSIONS: Aberrant IL-32α levels are participated in T2DM pathogenesis. IL-32α potently induces Th17-related factors and amplifies the proliferative function of T cells.HighlightsEnhanced serum levels of IL-32α in T2DM patients was correlated with FPG and HbA1c.IL-32α increases ROR-γt expression and IL-17 production, and induces Th17 cells.IL-32α enhances NF-κB expression and IL-2 production, and promotes Th proliferation.IL-32α is more effective for inducing Th17 cells and proliferation in the patients.IL-32α axis could be mentioned as a future therapeutic goal for the T2DM.

Comprehensive comparison of clinicoradiological, laboratory, and prognostic factors of community-acquired pneumonia in diabetic and nondiabetic hospitalized patients.

Background/aim: Community-acquired pneumonia (CAP) is one of the leading infectious causes of mortality, and diabetes mellitus is a globally prevalent disease. Consequently, the cooccurrence of these two disorders can be common and create challenging medical conditions. Therefore, it was aimed to compare the various aspects of CAP in diabetic and nondiabetic patients, in order to have a comprehensive and comparative picture of the differences. Materials and methods: In this cross-sectional study, CAP patients with and without diabetes were assessed for clinicoradiological signs, laboratory features, disease severity, and pneumonia outcomes. Results: Analyzed herein were 172 CAP patients (77 had diabetes and 95 were nondiabetic). Clinical and radiological signs of pneumonia were mostly similar between the groups, except for purulent sputum, which was more prevalent among the nondiabetic patients. The laboratory results were also mostly similar. However, analysis of the outcomes and prognosis showed different results. The diabetic patients had a longer mean duration of hospital stay (8.52 days vs. 7.93 days, p = 0.015), higher median pneumonia severity based on the CURB-65 criteria (3 vs. 2, p = 0.016), and higher intensive care unit (ICU) admission requirement (22.1% vs. 7.3%, p = 0.004). Moreover, the mortality rate for the diabetic patients was nonsignificantly higher (16.8% vs. 15.7%, p = 0.453). Furthermore, the results of the logistic regression analysis showed that the diabetic patients had significantly higher odds of experiencing more severe forms of pneumonia (adjusted odds ratio (AOR): 5.77, 95% CI: 2.52-13.20), requiring ICU hospitalization (AOR: 3.56, 95% CI: 1.39-9.11), and having a longer hospital stay (AOR: 2.01, 95% CI: 1.09-3.71). In addition, although there was no significant relationship between the severity of pneumonia and the amount of glycated hemoglobin (HbA1c) in the diabetic patients (p = 0.940), the higher level of HbA1c in the nondiabetic patients was significantly correlated with a higher severity of pneumonia (p = 0.002). Conclusion: While diabetic patients with CAP have the same clinicoradiological and laboratory features as nondiabetic patients, the presence of diabetes can significantly worsen the outcomes and prognosis of pneumonia.

Identifying associations between health services operational factors and health experience for patients with type 2 diabetes in Iran.

BACKGROUND: Facing limited health resources, healthcare providers need to rely on health service delivery models that produce the best clinical outcomes and patient experience. We aimed to contribute to developing a patient experience-based type 2 diabetes service delivery model by identifying operational structures and processes of care that were associated with clinical outcome, health experience, and service experience. METHODS: We conducted a cross-sectional survey of type 2 diabetes patients between January 2019 to February 2020. Having adjusted for demand variables, we examined relationships between independent variables (behaviours, services/processes, and structures) and three categories of dependent variables; clinical outcomes (HbA1c and fasting blood glucose), health experience (EuroQol quality of life (EQ-5D), evaluation of quality of life (visual analgene scale of EQ-5D), and satisfaction with overall health status), and service experience (evaluation of diabetes services in comparison with worst and best imaginable diabetes services and satisfaction with diabetes services). We analysed data using multivariate linear regression models using Stata software. RESULTS: After adjusting for demand variables; structures, diabetes-specific health behaviours, and processes explained up to 22, 12, and 9% of the variance in the outcomes, respectively. Based on significant associations between the diabetes service operations and outcomes, the components of an experience-based service delivery model included the structural elements (continuity of care, redistribution of task to low-cost resources, and improved access to provider), behaviours (improved patient awareness and adherence), and process elements (reduced variation in service utilization, increased responsiveness, caring, comprehensiveness of care, and shared decision-making). CONCLUSIONS: Based on the extent of explained variance and identified significant variables, health services operational factors that determine patient-reported outcomes for patients with type 2 diabetes in Iran were identified, which focus on improving continuity of care and access to providers at the first place, improving adherence to care at the second, and various operational process variables at the third place.

