Prevalence of maturity-onset diabetes of the young in phenotypic type 2 diabetes in young adults: a nationwide, multi-center, cross-sectional survey in China / 中华医学杂志(英文版)

BACKGROUND@#Maturity-onset diabetes of the young (MODY) is the most common monogenic diabetes. The aim of this study was to assess the prevalence of MODY in phenotypic type 2 diabetes (T2DM) among Chinese young adults.@*METHODS@#From April 2015 to October 2017, this cross-sectional study involved 2429 consecutive patients from 46 hospitals in China, newly diagnosed between 15 years and 45 years, with T2DM phenotype and negative for standardized glutamic acid decarboxylase antibody at the core laboratory. Sequencing using a custom monogenic diabetes gene panel was performed, and variants of 14 MODY genes were interpreted as per current guidelines.@*RESULTS@#The survey determined 18 patients having genetic variants causing MODY (6 HNF1A , 5 GCK , 3 HNF4A , 2 INS , 1 PDX1 , and 1 PAX4 ). The prevalence of MODY was 0.74% (95% confidence interval [CI]: 0.40-1.08%). The clinical characteristics of MODY patients were not specific, 72.2% (13/18) of them were diagnosed after 35 years, 47.1% (8/17) had metabolic syndrome, and only 38.9% (7/18) had a family history of diabetes. No significant difference in manifestations except for hemoglobin A1c levels was found between MODY and non-MODY patients.@*CONCLUSION@#The prevalence of MODY in young adults with phenotypic T2DM was 0.74%, among which HNF1A -, GCK -, and HNF4A -MODY were the most common subtypes. Clinical features played a limited role in the recognition of MODY.

Sleep-improving mechanisms of Jiu Wei Bu Xue Oral Liquid on regulating Glu/GABA balance in insomnia rats based on network pharmacology and experimental verification / 药学学报

This study aimed to investigate the mechanism of Jiu Wei Bu Xue Oral Liquid on insomnia rats combining the methods of network pharmacology, molecular docking and experimental verification. UPLC-Q-TOF-MS/MS method and TCMIP, TCMSP databases were used to collect the ingredients and targets of Jiu Wei Bu Xue Oral Liquid. Protein-protein interactions and network analysis were performed to screen the key network targets and putative active ingredients of Jiu Wei Bu Xue Oral Liquid in treatment of insomnia, and then following by biological function and KEGG pathway analysis. Then binding ability for key network targets and putative active ingredients were predicted with molecular docking. The prediction targets were validated in para-chlorophenylalanine (PCPA) induced insomnia rats with administration of Jiu Wei Bu Xue Oral Liquid (2, 4, 8 mL·kg-1) for 7 days. Pentobarbital sodium induced sleeping test were performed to evaluate the synergistic sleep-aiding effect of Jiu Wei Bu Xue Oral Liquid. Then glutamic acid (Glu), γ-aminobutyrate (GABA) content and glutamate decarboxylase 1 (GAD67) activity in hypothalamus or hippocampus were evaluated, and the expressions of GAD67, γ-aminobutyric acid receptor subunit α1 (GABRA1) and γ-aminobutyric acid receptor subunit β2 (GABRB2) in hippocampus were detected by qRT-PCR and Western blot methods. Animal experiments were approved by the Institutional Committee on Animal Care of Guangxi Institute of Chinese Medicine & Pharmaceutical Science (the number of permission: 2022060802). Results showed that 16 key network targets and 16 putative active ingredients were obtained by analyzing the herbs-ingredients-targets network of Jiu Wei Bu Xue Oral Liquid in treatment of insomnia. Network pharmacology and molecular docking all indicated these active ingredients, for example atractylenolide Ⅲ, showed better binding ability with GABRA1 and GABRB2. Animal study indicated that, compared to PCPA-induced insomnia model, Jiu Wei Bu Xue Oral Liquid remarkably shortened the sleeping latency and increased the sleeping duration, increased GAD67 activity and the production of GABA in hippocampus of insomnia rats, as well as the expressions of GAD67, GABRA1 and GABRB2, while decreased Glu content in hypothalamus, leading to decreasing of Glu/GABA ratio and recovery of Glu-GABA balance. These results indicated that Jiu Wei Bu Xue Oral Liquid improved insomnia symptoms and helped maintain the Glu-GABA balance within hypothalamus and hippocampus, and reduced the excitatory neurotoxicity within brain. The mechanism may due to the elevation of GAD67 expression and enzyme activity, and the enhancement of type-A GABA receptor (GABAAR)-mediated neurons inhibition.

