Type 1 diabetes mellitus and its oral tolerance therapy

As a T cell-mediated autoimmune disease,type 1 diabetes mellitus(T1DM)is marked by insulin defect resulting from the destruction of pancreaticβ-cells.The understanding of various aspects of T1DM,such as its epidemiology,pathobiology,pathogenesis,clinical manifestations,and complications,has been greatly promoted by valuable research performed during the past decades.However,these findings have not been translated into an effective treatment.The ideal treatment should safely repair the destroyed immune balance in a longlasting manner,preventing or stopping the destruction ofβ-cells.As a type of immune hypo-responsiveness to the orally administrated antigen,oral tolerance may be induced by enhancement of regulatory T cells(Tregs)or by anergy/deletion of T cells,depending on the dosage of orally administrated antigen.Acting as an antigen-specific immunotherapy,oral tolerance therapy for T1DM has been mainly performed using animal models and some clinical trials have been completed or are still ongoing.Based on the review of the proposed mechanism of the development of T1DM and oral tolerance,we give a current overview of oral tolerance therapy for T1DM conducted in both animal models and clinical trials.

Colonization by Superantigen Producing Staphylococcus aureus in Mice Enhances the Capacity to Develop Oral Tolerance

Microbial stimulation in early childhood may be necessary for proper maturation of the immune system. Infants colonized with Staphylococcus aureus have low risk of developing food allergy. Neonatal exposure to staphylococcal superantigen improves oral tolerance and enhances protection in experimental allergy models. Here, we used three wild-type strains of S. aureus, naturally harboring genes for different superantigens (SElM/SElO alone, or in combination with SEA or TSST-1). We first investigated their in vitro stimulatory capacity of splenocytes from germ-free mice. Secondly, germ-free mice were colonized with the strains and their capacity to develop oral tolerance was tested in a food allergy model. In vitro, S. aureus with only SElM/SElO genes promoted the strongest B-cell stimulation. S. aureus carrying gene for SEA induced the highest proportion of CD4+FoxP3+ T cells. The proportion of regulatory T cells was inversely correlated to B-cell proliferation, indicating suppressive ability of these cells. All strains were equally able to colonize the germ-free gut, initially achieving 1010CFU/g faeces, which decreased to 105 over a period of six weeks. Mice colonized with S. aureus carrying genes for SEA or TSST-1 had improved capacity to develop tolerance compared to germ-free mice. These results suggest that colonization by S. aureus producing superantigens may improve active tolerance to gut allergens.

A study on oral tolerance to treat traumatic brain injury in laboratory

Objective To explore the cerebral protective effects of oral tolerance therapy in rabbit-TBI-models established by lateral fluid percussion machine. Methods 58 rabbits were divided into four groups randomly (18 in control group,15 in CSF drained group,10 in CSF drained + feed group and 15 in CSF

Oral glucose tolerance test in diabetes,the old method revisited

The oral glucose tolerance test(OGTT)has been widely used both in clinics and in basic research for a long time.It is applied to diagnose impaired glucose tolerance and/or type 2 diabetes mellitus in individuals.Additionally,it has been employed in research to investigate glucose utilization and insulin sensitivity in animals.The main aim of each was quite different,and the details are also somewhat varied.However,the time or duration of the OGTT was the same,using the 2-h post-glucose load glycemia in both,following the suggestions of the American Diabetes Association.Recently,the use of 30-min or 1-h post-glucose load glycemia in clinical practice has been recommended by several studies.In this review article,we describe this new view and suggest perspectives for the OGTT.Additionally,quantification of the glucose curve in basic research is also discussed.Unlike in clinical practice,the incremental area under the curve is not suitable for use in the studies involving animals receiving repeated treatments or chronic treatment.We discuss the potential mechanisms in detail.Moreover,variations between bench and bedside in the application of the OGTT are introduced.Finally,the newly identified method for the OGTT must achieve a recommendation from the American Diabetes Association or another official unit soon.In conclusion,we summarize the recent reports regarding the OGTT and add some of our own perspectives,including machine learning and others.

