Nonalcoholic fatty liver disease(NAFLD)is quickly becoming one of the most prominent causes of liver disease worldwide.The increasing incidence of NAFLD is tied to the obesity epidemic and the subsequent metabolic der...Nonalcoholic fatty liver disease(NAFLD)is quickly becoming one of the most prominent causes of liver disease worldwide.The increasing incidence of NAFLD is tied to the obesity epidemic and the subsequent metabolic derangements brought along with it.Current efforts to elucidate the mechanism and causes of the disease have answered some questions,but much remains unknown about NAFLD.The aim of this article is to discuss the current knowledge regarding the pathogenesis of the disease,as well as the current and future diagnostic,preventative,and therapeutic options available to clinicians for the management of NAFLD.展开更多
目的探讨二甲双胍血糖控制不佳的2型糖尿病患者联合沙格列汀或吡格列酮的疗效。方法选择2015年1月至2016年1月安徽医科大第二附属医院内分泌门诊符合入选条件的2型糖尿病患者70例,随机被分为两组,观察组35例采用沙格列汀+二甲双胍治疗,...目的探讨二甲双胍血糖控制不佳的2型糖尿病患者联合沙格列汀或吡格列酮的疗效。方法选择2015年1月至2016年1月安徽医科大第二附属医院内分泌门诊符合入选条件的2型糖尿病患者70例,随机被分为两组,观察组35例采用沙格列汀+二甲双胍治疗,对照组35例患者采用吡格列酮+二甲双胍治疗,观察两组治疗前后的空腹血糖(FPG)、餐后2 h血糖(2 h PG)、糖化血红蛋白(Hb A1c)、空腹血清胰岛素水平、胰岛素抵抗指数(HOMA-IR)、体质指数(BMI)等。结果与治疗前比较,治疗16周后观察组、对照组患者的FPG、餐后2 h PG与Hb A1c明显降低,HOMA-IR改善,差异有统计学意义(P<0.05);但两组间差异无统计学意义(P>0.05)。与治疗前比较,治疗16周后观察组BMI无明显变化,差异无统计学意义(P>0.05),对照组患者BMI明显上升,差异有统计学意义(P<0.05),两组间差异有统计学意义(P<0.05)。结论沙格列汀或吡格列酮联合二甲双胍可有效控制2型糖尿病患者血糖、改善胰岛素敏感性,沙格列汀不增加体质量且不良反应小,联合二甲双胍治疗是一种安全可靠的治疗方法。展开更多
Arylidene thiazolineone derivatives are synthesized by solid state condensation of aromatic aldehydes with 2,4 thiazolidinedione or N phenylrhodanine in the presence of NaAc at 120~140 ℃ for 10 min with yields of 55...Arylidene thiazolineone derivatives are synthesized by solid state condensation of aromatic aldehydes with 2,4 thiazolidinedione or N phenylrhodanine in the presence of NaAc at 120~140 ℃ for 10 min with yields of 55%~81 2%. The effect of reaction conditions are discussed. This is a simple, time saving and environmental friendly method for the preparation of 5 arylidene thiazolineone derivatives.展开更多
Thiazolidinedione(TZD)is a powerful insulin sensitizer in the treatment of type 2 diabetes.It acts as a ligand to the nuclear receptor PPARγ(peroxisome proliferator-activated receptor-gamma)and induces transcription ...Thiazolidinedione(TZD)is a powerful insulin sensitizer in the treatment of type 2 diabetes.It acts as a ligand to the nuclear receptor PPARγ(peroxisome proliferator-activated receptor-gamma)and induces transcription of PPARγ-responsive genes.TZD controls lipid synthesis and storage in adipose tissue,liver and many other tissues through PPARg.Derivatives of TZD,such as rosiglitazone(Avandia)and pioglitazone(Actos),are more powerful than metformin or berberine in insulin sensitization.Although they have common side effects such as weight gain and edema,these did not influence their clinical application in general.However,recent findings of risk for congestive heart failure and bladder cancer have significantly impaired their future in many countries.European countries have prohibited those drugs,and US will terminate application of rosiglitazone in clinics and hospitals.The multiple country actions may mark the end of TZD era.As a result,there is a strong demand for identification of TZD substitute in the treatment of type 2 diabetes.In this regard,literature about PPARγ ligands and potential TZD substitute are reviewed in this article.Histone deacetylase(HDAC)inhibitor is emphasized as a new class of insulin sensitizer here.Regulators of SIRT1,CREB,NO,p38,ERK and Cdk5 are discussed in the activation of PPARγ.展开更多
