A predictive model for hyperuricemia among type 2 diabetes mellitus patients in Urumqi, China.

BACKGROUND: Patients with type 2 diabetes Mellitus (T2DM) are more likely to suffer from a higher uric acid level in blood-hyperuricemia (HUA). There are no conclusive studies done to predict HUA among T2DM patients. Therefore, this study aims to explore the risk factors of HUA among T2DM patients and finally suggest a model to help with its prediction. METHOD: In this retrospective research, all the date were collected between March 2017 and October 2019 in the Medical Laboratory Center of the First Affiliated Hospital of Xinjiang Medical University. The information included sociodemographic factors, blood routine index, thyroid function indicators and serum biochemical markers. The least absolute shrinkage and selection operator (LASSO) and multivariate binary logistic regression were performed to screen the risk factors of HUA among T2DM patients in blood tests, and the nomogram was used to perform and visualise the predictive model. The receiver operator characteristic (ROC) curve, internal validation, and clinical decision curve analysis (DCA) were applied to evaluate the prediction performance of the model. RESULTS: We total collected the clinical date of 841 T2DM patients, whose age vary from 19-86. In this study, the overall prevalence of HUA in T2DM patients was 12.6%. According to the result of LASSO-logistic regression analysis, sex, ethnicity, serum albumin (ALB), serum cystatin C (CysC), serum inorganic phosphorus (IPHOS), alkaline phosphatase (ALP), serum bicarbonate (CO2) and high-density lipoprotein (HDLC) were included in the HUA risk prediction model. The nomogram confirmed that the prediction model fits well (χ2 = 5.4952, P = 0.704) and the calibration curve indicates the model had a good calibration. ROC analysis indicates that the predictive model shows the best discrimination ability (AUC = 0.827; 95% CI: 0.78-0.874) whose specificity is 0.885, and sensitivity is 0.602. CONCLUSION: Our study reveals that there were 8 variables that can be considered as independent risk factors for HUA among T2DM patients. In light of our findings, a predictive model was developed and clinical advice was given on its use.

Metagenomics and Faecal Metabolomics Integrative Analysis towards the Impaired Glucose Regulation and Type 2 Diabetes in Uyghur-Related Omics.

OBJECTIVE: Gut microbiota and their metabolites play an important role in the development of type 2 diabetes mellitus (T2DM). This research was designed to study the relationship between gut microbiota and faecal metabolites of Uyghur newly onset T2DM and impaired glucose regulation (IGR) patients. MATERIALS AND METHODS: A total of 60 different glycemic Uyghur subjects were enrolled and divided into T2DM, IGR, and normal glucose tolerance (NGT) groups. Metagenomics and LC-MS-based untargeted faecal metabolomics were employed. Correlations between bacterial composition and faecal metabolomics were evaluated. RESULTS: We discovered that the composition and diversity of gut microbiota in newly onset T2DM and IGR were different from those in NGT. The α-diversity was higher in NGT than in T2DM and IGR; ß-diversity analysis revealed apparent differences in the bacterial community structures between patients with T2DM, IGR, and NGT. LC-MS faecal metabolomics analysis discovered different metabolomics features in the three groups. Alchornoic acid, PE (14 : 0/20 : 3), PI, L-tyrosine, LysoPC (15 : 0), protorifamycin I, pimelic acid, epothilone A, 7-dehydro-desmosterol, L-lysine, LysoPC (14 : 1), and teasterone are the most significant differential enriched metabolites. Most of the differential enriched metabolites were involved in metabolic processes, including carbohydrate metabolism, starch and sucrose metabolism, phenylpropanoid biosynthesis, and biosynthesis of amino acids. Procrustes analysis and correlation analysis identified correlations between gut microbiota and faecal metabolites. Matricin was positively correlated with Bacteroides and negatively correlated with Actinobacteria; protorifamycin I was negatively correlated with Actinobacteria; epothilone A was negatively correlated with Actinobacteria and positively correlated with Firmicutes; PA was positively correlated with Bacteroides and negatively correlated with Firmicutes; and cristacarpin was positively correlated with Actinobacteria; however, this correlation relationship does not imply causality. CONCLUSIONS: This study used joint metagenomics and metabolomics analyses to elucidate the relationship between gut microbiota and faecal metabolites in different glycemic groups, and the result suggested that metabolic disorders and gut microbiota dysbiosis occurred in Uyghur T2DM and IGR. The results provide a theoretical basis for studying the pathological mechanism for further research.

Risk and protective factors of co-morbid depression in patients with type 2 diabetes mellitus: a meta analysis.