Utility of oral glucose tolerance test in predicting type 2 diabetes following gestational diabetes:Towards personalized care

BACKGROUND Women with gestational diabetes mellitus(GDM)are at a seven-fold higher risk of developing type 2 diabetes(T2D)within 7-10 years after childbirth,compared with those with normoglycemic pregnancy.Although raised fasting blood glucose(FBG)levels has been said to be the main significant predictor of postpartum progression to T2D,it is difficult to predict who among the women with GDM would develop T2D.Therefore,we conducted a cross-sectional retrospective study to examine the glycemic indices that can predict postnatal T2D in Emirati Arab women with a history of GDM.AIM To assess how oral glucose tolerance test(OGTT)can identify the distinct GDM pathophysiology and predict possible distinct postnatal T2D subtypes.METHODS The glycemic status of a cohort of 4603 pregnant Emirati Arab women,who delivered in 2007 at both Latifa Women and Children Hospital and at Dubai Hospital,United Arab Emirates,was assessed retrospectively,using the International Association of Diabetes and Pregnancy Study Groups(IADPSG)criteria.Of the total,1231 women were followed up and assessed in 2016.The FBG and/or the 2-h blood glucose(2hrBG)levels after a 75-g glucose load were measured to assess the prevalence of GDM and T2D,according to the IADPSG and American Diabetes Association(ADA)criteria,respectively.The receiver operating characteristic curve for the OGTT was plotted and sensitivity,specificity,and predictive values of FBG and 2hrBG for T2D were determined.RESULTS Considering both FBG and 2hrBG levels,according to the IADPSG criteria,the prevalence of GDM in pregnant Emirati women in 2007 was 1057/4603(23%),while the prevalence of pre-pregnancy T2D among them,based on ADA criteria,was 230/4603(5%).In the subset of women(n=1231)followed up in 2016,the prevalence of GDM in 2007 was 362/1231(29.6%),while the prevalence of prepregnancy T2D was 36/1231(2.9%).Of the 362 pregnant women with GDM in 2007,96/362(26.5%)developed T2D;142/362(39.2%)developed impaired fasting glucose;29/362(8.0%)developed impaired glucose tolerance,and the remaining 95/362(26.2%)had normal glycemia in 2016.The prevalence of T2D,based on ADA criteria,stemmed from the prevalence of 36/1231(2.9%)in 2007 to 141/1231(11.5%),in 2016.The positive predictive value(PPV)for FBG suggests that if a woman tested positive for GDM in 2007,the probability of developing T2D in 2016 was approximately 24%.The opposite was observed when 2hrBG was used for diagnosis.The PPV value for 2hrBG suggests that if a woman was positive for GDM in 2007 then the probability of developing T2D in 2016 was only 3%.CONCLUSION FBG and 2hrBG could predict postpartum T2D,following antenatal GDM.However,each test reflects different pathophysiology and possible T2D subtype and could be matched with a relevant T2D prevention program.