Palmitate-induced IL6 expression ameliorated by chicoric acid through AMPK and SIRT1-mediated pathway in the PBMCs of newly diagnosed type 2 diabetes patients and healthy subjects.

Inhibition of inflammation is one of the possible therapeutic approaches for Insulin resistance (IR) during type 2 diabetes mellitus (T2DM). In the current study we investigated the effects of palmitate and chicoric acid (CA) on inflammation in peripheral blood mononuclear cells (PBMCs) of newly diagnosed T2DM patients and healthy subjects and explored the mechanism by which palmitate and CA influence inflammation. 20 newly diagnosed T2DM patients and 20 healthy subjects were recruited in our study. Blood sample were collected and PBMCs were isolated. Interleukin 6 (IL6), silent information regulator type 1 (SIRT1), AMP-activated protein kinase (AMPK) and phospho-AMPK (pAMPK) were evaluated both in vivo and in vitro. PBMCs were treated with palmitate and CA to investigate their effects on inflammation. IL6 and SIRT1 genes expression were evaluated by real-time PCR. The levels of IL6 in culture medium were measured by ELISA. Proteins levels of AMPK and pAMPK in PBMCs were detected by western blotting. IL6 expression was higher and SIRT1 expression and pAMPK levels were lower in PBMCs of diabetic patients and obese subjects compared to healthy subjects and non-obese subjects, respectively. CA significantly prevented against increased IL6 levels as well as its gene expression in PBMCs induced by palmitate. Also, CA returned reduction in SIRT1 expression and pAMPK levels mediated via palmitate to near control level. These findings reveal that CA reduces inflammation in PBMCs probably through upregulation of SIRT1 and pAMPK. Therefore, CA would be suggested as a novel agent for the treatment of T2DM.

The increased T helper cells proliferation and inflammatory responses in patients with type 2 diabetes mellitus is suppressed by sitagliptin and vitamin D3 in vitro.

OBJECTIVE: The probably effects of sitagliptin and vitamin D3 (VitD3) on proliferation capacity and cytokines production were investigated in type 2 diabetes mellitus (T2DM) in vitro. MATERIALS AND METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from 35 patients with T2DM and 26 healthy controls (HCs). CFSE-labeled PBMCs stimulated with phytohamagglutinin (PHA, 5 µg/mL) in the presence/absence of sitagliptin (200 mg/mL) with/without VitD3 (10-8 M) for 4 days. The proliferation of CD4+ T helper cells and non-CD4+ cells was analyzed using flow cytometry. The supernatant levels of IFN-γ, IL-17, IL-4, TGB-ß and IL-37 were detected using ELISA. RESULTS: The proliferation of CD4+ T cells in response to PHA was higher in T2DM patients compared with HCs. The production of IFN-γ and IL-17 in PHA-stimulated cultures was higher, and the levels of IL-4 and IL-37 were lower in T2DM patients compared to HCs. The addition of sitagliptin or VitD3 to the cultures decreased the CD4+ T cells and non-CD4+ cells proliferation in patients and HCs. Sitagliptin with VitD3 was more effective in suppression of proliferation, decreasing of IL-17 and enhancing of IL-37 production. CONCLUSION: Sitagliptin plus VitD3 effectively reduces the proliferative T cells response and modulates pro-inflammatory/anti-inflammatory cytokines production.

Effects of sitagliptin and vitamin D3 on T helper cell transcription factors and cytokine production in clinical subgroups of type 2 diabetes mellitus: highlights upregulation of FOXP3 and IL-37.

