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.

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.

Risk factors for impaired glucose tolerance in obese children and adolescents

AIM:To investigate which obese children have an increased risk for impaired glucose tolerance(IGT),a risk factor for later diabetes.METHODS:We studied 169 European untreated obese children and adolescents with normal glucose tolerance at baseline.Waist circumference,fasting glucose,lipids,blood pressure,pubertal stage,2 h glucose in oral glucose tolerance test(oGTT),and HbA1c were deter mined at baseline and 1 year later.RESULTS:One year after baseline,19(11.2) children demonstrated IGT,4(2.4) children had impaired fas ting glucose,no(0) child suffered from diabetes,and 146(86) children still showed normal glucose tolerance.At baseline,the children with IGT and with normal glucose tolerance in a one-year follow-up did not differ significantly in respect of any analyzed parameter,apart from pubertal stage.The children developing IGT entered puberty significantly more frequently(37 vs 3,P < 0.001).One year after baseline,the childr en with IGT demonstrated significantly increased waist circumference,blood pressure values,insulin and triglyceride concentrations,and insulin resistance index HOMA.The children remaining in the normal glucose tolerance status 1 year after baseline did not demonstrate any significant changes.CONCLUSION:During the study period of 1 year,more than 10 of the obese children with normal glucose tolerance converted to IGT.Repeated screening with oGTT seems meaningful in obese children entering puberty or demonstrating increased insulin resistance,waist circumference,blood pressure,or triglyceride concen trations.

Effects of Metformin and Pioglitazone on impaired glucose tolerance patients—An open level prospective study

Introduction: impaired glucose tolerance (IGT) often leads to type 2 diabetes (T2DM) and macro vascular disease;and usually associated with insulin resistance. Pioglitazone and metformin are commonly used insulin sensitizers (IS);and can prevent or delay the development T2DM and macro vascular disease. This study was deployed to search the better IS between these two in relation to plasma glucose and lipid control;and physical parameter altering effect. Materials and methods: 100 IGT patients selected randomly from outpatients department following prefixed inclusion and exclusion criteria. Pioglitazone and metformin were administered sequentially. Washout period was 2 weeks. Total follow up period was 24 weeks. Results: 70 IGT patients had completed the study. Metformin had reduced plasma glucose (fasting & postprandial), lipids and physical parameters significantly (p < 0.05) more than Pioglitazone. Discussion: Metformin, a hepatic insulin sensitizer, is more effective than PPAR-□ agonist Pioglitazone in the treatment of IGT;and this is due to the expression of PPAR-□ is more in adipose tissue but postprandial utilization of plasma glucose is more in muscle tissue.

Scleredema Diabeticorum in a Patient with the Normal Range of the Hemoglobin A1c Level and Impaired Glucose Tolerance

Scleredema diabeticorum is an uncommon skin disorder showing a diffuse, symmetrical, and non-pitting persistent in-duration developing initially on the nape. It usually occurs in patients with poorly controlled or insulin-resistant diabetes mellitus. We present a 57-year-old woman with scleredema diabeticorum with hemoglobin A1c 6.1% (normal, 4.7% - 6.2%) and impaired glucose tolerance. Alcian blue staining at pH 7.0 illustrated deposits of acid mucopolysaccharides between the collagen bundles in the reticular dermis, but the staining at pH 1.5 did not show the deposits. This case indicates that scleredema diabeticorum may be an early indicator of undiagnosed diabetes mellitus in some cases, and that impaired glucose tolerance test should be performed for individuals with scleredema even though the hemoglobin A1c level is within the normal range.

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

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.

Retinal microcirculation changes in prediabetic patients with shortterm increased blood glucose using optical coherence tomography angiography

BACKGROUND Retinal microcirculation alterations are early indicators of diabetic microvascular complications.Optical coherence tomography angiography(OCTA)is a noninvasive method to assess these changes.This study analyzes changes in retinal microcirculation in prediabetic patients during short-term increases in blood glucose using OCTA.AIM To investigate the changes in retinal microcirculation in prediabetic patients experiencing short-term increases in blood glucose levels using OCTA.METHODS Fifty volunteers were divided into three groups:Group 1[impaired fasting glucose(IFG)or impaired glucose tolerance(IGT)],Group 2(both IFG and IGT),and a control group.Retinal microcirculation parameters,including vessel density(VD),perfusion density(PD),and foveal avascular zone(FAZ)metrics,were measured using OCTA.Correlations between these parameters and blood glucose levels were analyzed in both the fasting and postprandial states.RESULTS One hour after glucose intake,the central VD(P=0.023),central PD(P=0.026),and parafoveal PD(P<0.001)were significantly greater in the control group than in the fasting group.In Group 1,parafoveal PD(P<0.001)and FAZ circularity(P=0.023)also increased one hour after glucose intake.However,no significant changes were observed in the retinal microcirculation parameters of Group 2 before or after glucose intake(P>0.05).Compared with the control group,Group 1 had a larger FAZ area(P=0.032)and perimeter(P=0.018),whereas Group 2 had no significant differences in retinal microcirculation parameters compared with the control group(P>0.05).Compared with Group 1,Group 2 had greater central VD(P=0.013)and PD(P=0.008)and a smaller FAZ area(P=0.012)and perimeter(P=0.010).One hour after glucose intake,Group 1 had a larger FAZ area(P=0.044)and perimeter(P=0.038)than did the control group,whereas Group 2 showed no significant differences in retinal microcirculation parameters compared with the control group(P>0.05).Group 2 had greater central VD(P=0.042)and PD(P=0.022)and a smaller FAZ area(P=0.015)and perimeter(P=0.016)than Group 1.At fasting,central PD was significantly positively correlated with blood glucose levels(P=0.044),whereas no significant correlations were found between blood glucose levels and OCTA parameters one hour after glucose intake.CONCLUSION A short-term increase in blood glucose has a more pronounced effect on retinal microcirculation in prediabetic patients with either IFG or IGT.