Repetitiveness of the oral glucose tolerance test in children and adolescents

BACKGROUND Data regarding the most suitable diagnostic method for the diagnosis of glucose impairment in asymptomatic children and adolescents are inconclusive.Furthermore,limited data are available on the reproducibility of the oral glucose tolerance test(OGTT)in children and adolescents who are obese(OB).AIM To investigate the usefulness of the OGTT as a screening method for glucose dysregulation in children and adolescents.METHODS Eighty-one children and adolescents,41 females,either overweight(OW),OB or normal weight(NW)but with a strong positive family history of type 2 diabetes mellitus(T2DM),were enrolled in the present observational study from the Outpatient Clinic of Paediatric Endocrinology of the University Hospital of Patras in Greece.One or two 3-h OGTTs were performed and glucose,insulin and Cpeptide concentrations were measured at several time points(t=0 min,t=15 min,t=30 min,t=60 min,t=90 min,t=120 min,t=180 min).RESULTS Good repetitiveness was observed in the OGTT response with regard to T2DM,while low repetitiveness was noted in the OGTT response with regard to impaired glucose tolerance(IGT)and no repetitiveness with regard to impaired fasting glucose(IFG).In addition,no concordance was observed between IFG and IGT.During the 1st and 2nd OGTTs,no significant difference was found in the glucose concentrations between NW,OW and OB patients,whereas insulin and C-peptide concentrations were higher in OW and OB compared to NW patients at several time points during the OGTTs.Also,OW and OB patients showed a worsening insulin and C-peptide response during the 2nd OGTT as compared to the 1st OGTT.CONCLUSION In mild or moderate disorders of glucose metabolism,such as IFG and IGT,a diagnosis may not be reached using only one OGTT,and a second test or additional investigations may be needed.When glucose metabolism is profoundly impaired,as in T2DM,one OGTT is probably more reliable and adequate for establishing the diagnosis.Excessive weight and/or a positive family history of T2DM possibly affect the insulin and C-peptide response in the OGTT from a young age.

The Use of Glycated Albumin in the Diagnosis of Gestational Diabetes Mellitus

Gestational diabetes mellitus is the most common endocrine disorder in pregnancy and a cause of maternal and fetal morbidities and mortalities. The oral glucose tolerance test is the gold standard for diagnosing gestational diabetes mellitus. Nevertheless, the oral glucose tolerance test is time-consuming and requires patient preparation. On the contrary, Glycated albumin does not require patient preparation or administration of any substance. Most studies on glycated albumin in pregnancy were among the non-African population, and black Americans have higher glycated albumin levels than Caucasians. This study determined the use of glycated albumin in diagnosing gestational diabetes mellitus among pregnant women. The study was a prospective study of 160 pregnant women between 24 and 28 weeks of gestation at the University of Port Harcourt Teaching Hospital. The diagnosis of gestational diabetes mellitus was based on the World Health Organization 2013 criteria. The diagnostic value of glycated albumin was determined using the area under the receiver operator characteristic curve. The prevalence of gestational diabetes mellitus was 9.4% and the mean glycated albumin was 16.91% (±2.77). The area under the receiver operator characteristic curve for glycated albumin was 0.845 (95% CI 0.733 - 0.956;p = 0.0001). The optimal cut-off value of glycated albumin in the diagnosis of gestational diabetes mellitus was 18.9%. Glycated albumin was useful in the diagnosis of gestational diabetes mellitus at 24 to 28 weeks of gestation.

Responses to oral glucose challenge differ by physical activity volume and intensity: A pilot study

Background:One-hour postprandial hyperglycemia is associated with increased risk of type 2 diabetes and cardiovascular disease.Physical activity(PA)has short-term beneficial effects on post-meal glucose response.This study compared the oral glucose tolerance test results of 3 groups of people with habitually different levels of PA.Methods:Thirty-one adults without diabetes(age 25.9±6.6 years;body mass index 23.8±3.8 kg/m^2;mean±SD)were recruited and divided into 3 groups based on self-reported PA volume and intensity:low activity<30 min/day of moderate-intensity activity(n=11),moderately active≥30 min/day of moderate-intensity PA(n=10),and very active≥60 min/day of PA at high intensity(n=10).Participants completed an oral glucose tolerance test(50 g glucose)with capillary blood samples obtained at baseline,15 min,30 min,45 min,60 min,90 min,and 120 min post-ingestion.Results:There were no significant differences between groups for age or body fat percentage or glycated hemoglobin(p>0.05).The groups were significantly different in terms of baseline glucose level(p=0.003)and,marginally,for gender(p=0.053)and BMI(p=0.050).There was a statistically significant effect of PA on the 1-h postprandial glucose results(p=0.029),with differences between very active and low activity groups(p=0.008)but not between the moderately active and low activity groups(p=0.360),even when baseline glucose level and gender differences were accounted for.For incremental area under the curve there was no significant effect of activity group once gender and body fat percentage had been accounted for(p=0.401).Those in the low activity group took 15 min longer to reach peak glucose level than those in the very active group(p=0.012).Conclusion:The results suggest that high levels of PA have a beneficial effect on postprandial blood glucose profiles when compared to low and moderate levels of activity.

