Monocarbonyl analogs of curcumin C66 and B2BrBC modulate oxidative stress, JNK activity, and pancreatic gene expression in rats with streptozotocin-induced diabetes.

The pathogenesis of type 1 diabetes mellitus (T1DM) involves oxidative stress and inflammation. Curcumin, a natural polyphenolic compound found in turmeric, known to exhibit antioxidative and anti-inflammatory properties, is characterized by poor chemical stability, low bioavailability, and rapid metabolism. Monocarbonyl analogs of curcumin (MACs) with a structural absence of ß-diketone and enhanced stability and bioavailability present a potential solution to the challenges associated with the use of curcumin. This study aimed to evaluate the effect of two MACs, C66 and B2BrBC, on oxidative stress markers, antioxidant enzyme activity, expression of diabetes-associated genes, and signaling pathway proteins in the context of T1DM. Streptozotocin (STZ)-induced male Wistar rats or rat pancreatic RIN-m cells were used for in vivo and in vitro experiments, respectively. C66 or B2BrBC were given either before or after STZ treatment. Oxidative stress markers and antioxidant enzyme activities were determined in various tissues. Expression of diabetes-associated genes was assessed using RT-qPCR, and the activity of signaling pathway proteins in the pancreas was determined through Western blot analysis. Treatment with C66 and B2BrBC significantly reduced oxidative stress markers and positively influenced antioxidant enzyme activities. Moreover, both compounds inhibited JNK activity in the pancreas while enhancing the expression of genes crucial for ß-cell survival and glucose and redox homeostasis. The findings highlight the multifaceted potential of C66 and B2BrBC in ameliorating oxidative stress, influencing gene expression patterns linked to diabetes, and modulating key signaling pathways in the pancreas. The findings suggest that these compounds can potentially address diabetes-related pathological processes.

Exploring maternal and neonatal outcomes in women with Type-1 Diabetes: A study from Pakistan.

Background & Objective: Pregnancy in women diagnosed with Type-1 diabetes mellitus poses a higher risk of experiencing complications related to the health of the fetus, the mother, and the newborn, along with potential obstetric issues. The objective of this study was to examine the maternal and fetal outcomes, as well as complications faced by pregnant women with type-1 diabetes, and to identify potential preventable factors. Methods: This retrospective cohort study, conducted at Baqai Institute of Diabetology and Endocrinology (BIDE), Baqai Medical University, Karachi, Pakistan (January 2022 - January 2023), focused on registered pregnancies of women with Type-1 diabetes. A predesigned questionnaire recorded demographic information, diabetes and obstetric history, clinical details, treatment specifics, maternal, perinatal, and neonatal outcomes. Results: This study included 100 women with pre-existing Type-1 diabetes (mean age: 15.11 ± 5.64 years at diabetes diagnosis). Of these, 72% reported unplanned pregnancies, with a mean HbA1C at conception 8.29%. Median gestational age at delivery was 32.15 ± 10.82 weeks. Delivery outcomes included 40% normal vaginal deliveries and 60% C-sections (9% emergency, 51% elective). Stillbirths occurred in 14 cases, while 16 women experienced one miscarriage, seven had two, and 10 had three miscarriages. Glycemic targets (fasting) were achieved in 55 women, and post-meal targets only in 29, whereas, neonatal complications included hypoglycemia in 13 and low birth weight in 12 neonates. Conclusion: The high frequency of unplanned pregnancies and cesarean sections along with poor management of pre-pregnancy care and poor glycemic control results in compromised maternal and perinatal outcomes in this high-risk group.

CTSG polymorphisms in Chinese children with type 1 diabetes mellitus.