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.

益气健脾汤治疗脾气亏虚型IGT患者的临床观察及对血糖变异系数的影响

目的:研究益气健脾汤治疗脾气亏虚型糖耐量减低(IGT)患者的疗效以及对血糖波动指数的影响。方法:纳入2023年12月—2024年2月在黑龙江中医药大学附属第三医院内分泌(老年病)科门诊、住院部的60例IGT(脾气亏虚型)患者,按照随机数字表法分为对照组和治疗组,每组30例。两组患者均给予饮食、宣教、运动等一般基础治疗。对照组在基础治疗的基础上给予阿卡波糖胶囊;治疗组在对照组基础上加用益气健脾汤联合治疗。两组患者均治疗6周。观察两组在治疗前后的空腹血糖(FPG)、2 h血糖(2 h PG)、糖化血红蛋白(HbA1c);甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白(LDL);血糖变异系数(GLUCV)、血糖标准差(GLUsd)、平均血糖值(GLUmean)、日内平均血糖波动幅度(MAGE)、日间血糖平均绝对差(MODD)及中医证候评分,并观察其疗程结束时的随访转归情况。结果:治疗6周后,两组患者的糖代谢指标、GLUsd、GLUmean、GLUCV、MAGE、中医证候评分均显著降低(P<0.05),治疗组的糖代谢指标、GLUsd、GLUCV、MAGE、中医证候评分显著低于对照组,差异有统计学意义(P<0.05)。结论:益气健脾汤能有效改善IGT患者症状,调节糖代谢,并能缩小血糖波动,延缓2型糖尿病发生发展,比单纯生活方式干预和阿卡波糖治疗持久有效。

Effect of Chinese Herbal Medicine Jinlida Granule in Treatment of Patients with Impaired Glucose Tolerance

Background：Diabetes mellitus （DM） remains a major health problem worldwide.Several clinical trials have shown the superiority of the Traditional Chinese Medicine in delaying or reversing the development and progression of DM.This study aimed to evaluate the efficacy of Jinlida （JLD） granule,a Chinese herbal recipe,in the treatment of impaired glucose tolerance （IGT） and its effect on the prevention of DM.Methods：Sixty-five IGT patients were randomized to receive one bag of JLD granules three times daily （JLD group,n =34） or no drug intervention （control group,n =31） 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：Sixty-one participants completed the trial （32 in JLD group and 29 in the control group）.There were statistically significant decreases in HbA1c （P 〈 0.001）,2-h plasma glucose （P 〈 0.001）,and HOMA-IR （P =0.029） in JLD group compared with the control group after 12 weeks of treatment.After 12 weeks of treatment,two （6.9%） patients returned to normal blood glucose,and five （17.2%） patients turned into DM in control group,while in the JLD group,14 （43.8%） returned to normal blood glucose and 2 （6.2%） turned into DM.There was a significant difference in the number of subjects who had normal glucose at the end of the study between two groups （P =0.001）.Conclusions：JLD granule effectively improved glucose control,increased the conversion of IGT to normal glucose,and improved the insulin resistance in patients with IGT.This Chinese herbal medicine may have a clinical value for IGT.