Establishment of rat model of dysphagia after stroke by thread embolism / 中国康复理论与实践

ObjectiveTo explore a feasible animal model of dysphagia after stroke. MethodsTwenty-two clean Sprague-Dawley rats were randomly divided into normal group (n = 11) and model group (n = 11). The model of dysphagia after stroke was established by the thread embolism, and the normal group received no intervention. The latency of the first swallowing attack and the number of swallowing were recorded three and seven days after modeling. The cerebral infarction was detected by TTC staining, and the neuronal apoptosis in ischemic brain was detected by TUNEL fluorescence staining. ResultsCompared with the normal group, the swallowing latency prolonged and the number of swallowing reduced three days in the model group, however, there was no significant difference (P > 0.05); seven days after modeling, the swallowing latency prolonged (P < 0.05), and the number of swallowing slightly reduced with little significant difference (P > 0.05). Compared with the normal group, the brain tissue showed obvious infarction area and a large number of apoptotic cells, while the body mass reduced in the model group (P < 0.05). ConclusionThe model rats express some features of dysphagia, which may become a transformation model of dysphagia after stroke.

Comparison of 68Ga-PSMA PET/CT and 18F-FDG PET/CT for preoperative TNM staging of patients with prostate cancer / 中华核医学与分子影像杂志

Objective:To compare the diagnostic efficacy of 68Ga-prostate specific membrane antigen (PSMA)-11 PET/CT and 18F-fluorodeoxyglucose (FDG) PET/CT in TNM staging before radical prostatectomy. Methods:From July 2018 to December 2019, a total of 67 patients ((67.5±6.8) years) with prostate cancer diagnosed pathologically by radical surgery in Renji Hospital, School of Medicine, Shanghai Jiao Tong University were retrospectively enrolled. All patients underwent 68Ga-PSMA-11 PET/CT and 18F-FDG PET/CT whole-body scans before surgery. Results of PET/CT were compared with pathological diagnosis after surgery to compare the diagnostic efficiencies of 68Ga-PSMA-11 PET/CT and 18F-FDG PET/CT for preoperative TNM staging ( χ2 test). The differences of the maximum standardized uptake value (SUV max) in primary lesions between 2 imaging methods were compared by Mann-Whitney U test. Patients were divided into low-risk, intermediate-risk and high-risk for stratified analysis. Results:Among 67 patients, 9 were with low-risk, 19 were with intermediate-risk, 39 were with high-risk. For T staging, 59 (88.06%, 59/67) patients showed positive results by 68Ga-PSMA-11 PET/CT imaging, with median SUV max of 13.80(7.30, 22.40) for 67 patients; 31(46.27%, 31/67) patients showed positive results in 18F-FDG PET/CT imaging, with median SUV max of 4.00(3.10, 5.60) ( U=62, P<0.05). Stratifed analysis showed that the detection rate of 68Ga-PSMA-11 PET/CT was higher than that of 18F-FDG PET/CT in intermediate-risk patients (17/19 vs 6/19; χ2=4.920, P<0.05). Among 67 patients, 10 were diagnosed as N1 stage based on the pathological results. The sensitivities, specificities, accuracies, positive predictive values and negative predictive values of 68Ga-PSMA-11 PET/CT and 18F-FDG PET/CT for detecting positive regional lymph nodes were 6/10, 87.72%(50/57), 83.58%(56/67), 6/13, 92.59%(50/54) and 4/10, 89.47%(51/57), 82.09%(55/67), 4/10, 89.47%(51/57), respectively. 68Ga-PSMA-11 PET/CT detected 15 patients (22.39%, 15/67) with M1 stage, and 18F-FDG PET/CT identified 9 patients (13.43%, 9/67; χ2=35.436, P<0.05). Conclusions:As for T staging, the detection rate of 68Ga-PSMA-11 PET/CT in the intermediate-risk group is better than 18F-FDG PET/CT. In N and M staging, the detection rates of 68Ga-PSMA-11 PET/CT are higher than those of 18F-FDG PET/CT.