The aim from this paper is to identify the main influencing factors of co-morbid depression among T2DM (Type 2 Diabetes Mellitus) patients and to provide reliable evidence for relative researches. A systematic review and meta-analysis of risk factors for co-morbid depression in T2DM was performed on all retrieved studies through an observational research of network database. Data were analyzed by Review Manager 5.3 from the extracted results, the heterogeneity index of the studies was determined using Chi-squared I2 tests and on the basis of heterogeneity, a fixed or random effect model was used to estimates the pooled effect of each influencing factor. Fourteen observational studies containing total of 82,239,298 cases that have been identified. Diabetic complications (OR = 2.91; 95%CI, 1.76-4.82, p < 0.0001), insulin use (OR = 1.71; 95%CI, 1.18-2.48, p = 0.005), education status (OR = 1.91; 95%CI, 1.30-2.81, p = 0.001) were confirmed as risk factors, while regular exercising (OR = 0.51; 95%CI, 0.27-0.96, p = 0.04), gender (OR = 0.56; 95%CI, 0.47-0.65, p < 0.0001), marital status (OR = 0.53; 95%CI, 0.34-0.83, p = 0.005), current social status (OR = 0.64; 95%CI, 0.47-0.88, p = 0.006) were confirmed as protective factors of co-morbid depression in the patients with T2DM. Subgroup analysis claimed age (≥60 years) was a risk factor and smoking was protective factor for co-morbid depression in the patients with T2DM. Being female, have diabetic complications, insulin use, education level less than secondary are risk factors. However, doing regular exercise, being married and on work are protective factors of co-morbid depression in patients with T2DM. As to the other influencing factors should be further studied.

Integrative Analysis Toward Different Glucose Tolerance-Related Gut Microbiota and Diet.

Objective: There is evidence that type 2 diabetes (T2DM) is affected by gut microbiota, and gut microbiota diversity modified by diet. To investigate its modifications in Uyghur patients with different glucose tolerance, we enrolled 561 subjects: newly diagnosed T2DM (n = 145), impaired glucose regulation (IGR) patients (n = 138) and in normal control (NC) population (n = 278). Methods: The nutrient intake in food frequency questionnaire was calculated by R language. The regions V3-V4 of 16S ribosomal RNA were sequenced by using Illumina Miseq platform. Sequences were clustered by operational taxonomy units, gut microbiota composition, and diversity was analyzed. Correlations between bacterial composition at different level and dietary factors were evaluated. Results: The α-diversity was highest in NC, followed by T2DM and IGR; ß-diversity distinguished between patients and NC. Compared to NC, Saccharibacteria was significantly increased in T2DM and IGR. Deferribacteres was significantly increased in T2DM compared to NC and IGR. Veillonella, Pasteurellaceae, and Haemophilus were over-represented in IGR. Abundance of Bacteroidetes was negatively correlated with LDL-C; Abundance of Tenericutes was negatively correlated with hip circumference and total cholesterol, positively correlated with HDL-C and cake intake; Actinobacteria was positively correlated with BMI and folic acid intake, negatively correlated with oil intake. Firmicutes was negatively correlated with beverage and alcohol intake. Spirochaetae was negatively correlated with fungus, fruits, beans, vitamin C, dietary fiber, and calcium. Fusobacteria was positively correlated with beans intake, and was negatively correlated with fat intake. Proteobacteria was positively correlated with tuber crops intake. Synergistetes was positively correlated with cholesterol, nicotinic acid, and selenium intake. Deferribacteres was negatively correlated with magnesium intake. Conclusions: At the phylum and genus level, the structure and diversity of intestinal microbiota of T2DM and IGR was altered, the number of OTUs, the relative abundance, and diversity were all decreased. The gut microbiota of the newly diagnosed T2DM, IGR, and NC were related to age, blood lipids, BMI, blood pressure, and dietary nutrient intake. Unbalanced nutrient intake in the three groups may affect the structure and abundance of the gut microbiota, which may play a role in the occurrence and development of T2DM.

Quantitative Evaluation of Serum Proteins Uncovers a Protein Signature Related to Maturity-Onset Diabetes of the Young (MODY).

Maturity-onset diabetes of the young (MODY) is an inherited monogenic type of diabetes. Genetic mutations in MODY often cause nonsynonymous changes that directly lead to the functional distortion of proteins and the pathological consequences. Herein, we proposed that the inherited mutations found in a MODY family could cause a disturbance of protein abundance, specifically in serum. The serum samples were collected from a Uyghur MODY family through three generations, and the serum proteins after depletion treatment were examined by quantitative proteomics to characterize the MODY-related serum proteins followed by verification using target quantification of proteomics. A total of 32 serum proteins were preliminarily identified as the MODY-related. Further verification test toward the individual samples demonstrated the 12 candidates with the significantly different abundance in the MODY patients. A comparison of the 12 proteins among the sera of type 1 diabetes, type 2 diabetes, MODY, and healthy subjects was conducted and revealed a protein signature related with MODY composed of the serum proteins such as SERPINA7, APOC4, LPA, C6, and F5.