Effect of impaired glucose tolerance on cardiac dysfunction in a rat model of prediabetes

Background The effect of impaired glucose tolerance （IGT） on cardiac function during the chronic prediabetes state is complicated and plays an important role in clinical outcome. However, the molecular mechanisms are not fully understood. This study was designed to observe cardiac dysfunction in prediabetic rats with IGT and to determine whether glucose metabolic abnormalities, inflammation and apoptosis are linked to it.Methods The IGT rat models were induced by streptozocin, and the heart functions were assessed by echocardiography. Myocardial glucose metabolism was analyzed by glycogen periodic acid-Schiff staining, and the pro-apoptotic effect of IGT was evaluated by TUNEL staining. Additionally, caspase-3 activation, macrophage migration inhibitory factor （MIF） and G-protein coupled receptor kinase 2 （GRK2） were detected by Western blotting in cardiac tissue lysates.Results Area-under-the-curve of blood glucose in rats injected with streptozotocin was higher than that in controls, increased by 16.28%, 38.60% and 38.61% at 2, 4 and 6 weeks respectively （F=15.370, P=0.003）. Abnormal cardiac functions and apoptotic cardiomyocytes were observed in the IGT rats, the ejection fraction （EF） being （68.594-6.62）% in IGT rats vs. （81.07±4.59）% in controls （t=4.020, P=0.002）. There was more glucose which was converted to glycogen in the myocardial tissues of IGT rats, especially in cardiac perivascular tissues. Compared to controls, the cleaved caspase-3, MIF and GRK2 were expressed at higher levels in the myocardial tissues of IGT rats.Conclusions IGT in the prediabetes period resulted in cardiac dysfunction linked to abnormal glycogen storage and apoptosis. Additionally, MIF and GRK2 may be involved in the pathogenesis of cardiac dysfunction in prediabetes and their regulation may contribute to the design of novel diagnostic and therapeutic strategies for those who have potential risks for diabetic cardiovascular complications.

Effect of Tang No.1 Granule (糖1号方) in Treating Patients with Impaired Glucose Tolerance

Objective： To observe the therapeutic effect of Tang No.1 granule （糖1号方, T1G） in treating patients with impaired glucose tolerance （IGT）. Methods： One hundred and forty patients with IGT and with Pi （脾）-Wei （胃） dampness-heat syndrome type were assigned randomly according to their visiting sequence into two equal groups. The control group received only general knowledge about IGT, but to the treated group, based on current knowledge available, T1G was given additionally for 6 months. Changes in related laboratory indexes, including fasting plasma glucose and insulin （FPG and FINS）, plasma glucose 2 h after meal （2hPG）, glycosylated hemoglobin （HbAlc）, serum triglyceride （TG）, low density lipoprotein cholesterol （LDL） and insulin resistance index （HOMA-IR）, were observed. Results： The levels of FPG, 2hPG, HbAlc, FINS, TG and HOMA-IR were significantly decreased after treatment in the treated group, showing a significant difference compared to the control group （P〈0.01）. Among them, HbAlc decreased from 7.08±1.41% to 6.56±1.29% in the treated group, while in the control group, it decreased from 7.02±1.37% to 6.93±1.31%. The level of LDL was also reduced in the treated group after treatment （P〈0.05）. In the treated group, 13 out of 68 patients （19.12%） had their glucose tolerance reversed to normal, while in the control group, only 2/64 （3.1%） got it reverse; a comparison between the two groups in terms of reversion rate showed a significant difference （P〈0.01）. No severe adverse reaction was found in the therapeutic course. Conclusions： T1G has good clinical effect as a treatment intervention for IGT, as it could improve glycometabolism, significantly depress the levels of post-prandial blood sugar and blood lipids, alleviate clinical symptoms of patients, and effectively cut-off and reverse the yielding and development of diabetes mellitus.

Long-Term Clinical Effect of Tangyiping Granules(糖异平颗粒)on Patients with Impaired Glucose Tolerance

Objective： To evaluate the long-term clinical effect of Tangyiping Granules（糖异平颗粒, TYP） on patients with impaired glucose tolerance（IGT） to achieve normal glucose tolerance（NGT） and hence preventing them from conversion to diabetes mellitus（DM）. Methods： In total, 127 participants with IGT were randomly assigned to the control（63 cases, 3 lost to follow-up） and treatment groups（64 cases, 4 lost to follow-up） according to the random number table. The control group received lifestyle intervention alone, while the patients in the treatment group took orally 10 g of TYP twice daily in addition to lifestyle intervention for 12 weeks. The rates of patients achieving NGT or experiencing conversion to DM as main outcome measure were observed at 3, 12, and 24 months after TYP treatment. The secondary outcome measures included fasting plasma glucose（FPG）, 2-h postprandial plasma glucose（2h PG）, glycosylated hemoglobin（Hb A1c）, fasting insulin（FINS）, 2-h insulin（2hI NS）, homeostatic model assessment of insulin resistance（HOMA-IR）, blood lipid and patients＇ complains of Chinese medicine（CM） symptoms before and after treatment. Results： A higher proportion of the treatment group achieved NGT compared with the control group after 3-, 12- and 24-month follow-up（75.00% vs. 43.33%, 58.33% vs. 35.00%, 46.67% vs. 26.67%, respectively, P〈0.05）. The IGT to DM conversion rate of the treatment group was significantly lower than that of the control group at the end of 24-month follow-up（16.67% vs. 31.67%, P〈0.05）. Before treatment, FPG, 2h PG, Hb A1 c, FINS, 2h INS, HOMA-IR, triglyceride（TG）, total cholesterol, low- and high-density lipoprotein cholesterol levels had no statistical difference between the two groups（P〉0.05）. After treatment, the 2hP G, HbA 1c, HOMA-IR, and TG levels of the treatment group decreased significantly compared with those of the control group（P〈0.05）. CM symptoms such as exhaustion, irritability, chest tightness and breathless, spontaneous sweating, constipation, and dark thick and greasy tongue were significantly improved in the treatment group as compared with the control group（P〈0.05）. No severe adverse events occurred. Conclusion： TYP administered at the IGT stage with a disciplined lifestyle delayed IGT developing into type 2 DM.