Clinical characteristics and diagnostic models of latent autoimmune diabetes in adults with newly diagnosed type 2 diabetes mellitus / 中国医师杂志

Objective:To analyze the clinical features of latent autoimmune diabetes (LADA) in adults among newly diagnosed type 2 diabetes mellitus (T2DM), and to explore whether LADA diagnostic models can be established based on this.Methods:From May 2016 to January 2017, 302 patients with newly diagnosed T2DM in the outpatient and inpatient department of metabolism and endocrinology of Yueyang Central Hospital were analyzed. All of them were tested for glutamic acid decarboxylase antibody (GADA). According to the consensus of the Chinese Medical Association Diabetes Association (CDS) LADA diagnosis and treatment, they were divided into LADA group (18 cases) and T2DM group (284 cases). The general clinical data and clinical biochemical indexes of the two groups were analyzed; Multiple linear regression method was used to evaluate the feasibility of establishing LADA diagnostic model.Results:⑴ Compared with patients in the T2DM group, the patients in the LADA group had a younger age of onset, and " three more and one less" symptoms were more common ( P<0.05); the weight, body mass index (BMI), waist circumference, waist-to-hip ratio (WHR), triglycerides (TG), fasting C peptide (FCP), postprandial 2 h C peptide (2 h-CP), modified islet function index HOMA-islet (CP-DM), and modified insulin resistance index HOMA-IR (CP) in the LADA group were all lower, while high-density lipoprotein cholesterol (HDL-C) and HbA1c were higher ( P<0.05). ⑵ the linear regression method was used to analyze the multicollinearity of patients in LADA group and T2DM group. The biochemical indexes with statistically significant difference were selected as independent variables through correlation analysis, and the GADA value was used as dependent variable. The statistical results showed that the independent variables could not fully meet the conditions of multicollinearity regression analysis. Conclusions:⑴ Related clinical features and glucose metabolism indicators have differential diagnosis significance for LADA, but this study cannot be used for multiple linear regression analysis, and it is difficult to establish a diagnostic model for LADA. ⑵ LADA diagnosis is a comprehensive diagnosis, which should be combined with the results of islet autoantibody and clinical features.

Glutamic Acid Decarboxylase Autoantibody Detection by Electrochemiluminescence Assay Identifies Latent Autoimmune Diabetes in Adults with Poor Islet Function

Background@#The detection of glutamic acid decarboxylase 65 (GAD65) autoantibodies is essential for the prediction and diagnosis of latent autoimmune diabetes in adults (LADA). The aim of the current study was to compare a newly developed electrochemiluminescence (ECL)-GAD65 antibody assay with the established radiobinding assay, and to explore whether the new assay could be used to define LADA more precisely. @*Methods@#Serum samples were harvested from 141 patients with LADA, 95 with type 1 diabetes mellitus, and 99 with type 2 diabetes mellitus, and tested for GAD65 autoantibodies using both the radiobinding assay and ECL assay. A glutamic acid decarboxylase antibodies (GADA) competition assay was also performed to assess antibody affinity. Furthermore, the clinical features of these patients were compared. @*Results@#Eighty-eight out of 141 serum samples (62.4%) from LADA patients were GAD65 antibody-positive by ECL assay. Compared with ECL-GAD65 antibody-negative patients, ECL-GAD65 antibody-positive patients were leaner (P<0.0001), had poorer β-cell function (P<0.05), and were more likely to have other diabetes-associated autoantibodies. The β-cell function of ECLGAD65 antibody-positive patients was similar to that of type 1 diabetes mellitus patients, whereas ECL-GAD65 antibody-negative patients were more similar to type 2 diabetes mellitus patients. @*Conclusion@#Patients with ECL-GAD65 antibody-negative share a similar phenotype with type 2 diabetes mellitus patients, whereas patients with ECL-GAD65 antibody-positive resemble those with type 1 diabetes mellitus. Thus, the detection of GADA using ECL may help to identify the subtype of LADA.