Cathepsin G (CTSG) plays an important role in the regulation of immune processes. Accumulated studies show that CTSG is involved in the onset and development of type 1 diabetes mellitus (T1DM). As the genetic background of T1DM varies widely among populations, we aimed to study the relationship between genetic polymorphisms in CTSG and T1DM susceptibility in Chinese populations. A total of 141 patients with T1DM and 200 healthy controls were enrolled in the study. Serum CTSG expression was detected using enzyme-linked immunosorbent assay (ELISA). Genotyping of two selected single nucleotide polymorphisms (SNPs) (rs2236742 and rs2070697) of CTSG was performed using PCR and Sanger sequencing. CTSG expression in patients with T1DM was significantly higher than in the control group. Alleles C and T of CTSG SNP rs2236742 were increased in T1DM. No significant associations were found for the SNP rs2070697. Our results indicate that the CTSG rs2236742 allele (C/T) is associated with T1DM in Chinese children and may serve as a new biomarker for predicting T1DM susceptibility.

The Burden of Inpatient Hospitalizations with Cardiac and Cerebrovascular Diseases in Patients with Type 1 Diabetes: Insights from the National Inpatient Sample in the US.

BACKGROUND: This study aimed to evaluate the burden and impact of cardiac and cerebrovascular disease (CCD) on hospital inpatients with type 1 diabetes mellitus (T1DM). METHODS: This is a retrospective nationwide cohort study of people with T1DM with or without CCD in the US National Inpatient Sample between 2016 and 2019. The in-hospital mortality rates, length of stay (LoS), and healthcare costs were determined. RESULTS: A total of 59,860 T1DM patients had a primary diagnosis of CCD and 1,382,934 did not. The median LoS was longer for patients with CCD compared to no CCD (4.6 vs. 3 days). Patients with T1DM and CCD had greater in-hospital mortality compared to those without CCD (4.1% vs. 1.1%, p < 0.001). The estimated total care cost for all patients with T1DM with CCD was approximately USD 326 million. The adjusted odds of mortality compared to patients with non-CCD admission was greatest for intracranial hemorrhage (OR 17.37, 95%CI 12.68-23.79), pulmonary embolism (OR 4.39, 95%CI 2.70-7.13), endocarditis (OR 3.46, 95%CI 1.22-9.84), acute myocardial infarction (OR 2.31, 95%CI 1.92-2.77), and stroke (OR 1.47, 95%CI 1.04-2.09). CONCLUSIONS: The burden of CCD in patients with T1DM is substantial and significantly associated with increased hospital mortality and high healthcare expenditures.

The potential therapeutic role of IL-35 in pathophysiological processes in type 1 diabetes mellitus.

A chronic autoimmune condition known as type 1 diabetes mellitus (T1DM) has characteristics marked by a gradual immune-mediated deterioration of the ß-cells that produce insulin and causes overt hyperglycemia. it affects more than 1.2 million kids and teenagers (0-19 years old). In both, the initiation and elimination phases of T1DM, cytokine-mediated immunity is crucial in controlling inflammation. T regulatory (Treg) cells, a crucial anti-inflammatory CD4+ T cell subset, secretes interleukin-35 (IL-35). The IL-35 has immunomodulatory properties by inhibiting pro-inflammatory cells and cytokines, increasing the secretion of interleukin-10 (IL-10) as well as transforming Growth Factor- ß (TGF-ß), along with stimulating the Treg and B regulatory (Breg) cells. IL-35, it is a possible target for cutting-edge therapies for cancers, inflammatory, infectious, and autoimmune diseases, including TIDM. Unanswered questions surround IL-35's function in T1DM. Increasing data suggests Treg cells play a crucial role in avoiding autoimmune T1DM. Throughout this review, we will explain the biological impacts of IL-35 and highlight the most recently progresses in the roles of IL-35 in treatment of T1DM; the knowledge gathered from these findings might lead to the development of new T1DM treatments. This review demonstrates the potential of IL-35 as an effective autoimmune diabetes inhibitor and points to its potential therapeutic value in T1DM clinical trials.

Abdominal Obesity-Metabolic Syndrome 3 Misclassified as Type 1 Diabetes Mellitus.

