Amylase intrapancreatic infusion delays insulin release during an intravenous glucose tolerance test,proof of acini–islet–acinar interactions

BACKGROUND The possible existence of an acini–islet–acinar(AIA)reflex,involving mutual amylase and insulin interactions,was investigated in the current acute experiment on pigs.AIM To confirm the existence of an AIA reflex and justify the placement of the exocrine and endocrine pancreatic components within the same organ.METHODS The study was performed on six pigs under general anesthesia.An intravenous glucose tolerance test was performed,with a bolus infusion of 50%glucose to the jugular vein,while amylase(5000 U/kg)or vehicle intrapancreatic infusions were administered via the pancreaticoduodenalis cranialis artery during 30 min with a 1 mL/min flow rate.RESULTS The amylase infusion to pancreatic arterial circulation inhibited and delayed the insulin release peak which is usually associated with the highest value of blood glucose and is typically observed at 15 min after glucose infusion,for>1 h.The intrapancreatic infusion of the vehicle(saline)did not have any effect on the time frame of insulin release.Infusion of 1%bovine serum albumin changed the insulin release curve dramatically and prolonged the high range of insulin secretion,far beyond the glucose peak.CONCLUSION Intrapancreatic arterial infusion of amylase interrupted the integrated glucose–insulin interactions.This confirms an AIA reflex and justifies placement of the exocrine and endocrine pancreatic components within the same organ.

Hypoglycaemia in screening oral glucose tolerance test in pregnancy with low birth weight fetus

Maternal hypoglycemia,a condition characterized by lower than normal blood glucose levels in pregnant women,has been increasingly associated with adverse pregnancy outcomes,including low birth weight(LBW)in neonates.LBW,defined as a birth weight of less than 2500 g,can result from various factors,including maternal nutrition,health status,and metabolic conditions like hypoglycemia.Maternal hypoglycemia may affect fetal growth by altering the supply of essential nutrients and oxygen to the fetus,leading to restricted fetal development and growth.This condition poses significant risks not only during pregnancy but also for the long-term health of the child,increasing the likelihood of developmental delays,health issues,and chronic conditions later in life.Research in this area has focused on understanding the mechanisms through which maternal hypoglycemia influences fetal development,with studies suggesting that alterations in placental blood flow and nutrient transport,as well as direct effects on fetal insulin levels and metabolism,may play a role.Given the potential impact of maternal hypoglycemia on neonatal health outcomes,early detection and management are crucial to minimize risks for LBW and its associated complications.Further investigations are needed to fully elucidate the complex interactions between maternal glucose levels and fetal growth,as well as to develop targeted interventions to support the health of both mother and child.Understanding these relationships is vital for improving prenatal care and outcomes for pregnancies complicated by hypoglycemia.

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.

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.

Subclinical abnormal glucose tolerance is a predictor of death in liver cirrhosis

AIM: To determine if subclinical abnormal glucose tolerance (SAGT) has influence on survival of non-diabetic patients with liver cirrhosis.

Changes of ghrelin following oral glucose tolerance test in obese children with insulin resistance