Association of NLRP2 gene polymorphisms with type 1 diabetes mellitus in Chinese Han population / 中华内分泌代谢杂志

Objective@#To evaluate the association between NLRP2(NLR Family Pyrin Domain Containing 2) gene polymorphisms and classical type 1 diabetes mellitus(T1DM) in Chinese Han population.@*Methods@#A case-control study was conducted in 510 classical T1DM patients from the Department of Metabolism and Endocrinology in the Second Xiangya Hospital affiliated to Central South University and 531 healthy controls in this region. The polymorphisms of rs1043673 in NLRP2 gene were analyzed by MassARRAY. Mann-Whitney U test and χ2 test were used to compare the differences between patients and controls. Logistic regression analysis and χ2 test were performed to compare the distributions of the alleles and genotypes between T1DM patients and controls. Kruskal-Wallis H test was used to compare the clinical characteristics of different genotypes in T1D patients.@*Results@#The differences of the allele and genotype distributions in rs1043673 of NLRP2 gene were not significant between patients and controls. The polymorphisms of rs1043673 were associated with fasting C-peptide(P=0.029), postprandial 2-h C-peptide(P=0.017), and titer of GADA(P=0.043) in T1DM patients.@*Conclusion@#The polymorphisms of NLRP2 gene were associated with the characteristics of T1DM patients.

Association of NLRP2 gene polymorphisms with type 1 diabetes mellitus in Chinese Han population / 中华内分泌代谢杂志

Objective:To evaluate the association between NLRP2(NLR Family Pyrin Domain Containing 2) gene polymorphisms and classical type 1 diabetes mellitus(T1DM) in Chinese Han population.Methods:A case-control study was conducted in 510 classical T1DM patients from the Department of Metabolism and Endocrinology in the Second Xiangya Hospital affiliated to Central South University and 531 healthy controls in this region. The polymorphisms of rs1043673 in NLRP2 gene were analyzed by MassARRAY. Mann- Whitney U test and χ2 test were used to compare the differences between patients and controls. Logistic regression analysis and χ2 test were performed to compare the distributions of the alleles and genotypes between T1DM patients and controls. Kruskal- Wallis H test was used to compare the clinical characteristics of different genotypes in T1D patients. Results:The differences of the allele and genotype distributions in rs1043673 of NLRP2 gene were not significant between patients and controls. The polymorphisms of rs1043673 were associated with fasting C-peptide( P=0.029), postprandial 2-h C-peptide( P=0.017), and titer of GADA( P=0.043) in T1DM patients. Conclusion:The polymorphisms of NLRP2 gene were associated with the characteristics of T1DM patients.

Clinical features for hospitalized type 1 diabetic patients with different ages of onset / 中南大学学报(医学版)

To explore the clinical features and complications of 545 hospitalized type 1 diabetic patients.
 Methods: All data of 545 patients with typical type 1 diabetes (T1DM) who were hospitalized in the Department of Endocrinology, the Second Xiangya Hospital, Central South University were collected. The data were analyzed retrospectively to explore the clinical features and complications. Clinical and biochemical characteristics were analyzed through comparison between different subgroups according to the onset age (≤13 years old, 14-29 years old, ≥30 years old).
 Results: The median onset age of T1DM patients was 27.0 (15.0, 40.0) years, and the middle-onset was 42.1%. Among the 3 groups, the proportion of female (58.0%) was the highest in the ≤13 years old group, concomitant with the lowest SBP and serum creatinine levels as well as the lowest incidence of all microvascular complications (21.0% of diabetic nephropathy, 23.3% of diabetic retinopathy, 34.1% of diabetic peripheral neuropathy; all P<0.05). Moreover, the fasting C peptide and peak C peptide levels were the lowest in ≥30 years old group compared with the other two groups, and the incidence of ketosis (33.5%) and all macrovascular complications were the highest among the three groups (all P<0.05).
 Conclusion: There are about half of the hospitalized patients with T1DM whose onset ages are ≥30 years. The incidence of ketosis at the onset and the risk for various microvascular and macrovascular complications after onset are higher than those with the onset age <30 years.