Age is no longer the most important differentiating feature between type 1 and type 2 diabetes, as obesity and metabolic syndrome are on the rise in the pediatric population. Here we present a case of a 30-year-old male individual initially diagnosed with uncontrolled type 1 diabetes mellitus (T1DM) since the age of 15, and treatment with high insulin doses has been unsuccessful. He was later identified as having abdominal obesity-metabolic syndrome 3 (AOMS3) based on strong family history and the presence of insulin resistance features. AOMS3 is characterized by early-onset coronary artery disease, central obesity, hypertension, and diabetes. Early detection of this condition is crucial to implement timely interventions and preventing the onset of complications.

Lipid profile alterations and biomarker identification in type 1 diabetes mellitus patients under glycemic control.

BACKGROUND: Type 1 diabetes mellitus (T1DM) is well-known to trigger a disruption of lipid metabolism. This study aimed to compare lipid profile changes in T1DM patients after achieving glucose control and explore the underlying mechanisms. In addition, we seek to identify novel lipid biomarkers associated with T1DM under conditions of glycemic control. METHODS: A total of 27 adults with T1DM (age: 34.3 ± 11.2 yrs) who had maintained glucose control for over a year, and 24 healthy controls (age: 35.1 + 5.56 yrs) were recruited. Clinical characteristics of all participants were analyzed and plasma samples were collected for untargeted lipidomic analysis using mass spectrometry. RESULTS: We identified 594 lipid species from 13 major classes. Differential analysis of plasma lipid profiles revealed a general decline in lipid levels in T1DM patients with controlled glycemic levels, including a notable decrease in triglycerides (TAGs) and diglycerides (DAGs). Moreover, these T1DM patients exhibited lower levels of six phosphatidylcholines (PCs) and three phosphatidylethanolamines (PEs). Random forest analysis determined DAG(14:0/20:0) and PC(18:0/20:3) to be the most prominent plasma markers of T1DM under glycemic control (AUC = 0.966). CONCLUSIONS: The levels of all metabolites from the 13 lipid classes were changed in T1DM patients under glycemic control, with TAGs, DAGs, PCs, PEs, and FFAs demonstrating the most significant decrease. This research identified DAG(14:0/20:0) and PC(18:0/20:3) as effective plasma biomarkers in T1DM patients with controled glycemic levels.

Exploring the Diagnostic Complexity of Diabetes Subtypes in Pediatric Obesity: A Case Report of an Adolescent With Prader-Willi Phenotype and Literature Review.

Obesity among adolescents poses a significant global health concern with profound short- and long-term impact on physical and mental well-being. The intricate relationship between obesity and the onset of diabetes remains ambiguous, particularly in cases where the manifestation may differ from that observed in individuals with uncomplicated obesity. Herein, we present the case of a 14-year-old male adolescent with Prader-Willi phenotype and subsequent obesity, exhibiting symptoms of polyuria and polydipsia over a 10-day period, indicative of potential diabetes mellitus (DM). Laboratory assessments revealed a hemoglobin A1c level of 10%, confirming the suspected diagnosis. Notably, despite the absence of ketosis, elevated C-peptide levels and the presence of slightly positive islet-cell antibodies warranted further investigation. While the presence of antibodies typically aligns with a diagnosis of type 1 DM, recent research has highlighted the occurrence of anti-insulin pancreatic cell antibodies in type 2 DM cases. This article aims to delve into the multifaceted issues surrounding adolescent obesity, atypical presentations of DM with positive antibodies, and the long-term management of patients with genetic syndromes.

Osteocalcin, miR-143, and miR-145 Expression in Long-Standing Type 1 Diabetes Mellitus and Their Correlation with HbA1c.