Objective: Gene expression level of T helper cell transcription factors and cytokines production in type-2 diabetes mellitus (T2DM) patients treated with mono- or combined sitagliptin and vitamin D3 (VitD3) were evaluated. Methods: Fifty-four nephropathic and 57 non-nephropathic T2DM patients were divided into the subgroups based on their treatment with/without sitagliptin and VitD3. The expression of T-bet, RORγt, BCL6, and FOXP3 was evaluated using real-time PCR. The levels of IFN-γ, IL-6, IL-17, IL-21, TGF-ß, and IL-37 were assessed in PBMC supernatants using ELISA. Results: The production of IFN-γ and IL-17 was increased in untreated (without sitagliptin and VitD3) nephropathic and non-nephropathic T2DM patients compared with healthy controls, whereas FOXP3 expression was decreased. Treatment with sitagliptin alone or in combination with VitD3 reduced the production of IFN-γ in the patients. Production of IL-17 and IL-21 and the expression of RORγt and BCL6 was diminished in patients treated with combined sitagliptin and VitD3, whereas the production of IL-37 and FOXP3 expression were increased in the patients treated with sitagliptin or sitagliptin plus VitD3. Conclusion: These data demonstrate that sitagliptin in combination with VitD3 may accelerate the process of T2DM treatment by exerting synergic anti-inflammatory effects on immune system through upregulation of FOXP3 and IL-37, and downregulation of RORγt and BCL6 as well as IFN-γ, IL-17 and IL-21 production. Combined sitagliptin and VitD3 can be safely utilized to modulate the inflammatory conditions of T2DM.

Decreased regulatory function of CD4+CD25+CD45RA+ T cells and impaired IL-2 signalling pathway in patients with type 2 diabetes mellitus.

In this study, the frequency and function of CD4+CD25+CD45RA+ regulatory T cells (Treg) and intracellular IL-2 signalling molecules in patients with type 2 diabetes mellitus (T2DM) were investigated. Tregs and responder T cells (Tresp, CD4+CD25- T cells) were sorted and suppression assays were performed using flow cytometry. Phosphorylation of signal transducer and activator of transcription-5 (pSTAT5) were assessed using flow cytometry. Gene expression of FOXP3 was performed with the SYBR green Real Time PCR method. Production of IL-2 from cultured cells was assessed using ELISA. We observed a functional defect of CD4+CD25+CD45RA+ Tregs in T2DM patients with higher proliferation of Tresp cells, in response to anti-CD3 and anti CD28 stimulation in the presence of Tregs in vitro. The results showed that the proliferation of Tresps in the absence of Treg cells was higher in T2DM patients than in healthy controls. Decreased FOXP3 mRNA expression and pSTAT5 were observed within the Tregs of the patients, whereas the level of secreted IL-2 from PBMCs culture was not statically different between T2DM patients and healthy individuals. Changes in intracellular IL-2 pathways and FOXP3 gene expression may contribute to the defect of Tregs in T2DM patients. These findings indicating that the purified CD4+CD25+CD45RA+ Treg cells have reduced functional capacity together with impaired IL-2 pathway in T2DM, and the Tregs could be used for a potential novel therapeutic target.

Sleep quality and glycemic control in adults with type 2 diabetes mellitus.

Aim: Type 2 diabetes mellitus (T2DM) is a common disease that imposes a substantial burden on the healthcare system and patients. Lifestyle modification such as sleep hygiene plays a crucial role in glycemic control. Sleep disorders impact many aspects of health. In this study, we aimed to investigate the correlation between sleep quality and glycemic control in T2DM. Method: This cross-sectional study was performed on 163 T2DM patients, attending Shahid Beheshti Hospital in Hamadan, Iran from March 2020 to 2021. Besides recording the demographic data and HbA1c level of participants, they were asked the Pittsburgh Sleep Quality Index questionnaire for evaluating sleep quality. We employed SPSS ver. 21 for data analysis and considered 0.05 as a significant level. Results: Among all participants, 62 (38%) were female and 30.7% were illiterate. The mean age was 56.67 ± 12.90 years, and HbA1c was 9.03 ± 1.92 mg/dL. Among sleep metrics, mean waking time was 8.74 ± 1.74 hours, and average sleep time was 12.90 ± 4.90 hours. Overall, 58.2% of the participants had poor glycemic control and 44.8% were suffering from poor sleep quality. We found that patients with poor glycemic control exhibited significantly higher levels of sleep disturbances compared to those with good glycemic control (P < 0.001). Conclusion: Sleep quality is associated with glycemic control in patients with T2DM. Sleep disorders are common among diabetic patients. Thus, healthcare providers need to consider sleep quality improvement in their holistic approach to diabetes management.