Expression of miR-142 and miR-143 in peripheral blood mononuclear cells from patients with autoimmune diabetes / 中华内分泌代谢杂志

Objective To investigate the microRNA ( miRNA ) expression level of peripheral blood mononuclear cell ( PBMC) in autoimmune diabetes mellitus ( ADM) which includes type 1 diabetes mellitus ( T1DM) and latent autoimmune diabetes in adults ( LADA ) , T2DM patients, and matched healthy individuals. Methods Patients of T1DM, LADA, and T2DM were recruited in the Second Xiangya Hospital of Central South University from January 2015 to December 2016. The subjects were divided into two groups. The first group was used for high-throughput screening of differentially expressed microRNAs. The second group was used to validate the expression of miR-142-5p and miR-143-3p by real-time quantitative polymerase chain reaction (RT-qPCR). Results (1)The different miRNA expression patterns of PBMC were found among T1DM patients, LADA patients, T2DM patients, and health individuals. ( 2) Compared with T2DM patients and healthy controls, LADA and T1DM patients had down-regulated PBMC miR-142-5p expression, and up-regulated miR-143-3p expression. (3)RT-qPCR validation showed that the expression of miR-142-5p in LADA patients was significantly lower than that in T2DM patients (0.30±0.24 vs 1.33 ± 1.29, P<0.05) . The expression of miR-143-3p in T1DM and LADA was higher than that in T2DM and health individuals. However, no significant differences were found. Conclusion The miRNA expression patterns are different in the PBMC of T1DM patients, LADA patients, T2DM patients, and healthy individuals; the abnormal expressions of miR-142-5p and miR-143-3p may participate in the development of ADM by affecting apoptosis and immune cell differentiation.

Comparative study on fixation effects of intramedullary nail and medial locking plate for distal tibial fractures / 中华创伤杂志

Objective A finite element analysis was conducted on the biomechanics of the locking plate and intramedullary nail fixation for the treatment of distal tibial fractures,and the resuhs were verified combined with clinical cases,so as to provide references for clinical treatment.Methods (1) Finite element analysis:the three-dimensional CT data of the lower limbs of a healthy male volunteer were used to establish a finite element model.The internal stress distribution of the tibial plateau was set to 60％ of the total load by intramedullary nail and locking plate respectively,and the tibia end was fixed effectively.400 N axial pressure load which equaled to that of adult knee joint during single axis standing was simulated.The equivalent stress and displacement of the model by different fixations were compared.(2) Clinical verification:a retrospective case control study was performed on the clinical data of 37 cases of distal tibia1 fractures treated with internal fixation from June 2015 to December 2016,including 17 cases in intramedullary nail group and 20 in locking plate group.The operation time,intraoperative blood loss,postoperative fracture healing time,and postoperative Johner-Wruhs score of patients were recorded for comprehensive assessment of recovery.Results (1) The finite element analysis results:the maximum stress value was 5.907 MPa for intramedullary nail and 5.821 MPa for locking plate model (P ＞0.05),respectively.The maximum displacement of intramedullary nail model was 2.313 mm,lower than that of locking plate fixation system (3.854 rmm) (P ＜ 0.05).(2) Clinical verification:the operation time and intraoperative blood loss of intramedullary nail were both lower than those of locking plate [(114.1 ±21.6)minutes):(129.8±21.4)minutes and (152.9 ±64.88)ml:(212.5 ±98.5)ml](P ＜0.05).The average fracture healing time was (17.7 ± 2.8)weeks for intramedullary nail and (20.6 ± 4.1) weeks for locking plate (P ＜ 0.05),respectively.In the intramedullary nail group,the Johner Wruhs score was excellent in 13 cases and good in four cases,with excellent and good rate of 100％,while in the locking plate group,nine cases were excellent,eight were good,and three were fair,with excellent and good rate of 85％ (P ＞ 0.05).Conclusions In terms of biomechanics and clinical effect,intramedullary nail fixation is superior than the medial locking plate fixation for the treatment of the distal tibial fractures.Intramedullary nail fixation can reduce surgical trauma and bone displacement after fixation and promote fracture healing.

Application of magnetic resonance diffusion tensor imaging in normal brain aging / 中国医学影像技术

Brain aging refers to the gradual decline of brain tissue structure,function and morphology with age.The cognitive dysfunction is an important marker of brain aging.Degenerative brain white matter changes may be an important factor in brain aging.DTI and its image processing techniques can noninvasively display the microstructure of human brain in vivo.Additionally,it is beneficial to analyze aging process of brain and related diseases of brain aging.The current status and progresses of diffusion tensor imaging in normal brain aging were reviewed in this article.