Inadequate management and control of hyperglycemia predisposes diabetic patients to a wide range of complications. Thus, this opens new windows for exploring and scrutinizing novel candidate biomarkers. This study was designed to scrutinize the relationship between HbA1c, osteocalcin, calcium, phosphorus, and expression levels of miR-143 and miR-145 in individuals with T1DM and explore their correlations and diagnostic potential for T1DM. 120 unrelated participants were included (i.e., 90 participants with type 1 diabetes mellitus and 30 healthy controls) and were allocated into two groups. Participants with T1DM were allocated into three subgroups (i.e., below 1 year, 1-8 years, and over 8 years) based on diabetic duration. Participants with T1DM experienced noticeable HbA1c elevation. However, osteocalcin, phosphorus, and calcium profiles notably declined in participants with diabetes compared with those in healthy controls. Moreover, the expression levels of miR-143 and miR-145 decreased in participants with diabetes with a significant difference between participants with diabetes and healthy controls. Additionally, significant alterations in HbA1c, osteocalcin, phosphorus, and calcium profiles and expression levels of miR-143 and miR-145 were observed with increasing diabetic duration (T1DM > 8 years compared with those with a diabetes duration of less than 1 year). This study suggests that miR-143 and miR-145 are prospective biomarkers of diabetes mellitus, which may help predict the progression of complications.

Impact of Thyroid Autoimmunity on the Clinical and Biochemical Characteristics of Type 1 Diabetes Mellitus Patients.

INTRODUCTION: Type 1 diabetes mellitus (T1DM) is frequently associated with other autoimmune disorders that are characterized by the presence of organ-specific autoantibodies. Autoimmune thyroid disease (AIT) is the most frequent autoimmune disorder associated with T1DM. Thyroid peroxidase antibodies (TPOAb) serve as a marker for diagnosing AIT. Prior research indicates that thyroid dysfunction can negatively impact linear growth and glycemic control in subjects with T1DM. The present study was done to determine the impact of thyroid autoimmunity on the clinical and biochemical characteristics of patients with newly diagnosed T1DM. METHODS: In this single-center, hospital-based, observational cross-sectional study, we enrolled 70 patients with newly diagnosed T1DM ≤18 years of age. Type 1 diabetes mellitus was diagnosed based on the acute onset of osmotic symptoms with or without diabetic ketoacidosis (DKA), severe hyperglycemia (blood glucose >13.9 mmol/l (>250 mg/dl)), and insulin requirement from the onset of diabetes. Secondary diabetes, pancreatic diabetes (Type 3c), and maturity-onset diabetes of the young (MODY) were excluded. Participants were screened for AIT disease using TPOAb testing. Based on the presence or absence of TPOAb, the participants were categorized into two groups: Group A comprised individuals with T1DM who tested positive for TPOAb, while Group B consisted of those who tested negative for TPOAb. RESULTS: Out of 70 patients, 41.4% were girls and 58.6% were boys, with a mean age of 9.8±4.4 years. The prevalence of TPOAb among the cohort was 18.6%. A significant majority of patients (71.4%), presented with DKA. Group A showed significantly lower mean height standard deviation scores (SDS) compared to Group B (-0.3±0.6 vs. -0.8±0.5, p = 0.004), but no differences in weight SDS or BMI SDS. Hemoglobin A1C (HbA1c) levels, C-peptide levels, and frequency of DKA did not differ between groups. Group A had higher mean thyroid-stimulating hormone (TSH) levels (4.8±3.7 µU/ml vs. 2.6±1.5 µU/ml, p = 0.001) and a greater proportion of patients with TSH levels above the upper limit of normal compared to Group B (38.4% vs. 7.1%, p = 0.008). Additionally, Group A exhibited a higher frequency of glutamic acid decarboxylase antibody (GADA) positivity compared to Group B (46.1% vs. 17.5%, p = 0.04). CONCLUSION: Patients positive for TPOAb exhibited significantly lower height SDS compared to TPOAb-negative patients. Additionally, T1DM patients with TPOAb positivity showed an increased frequency of GADA compared to those without TPOAb. However, no significant differences were found in HbA1c levels, C-peptide levels, or hematological parameters between TPOAb-positive and TPOAb-negative patients. These findings emphasize the impact of TPOAb on growth parameters in T1DM and advocate for routine screening of TPOAb in all T1DM patients, starting at the time of diabetes diagnosis.

A bibliometric study of global trends in T1DM and intestinal flora research.