AIM： To characterize changes in ghrelin levels in response to oral glucose tolerance test （OGTT） and to correlate changes in ghrelin levels with changes in insulin and glucose following OGTT in Chinese obese children of Tanner Ⅰ and Ⅱ stage with insulin resistance. METHODS： 22 obese children with insulin resistance state were divided into four groups according to their Tanner stage and gender： boys of Tanner Ⅰ （fir- Ⅰ ）, boys of Tanner Ⅱ（BT-Ⅱ ）, girls of Tanner Ⅰ （GT- Ⅰ ）, girls of Tanner Ⅱ （GT-Ⅱ）. Ghrelin, insulin and glucose were measured at 0, 30, 60 and 120 rain following OGTT. The control children with normal BMI were divided into control boys of Tanner Ⅰ （CBT- Ⅰ, n = 6）, control boys of Tanner Ⅱ （CBT-Ⅱ, n = 5）, control girls of Tanner Ⅰ （CGT- Ⅰ, n = 6）, control girls of Tanner Ⅱ （CGT-Ⅱ, n = 5）. Fasting serum ghrelin levels were analyzed. RESULTS： Ghrelin levels were lower in obese groups. Ghrelin levels of control group decreased in Tanner Ⅱ stage （CGT- Ⅰ vs CGT-Ⅱ t = -4.703, P = 0.001; CBT- Ⅰ vs CBT- Ⅱ t = -4.794, P = 0.001）. Basal ghrelin levels in fir-Ⅱ decreased more significantly than that in BT- Ⅰ group （t = 2.547, P = 0.029）. Ghrelin levels expressed a downward trend after OGTT among obese children. The decrease in ghrelin levels at 60 min with respect to basal values was 56.9% in BT- Ⅰ. Ghrelin concentrations at 0 min correlated directly with glucose level at 0 min in fir- Ⅰ （r = 0.898, P = 0.015）. There wasn＇t a significant correlation of ghrelin changes with glucose changes and insulin changes during OGTT in obese children with insulin resistance. CONCLUSION： In conclusion, in obese children with insulin resistance, ghrelin levels decreased with advancing pubertal stage. Ghrelin secretion suppression following OGTT was influenced by gender and pubertal stage. Baseline ghrelin levels and ghrelin suppression after OGTT did not significantly correlate with the degree of insulin resistance and insulin sensitivity.

Helianthus tuberosus(Jerusalem artichoke) tubers improve glucose tolerance and hepatic lipid profile in rats fed a high-fat diet

Objective:To analyze the effects of feeding Helianthus tuberosus(HT) tubers on glucose tolerance and lipid profile in rats fed a high-fat diet(HFD). Methods:A normal HFD or HFD including 10 w/w% HT tubers(HFD + HT) was fed to F334/Jcl rats. After 10 weeks,organ weights,glucose tolerance,and lipid profile were analyzed. Results:The body weight,liver weight,and epidermal fat content in the HFD group were higher than those of the normal group,and similar to those of the HFD + HT group. The oral glucose tolerance test at 10 weeks revealed that the blood glucose level 30 minutes after beginning the test in the HFD + HT group was significantly lower than that in the HFD group. Liver triglyceride and total cholesterol levels in the HFD + HT group were significantly lower than those in the HFD group. Fecal triglyceride and total cholesterol levels in the HFD + HT group were higher than those in the HFD group. Histological analyses revealed that fat and glycogen accumulation increased in the HFD group,but decreased in the HFD + HT group. Conclusions:These results indicate that HT tubers have anti-fatty liver effects based on improvements in glucose tolerance and the hepatic lipid profile.

Central sensibility of human cases with different body mass during oral glucose tolerance test using functional magnetic resonance imaging

BACKGROUND： Because of the limitation of technique, there are few researches on regulating function o central hypothalamus by metabolism, especially the researches on real-time function. OBJECTIVE： To evaluate the response of hypothalamus to oral glucose tolerance test （OGTT） in differen body-weighted subjects by using functional magnetic resonance imaging （fMRI） so as to investigate th relationship between the sensitivity of hypothalamus in glycoregulation and disturbance of carbohydrate metabolism. DESIGN： Paired design. SETTING： Department of Radiology and Beijing Geriatrics Institute, Beijing Hospital, National Publi Health Bureau. PARTICIPANTS： A total of twenty healthy volunteers were selected from Beijing Geriatrics Institute National Public Health Bureau, including 10 subjects with obesity （5 males and 5 females; body mass 〉 28.0 kg/m2） and 10 subjects with normal body mass （5 males and 5 females; body mass from 18.5 to 23.9 kg/m2）. All subjects gave written informed consent before participating in the study. METHODS： fMRI study was performed on GE 1.5 T Signa Twinspeed Infinity with Excite. Each voluntee was ingested of glucose during the fMRI scan. T2＊ images were acquired using a single-shot gradient echo （EPI） technique. The parameters of EPI included： TR 3 000 ms, TE 40 ms, Flip angle 90°, field of view （FOV） 24 cm × 24 cm, thickness 5 mm, gap 0 mm, matrix 64 × 64, number of excitation 1. All 10 subjects with normal body mass underwent a repeat fMRI scan after consuming an equivalent amount o water without glucose on a separate day. The procedure for the fMRI scan with water intake was the same a for glucose ingestion. fMRI data were processed with Intensity Averaging Method. MAIN OUTCOME MEASURES： The central response of hypothalamus and feedback orientation during OGTT in different body-weighted subjects. RESULTS： An acute transient decrease of fMRI intensity in posterior inferior and anterior inferior o hypothalamus was observed in all subjects within 2 minutes after oral glucose intake. This decrease wa followed by a recovery to the baseline. However, obese subjects had a delayed intensity decrease [（1.96± 1.06） minutes vs. （1.04±0.71） minutes, t =2.14, P 〈 0.05] and longer recovery time [（26.62±7.35 minutes vs. （16.29±6.42） minutes, t =3.67, P 〈 0.01] as compared with normal body-weight subjects Furthermore, decreased fMRI intensity was significant different from baseline intensity [（5.7±2.5）% vs （14.3±5.5）%, t =2.56, P 〈 0.05] in obese subjects, but not in normal body-weight subjects. The area o hypothalamus in normal body-weight volunteers demonstrated no significant signal change before and afte oral water ingestion （P 〉 0.05）. CONCLUSION： Hypothalamus response to glucose loading is different in normal body-weighted and obes subjects. This suggests that fMRI is a useful tool to evaluate the central regulation of glucose metabolism.