Is there a healthy obese subtype in cohort undergoing test for endothelial dysfunction ? / 中华内科杂志

Objective To investigate whether there existed a healthy obese subtype.Methods A total of 116 healthy subjects were recruited.They were divided into 3 groups according to BMI and metabolic disorders:40 cases of normal weight and metabolic normality (NMN),36 cases of obesity and metabolic normality (OMN) and 40 cases of obesity and metabolic abnormality (OMA).Anthropometic parameters as height,weight,waist circumference,hip circumference and blood pressure was recorded.Blood glucose,lipids,insulin,high-sensitivity C-reactive protein (hs-CRP) was detected.Body fat distribution was detected by dual-energy X-ray absorptiometry (DXA).Serum von Willebrand factor (vWF),a marker of endothelial dysfunction,were detected by ELISA.Results Both serum vWF levels in OMN group [(733.6±86.2)U/L] and OMA group[(809.2 ±46.3)U/L] are higher than that in NMN group [(466.9 ±65.3)U/L,P ＜0.05] with serum vWF level in OMA group is higher than in OMN group (P ＜ 0.05).Among android fat mass percentage (AFM％),BMI,waist height ratio,waist circumference,hs-CRP,weight,hip circumference and trunk fat mass,AFM％,BMI and hs-CRP are main influencing factors of vWF.Conclusions Endothelial dysfunction existed in obese adults regardless of their metabolic status.There is no healthy obese subtype.AFM％,BMI and hs-CRP are the main influencing factors of endothelial dysfunction.

Current and Future Clinical Applications of Zinc Transporter-8 in Type 1 Diabetes Mellitus / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To evaluate the utility of zinc transporter-8 (ZnT8) in the improvement of type 1 diabetes mellitus (T1DM) diagnosis and prediction, and to explore whether ZnT8 is a potential therapeutic target in T1DM.</p><p><b>DATA SOURCES</b>A search was conducted within the medical database PubMed for relevant articles published from 2001 to 2015. The search terms are as follows: "ZnT8," "type 1 diabetes," "latent autoimmune diabetes in adults," "type 2 diabetes," "islet autoantibodies," "zinc supplement," "T cells," "β cell," "immune therapy." We also searched the reference lists of selected articles.</p><p><b>STUDY SELECTION</b>English-language original articles and critical reviews concerning ZnT8 and the clinical applications of islet autoantibodies in diabetes were reviewed.</p><p><b>RESULTS</b>The basic function of ZnT8 is maintaining intracellular zinc homeostasis, which modulates the process of insulin biosynthesis, storage, and secretion. Autoantibodies against ZnT8 (ZnT8A) and ZnT8-specific T cells are the reliable biomarkers for the identification, stratification, and characterization of T1DM. Additionally, the results from the animal models and clinical trials have shown that ZnT8 is a diabetogenic antigen, suggesting the possibility of ZnT8-specific immunotherapy as an alternative for T1DM therapy.</p><p><b>CONCLUSIONS</b>ZnT8 is a novel islet autoantigen with a widely potential for clinical applications in T1DM. However, before the large-scale clinical applications, there are still many problems to be solved.</p>

Anatomical research and clinical application of anterior approach for pelvic and acetabular fractures / 中华创伤杂志

Objective To perform an anatomical study on anterior approach to fractures of the pelvis and acetabulum in an attempt to testify feasibility of the approach.Methods Position and variation of anatomical structure of the hypogastric abdominal wall and pelvic cavity were observed in 10 cadaveric adults (20 sides).Based on the anatomical study,anterior approach to pelvic fractures (n =20)and acetabular fractures (n =15) were performed and clinical results were observed.Results Anterior pelvic incision revealed no splitting or exposure of the spermatic cord/round ligament of uterus.Vertical incision through the muscle layer of abdominal wall located at lateral rectus abdominis and medial initial segment of hypogastric arteries/veins.In clinical practice,the approach revealed the mean incision length of 10 cm (range,9-12 cm) and mean blood loss of (225.5 ± 30.5) ml (range,170-350 ml).No injuries to femoral nerve and sciatic nerve occurred and there was no deep vein thrombosis.Surgical incision healed primarily.Bone union were recorded at the 18-month follow-up (11-35 months).Conclusions Anterior pelvic approach stretches the operative field from pubic symphysis to anterior-lateral cacroiliac joint and quadrilateral surface,allowing full exposure of the fracture site.The approach has benefits of high safety,minor trauma,large exposure,and satisfactory results and hence deserves wide application in clinical settings.