Background: Type 1 diabetes mellitus (T1DM) is a chronic metabolic disease that seriously jeopardizes human physical and mental health and reduces quality of life. Intestinal flora is one of the critical areas of exploration in T1DM research. Objective: This study aims to explore the research hotspot and development trend of T1DM and intestinal flora to provide research direction and ideas for researchers. Methods: We used the Web of Science (WOS) Core Collection and searched up to 18 November 2023, for articles on studies of the correlation between T1DM and intestinal flora. CiteSpace, VOSviewers and R package "bibliometrix" were used to conduct this bibliometric analysis. Results: Eventually, 534 documents met the requirements to be included, and as of 18 November 2023, there was an upward trend in the number of publications in the field, with a significant increase in the number of articles published after 2020. In summary, F Susan Wong (UK) was the author with the most publications (21), the USA was the country with the most publications (198), and the State University System of Florida (the United States) was the institution with the most publications (32). The keywords that appeared more frequently were T cells, fecal transplants, and short-chain fatty acids. The results of keywords with the most robust citation bursts suggest that Faecalibacterium prausnitzii and butyrate may become a focus of future research. Conclusion: In the future, intestinal flora will remain a research focus in T1DM. Future research can start from Faecalibacterium prausnitzii and combine T cells, fecal bacteria transplantation, and short-chain fatty acids to explore the mechanism by which intestinal flora affects blood glucose in patients with T1DM, which may provide new ideas for the prevention and treatment of T1DM.

HUPA-UCM diabetes dataset.

This dataset provides a collection of Continuous Glucose Monitoring (CGM) data, insulin dose administration, meal ingestion counted in carbohydrate grams, steps, calories burned, heart rate, and sleep quality and quantity assessment ac- quired from 25 people with type 1 diabetes mellitus (T1DM). CGM data was acquired by FreeStyle Libre 2 CGMs, and Fitbit Ionic smartwatches were used to obtain steps, calories, heart rate, and sleep data for at least 14 days. This dataset could be utilized to obtain glucose prediction models, hypoglycemia and hyperglycemia prediction models, and research on the relationships among sleep, CGM values, and the rest of the mentioned variables. This dataset could be used directly from the preprocessed version or customized from raw data. The data set has been used previously with different machine learning algorithms to predict glucose values, hypo, and hyperglycemia and to analyze influences among the features and the quality and quantity of sleep in people with T1DM.

Rapid Improvement in Weight, Body Composition, and Glucose Variability With Semaglutide in Type 1 Diabetes.

The efficacy of glucagon-like peptide-1 receptor agonists (GLP1-RA) in type 2 diabetes mellitus is well-established. GLP1-RAs are not approved for use in type 1 diabetes mellitus (T1DM). A 34-year-old woman with a 23-year history of T1DM presented for review for weight gain (weight 63 kg, BMI 26.9 kg/m2) and increased HbA1c (8.3%) and glycemic variability. Subcutaneous semaglutide (1 mg weekly) was commenced. After two months, there was decrease in weight by 12 kg, body fat percent by 15%, visceral fat by 7%, and a reduction in insulin dose, glycemic variability, and HbA1c. Semaglutide could be an important adjunct to insulin treatment in T1DM.

Association of CIITA (rs8048002) and CLEC2D (rs2114870) gene variants and type 1 diabetes mellitus.