Diabetic foot ulcers risk prediction in patients with type 2 diabetes using classifier based on associations rule mining.

Identifying diabetic patients at risk of developing foot ulcers, as one of the most significant complications of diabetes, is a crucial healthcare concern. This study aimed to develop an associative classification model (CBA) using the Apriori algorithm to predict diabetic foot ulcers (DFU). This retrospective cohort study included 666 patients with type 2 diabetes referred to Shahid Beheshti Hospital in Iran between April 2020 and August 2022, of which 279 (42%) had DFU. Data on 29 specific baseline features were collected, which were preprocessed by discretizing numerical variables based on medical cutoffs. The target variable was the occurrence of DFU, and the minimum support, confidence, and lift thresholds were set to 0.01, 0.7, and 1, respectively. After data preparation and cleaning, a CBA model was created using the Apriori algorithm, with 80% of the data used as a training set and 20% as a testing set. The accuracy and AUC (area under the roc curve) measure were used to evaluate the performance of the model. The CBA model discovered a total of 146 rules for two patient groups. Several factors, such as longer duration of diabetes over 10 years, insulin therapy, male sex, older age, smoking, addiction to other drugs, family history of diabetes, higher body mass index, physical inactivity, and diabetes complications such as proliferative and non-proliferative retinopathy and nephropathy, were identified as major risk factors contributing to the development of DFU. The CBA model achieved an overall accuracy of 96%. Also, the AUC value was 0.962 (95%CI 0.924, 1.000). The developed model has a high accuracy in predicting the risk of DFU in patients with type 2 diabetes. The creation of accurate predictive models for DFU has the potential to significantly reduce the burden of managing recurring ulcers and the need for amputation, which are significant health concerns associated with diabetes.

Simultaneous onset of Crohn's disease and Psoriasis in a Multiple Sclerosis patient treated with Teriflunomide: A novel case report highlighting potential autoimmune interactions.

Teriflunomide (TFN) is an oral Disease-modifying therapy (DMT) widely used in the treatment of relapsing forms of Multiple Sclerosis (MS). Although TFN has demonstrated efficacy in reducing MS activity, recent evidence suggests a possible association between TFN and the onset of rare and severe medical conditions. We present a novel case report of a 47-year-old woman with a history of MS who developed concurrent Crohn's disease and Psoriasis following TFN treatment. This unique occurrence has not been previously documented in the literature. The patient experienced gastrointestinal symptoms and changes in nail color while on TFN. Colonoscopy and biopsy revealed crypt architectural distortion and lamina propria expansion, indicative of Crohn's disease, while dermatological evaluation suggested Psoriasis. Consequently, TFN was discontinued and switched to alternative therapy (Glatiramer acetate), and the patient underwent close observation and regular evaluations. Three months after stopping the TFN, the patient's nail lesions disappeared completely, her abdominal pain and diarrhea were resolved, and the follow-up colonoscopy was completely normal. In this regard, the association between MS, Inflammatory Bowel Disease (IBD), and Psoriasis has been reported in previous studies, with potential involvement of Th17 and IL-17 pathways. Although gastrointestinal side effects with TFN use are typically mild and transient, rare cases of TFN-induced IBD have been reported. Dermatological disorders, including Psoriasis, have also been linked to TFN use, with similarities to our case report. Further research and awareness are warranted to better understand the potential side effects and long-term implications of TFN in the management of MS.

Hypothyroidism Evaluation after Radiotherapy of Breast and Supraclavicular in Patients with Breast Cancer.

Background: This study aims to evaluate the risk of hypothyroidism (HT) after radiotherapy (RT) of breast and supraclavicular in patients with breast cancer (BC). Materials and Methods: In a historical cohort study, the records of all patients with BC who had been referred to the Mahdieh radiotherapy Center of Hamadan from 2017 to 2019 were reviewed. Demographic characteristics, clinical information, previous and current used treatment methods (surgery, radiotherapy, chemotherapy), number of RT sessions and doses, and HT (TSH >5 mIU/L) were extracted from the patient's documents. Data were analyzed using SPSS software version 16. Results: Out of 304 patients referred to the Center, 266 patients were investigated. The mean TSH was 6.3 ± 7.9 ml/L (1.5 to 65.4). Approximately half of the patients were in Stage 2 of the disease. 37 (16.4%) patients were diagnosed with HT, of which 8.8% were clinical, and 7.5% were subclinical. The mean total dose of HT patients (5621.62 ± 491.67) was significantly higher than other patients (5304.76 ± 937.98). 21 patients (56.8%) in Stage 3 and 4 and 16 (43.2%) patients in Stages 1 and 2 had HT (P = 0.006). Spearman correlation coefficient showed that there was a significant relationship between total dose and TSH hormone (r = 0.624), the number of RT sessions with TSH hormone (r = 0.237), and total dose with T4 hormone (r = -0.232). Conclusion: The findings of this study showed that the risk of HT increases significantly in patients with BC who undergo RT of breast and supraclavicular. Patients with higher stage, more radiation, and more RT sessions are at higher risk of HT.