The knowledge, attitudes and practices on influenza among medical college students in Northwest China.

Objective This study aimed to understand the knowledge, attitudes and practices (KAP) on seasonal influenza among medical college students in a low-income multiethnic society. Methods A cross-sectional questionnaire survey collected information of KAP related to influenza. A knowledge score was calculated according to the total number of correct points out of 9 questions. Logistic regression was used to identify factors associated with influenza vaccine uptake. Results 856 valid questionnaires were obtained. The average knowledge score was 14.8 ± 3.1 out of 22 correct points. Han Chinese got higher score than minorities (p < 0.001). Knowledge score increased with grade (p < 0.001). Students majoring in pharmacy had lower score than others. Questions on mode of transmission, symptoms, precautions, high risk groups and vaccination schedule had a correct rate lower than 50%. Hand hygiene was practiced by less than 40% of students after touching objects in public areas or sneezing. The proportion of participants received influenza vaccine in the past 3 y was 4.1%, 9.2% and 6.1% respectively. Willingness to receive free vaccine (OR = 2.49, 95% CI 1.31∼4.28), and awareness of the vaccine effectiveness (OR = 1.67, 95% CI 1.08∼2.56) were significantly associated with vaccine uptake, while the general knowledge about influenza, perceived susceptibility and severity, and demographic factors were not. The top 3 reasons for not being vaccinated were poor knowledge of the vaccine (46%), no perceived need due to good health (45%) and worry about adverse reactions (33%). Conclusion Health education is needed to improve the awareness of basic facts about influenza and vaccine, and more attention should be paid to minority groups. The coverage of seasonal influenza vaccine is quite low. Besides individual level behavior change, social and structural factors should be considered to increase the uptake of influenza vaccine.

Association of rs7754840 G/C polymorphisms in CDKAL1 with type 2 diabetes: a meta-analysis of 70141 subjects.

The reported association of the CDKAL1 rs7754840 G/C gene polymorphism with T2DM susceptibility remains controversial. In this study, this association was further investigated using a meta-analysis of 33,149 patients and 36,992 controls from 32 independent studies. The random-effect models were used in order to evaluate the pooled odds ratios (ORs) and their 95% confidence intervals (CIs). A significant relationship between the CDKAL1 rs7754840 G/C gene polymorphism and T2DM was observed under allelic (OR: 1.37, 95% CI: 1.22, 1.55, P < 0.001), recessive (OR: 1.58, 95% CI: 1.20-2.08, P < 0.001), dominant (OR: 1.13, 95% CI: 1.21-1.33, P = 0.01), and homozygous (OR: 1.27, 95% CI: 1.21-1.33, P < 0.001), and heterozygous (OR: 0.83, 95% CI: 0.75-0.93, P < 0.001). Overall, the CDKAL1 rs7754840 G/C gene polymorphism was found to be significantly associated with an increased T2DM risk; the C allele of the CDKAL1 rs7754840 G/C gene polymorphism may confer susceptibility to T2DM.

Meta-analysis of the relationship of NeuroD1 Ala45Thr polymorphism with type 2 diabetes / 中华内分泌代谢杂志

Objective To investigate the association of neural differentiation factor 1 (NeuroD1) Ala45Thr polymorphism with type 2 diabetes by meta-analysis.Methods The electronic databases were retrieved from PubMed,EMBASE,CNKI,VIP fulltext database,and Wanfang fulltext database.Literatures about the association of NeuroD1 Ala45Thr polymorphism with type 2 diabetes from 2004 to 2012 were searched.The selected studies from 2004 to 2012 were included to analyze data based on the published meta-analysis of the NeuroD1 (Ala45Thr) gene polymorphism and type 2 diabetes written by Kavvoura,et al.The odds ratio of NeuroD1 (Ala45Thr) genotype distributions in type 2 diabetic patients compared with healthy control were analyzed.Rev-Man 5.0 software was applied for investigating hereogeneity among individual studies and summarizing effects with proper statistical methods.Thirteen case control studies were enrolled.Results A total of 3 896 patients and 3 186 control subjects were enrolled for the study.The pooled ORs of Thr45Thr45/(Ala45Thr+ Ala45Ala45) genotype in type 2 diabetes mellitus and control groups were 3.16 (95％ CI0.99-10.11) in the subgroup of yellow race and 1.09(95％ CI0.90-1.32) in the subgroup of white race,with no statistically significant difference(P＞0.05).The pooled OR of G/A allele in type 2 diabetes mellitus and control groups was 0.85 (95 ％ CI 0.72-0.99)/1.18 (95％ CI 1.07-1.38),with statistically significant difference (Z =2.02,P =0.04).Conclusions The A allele of NeuroD1 (Ala45Thr) locus may be a risk factor for type 2 diabetes mellitus.