STUDY ON OBESITY RELATED FACTORS: FFA, LEPTIN AND ADIPONECTIN IN SUBJECTS WITH VARYING GLUCOSE TOLERANCE

Objective To study the fasting serum levels of obesity related factors: FFA, leptin and adi-ponectin in subjects with varying glucose tolerance and their relationship with BMI, insulin sensitivity index and isletbeta-cell function. Methods Serum levels of FFA, leptin and adiponectin in 24 normal, 32 simple obese, 34IGT and 36 T2DM subjects were measured by ACS-ACOD assay or RIA. Results The serum levels of leptin andFFA in three groups:simple obese, IGT and DM were much higher than those in normal control (P <0. 001). Incontrast, serum level of adiponectin of simple obese, IGT and DM groups were significant lower than that of normalcontrol, among them DM subjects had the lowest level (P <0. 001). Correlation analysis showed that FFA was pos-itively correlated to BMI, WHR, FBG, fasting insulin level and negatively correlated to SI; adiponectin was negativelycorrelated to BMI, WHR, FBG, PBG, but positively correlated to SI and AIRg; and leptin was positively correlated toBMI, fasting insulin and AIRg when negatively correlated to FBG and SI. None of them was correlated to age.Conclusion Subjects with insulin resistance have high serum FFA and leptin levels but low serum adiponectin level.With the glucose tolerance deterioration, serum FFA level increases much higher while the adiponectin deceases muchlower. Unlike insulin, none of these obesity related factors can be used as the simple indicating or determining factorof SI, though each of them, to different extent, takes part in the development of insulin resistance.

Vascular endothelial growth factor B improves impaired glucose tolerance through insulin-mediated inhibition of glucagon secretion

BACKGROUND Impaired glucose tolerance(IGT)is a homeostatic state between euglycemia and hyperglycemia and is considered an early high-risk state of diabetes.When IGT occurs,insulin sensitivity decreases,causing a reduction in insulin secretion and an increase in glucagon secretion.Recently,vascular endothelial growth factor B(VEGFB)has been demonstrated to play a positive role in improving glucose metabolism and insulin sensitivity.Therefore,we constructed a mouse model of IGT through high-fat diet feeding and speculated that VEGFB can regulate hyperglycemia in IGT by influencing insulin-mediated glucagon secretion,thus contributing to the prevention and cure of prediabetes.AIM To explore the potential molecular mechanism and regulatory effects of VEGFB on insulin-mediated glucagon in mice with IGT.METHODS We conducted in vivo experiments through systematic VEGFB knockout and pancreatic-specific VEGFB overexpression.Insulin and glucagon secretions were detected via enzyme-linked immunosorbent assay,and the protein expression of phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)was determined using western blot.Further,mRNA expression of forkhead box protein O1,phosphoenolpyruvate carboxykinase,and glucose-6 phosphatase was detected via quantitative polymerase chain reaction,and the correlation between the expression of proteins was analyzed via bioinformatics.RESULTS In mice with IGT and VEGFB knockout,glucagon secretion increased,and the protein expression of PI3K/AKT decreased dramatically.Further,in mice with VEGFB overexpression,glucagon levels declined,with the activation of the PI3K/AKT signaling pathway.CONCLUSION VEGFB/vascular endothelial growth factor receptor 1 can promote insulin-mediated glucagon secretion by activating the PI3K/AKT signaling pathway to regulate glucose metabolism disorders in mice with IGT.