Validity and reliability of the Persian version of the Suboptimal Health Status Questionnaire among university staff in Iran.

Background: Suboptimal Health Status Questionnaire-25 (SHSQ-25) is an established tool for measuring a precision health state between health and illness. The present study aims to assess the validity and reliability of a Persian version of SHSQ-25 (P-SHSQ-25) in a university staff Iranian population. Methods: A sample of 316 academic and supporting staff (163 males, age range from 23 to 64 years old) from Hamadan University of Medical Sciences, Hamadan, Iran was recruited in this population-based cross-sectional study with a questionnaire validation from Apri1 to October 2022. Forward-backward translation method was performed for the SHSQ-25 translation from English to Persian. Internal reliability, content, convergence, discriminative and construct validity of the P-SHSQ-25 were examined. The factorial structure of the P-SHSQ-25 across groups was examined using measurement invariant test. Results: In the translation process, the conceptual equivalence of the P-SHSQ-25 with the English version was confirmed. The item-content validity index and content validity ratio of all P-SHSQ-25 items were higher than the cut-off values of 0.70 and 0.62, respectively. Cronbach's α was higher than 0.70 for all P-SHSQ-25 domains. The confirmatory factor analysis (CFA) showed the fitness of five factors on the data set (comparative fit index = 0.88, and root mean square error of approximation = 0.07). The CFA model fit did not change substantially across sex, age, occupation, economic status, and body mass index (Δ comparative fit index (CFI)<0.01). Conclusions: The P-SHSQ-25 can be used as a reliable and valid tool to measure health status for screening pre-chronic disease conditions in a primary care setting among Iranian population.

Adrenal Mass in a 70-Year-Old Woman.

Introduction: Adrenocortical carcinoma is a rare endocrine malignancy with a bimodal age distribution pattern that affects women more than men. More than half of the patients present with hormone excess manifestations such as Cushing's syndrome and virilization. Non-functional tumors usually are diagnosed incidentally following imaging studies due to a mass effect or metastatic disease. Surgical resection is considered the best curative treatment for these tumors. Case Presentation. A 70-year-old woman presented with a 3-month history of diffuse intermittent abdominal discomfort, weight loss, and additional hair growth. Imaging investigations revealed a large 187 × 85 × 140 mm mass between the liver and upper pole of the right kidney which has displaced the adjacent structures. Hormonal evaluations detected high levels of cortisol and adrenal androgens. She underwent open adrenalectomy and right nephrectomy due to severe adhesion of the mass. Histopathological evaluations revealed adrenocortical carcinoma and the patient received adjuvant radiotherapy. Conclusion: Precise physical examination, hormonal evaluation, and imaging studies play a key role in differentiating malignant adrenal masses in all patients, especially in those with vague symptoms. Radical excision of the mass and appropriate adjuvant chemotherapy or radiotherapy improve the outcome for patients.

Effects of Hypertension Alone and in Comorbidity with Diabetes on Death within 30 Days among Inpatients with COVID-19 Infection.