Change of glutamic acid decarboxylase antibody and protein tyrosine phosphatase antibody in Chinese patients with acute-onset type 1 diabetes mellitus / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Glutamic acid decarboxylase antibody (GADA) and protein tyrosine phosphatase antibody (IA-2A) are two major autoantibodies, which exert important roles in the process of type 1 diabetes mellitus (T1D). Our study aimed to investigate the changes in positivity and titers of GADA and IA-2A during the course of Chinese acute-onset T1D patients and their relationships with clinical features.</p><p><b>METHODS</b>Two hundreds and forty-seven Chinese newly diagnosed acute-onset T1D patients were consecutively recruited. GADA and IA-2A were detected at the time of diagnosis, one year later, 3-5 years later after diagnosis during the follow-up; all the clinical data were recorded and analyzed as well.</p><p><b>RESULTS</b>During the course of acute-onset T1D, the majority of patients remained stable for GADA or IA-2A, however, a few patients changed from positivity to negativity and fewer patients converted from negativity to positivity. The prevalence of GADA was 56.3% at diagnosis, decreasing to 50.5% one year later, and 43.3% 3-5 years later while the corresponding prevalence of IA-2A were 32.8%, 31.0% and 23.3%, respectively. The median GADA titers were 0.0825 at diagnosis, declining to 0.0585 one year later and 0.0383 3-5 years later (P < 0.001), while the corresponding median titers were 0.0016, 0.0010, 0.0014 for IA-2A, respectively. Fasting C-peptide (FCP) and postprandial C-peptide 2 hours (PCP2h) levels of GADA or IA-2A negativity persistence patients were higher than those of positivity persistence and negativity conversion patients (P < 0.05) which indicated GADA or IA-2A negativity persistence T1D patients had a less loss of β cell function.</p><p><b>CONCLUSION</b>Our data suggest that repeated detection of GADA and IA-2A are necessary for differential diagnosis of autoimmune diabetes and the indirect prediction of the β cell function in Chinese patients.</p>

Gene expression changes in patients with fulminant type 1 diabetes / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Fulminant type 1 diabetes (F1D) is a complex disease. Microarray analysis was used to identify gene expression changes and obtain understanding of the underlying mechanisms.</p><p><b>METHODS</b>Microarray analysis was performed on peripheral blood mononuclear cells from six F1D patients and six matched healthy subjects. Real-time polymerase chain reaction was used to verify the differentially expressed genes. NK cell activity was detected by methyl thiazoleterazolium assay.</p><p><b>RESULTS</b>Microarray analysis identified 759 genes differing in expression between F1D patients and controls at a false discovery rate of 0.05. Expression of TLR9, ELF4 and IL1RAP were verified and consistent with changes in microarray results. NK cell activity was decreased in F1D. With use of a knowledge base, differentially expressed genes could be placed within different pathways with predicted functions including interleukin-1, and tumor necrosis factor-α signaling.</p><p><b>CONCLUSIONS</b>These results identify several genes indicating possible mechanisms in F1D. NK cell dysfunction resulting from changes in expression of TLR9, ELF4 and IL1RAP, and pathways of interleukin-1 and tumor necrosis factor-α signaling might be involved in F1D through inducing β-cell dysfunction.</p>

Immunological characteristics and pancreatic β-cell function in first-degree relatives of type 1 diabetes mellitus / 中华内分泌代谢杂志