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.

Effect of Jiangtang Bushen Recipe (降糖补肾方) in Intervention Treatment of Patients with Impaired Glucose Tolerance

Objective:To evaluate the intervention effect of diet, exercise and Jiangtang Bushen Recipe (JBR, 降糖补肾方), a Chinese herbal recipe, in preventing the progress of patients with impaired glucose tolerance ( IGT ) to diabetes mellitus (DM) type 2. Methods: Fifty-one IGT patients with their diagnosis conformed to the diagnosis standard of WHO, 1999, were randomly divided into the control group (n = 26) and the TCM group (n=25). Patients in the control group attended to the educational course for DM and received dietotherapy and kinetotherapy, and to those in the TCM group, under these treatments, JBR was given additionally. Oral glucose tolerance test (OGTT), body weight index (BWI), levels of blood lipids and fasting insulin of all the patients were examined after 3 months, 6 months and 12 months of treatment. The total observation time was 1 year. Results:Except the 6 cases out of the 51 patients (11.7%), on whom the observa-tion discontinued, in the control group, as compared with before treatment, levels of fasting insulin and fasting blood glucose after treatment were not changed significantly ( P > 0. 05 ) , also insignificant difference was shown in levels of total cholesterol (TC) and triglyceride (TG), thoughthe two indexes lowered slightly after treatment (P>0. 05), but significant difference was shown in comparison of OGTT/2h, blood glucose and BWI (P<0. 05). While in the TCM group, fasting blood glucose was changed insignificantly (P> 0. 05) , but there was significant difference in comparison of fasting insulin, TC, BWI, OGTT/2h and plasma glucose levels (P<0. 01) respectively before and after treatment. At the end of the stud-y, the cumulative cases with conversion to diabetes were 3 (13. 6%) in the control group, and 1 (4. 3%) in the TCM group, x2 test showed insignificant difference in comparison of diabetes conversion rate between the two groups (P>0. 05), however, the TCM group showed a better year conversion rate of normal glucose tolerance than that in the control group (x2 = 8. 31, P<0. 01). Conclusion: TCM intervention is possibly effective in delaying the conversion of IGT to DM type 2, and plays integrative effeciency in impelling IGT patients to health. The favorable education and treatment of DM controlling, including dieto- and kineto-therapy may also be advantageous in IGT intervention, but could not be effective in blocking the advance of IGT.Original article on CJITWM (Chin) 2004 ;24 (4): 317

Effects of Chinese Patent Drug Zishen Pills in Treatment of Elderly Patients with Impaired Glucose Tolerance(IGT)

[Objectives]To evaluate the efficacy of Zishen Pills(ZSP),a Chinese patent drug,in the treatment of elderly patients with impaired glucose tolerance(IGT)and its effects on the prevention of diabetes mellitus(DM).[Methods]Thirty-five IGT patients were randomized to receive 10 g of ZSP three times daily(ZSP group,n=24)or no drug intervention(control group,n=11)for 12 weeks.Oral glucose tolerance test,glycated hemoglobin A1c(HbA1c),body mass index,blood lipids levels,fasting insulin,and insulin resistance calculated using homeostatic model assessment(HOMA-IR)of all the patients were observed and compared before and after the treatment.[Results]Thirty participants completed the trial(20 in ZSP group and 10 in the control group).There were statistically significant decreases in plasma triglycerides(TG),fasting blood-glucose(FBG),2-h plasma glucose(2-h PG),HbA1c,and HOMA-IR in ZSP group compared with the control group after 12 weeks of treatment(P<0.05 or P<0.01).After 12 weeks of treatment,2(20.0%)patients returned to normal blood glucose,and 2(20.0%)patients turned into DM in control group,while in the ZSP group,9(45.0%)patients returned to normal blood glucose and 1(5.0%)patient turned into DM.[Conclusions]ZSP effectively improved glucose control,increased the conversion of IGT to normal glucose,and improved the insulin resistance in elderly patients with IGT.This Chinese patent drug may have a clinical value for IGT.