BACKGROUND: Hypertension and diabetes are common comorbidities in patients with COVID-19 and could be influencing the mortality of such patients. The present study aimed to evaluate the effects of hypertension alone and in comorbidity with diabetes on the death within 30 days among inpatients with COVID-19 in presence of well-known determinates of COVID-19 death. STUDY DESIGN: A case-control study. METHODS: Four groups of COVID-19 inpatients including controls, diabetes alone, hypertension alone, and hypertension and diabetes comorbidities were defined. Each study groups did not have underlying diseases other than hypertension and diabetes. Demographic and general characteristics, underlying diseases, and hospital course events were extracted from medical records. The outcome of interest was alive at discharge/ death within 30 days after admission. Multivariable binary logistic analysis was employed to estimate the effect measures. RESULTS: The number of death within 30 days among controls (n=1359), diabetes alone (159), hypertension alone (406) and hypertension and diabetes comorbidities (188) were 12.68%, 15.72%, 20.74% and 26.74%, respectively. According to three multivariable analyses after adjusting older age, hospital length of stay, and intensive care unit (ICU) admission separately, the odds of death within 30 days in COVID-19 patients with having hypertension and diabetes comorbidities was 1.58, 2.13 and 1.91 times of patients without such comorbidities, respectively (P<0.015). The effect of hypertension alone was also significant after adjusting hospital length of stay and ICU admission but not for older age. CONCLUSION: Our results suggest that comorbidities, such as hypertension and diabetes may be associated with COVID-19-related deaths independent of other underlying diseases, older age, and adverse hospital course events.

The positive effect of short-term nano-curcumin therapy on insulin resistance and serum levels of afamin in patients with metabolic syndrome.

OBJECTIVE: Metabolic syndrome (MS) is a cluster of cardio-metabolic risk factors. MS is known as a highly prevalent disease worldwide. According to the existing evidence, consuming curcumin has positive effects on lipids profile, glucose, and body weight. This study aimed to evaluate the effects of nano-curcumin therapy on insulin resistance and serum level of afamin in patients with MS. MATERIALS AND METHODS: Thirty MS patients (15 males and 15 females) received 80 mg/daily nano-curcumin for two months. The samples of fasting blood were collected from the participants at the beginning and 60 days after initiation of the intervention to measure biomarkers. RESULTS: Comparing pre- and post-treatment with nano-curcumin values revealed a significant decrease in fasting plasma glucose (FPG) (p=0.017), insulin, homeostatic model assessment of insulin resistance (HOMA-IR) (p=0.006), and afamin (p=0.047). Moreover, there was a significantly negative relationship between afamin and high-density lipoprotein cholesterol (HDL-C) (p=0.044), as well as a significantly positive relationship between afamin and systolic (SBP) (p<0.001) and diastolic (DBP) (p<0.001) blood pressures. CONCLUSION: Results suggest that taking nano-curcumin for 60 days may have positive effects on afamin, FPG, insulin, and HOMA-IR in patients with MS, but would not significantly affect other metabolic profiles. More studies with larger sample sizes are required to confirm these findings.

Changes in T helper cell-related factors in patients with type 2 diabetes mellitus after empagliflozin therapy.

The immune factors related to T helper (Th) 1 (T-bet, STAT1, and IFN-γ), Th17 (ROR-γt, STAT3, and IL-17), and Treg (FOXP3, STAT5, and IL-10) cells, and SOCS1/3 and the proliferation of Th cells were investigated in type 2 diabetes mellitus patients before (baseline) and after empagliflozin therapy. A total of 56 patients on metformin and gliclazide were separated into two groups: Group 1 did not receive empagliflozin (EMPA-) and the Group 2 received 10 mg/day of empagliflozin for 6 months (EMPA+). The expressions of T-bet, ROR-γt, FOXP3, STAT1/3/5 and SOCS1/3 were evaluated in CD4+ T cells with real-time PCR. The production of IFN-γ, IL-17, and IL-10 from CD4+ T cells was measured using ELISA. The proliferation of Th cells was assessed with flow cytometry. Six months of empagliflozin therapy significantly reduced the expression of ROR-γt and increased FOXP3 and STAT5 expression, compared to baseline. Production of IL-17 decreased after empagliflozin treatment, while IL-10 was enhanced in the EMPA+ group. Oral administration of empagliflozin or the addition of empagliflozin to the cell cultures diminished the proliferation of Th cells. Empagliflozin showed anti-inflammatory effects on Th cells by decreasing Th17-related factors, reducing proliferation capacity, and increasing Treg cell properties.

Reduced frequency and functional potency of CD49d- T regulatory cells in patients with newly diagnosed type 2 diabetes mellitus.