Background: Type I diabetes mellitus (T1DM) is a significant health challenge, especially for children, owing to its chronic autoimmune nature. Although the exact etiology of T1DM remains elusive, the interplay of genetic predisposition, immune responses, and environmental factors are postulated. Genetic factors control immune reactivity against ß-cells. Given the pivotal roles of CIITA and CLEC2D genes in modulating a variety of immune pathologies, we hypothesized that genetic variations in CIITA and CLEC2D genes may impact T1DM disease predisposition. This study was designed to explore the association between gene polymorphisms in CIITA (rs8048002) and CLEC2D (rs2114870) and type 1 diabetes (T1DM), with a focus on analyzing the functional consequence of those gene variants. Methods: The study enlisted 178 healthy controls and 148 individuals with type 1 diabetes (T1DM) from Suez Canal University Hospital. Genotyping for CIITA and CLEC2D was done using allelic-discrimination polymerase chain reaction (PCR). Levels of glycated hemoglobin (HbA1c) and lipid profiles were determined through automated analyzer, while fasting blood glucose and insulin serum levels were measured using the enzyme-linked immunosorbent assay (ELISA) technique. RegulomeDB was used to examine the regulatory functions of CIITA (rs8048002) and CLEC2D (rs2114870) gene variants. Results: Analysis of the genotype distribution of the CIITA rs8048002 polymorphism revealed a significantly higher prevalence of the rare C allele in T1DM patients compared to the control group (OR = 1.77; P = 0.001). Both the CIITA rs8048002 heterozygote TC genotype (OR = 1.93; P = 0.005) and the rare homozygote CC genotype (OR = 3.62; P = 0.006) were significantly more frequent in children with T1DM when compared to the control group. Conversely, the rare A allele of CLEC2D rs2114870 was found to be significantly less frequent in T1DM children relative to the control group (OR = 0.58; P = 0.002). The heterozygote GA genotype (OR = 0.61; P = 0.033) and the rare homozygote AA genotype (OR = 0.25; P = 0.004) were also significantly less frequent in T1DM patients compared to the control group. Both CIITA (rs8048002) and CLEC2D (rs2114870) gene variants were predicted to have regulatory functions, indicated by a RegulomeDB score of (1f) for each. Conclusion: The rare C allele of CIITA rs8048002 genetic variant was associated with an increased risk of developing T1DM, while the less common A allele of CLEC2D rs2114870 was associated with a reduced risk of T1DM. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-024-01402-w.

Patient-Centered Positive Factors Influencing Glycemic Control in Adolescents with Type 1 Diabetes Mellitus in China: A Cross-Sectional and Longitudinal Study.

Objective: This study aimed to explore the stable longitudinal patient-centered self-protective factors of glycosylated hemoglobin (HbA1c) in adolescents with type 1 diabetes mellitus (T1DM). Methods: We used both cross-sectional and longitudinal datasets at the Diabetes Education Center and National Endocrine and Metabolism Centre of a university hospital in China from April 2020 to July 2022. Participants were assessed using the Adolescent Diabetic Behavior Rating Scale (DBRS), Diabetes Strengths and Resilience Measure for Adolescents (DSTAR-Teen). HbA1c and other clinical variables were obtained from the medical record at the same time. 266 adolescents (131 male, age 14.1±3.9 years) completed the cross-sectional assessments and 131 (62 male, age 14.6±3.3 years) participated in a follow-up at a 1-year visit interval. Results: Logistic regression analysis of cross-sectional data of 266 cases showed that there were significant positive effects between pump treatment (ß=0.090, OR 2.460, P=0.005), DBRS scores (ß=2.593, OR 13.366, P=0.002) and the meeting of standard HbA1c (<7.5%, 58 mmol/mol). Disease duration (ß=-0.071, OR 0.932, P=0.033) was negatively correlated with it. The longitudinal multivariate generalized estimation equation model showed that DBRS scores (ß=3.165, OR 23.681, P=0.009) and DSTAR-Teen scores (ß=0.050, OR 1.051, P=0.012) had a positive influence on the meeting of standard HbA1c over one year time of 131 cases. Conclusion: Self-care and resilience had higher cross-temporal stability in influencing glycemic control over time. To reach a better glycemic control and improve long-term health outcomes, attention should be paid to the detection and enhancement of these patient-centered promoters.

Network Cluster Analysis of PPI and Phenotype Ontology for Type 1 Diabetes Mellitus.