Prevalence and characteristics of MAFLD in Chinese adults aged 40 years or older:A community-based study

Background: Nonalcoholic fatty liver disease(NAFLD) was recently proposed to be renamed metabolic dysfunction-associated fatty liver disease(MAFLD) with the diagnostic criteria revised. We investigated the similarities and differences in the prevalence and clinical characteristics of MAFLD and NAFLD in Chinese adults. Methods: A cross-sectional study of 9980 Chinese individuals aged 40 years or older was performed between 2011 and 2012 using randomized, stratifed cluster sampling in Shanghai, China. A detailed questionnaire and the results of abdominal ultrasonography, a standardized 2-h 75-g oral glucose tolerance test and blood biochemical examinations were collected. Results: A total of 9927 subjects were included in this study. The prevalence of MAFLD(40.3%) was significantly higher than that of NAFLD(36.9%)( P < 0.05). MAFLD was highly prevalent in type 2 diabetes mellitus(T2DM)(53.8%), impaired fasting glucose(35.7%) and impaired glucose tolerance(40.9%). High risk of advanced fbrosis based on fbrosis-4 was highly prevalent(14.7%) in lean MAFLD with T2DM. Among 9927 subjects, 3481(35.1%) fulflled the diagnostic criteria for MAFLD and NAFLD(MAFLD + NAFLD +), 521(5.2%) MAFLD + NAFLD-, and 181(1.8%) MAFLD-NAFLD +. The MAFLD + NAFLD-group had more signifcant metabolic disorders than those in the MAFLD + NAFLD + group(all P < 0.05). Among MAFLD-NAFLD + subjects, 82.9% had metabolic disorders. Conclusions: The new defnition of MAFLD may better reflect the pathogenesis related to metabolism. Future research should focus on studying the natural history, pathogenesis and treatment effectivity of the overlap and non-overlap of NAFLD and MAFLD subjects.

Insulin Expression in Rats Exposed to Cadmium

To investigate the effects of cadmium exposure on insulin expression in rats. Methods Eighteen adult SD rats were administered cadmium subcutaneously （0.5, 1.0, and 2.0 mg/kg bw）. The effects on endocrine of pancreas were assessed. The levels of cadmium and zinc in pancreas, blood and urine glucose, serum insulin and urine NAG （N-acyetyl-β-glucosaminidase） were determined. The gene expressions of metallothionein （MT） and insulin were also measured, and the oral glucose tolerance tests （OGTT） were carried out. Results The contents of cadmium in pancreas in cadmium-treated rats were higher than that in the control group, which was associated with slight increase of zinc in pancreas. Cadmium-exposed rats （1.0 and 2.0 mg/kg bw） demonstrated a marked glucose intolerance. But the levels of serum insulin did not change significantly after cadmium administration, and the UNAG had no change in Cd-treated group. The gene expression of insulin decreased in 1.0 and 2.0 mg/kg bw cadmium-exposed groups, compared with the control group. The expression of MT-I was higher in the groups exposed to 1.0 and 2.0 mg/kg bw cadmium while the expression of MT-II was higher in the group exposed to 2.0 mg/kg bw cadmium. Conclusions Cadmium may be accumulated in the pancreas, resulting in the change of the expression of insulin, MT-I and MT-Ⅱ genes. Cadmium can influence the biosynthesis of insulin, but does not induce the release of insulin. The dysfunction of pancreas occurs earlier than that of kidney after administration of cadmium.