Comparison of Serum Lipid Profile between Gestational Diabetes Mellitus and Pregnant Women with Normal Glucose Tolerance

Background: Aberrant lipid metabolism presumed to have important relationship with gestational diabetes mellitus (GDM), though previous studies revealed inconsistent results on this area. Objectives: To identify the difference of serum lipid profile between gestational diabetes mellitus (GDM) and pregnant woman with normal glucose tolerance (NGT). Methods: This cross sectional study was conducted from January 2017 to December 2017 at Department of Endocrinology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh with 31 GDM and equal number of NGT pregnant women diagnosed on the basis of WHO criteria-2013, during 24 - 40 weeks of gestation. Glucose was measured by glucose oxidase method and fasting serum lipid profile [Total cholesterol (TC), High Density Lipoprotein-cholesterol (HDL-C) and Triglyceride (TG)] was measured by enzymatic-colorimetric method. Data were analyzed and compared by statistical tests. Results: Among total sixty-two (62) study subjects, 31 were GDM (age: 27.52 ± 4.8 years, body mass index (BMI): 27.17 ± 3.3 kg/m2) and 31 were pregnant women with NGT (age: 24.94 ± 4.2 years, BMI: 25.43 ± 6.5 kg/m2). Mean age of GDM group was significantly higher than that of NGT group (p = 0.028). Women with GDM showed relatively higher BMI than NGT women but that was not statistically significant (p = 0.194). Fasting lipid profiles between GDM and NGT (GDM vs. NGT;total cholesterol: 194.21 ± 42.18 vs. 208.52 ± 42.18 mg/dl, p = 0.187;HDL-C: 47.50 ± 16.17 vs. 47.18 ± 11.71 mg/dl, p = 0.928;LDL-C: 109.25 ± 28.80 vs. 119.30 ± 34.76 mg/dl, p = 0.220 and triglyceride 204.78 ± 58.50 vs. 202.34 ± 79.18 mg/dl, p = 0.891) were not significantly different. The variations in all lipid fraction values were not statistically significant among GDM women when analyzed between BMI groups holding BMI cut-off at 23 kg/m2. No significant differences of any values of lipid profile were found in GDM women according to various age categories (Age < 25 years vs. ≥25 years). Conclusions: Lipid profile does not differ between women with GDM and pregnant woman with NGT.

Meta-analysis of clinical efficacy and safety of the treatment of impaired glucose tolerance by Tianqijiangtang Capsule

Objective： To evaluate the clinical efficacy and safety of Tianqijiangtang Capsule （TG） during the treatment ofimpaired glucose tolerance （IGT）. Methods： Using Chinese words of “impaired glucose tolerance, abnormalglucose tolerance, IGT” and “TG” as search terms, China National Knowledge Infrastructure, VIP, Wanfang Dataand Pubmed were searched from database inception until October 2017. All the controlled clinical researches on thetreatment of IGT by TG meeting the inclusion and exclusion criteria were retrieved and analyzed by ReviewManager 5.3 software. Results： A total of 7 articles including 1082 participants were enrolled. Meta-analysisshowed that the OR value of inversion rate was 2.17, 95% CI （1.65, 2.84）. Weighted mean difference （WMD） valueof fasting plasma glucose was -0.25, 95% CI （-0.39, -0.11）. After 2 h, the WMD value of serum glucose was -0.73,95% CI （-0.96, -0.51）, all of which were better than these of control group. The OR value of progression rate （type2 diabetes mellitus） was 0.44, 95% CI （0.32, 0.59）, less than the control group. All of the differences werestatistically significant. No hepatic and renal toxicity case was reported. Only 1 article reported adverse reactions inthe course of treatment. Conclusion： TG could treat IGT effectively, delay and even invert the progress of IGT, butits security still needed further discussion.