Background: Our knowledge of Type 1 Diabetes Mellitus (T1DM) etiology is incomplete; however, the pathogenesis of the disease includes T-cell-mediated destruction of ß-cells. Objective: The present study aimed to investigate the key gene pathways and co-expression networks in T1DM disease. Material and Methods: TIDM-associated genes were identified from 13 databases, enrichment of pathways annotated with functional annotations, and analysis of protein-protein network interactions. Next, functional modules and transcription factor networks were constructed. The analysis of gene co-expression networks was conducted to discover associated pivotal modules. Results: A total of 172 expressed genes and four variants (SNP) were filtered in the of T1DM disease; pathway enrichment analysis identified key pathways, such as inflammatory bowel disease, type I diabetes mellitus, cytokine-cytokine receptor interaction, Th17 cell differentiation, JAK-STAT signaling pathway, and graft-versus-host disease. A weighted correlation network analysis revealed one module that was strongly correlated with T1DM. Functional annotation revealed that the module was mainly enriched in pathways such as T cell activation, regulation of immune system process, and response to the organic substance. IRF2, IRF4, IRF8, and CDX2 were regulated in the module at a significant level. Conclusion: The study identified IL-2 as a significant T1DM hotspot and highlighted the role of hub genes and transcription factors in the autoimmune disease, offering potentials for treatment and prevention.

A pilot study on the characterization and correlation of oropharyngeal and intestinal microbiota in children with type 1 diabetes mellitus.

Background: Type 1 Diabetes Mellitus (T1DM) is one of the most common endocrine disorders of childhood and adolescence, showing a rapidly increasing prevalence worldwide. A study indicated that the composition of the oropharyngeal and gut microbiota changed in T1DM. However, no studies have yet associated the changes between the microbiomes of the oropharyngeal and intestinal sites, nor between the flora and clinical indicators. In this study, we examined the composition and characteristics of oropharyngeal and intestinal flora in patients with T1DM in compared to healthy children. We identified correlations between oropharyngeal and intestinal flora and evaluated their association with clinical laboratory tests in patients with T1DM. Methods: The oropharyngeal and fecal samples from 13 T1DM and 20 healthy children were analyzed by high-throughput sequencing of the V3-V4 region of 16S rRNA. The associations between microbes and microorganisms in oropharyngeal and fecal ecological niches, as well as the correlation between these and clinical indicators were further analyzed. Results: It was revealed that T1DM children had distinct microbiological characteristics, and the dominant oropharyngeal microbiota genus included Streptococcus, Prevotella, Leptotrichia, and Neisseria; that of intestinal microbiota included Blautia, Fusicatenibacter, Bacteroides, and Eubacterium_hallii_group. Furthermore, oropharyngeal Staphylococcus was significantly positively correlated with intestinal norank_f__Ruminococcaceae and Ruminococcus_torques_group in TIDM children. Moreover, in these children, differential genes in oropharyngeal and intestinal samples were enriched in metabolic pathways such as amino acid generation, fatty acid metabolism, and nucleotide sugar biosynthesis. Additionally, correlation analysis between the oropharyngeal/intestinal microbiome with laboratory tests showed significant correlations between several bacterial taxa in the oropharynx and intestines and glycated hemoglobin and C-peptide. Conclusion: Unique microbial characteristics were found in the oropharynx and intestine in children with T1DM compared to healthy children. Positive correlations were found between changes in the relative abundance of oropharyngeal and gut microbiota in children with T1DM. Associations between the oropharyngeal/intestinal microbiota and laboratory investigations in children with T1DM suggest that the composition of the oropharyngeal and intestinal flora in children with T1DM may have some impact on glycemic control.

Investigation of missense mutation-related type 1 diabetes mellitus through integrating genomic databases and bioinformatic approach.

Though genes are already known to be responsible for type 1 diabetes mellitus (T1DM), the knowledge of missense mutation of that disease gene has still to be under covered. A genomic database and a bioinformatics-based approach are integrated in the present study in order to address this issue. Initially, nine variants associated with T1DM were retrieved from the GWAS catalogue. Different genomic algorithms such as PolyPhen2.0, SNPs and GTEx analyser programs were used to study the structural and functional effects of these mutations. Subsequently, SNPnexus was also employed to understand the effect of these mutations on the function of the expressed protein. Nine missense variants of T1DM were identified using the GWAS catalogue database. Among these nine SNPs, three were predicted to be related to the progression of T1DM disease by affecting the protein level. TYK2 gene variants with SNP rs34536443 were thought to have a probably damaging effect. Meanwhile, both COL4A3 and IFIH1 genes with SNPs rs55703767 and rs35667974, respectively, might alter protein function through a possibly damaging prediction. Among the variants of the three genes, the TYK2 gene with SNP rs34536443 had the strongest contribution in affecting the development of T1DM, with a score of 0.999. We sincerely hope that the results could be of immense importance in understanding the genetic basis of T1DM.