The role of oral glucose tolerance test in screening for diabetes mellitus in the elderly of Harbin, China

Though diabetes is common worldwide, the proportion of cases diagnosed is not high. Nearly fifty percent of patients with diabetes mellitus (DM) in US are undiagnosed.~1 The ratio might be higher in China. It has been suggested that diabetes may be present 4 to 7 years before diagnosis.~2 (Many of) the complications appear to be present at the time of diagnosis of the diabetic status.~1 (Screening for) diabetes in early stage of diabetes is thus a worthwhile exercise.

Study on the correlation and predictive value of serum pregnancyassociated plasma protein A, triglyceride and serum 25-hydroxyvitamin D levels with gestational diabetes mellitus

BACKGROUND Gestational diabetes mellitus(GDM)is a concern due to its rapid increase in incidence in recent years.AIM To investigate the correlation and predictive value of serum pregnancyassociated plasma protein A(PAPP-A),triglyceride(TG),and 25-hydroxyvitamin D[25-(OH)D]with GDM in early pregnancy.METHODS A total of 99 patients in early pregnancy admitted to Peking University International Hospital from November 2015 to September 2017 were included,and underwent a fasting glucose test and oral glucose tolerance test screening at 24-28 wk of pregnancy.Of these cases with GDM,51 were assigned to group A and the remaining 48 cases without GDM were enrolled in group B.Serum PAPP-A,TG and 25-(OH)D in the two groups were compared and their correlation with blood sugar was analyzed.In addition,their diagnostic value in GDM was determined using receiver operating characteristic(ROC)curve analysis.RESULTS Group A had markedly lower serum PAPP-A and 25-(OH)D levels and a significantly higher serum TG level than group B,with statistical significance(P<0.05).Furthermore,Pearson analysis identified that PAPP-A and 25-(OH)D levels were negatively correlated with fasting blood glucose(FBG)levels(r=-0.605,P<0.001),(r=-0.597,P<0.001),while TG and FBG levels were positively correlated(r=0.628,P<0.001).The sensitivity,specificity,area under the curve(AUC)and optimal cut-off value of serum PAPP-A level in the diagnosis of GDM were 72.55%,82.35%,0.861 and 16.340,respectively,while the sensitivity of TG in diagnosing GDM was 86.27%,the specificity was 66.67%,the AUC was 0.813,with an optimal cut-off value of 1.796.The corresponding sensitivity,specificity,AUC and optimal cut-off value of serum 25-(OH)D were 64.71%,70.59%,0.721 and 23.140,respectively.Moreover,multivariate logistic regression analysis revealed that FBG,vascular endothelial growth factor,Flt-1,serum PAPP-A,TG,and 25-(OH)D were related risk factors leading to GDM in patients.CONCLUSION Serum PAPP-A,TG,and 25-(OH)D levels are all correlated with blood glucose changes in GDM,and are independent factors affecting the occurrence of GDM and have certain value in the diagnosis of GDM.

Repeat OGTT at 34 - 36 Weeks to Detect the Late Occurrence of GDM: A Descriptive Cross-Sectional Study Conducted at the Professorial Unit, Teaching Hospital Peradeniya, Sri Lanka

Aim: Evaluation of the occurrence of glucose intolerance after 34 - 36 weeks in pregnant mothers attending the Teaching Hospital, Peradeniya. Materials & Method: This is a descriptive cross-sectional study carried out from October 2017 to March 2018 among 183 pregnant mothers attending antenatal clinic at Teaching Hospital Peradeniya. After informed consent a repeat Oral Glucose Tolerance Test (OGTT) was done among the pregnant mothers, at period of amenorrhoea of 34 - 36 weeks, whose initial OGTT values were normal. Gestational diabetes was diagnosed according to the NICE guideline cut off values and the percentage of late occurrence of Gestational diabetes (GDM) was analyzed. Results: Mean age of the population was 29.1 years and the age range in this group was 18 to 45 years and the majority (73.9%) of women were primipara. There were 3.3% of teenage pregnancies and 14% of mothers were over 35 years. Majority (59.7%) of mothers underwent repeat OGTT test at 34 weeks of gestation and the rest (40.3%) underwent test between 34 to 36 weeks of gestation. Although the mean BMI was 23.74, 9.7% of mothers were obese (>30 kg/m2), 30.3% of mothers were pre-obese (25.0 - 29.9 kg/m2). 8.2% of mothers were diagnosed with Gestational diabetes at 34 - 36 weeks whose initial OGTT values were normal. Conclusion: In view of reducing feto-maternal morbidity and mortality, considering a repeat OGTT at a later gestation (34 - 36 weeks of gestation) should be considered in mothers, whose initial OGTT values are normal as Sri Lanka is a high risk country for GDM. Clinical Significance: The study may play an important role in guideline alteration process and screening for gestational diabetes in Sri Lankan set-up.