Mechanism Analysis of Gui Jianyu in treating Hypertension complicated with Impaired Glucose Tolerance Based on Network Pharmacology and Molecular Docking

Objective To explore the mechanism of Gui Jianyu(Euonymus alatus(Thunb.)Sieb.)in treating hypertension(HT)complicated with impaired glucose tolerance(IGT)based on network pharmacology and molecular docking technology.Methods The main chemical components and targets of Gui Jianyu were obtained from TCMSP database.The Swiss Target Prediction platform was used to predict drug-related targets for supplement.Main disease targets of HT complicated with IGT were obtained from GenCards,OMIM and DrugBank databases.The intersection targets of drugs and two diseases were obtained by R and Veen Diagram was drawn.The protein-protein interaction(PPI)network model was constructed in STRING platform and visualized by Cytoscape tool.GO and KEGG analysis on Metascape platform were used to analyse the common targets.Network of main drug components-disease targets-pathways was established with Cytoscape tool.Finally,the molecular docking between the core regulatory active components of Gui Jianyu and the core targets were verified by Autodock vina.Results Eight active components and 357 corresponding targets were obtained.681 HT related targets and 727 IGT related targets,196 disease intersection targets,and 57 Gui Jianyu targets in the treatment of HT complicated with IGT were confirmed.20 GO and 19 KEGG main pathways were enriched.Molecular docking of 2 key active ingredients with 2 key targets showed that all results scores were less than-5.0 kcal·mol-1.Quercetin and kaempferol,the key active components,had good binding activity with AKT1 and TP53.Conclusion Gui Jianyu may play a key role in the treatment of HT complicated with IGT by reducing insulin resistance.This work explored the common pathogenesis of HT complicated with IGT,and also provided a reference for further pharmacological research and exploration the efficacy of Gui Jianyu for HT complicated with IGT.

Microbiome and metabolome dysbiosis analysis in impaired glucose tolerance for the prediction of progression to diabetes mellitus

Gut microbiota and circulating metabolite dysbiosis predate important pathological changes in glucose metabolic disorders;however,comprehensive studies on impaired glucose tolerance(IGT),a diabetes mellitus(DM)precursor,are lacking.Here,we perform metagenomic sequencing and metabolomics on 47 pairs of individuals with IGT and newly diagnosed DM and 46 controls with normal glucose tolerance(NGT);patients with IGT are followed up after 4 years for progression to DM.Analysis of baseline data reveals significant differences in gut microbiota and serum metabolites among the IGT,DM,and NGT groups.In addition,13 types of gut microbiota and 17 types of circulating metabolites showed significant differences at baseline before IGT progressed to DM,including higher levels of Eggerthella unclassified,Coprobacillus unclassified,Clostridium ramosum,L-valine,L-norleucine,and L-isoleucine,and lower levels of Eubacterium eligens,Bacteroides faecis,Lachnospiraceae bacterium 3_1_46FAA,Alistipes senegalensis,Megaspaera elsdenii,Clostridium perfringens,α-linolenic acid,10E,12Z-octadecadienoic acid,and dodecanoic acid.A random forest model based on differential intestinal microbiota and circulating metabolites can predict the progression from IGT to DM(AUC=0.87).These results suggest that microbiome and metabolome dysbiosis occur in individuals with IGT and have important predictive values and potential for intervention in preventing IGT from progressing to DM.