Ranolazine ameliorates T1DM-induced testicular dysfunction in rats; role of NF-κB/TXNIP/GSDMD-N/IL-18/Beclin-1 signaling pathway.

Approximately 90% of diabetic males have varying degrees of testicular dysfunction. The current study investigates the possible beneficial consequences of ranolazine against T1DM-induced testicular dysfunction in rats. Thirty-two male Sprague Dawley rats were assorted into 4 groups; normal, diabetic (single 50 mg/kg STZ, I.P.) and ranolazine (40 and 80 mg/kg, orally). The present investigation revealed that the hypoglycemic impact of ranolazine significantly improved the testicular weight and body weight of the final rats, as well as the concentration of blood testosterone, sperm count, and viability, all of which were associated with STZ-induced testicular dysfunction. Furthermore, as demonstrated by elevated reduced glutathione (GSH) activity and lowered malondialdehyde (MDA) levels, diabetic rats administered ranolazine showed a noteworthy improvement in the oxidant/antioxidant ratio. Furthermore, a substantial rise in beclin-1 concentration was seen in conjunction with a significant decrease in thioredoxin-interacting protein (TXNIP) and interleukin-18 (IL-18) concentrations when ranolazine was administered. Although ranolazine exhibited a reduction in inflammation as seen by lower expression of nuclear factor-κB (NF-κB) and cluster of differentiation (CD68) in the testicles, these biochemical findings were validated by improvements in the morphological and histopathological outcomes of both the pancreatic and testicular tissues. In conclusion, daily oral administration of ranolazine (40 and 80 mg/kg) for 8 weeks could be a promising therapy for T1DM-induced testicular dysfunction through its dose-dependent anti-oxidant and anti-inflammatory effects.

Health-related quality of life in pregnant women with type 1 diabetes and associations with maternal and neonatal complications.

PURPOSE: Preexisting type 1 diabetes is a stressful situation for women in pregnancy. We aimed to evaluate health-related quality of life (HRQoL) during pregnancy in women with type 1 diabetes and examine the association between HRQoL and pregnancy outcomes. METHODS: This multicenter prospective cohort study involved 115 pregnant women with type 1 diabetes from 11 participating centers in China. HRQoL was investigated in three trimesters using European Quality-of-life 5-Dimension 5-Level questionnaire (EQ-5D-5 L). Chinese time trade-off value method was used to calculate the EQ-5D-5 L score. Multivariable logistic regression model was used to evaluate the effect of HRQoL on maternal and neonatal outcomes. Receiver operating characteristic curves and distribution-based methods were employed to estimate minimally important differences of clinically important decline in HRQoL. RESULTS: 50.43% of the studied women with type 1 diabetes reported impaired HRQoL in pregnancy. Estimated maternal HRQoL significantly decreased from early to mid-pregnancy (mean EQ-5D-5 L score 0.97 in the first trimester and 0.91 in the second trimester) and improved slightly in late pregnancy (mean EQ-5D-5 L score 0.95). Multivariable regression model showed that women who experienced impaired HRQoL in pregnancy had higher risk of hypertensive disorder, preterm birth, and composite pregnancy outcome. The estimated minimally important difference for composite pregnancy outcome was -0.045 to -0.043. CONCLUSIONS: Experiencing impaired HRQoL during pregnancy was associated with a higher risk of hypertensive disorder and preterm birth in women with type 1 diabetes. The estimated minimally important difference of EQ-5D-5 L might serve as a clinically important tool in prenatal care. TRIAL REGISTRATION: No.ChiCTR1900025955.