Postprandial response of bone turnover markers in patients with Crohn's disease

AIM:To investigate the postprandial response of bone turnover markers in patients with Crohn’s disease(CD).METHODS:Fifty nine patients with CD aged 38±14years,and 45 healthy individuals matched for age and body mass index were included in the study.All participants underwent an oral glucose tolerance test(OGTT)after an overnight fast and serum levels of the bone resorption marker C-terminal crosslinking telopeptide of type?Ⅰ?collagen(CTX-Ⅰ)and the bone formation marker procollagen type?Ⅰ?N propeptide were measured.Activity of the disease was assessed by calculation of the Crohn’s disease activity index(CDAI).RESULTS:Serum CTX-I was significantly higher in patients compared to controls(CTX-I:453±21 pg/mL vs 365±25 pg/mL,P=0.008),and values were significantly correlated with the activity of the disease(r=0.435,P=0.001).Results from OGTT-induced suppression of CTX-I showed two different trends.Patients with more active disease(assessed as CDAI>150)had a more excessive suppression of CTX-I compared to controls(55%vs 43%P<0.001),while patients on remission(assessed as CDAI<150)demonstrated an attenuated CTX-I suppression(30%vs 43%P<0.001).In line with this,CTX-I suppression after oral glucose load was significantly correlated with the activity of the disease(r=0.913,P<0.001).CONCLUSION:The physiological skeletal response of postprandial suppression of bone resorption is maintained in patients with CD and is strongly dependent to the activity of the disease.

Protective effect of modified Yu-Ye decoction on type 2 diabetes mellitus rats

Background:Yu-Ye decoction is a classic prescription therapy that is widely used in the treatment of type 2 diabetes mellitus(T2DM).In this study,we evaluate and exhibit the protective effect of modified Yu-Ye decoction on T2DM rats.Methods:Sixty rats with T2DM were included in this study that was induced by high-fat high-glucose diet for 6 weeks.following 6 weeks later,1%streptozotocin 30 mg/kg was injected intraperitoneally,and the T2DM rats were randomly divided into the model group,the metformin(90 mg/kg)positive control group,and the modified Yu-Ye decoction(6.4 g/kg,12.7 g/kg,25.4 g/kg)group.In contrast,standard chow was provided to the 10 rats in the control group.The drug was administered for four weeks,and fasting blood glucose was monitored.After four weeks of treatment,oral glucose tolerance test experiments were carried out.Serum was collected for the detection of alanine aminotransferase,aspartate aminotransferase,creatinine,blood urea nitrogen,low density lipoprotein,high density lipoprotein,and total cholesterol,triglyceride.Hematoxylin-eosin staining was used to assess potential pathological changes in the liver,kidneys,and pancreas.Results:Results from fasting blood glucose monitoring and oral glucose tolerance test showed that modified Yu-Ye decoction could significantly improve the blood glucose concentration and insulin resistance,compared to the model group.In addition,modified Yu-Ye decoction could significantly reduce the serum levels of alanine aminotransferase,aspartate aminotransferase,creatinine,blood urea nitrogen,low density lipoprotein,total cholesterol,triglyceride,and increase the level of high density lipoprotein.At the same time,hematoxylin-eosin results exhibited that modified Yu-Ye decoction could increase the number of islet cells,reduce the volume of islet cells,improve liver edema and inflammation,and improve renal glomerular hypertrophy.Conclusion:This study shows that modified Yu-Ye decoction ameliorates T2DM because it can reduce fasting blood glucose concentration,improve glucose tolerance,protect liver and kidney function,and improve livers,kidneys,and pancreas tissue morphology.