This study set out to check the quantitative and qualitative properties of peripheral CD4+CD25+CD49d- T regulatory (CD49d- Treg) cells in type 2 diabetes mellitus (T2DM) patients. This work comprised 35 newly diagnosed patients and 35 healthy controls (HCs). The frequency of FoxP3 expressing CD49d- Treg cells was determined by flow cytometry. The gene expression of FoxP3 and CD49d was assessed by real-time PCR. Suppression assays with purified CD49d- Treg cells and CD4+CD25- T conventional (Tconv) cells were done by flow cytometry. The supernatants of Tconv/CD49d- Treg co-cultures were tested for IFN-γ, IL-4, IL-17, and IL-10 using ELISA. The frequency of CD49d- Treg cells (by both CD4+CD25+CD49d- and CD4+CD25++CD49d- phenotypes) observed to be reduced in patients versus HCs. In the patients, decreased protein and gene expression of FoxP3 was seen in CD49d- Treg cells. Suppressive potency of CD49d- Treg cells to inhibit Tconv cells proliferation was diminished, and inversely related to fasting plasma glucose and hemoglobin A1c in the patients. Tconv cells from T2DM patients released higher amount of IL-17 and lower concentration of IL-10 versus HCs. In Tconv/CD49d- Tregs co-cultures, decreased IL-17 and increased IL-10 levels were seen in HCs, but not T2DM patients. CD49d- Treg cells from the patients have a fundamental defect and Treg cells fail to inhibit the aggressive inflammatory responses.

Comparison of Salivary Antioxidants and Oxidative Stress Status in Gestational Diabetes Mellitus and Healthy Pregnant Women.

BACKGROUND: One of the most common complications of pregnant women is gestational diabetes mellitus (GDM). Oxidative stress can play an important role in GDM. OBJECTIVE: The aim of this study was to evaluate salivary antioxidants and oxidative stress markers in GDM. METHODS: Twenty pregnant women with GDM and 20 healthy pregnant women with normal blood glucose test participated in this study. Five mL of unstimulated saliva samples were collected. Spectrophotometric assay was carried out for sialo-chemical analysis. Stata software was used for data analysis. RESULTS: The GDM group exhibited no significant difference in salivary total antioxidant capacity and malondialdehyde compared to the healthy control group. All antioxidants markers, the uric acid, total antioxidant, peroxidase and catalase, decreased in GDM group that the difference of peroxidase and catalase was statistically significant. All of oxidative stress markers, the salivary malondialdehyde, total oxidative stress and total thiol, increased in GDM group. GDM group exhibited significantly higher salivary total oxidative stress levels. CONCLUSION: Catalase level was significantly lower and total oxidative stress was significantly higher. These two markers might have significant importance and might exhibit early changes compared to other factors in GDM. Some salivary antioxidants might have diagnostic, prognostic or therapeutic implications in GDM. Other studies with large sample size on salivary and blood samples need to be done to confirm these properties and salivary samples using instead of blood samples in GDM biomarkers changes.

Predictors of COVID-19 related death in diabetes patients: A case-control study in Iran.

BACKGROUND: Identifying the predictors of COVID-19 related death in diabetes patients can assist physicians for detecting risk factors related to the worse outcome in these patients. In this study we investigated the predictors of the death in patients with diabetes compared with non-diabetic COVID-19 patients. METHODS: In the present case-control study, the case group were diabetic patients with COVID-19 and the control group included Non-diabetic COVID-19 patients. The data source regarding the demographic characteristics, clinical symptoms, laboratory, and radiological findings on admission as well as the complications, treatment, and outcomes during hospitalization were gathered from their medical record through two trained nurses. Adjusted and unadjusted odds ratios (OR) estimate were calculated using the simple and multiple logistic regression through backward model. RESULTS: The mean (SD) age of the case group was higher than that of the control group; [65.24 (12.40) years vs. 59.35 (17.34) years, respectively (P < 0.001)]. Results of the adjusted logistic regression model showed that, advanced age (+60 year) (OR = 5.13, P = 0.006), addiction (OR = 5.26, P = 0.033), high level of Blood urea nitrogen (OR = 5.85, P < 0.001), and high level of Alkaline Phosphatase (OR = 3.38, P = 0.012) in diabetic patients were significantly associated with increase the odds of death in COVID-19 patients. CONCLUSION: We found that in COVID-19 patients with diabetes; advanced age, addiction, high level of BUN and Alp and in non-diabetic COVID-19 patients advanced age, dyspnea, high level of BUN and SGOT were associated with increase risk of death in these patients.