BACKGROUND Chiglitazar is an emerging pan-agonist of all peroxisome proliferator activated receptors(PPAR)-α,δandγ,and has therapeutic potential for type 2 diabetes(T2D).However,to date,no clinical studies or meta-...BACKGROUND Chiglitazar is an emerging pan-agonist of all peroxisome proliferator activated receptors(PPAR)-α,δandγ,and has therapeutic potential for type 2 diabetes(T2D).However,to date,no clinical studies or meta-analyses have compared the efficacy and safety of chiglitazar and traditional PPAR-γagonist thiazolidinediones(TZDs).A meta-analysis concerning this topic is therefore required.AIM To compare the efficacy and safety of chiglitazar and TZD in patients with T2D.METHODS PubMed,Medline,Embase,the Cochrane Central Register of Controlled Trials,Reference Citation Analysis and Clinicaltrial.gov websites were searched from August 1994 to March 2022.Randomized controlled trials(RCTs)of chiglitazar or TZD vs placebo in patients with T2D were included.Indirect comparisons and sensitivity analyses were implemented to evaluate multiple efficacy and safety endpoints of interest.RESULTS We included 93 RCTs that compared TZD with placebo and one that compared chiglitazar with placebo.For efficacy endpoints,the augmented dose of chiglitazar resulted in greater reductions in hemoglobin(Hb)A1c[weighted mean difference(WMD)=-0.15%,95%confidence interval(CI):-0.27 to-0.04%],triglycerides(WMD=-0.17 mmol/L,95%CI:-0.24 to-0.11 mmol/L)and alanine aminotransferase(WMD=-5.25 U/L,95%CI:-8.50 to-1.99 U/L),and a greater increase in homeostasis model assessment-β(HOMA-β)(WMD=17.75,95%CI:10.73-24.77)when compared with TZD treatment.For safety endpoints,the risks of hypoglycemia,edema,bone fractures,upper respiratory tract infection,urinary tract infection,and weight gain were all comparable between the augmented dose of chiglitazar and TZD.In patients with baseline HbA1c≥8.5%,body mass index≥30 kg/m^(2)or diabetes duration<10 years,the HbA1c reduction and HOMA-βincrease were more conspicuous for the augmented dose of chiglitazar compared with TZD.CONCLUSION Augmented dose of chiglitazar,a pan-activator of PPARs,may serve as an antidiabetic agent with preferable glycemic and lipid control,betterβ-cell function preserving ca展开更多
文摘Nonalcoholic fatty liver disease(NAFLD)is quickly becoming one of the most prominent causes of liver disease worldwide.The increasing incidence of NAFLD is tied to the obesity epidemic and the subsequent metabolic derangements brought along with it.Current efforts to elucidate the mechanism and causes of the disease have answered some questions,but much remains unknown about NAFLD.The aim of this article is to discuss the current knowledge regarding the pathogenesis of the disease,as well as the current and future diagnostic,preventative,and therapeutic options available to clinicians for the management of NAFLD.
文摘目的探讨二甲双胍血糖控制不佳的2型糖尿病患者联合沙格列汀或吡格列酮的疗效。方法选择2015年1月至2016年1月安徽医科大第二附属医院内分泌门诊符合入选条件的2型糖尿病患者70例,随机被分为两组,观察组35例采用沙格列汀+二甲双胍治疗,对照组35例患者采用吡格列酮+二甲双胍治疗,观察两组治疗前后的空腹血糖(FPG)、餐后2 h血糖(2 h PG)、糖化血红蛋白(Hb A1c)、空腹血清胰岛素水平、胰岛素抵抗指数(HOMA-IR)、体质指数(BMI)等。结果与治疗前比较,治疗16周后观察组、对照组患者的FPG、餐后2 h PG与Hb A1c明显降低,HOMA-IR改善,差异有统计学意义(P<0.05);但两组间差异无统计学意义(P>0.05)。与治疗前比较,治疗16周后观察组BMI无明显变化,差异无统计学意义(P>0.05),对照组患者BMI明显上升,差异有统计学意义(P<0.05),两组间差异有统计学意义(P<0.05)。结论沙格列汀或吡格列酮联合二甲双胍可有效控制2型糖尿病患者血糖、改善胰岛素敏感性,沙格列汀不增加体质量且不良反应小,联合二甲双胍治疗是一种安全可靠的治疗方法。
文摘Arylidene thiazolineone derivatives are synthesized by solid state condensation of aromatic aldehydes with 2,4 thiazolidinedione or N phenylrhodanine in the presence of NaAc at 120~140 ℃ for 10 min with yields of 55%~81 2%. The effect of reaction conditions are discussed. This is a simple, time saving and environmental friendly method for the preparation of 5 arylidene thiazolineone derivatives.