Oral administration of insulin to female nonobese diabetic mice inhibited diabetes and induced Fas ligand expression on islets of Langerhans

To detect oral administration of recombinant human insulin to nonobese diabetic (NOD) mice for preventing them from diabetes and insulitis and to detect the effects of oral administration of insulin on Fas and Fas ligand expression on islet of Langerhans Methods Sixty four female NOD mice were divided into two groups One group (34) was orally administered recombination human insulin 1?mg in 500?μl PBS and the other (30) 500?μl PBS only at age of 5 weeks old, twice a week for the first week, then weekly until 30 weeks of age Results Oral administration of insulin to female NOD mice can significantly suppress diabetes and insulitis The insulitis was less severe in the group fed with insulin than that in the control group (score of insulitis: 1 25±0 45 vs 3 0±0 76 at 16 weeks of age, P <0 01) We examined Fas ligand and Fas expression on islets of Langerhans in both groups of NOD mice by using immunohistochemical techniques We find that Fas only expressed on islets when the mice suffered the diabetes, whereas Fas ligand expressed on islets of the mice fed with insulin at 16 and 20 week of ages We did not find Fas ligand positive staining on the islet feeding with PBS Conclusion We speculated that oral insulin may induce Fas ligand expression on the islets and plays a role in protecting the pancreatic β cell from autoimmune destruction These results show that oral insulin affected autoimmune diabetes and insulitis in NOD mice The immune mechanism of oral tolerance is closely related to the change of Fas ligand and Fas system

Changes of CD8＋ T cells in dextran sulfate sodium-induced colitis mice pretreated with oral immune regulation

Background It has been reported that CD8＋ regulatory cells could be induced upon oral tolerance. The purpose of this study was to investigate the changes of CD8a＋ T cells in dextran sulfate sodium （DSS）-induced colitis mice pretreated by oral immune regulation. Methods The effects of five low oral doses of colitis-extracted proteins （CEP） on colitis were evaluated by clinical manifestation and histological lesions. The percentages of CD8a＋ T cells gating on CD3＋ T cells were evaluated in the gut-associated lymphoid tissues （GALT） and the spleens by flow cytometry. Differences between the two groups were compared by Student＇s t test or Mann-Whitney U test. Results Compared to bovine serum albumin （BSA）-fed control mice, administration of CEP resulted in marked alleviation of colitis. The proportion of CDSa＋ T ceils, not only in intraepithelial lymphocytes （IELs） and lamina propria lymphocytes （LPLs） of the large intestine （LI） but also in spleen from CEP-fed colitis mice, was significantly higher than that from BSA-fed colitis mice （LI-IELs： （71.5±5.4）% vs. （60.1±4.3）%, P 〈0.01; LI-LPLs： （60.7±5.2）% vs. （51.9±4.7）%, P 〈0.01; spleen： （24.1±3.6）% vs. （20.3±4.1）%, P 〈0.05; n=8）. Mucosal repair in repair-period mice five days after termination of DSS treatment was also accompanied by an increase of CD8a＋ T cells in large intestinal mucosal lymphocytes （LI-IELs： （72.1±3.7）% vs. （61.5±4.5）%, P 〈0.01; LI-LPLs： （62.1±5.7）% vs. （52.7±3.6）%, P 〈0.01; n=8）. The proportion of CD3＋ T cells increased in Peyer＇s patches （PPs） and decreased in mesenteric lymph nodes （MLNs） from colitis mice compared to untreated mice, whereas the change pattern of CD3＋T cells in PPs and MLNs from CEP-fed colitis mice was just on the contrary. Conclusion Improvement of DSS-induced colitis resulted from oral immune regulation is associated with an increase in CD8a＋T cells in spleen and large intestinal mucosa.