Oral glucose tolerance test(OGTT)was performed in 419 first-degree relatives(FDRs)of type 1 diabetes mellitus. GADA, IA-2A, and IAA were determined by radioligand assay, and the positive rates were 7.16%, 1.43%, and 1.26%, respectively. Intravenous glucose tolerance test(IVGTT)and nateglinide-OGTT were performed in 39 controls, 11 first-degree relatives with positive autoantibody(Ab+group), 14 ones with negative autoantibody(Ab-group)during 5-7 days.The first-phase insulin release(FPIR), area under insulin release during 0-10 min [AUC0-10] of IVGTT and the value of(ΔI30/ΔG30)of nateglinide-OGTT in Ab+group were lower than those of control and(2.75±0.37 vs 3.61±1.05)mU/mmol, all P＜0.05]. The 1st min insulin release in Ab+group was lower than that of Ab-group [(3.80±0.30 vs 4.52±0.70)mU/L, P＜0.05]. The HOMA-IR was higher in Ab-group than that in control group(2.92±1.04 vs 1.96±1.22, P＜0.05). The results suggest that the positivity rates of autoantibodies in FDRs of type 1 diabetes mellitus are very close to those of Caucasian. There exist insulin secretion defects in FDRs with positive autoantibody while insulin resistance in FDRs with negative autoantibody.

Relation between insulin resistance and glutamic acid decarboxylase antibody titers in latent autoimmune diabetes in adults / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the relation between insulin resistance and glutamic acid decarboxylase antibody (GAD-Ab) titers in latent autoimmune diabetes in adults (LADA).</p><p><b>METHODS</b>The patients with phenotypic type 2 diabetes were screened for GAD-Ab positivity, and the 141 positive patients were divided into two subgroups according to the GAD-Ab titer, namely the high-titer group (LADA-1 subtype) and low-titer group (LADA-2 subgroup). The clinical features and insulin resistance were compared between the two groups. Insulin resistance was calculated by HOMA 2 software, and GAD-Ab and C peptide were determined with radioligand and radioimmune assay, respectively.</p><p><b>RESULTS</b>Compared with low-titer LADA patients, the patients with high titers had younger age of onset, lower BMI, higher HbA1c level, and worse fasting and postprandial C peptide levels. The insulin resistance index by HOMA 2 was significantly lower in LADA-1 group than in LADA-2 group (1.6-/+1.1 vs 2.1-/+1.1, P=0.001). The HOMA2-IR index showed a negative correlation to GAD-Ab titer.</p><p><b>CONCLUSION</b>The degree of insulin resistance is correlated to GAD-Ab titers in LADA, and low titer patients have higher insulin resistance level.</p>

Change of serum soluble CD14 level in newly diagnosed type 2 diabetes and its significance / 中南大学学报(医学版)

OBJECTIVE@#To determine the correlation of serum soluble CD14 (sCD14) level with the injury of vascular endothelial cells and chronic low grade inflammation in newly diagnosed Type 2 diabetes (T2DM).@*METHODS@#ELISA was used to examine serum sCD14 and serum soluble E-selectin (sE-selectin) level, while immunoturbidimetric assay was used to detect serum high sensitivity C reactive protein (hsCRP).@*RESULTS@#The levels of serum sCD14, sE-selectin, and hsCRP in newly diagnosed T2DM group were higher than those in the euglycemic group [sCD14: (300.7+/-136.6) ng/mL vs. (273.3+/-86.0) ng/mL); sE-selectin: (21.3+/-7.7) ng/mL vs. (32.9+/-11.4) ng/mL; hsCRP: (1.45+/-1.21) mg/L vs. (2.37+/-1.45)mg/L], and there was a significant difference in the latter two parameters between the 2 groups(P<0.01). In the patients with newly diagnosed T2DM, after matching blood pressure, blood sugar, and blood lipid, the levels of serum sCD14, sE-selectin, and hsCRP in the obese group were higher than those in the non-obese group. There was no significant difference in the former 2 parameters between the 2 groups. The serum sE-selectin was correlated with fasting blood sugar (r=0.369, P<0.001), 2-hour postprandial blood sugar (r=0.421, P<0.001), glycosylated hemoglobin (r=0.291, P=0.005), sCD14(r=0.312, P=0.002), and homeostasis model assessment-insulin resistance(r=0.247, P=0.018) in the newly diagnosed T2DM group. Stepwise regression ana-lysis showed that the serum sCD14 was one of the chief influencing factors on serum sE-selectin.@*CONCLUSION@#Serum sCD14 levels tend to increase in newly diagnosed T2DM patients, especially in the obese diabetic patients, which is one of the chief influencing factors to induce the injury of vascular endothelial cells. The innate immunity mediated by Toll-like receptor 4 may take part in the injury of vascular endothelial cells in newly diagnosed T2DM patients.