基金supported by NIH Grant DK068036 and DK085495 to J Ye.
文摘Thiazolidinedione(TZD)is a powerful insulin sensitizer in the treatment of type 2 diabetes.It acts as a ligand to the nuclear receptor PPARγ(peroxisome proliferator-activated receptor-gamma)and induces transcription of PPARγ-responsive genes.TZD controls lipid synthesis and storage in adipose tissue,liver and many other tissues through PPARg.Derivatives of TZD,such as rosiglitazone(Avandia)and pioglitazone(Actos),are more powerful than metformin or berberine in insulin sensitization.Although they have common side effects such as weight gain and edema,these did not influence their clinical application in general.However,recent findings of risk for congestive heart failure and bladder cancer have significantly impaired their future in many countries.European countries have prohibited those drugs,and US will terminate application of rosiglitazone in clinics and hospitals.The multiple country actions may mark the end of TZD era.As a result,there is a strong demand for identification of TZD substitute in the treatment of type 2 diabetes.In this regard,literature about PPARγ ligands and potential TZD substitute are reviewed in this article.Histone deacetylase(HDAC)inhibitor is emphasized as a new class of insulin sensitizer here.Regulators of SIRT1,CREB,NO,p38,ERK and Cdk5 are discussed in the activation of PPARγ.
基金Beijing Natural Science Foundation,No.7202216National Natural Science Foundation of China,No.81970698 and No.81970708.
文摘BACKGROUND Chiglitazar is an emerging pan-agonist of all peroxisome proliferator activated receptors(PPAR)-α,δandγ,and has therapeutic potential for type 2 diabetes(T2D).However,to date,no clinical studies or meta-analyses have compared the efficacy and safety of chiglitazar and traditional PPAR-γagonist thiazolidinediones(TZDs).A meta-analysis concerning this topic is therefore required.AIM To compare the efficacy and safety of chiglitazar and TZD in patients with T2D.METHODS PubMed,Medline,Embase,the Cochrane Central Register of Controlled Trials,Reference Citation Analysis and Clinicaltrial.gov websites were searched from August 1994 to March 2022.Randomized controlled trials(RCTs)of chiglitazar or TZD vs placebo in patients with T2D were included.Indirect comparisons and sensitivity analyses were implemented to evaluate multiple efficacy and safety endpoints of interest.RESULTS We included 93 RCTs that compared TZD with placebo and one that compared chiglitazar with placebo.For efficacy endpoints,the augmented dose of chiglitazar resulted in greater reductions in hemoglobin(Hb)A1c[weighted mean difference(WMD)=-0.15%,95%confidence interval(CI):-0.27 to-0.04%],triglycerides(WMD=-0.17 mmol/L,95%CI:-0.24 to-0.11 mmol/L)and alanine aminotransferase(WMD=-5.25 U/L,95%CI:-8.50 to-1.99 U/L),and a greater increase in homeostasis model assessment-β(HOMA-β)(WMD=17.75,95%CI:10.73-24.77)when compared with TZD treatment.For safety endpoints,the risks of hypoglycemia,edema,bone fractures,upper respiratory tract infection,urinary tract infection,and weight gain were all comparable between the augmented dose of chiglitazar and TZD.In patients with baseline HbA1c≥8.5%,body mass index≥30 kg/m^(2)or diabetes duration<10 years,the HbA1c reduction and HOMA-βincrease were more conspicuous for the augmented dose of chiglitazar compared with TZD.CONCLUSION Augmented dose of chiglitazar,a pan-activator of PPARs,may serve as an antidiabetic agent with preferable glycemic and lipid control,betterβ-cell function preserving ca