An analysis of diet and nutrition status of Uyghur families with maturity onset diabetes of young / 中华内分泌代谢杂志

To study the status of diet and nutrition in Uyghur families with maturity onset diabetes of young (MODY).Four MODY families were composed of four generations of Uyghur with 50 members collected from Kashgar,Shanshan,and Ili regions of Xinjiang Uyghur Autonomous Region.A dietary survey with a semi-quantitative food frequency questionnaire was conducted.According to the sex and different intensities of physical activity,the nutrient intake was calculated by nutrition calculator software,and the results were compared with recommended nutrients intake(RNI).Cereals,livestock,and poultry meat,being the main food stuff in Uyghur MODY families,accounted for 54.11％ and 13.87％ of total energy respectively,while fruit,fish,and shrimps were seldom taken,and accounted for 0.41％ and 0.26％ of total energy respectively.Carbohydrate,protein,and fat accounted for 55.0％,16.7％,and 28.4％ of total energy intake respectively,within the scope of the RNI for diabetes suggested by both Chinese Diabetes Society and the American Diabetes Association.The total energy and all three major nutrients were excessively taken by subjects of different genders and different intensities physical activity from Uyghur MODY families in Xinjiang.Uyghur diets lead to excessive calorie intake in the Uyghur MODY family members.The Health education of Uyghur language and text should be strengthened,so as to improve the scientific dietary knowledge.

Serum metabonomic study of two Uyghur families with maturity-onset diabetes of the young / 中华内分泌代谢杂志

ObjectiveTo study the characteristics of serum metabolites in two Uyghur families with maturityonset diabetes of the young(MODY).MethodsTwo MODY families were composed of four generations of Uyghur with 52 members collected from Kashgar region,Xinjiang Uyghur Autonomous Region.The general information,blood glucose and lipid levels,and blood pressure were analyzed.Using 1H nuclear magnetic resonance (1H NMR )spectroscopy,serum metabolites were measured for each subject.After having conducted data pretreatment on the spectrogram,orthogonal partial least squares discriminant analysis ( OPLS-DA ) was used to interpret data.The subjects were divided into two groups according to blood glucose ( diabetes and non-diabetes ),blood pressure,body mass index ( BMI ) for comparing differences in the metabolites.The differences of serum metabolic components between two groups were determined using pearson correlation coefficients with significant difference detection and two-dimensional spectrum technology.Results lsoleucine and tyrosine levels in diabetes group were decreased significantly,while α-glucose and β-glucose levels were increased significantly compared with non-diabetes group( all P＜0.05 ).Citrate,phaseomannite,1 -methyl histidine,and tyrosine levels in hypertension group were all decreased significantly compared with normal blood pressure group( all P＜0.05 ).No significant metabonomic differences were observed between normal BMI group and high BMI group.ConclusionsMetabonomic changes in diabetic patients from MODY families indicate that diabetic patients suffer from disordered tricarboxylic acid cycle ( TCA cycle )metabolism,with reduced glycolysis of glycogen in liver and muscle.There exist the metabolic disorder in TCA cycle and obstruction of fat metabolism in patients with hypertension from the MODY families.

Exome sequencing: an efficient strategy for identifying the causative genes of monogenic disorders / 中华医学遗传学杂志

The development of new generation sequencing technologies has brought new opportunities for the study of diseases. Exome sequencing has shown to be an effective, rapid, high performance technique that has already been used in research of inherited diseases such as monogenic disorders. It has already been approved by scientists in the field of monogenic disorder study, and will become widely used. This approach will accelerate discovery of the causative genes of Mendelian disorders. This article reviews some recent applications of exome sequencing in the study of gene-related diseases.

Serum metabolic profiling of abnormal savda by liquid chromatography/mass spectrometry.

Abnormal savda is a special symptom in Uigur medicine. The understanding of its metabolic origins is of great importance for the subsequent treatment. Here, a metabonomic study of this symptom was carried out using LC-MS based human serum metabolic profiling. Orthogonal signal correction partial least-squares discriminant analysis (OSC-PLS-DA) was used for the classification and prediction of abnormal savda. Potential biomarkers from metabonomics were also identified for a metabolic understanding of abnormal savda. As a result, our OSC-PLS-DA model had a satisfactory ability for separation and prediction of abnormal savda. The potential biomarkers including bilirubin, bile acids, tryptophan, phenylalanine and lyso-phosphatidylcholines indicated that abnormal savda could be related to some abnormal metabolisms within the body, including energy metabolism, absorption of nutrition, metabolism of lecithin on cell membrane, etc. To the best of our knowledge, this is the first study of abnormal savda based on serum metabolic profiling. The LC/MS-based metabonomic platform could be a powerful tool for the classification of symptoms and for the development of this traditional medicine into an evidence-based one.