Relationship between Oral Glucose Tolerance Test Characteristics and Adverse Pregnancy Outcomes among Women with Gestational Diabetes Mellitus

Background： Hyperglycemia is associated with adverse pregnancy outcomes. However, the relationships between them remain ambiguous. This study aimed to analyze the effect of different oral glucose tolerance test （OGTT） results on adverse perinatal outcomes. Methods： This retrospective cohort study included data from 15 hospitals in Beijing from June 20, 2013 to November 30, 2013. Women with gestational diabetes mellitus （GDM） were categorized according to the number and distribution of abnormal OGTT values, and the characteristics of adverse pregnancy outcomes were evaluated. Chi-square test and logistic regression analysis were used to determine the associations. Results： in total, 14,741 pregnant women were included in the study population, 2927 （19.86%） of whom had G DM. As the number of hyperglycemic values in the OGTT increased, the risk of cesarean delivery, preterm births, large-for-gestational age （LGA）, macrosomia, and neonatal complications significantly increased. Fasting hyperglycemia bad clear associations with macrosomia （odds ratios [ORs]：1.84, 95% confidence intervals [CIs]： 1.39-2.42, P 〈 0.001）, L（SA （OR： 1.70, 95% CI： 1.29-2.25. P 〈 0.001）, and cesarean delivery （OR： 1.33, 95% CI： 1.15-1.55, P 〈 0.001）. The associations were stronger as tasting glucose increased. GDM diagnosed by hyperglycemia at OGTT-2 h was more likely to lead to preterm birth （OR： 1.50, 95% Cl： 1. 11-2.03, P 〈 0.01）. Conclusions： Various characteristics of OGTTs are associated with different adverse outcomes. A careful reconsideration ofGDM wiih hierarchical and individualized management according to OGTT characteristics is needed.

Analysis of oral glucose tolerance test in pregnant women with abnormal glucose metabolism

Background Due to the controversy of the oral glucose tolerance test (OGTT), diagnostic criteria for gestational diabetes mellitus (GDM) in the world and researches on GDM remain undeveloped in China. American Diabetes Association recently recommended the clinicians to diagnose GDM by OGTT results without the third-hour glucose value. This new criteria has not been used in China. Research on the value and sensitivity of the criteria in detecting GDM is rare. The aim of our study is to analyze the characteristics of OGTT in Chinese women with GDM or gestational impaired glucose tolerance (GIGT) and to evaluate the effect of omission of the third-hour plasma glucose (PG) level in OGTT on the sensitivity of diagnosing GDM and GIGT, and the relationship between PG values of 50 g GCT or OGTT and insulin therapy. Methods A retrospective analysis was performed on medical records of 647 cases with GDM from January 1, 1989 to December 31, 2002, and 233 with GIGT. Among 647 cases of GDM, 535 cases were diagnosed by 75 g OGTT. All OGTT results including 535 cases of GDM and 233 patients with GIGT were evaluated. Results There were 112 cases of GDM diagnosed by elevated fasting PG (FPG) without OGTT performed. Of 535 cases of GDM diagnosed by OGTT, 49.2% (263/535) women had FPG value ≥5.8 mmol/L; 90.1% (482/535) women with 1-hour PG values ≥10.6 mmol/L; 64.7% (359/535) with 2-hour PG levels ≥9.2 mmol/L. There were only 114 cases (21.3%) with abnormal 3-hour PG levels among 535 women with OGTT. Among those with abnormal 3-hour PG level, 49.1% (56/114) had abnormal glucose values in the other three points of OGTT, and 34.2% (39/114) with two other abnormal values of OGTT. Our study showed that omission of the 3-hour PG of OGTT only missed 19 cases of GDM and they would be diagnosed as GIGT. Among the 233 women with GIGT, only 4 cases had abnormal 3-hour PG. So, omission of the third-hour glucose value of OGTT only resulted in failure to diagnose 3.6% (19/535) women with GDM diagnosed by OGTT, which means 2.9% (19/647) of all the GDM and 1.7% (4/233) of GIGT in Chinese women. PG levels ≥11.2 mmol/L following 50 g GCT was highly associated with GDM necessitating insulin therapy (75.4%). An elevated FPG level was also associated with insulin therapy (59.7%). Conclusions Omission of the third-hour glucose tolerance test value still yield a higher sensitivity in diagnosing GDM and GIGT. In Chinese women, it is practicable to omit third-hour post-glucose ingestion value of the OGTT in Chinese women. PG levels ≥11.2 mmol/L following 50 g GCT mostly indicates that the requirement of insulin therapy.