Protective effects of Modified Linggui Zhugan Decoction combined with short-term very low calorie diets on cardiovascular risk factors in obese patients with impaired glucose tolerance

OBJECTIVE:To observe the protective effects of modified Linggui Zhugan Decoction combined with short-term very low calorie diets(VLCDs) on cardiovascular risk factors in obese patients with impaired glucose tolerance(IGT).METHODS:Eighty-five obese patients with IGT of spleen hypofunction and dampness accumulation type were randomly divided into treated group(n=45)and control group(n=40).The treated group was given Linggui Zhugan Decoction combined short-term VLCDs.The control group was given basic weight-reduction treatment.The total course was 6 months.Changes of fasting plasma glucose(FPG),2-hour postprandial blood glucose(2hPG),glycosylated hemoglobin(HbA1c),fasting insulin(FINS),lipid metabolism,blood pressure,body mass index(BMI) and waist circumference(WC) were observed,and the outcomes were reviewed after the treatment.RESULTS:Compared with the control group,the levels of FPG,2hPG,HbA1c,FINS,HOMA-IR decreased significantly(P<0.05),and the indexes of total cholesterol(TC),triglyceride(TG),low-density lipoprotein(LDL),systolic blood pressure(SBP),diastolic blood pressure(DBP),BMI and WC were improved significantly(P<0.05) in the treated group.The transformation rate of normal glucose tolerance(NGT) was higher in treatment group than control group(P<0.01).No severe adverse reaction was found in the therapeutic course.CONCLUSION:The modified Linggui Zhugan Decoction combined with short-term VLCDs has good protective effects on cardiovascular risk factors as a treatment intervention for IGT with obesity,as it could improve glycometabolism,significantly decrease the levels of blood pressure,blood lipids,BMI,WC and effectively cut-off and reverse the development of diabetes mellitus.

Transcutaneous auricular vagus nerve stimulation for impaired glucose tolerance:a randomized controlled trial Protocol

Background:impaired glucose tolerance(IGT)is the early stage of diabetes and it would be deteriorated to type 2 diabetes mellitus(T2 DM)easily if no intervention provided.In western medicine,drug therapy assisted with the intervention of lifestyle is predominated.However,drug therapy brings serious side effect and high prices,while lifestyle intervention is difficult to be insisted on by patients.Therefore,a green and effective intervention mode is urgently needed.Transcutaneous auricular vagus nerve stimulation(taVNS)is a noninvasive and green therapeutic method based on the theory of traditional Chinese medicine(TCM),which can regulate glucose metabolism and reduce blood glucose,but the clinical effect of it has not been clarified yet at present.Hence,this randomized controlled trial(RCT)aims at exploring the effectiveness and safety of taVNS in the treatment of IGT.Methods:a total of 158 patients with IGT will be randomized into a taVNS group and a transcutaneous non-auricular vagus nerve stimulation(tnVNS)group,79 cases in each one.In the taVNS group and the tnVNS group,electric stimulation would be applied to Yidan(胰胆pancreas and gallbladder,CO11)and Pi(脾spleen,CO13)on auricular concha and Jian(肩shoulder SF4,5)on auricular rim respectively.The electric stimulation parameters would be the same in the patients of two groups,for 30 min in each treatment,twice a day,6 weeks as one course and 2 courses of treatment required totally.In week 0,6 and 12 of intervention,the effectiveness indicators would be determined,i.e.fasting plasma glucose(FPG),2 h plasma glucose(2 hPG)and glycosylated hemoglobin(HbA1c)successively.On week 0 and 12,body mass index(BMI)would be calculated,respiration,pulse and blood pressure would be recorded separately.Discussion:through observing the regulatory effect of taVNS on FPG,2 hPG,HbAlc and BMI as well as the adverse reactions,the effectiveness and safety of taVNS in treatment of IGT would be evaluated.This study will provide a safe,effective,convenient and nontoxic side effect intervention for clinical treatment of IGT and prevention from the occurrence and development of T2DM.