Difference between 2 h and 3 h 75 g glucose tolerance test in the diagnosis of gestational diabetes mellitus(GDM):Results from a national survey on prevalence of GDM

The possibility of the 2 h oral glucose tolerance test(OGTT)as an alternative to the 3 h OGTT was investigated based on data from a national survey on pregnancy-associated diabetes.Data were retrieved from 4179 pregnant women who had OGTT performed after an abnormal 50 g glucose challenge test(GCT).All of the 4 glucose levels during their OGTT were collected and analyzed.According to American Diabetes Association(ADA)gestational diabetes mellitus(GDM)diagnostic criteria,among the 4179 pregnant women who required OGTT,3429(82.1%)were normal and 750(17.9%)were diagnosed as GDM.If the 3rd h glucose levels were omitted from OGTT,79 cases of GDM(10.5%)would be overlooked.No trend was shown where women with more risk factors were more likely to be overlooked if the 3rd h test was omitted(χ^(2) for trend=0.038,P>0.05).No significant differences were found in the rate of cesarean section(CS),preterm births or macrosomia between the 79 cases and those with normal OGTT results and in the gestational weeks when OGTT was performed.It shows that in order to diagnose one woman with GDM,another 52 pregnant women would have an innocent 3rd h glucose test.Omission of the 3rd h glucose test in OGTT might be reasonable due to its convenience,better compliance and a small number of possibly miss-diagnosed cases,and their pregnancy outcomes have no significant difference from those of normal pregnant women.

Construction of a Der p2-transgenic plant for the alleviation of airway inflammation

In clinical therapy,the amount of antigen administered to achieve oral tolerance for allergic diseases is large,and the cost is a major consideration.In this study,we used tobacco plants to develop a large-scale protein production system for allergen-specific immunotherapy,and we investigated the mechanisms of oral tolerance induced by a transgenic plant-derived antigen.We used plants(tobacco leaves)transgenic for the Dermatophagoides pteronyssinus 2(Der p2)antigen to produce Der p2.Mice received total protein extract from Der p2 orally once per day over 6 days(days 0–2 and days 6–8).Mice were also sensitized and challenged with yeast-derived recombinant Der p2(rDer p2),after which the mice were examined for airway hyper-responsiveness and airway inflammation.After sensitization and challenge with rDer p2,mice that were fed with total protein extracted from transgenic plants showed decreases in serum Der p2-specific IgE and IgG1 titers,decreased IL-5 and eotaxin levels in bronchial alveolar lavage fluid,and eosinophil infiltration in the airway.In addition,hyper-responsiveness was also decreased in mice that were fed with total protein extracted from transgenic plants,and CD4^(+)CD25^(+)Foxp3^(+) regulatory T cells were significantly increased in mediastinal and mesenteric lymph nodes.Furthermore,splenocytes isolated from transgenic plant protein-fed mice exhibited decreased proliferation and increased IL-10 secretion after stimulation with rDer p2.The data here suggest that allergen-expressing transgenic plants could be used for therapeutic purposes for allergic diseases.

Comparing the Diagnostic Criteria for Gestational Diabetes Mellitus of World Health Organization 2013 with 1999 in Chinese Population

INTRODUCTION Gestational diabetes mellitus （GDM） was earlier defined as ＂hyperglycemia first recognized during pregnancy＂ and has more recently been described by American Diabetes Association （ADA） （2012） as diabetes diagnosed during pregnancy that is not clearly overt diabetes. The hyperglycemia and adverse pregnancy outcomes study （HAPO） demonstrated that the risk of adverse maternal,fetal,and neonatal outcomes continuously increase as a function of maternal glycemia at 24-28 weeks,even within ranges previously considered normal for pregnancy.