The incidence of metabolic associated fatty liver disease(MAFLD)and diabetes mellitus(DM)is gradually increasing in China.Both are metabolic diseases and influence each other.MAFLD increases the likelihood of chronic complications in patients with DM.This article reviews the research progress of MAFLD and chronic complications of DM.
Objective To investigate the effect of C1q/tumor necrosis factor-related protein 13 protein(CTRP13)on the autophagy function of primary rat liver sinusoidal endothelial cells(rLSECs)induced by high glucose through AMP-activated protein kinase/mammalian target of rapamycin complex(AMPK/mTOR)pathway.Methods After isolation,identification and culture,original rat liver sinusoid endothelial cells(rrLSECs)were divided into normal control(NC)group,high glucose(HG)group,HG +LV-CTRP13 group,HG+ lentiviral empty vector(LV-Con)group(HG+LV-Con).CTRP13 lentivirus over expression vector(LV-CTRP13)and lentivirus empty vector(LV-Con)were constructed and transfected into rrLSECs.According to the intervention methods of AMPK inhibitor Compound C,mTOR inhibitor Torin1 and autophagy inhibitor 3MA,the transfected cell were divided into normal control(NC)group,high glucose(HG)group,HG+LV-CTRP13 group,HG+lentiviral empty vector(LV-Con)group(HG+ LV-Con).qRT-PCR and western blot were used to detect the mRNA and protein expression levels of CTRP13,autophagy related protein Beclin1,human microtubule-associated protein light chain 3II(LC3II),human plasma membrane membrane vesicle association proteins(PLVAP)and p-AMPK and p-MTOR in rat rLSECs of each group.Results Compared with NC group,the number of autophagosome was decreased in HG and HG+LV-CTRP13 group(P＜0.05).Compared with HG group,the number of autophagosome bodies was increased in HG +LV-CTRP13 group(P＜0.05).The CTRP13 mRNA and protein expression was higher in NC and HG + LV-CTRP13 groups than in HG and HG + LV-Con groups(P＜0.05).In HG+LC-CTRP13 group,Beclin1,LC3II,p-AMPK,and AMPK mRNA,Beclin1,LC3II/LC3I protein expression were higher than HG and HG + LV-Con group(P＜0.05),PLVAP,p-mTOR,mTOR mRNA,and PLVAP protein expression were lower than HG and HG+LV-Con group(P＜0.05).Comparison with HG + LV-CTRP13,p-mTOR protein expression in HG+LV-CTRP13+Compound C group increased(P＜0.05),while expressions of CTRP13,Beclin1 and LC3II/LC3I protein decreased(P＜0.05);the protein expressions of p-AMPK,Beclin1 and LC3II/LC3I were increased in HG+LV+ CTRP13+Torin1 group(P＜0.05),while CTRP13 and p-mTOR protein expression was decreased(P＜0.05);protein expressions of p-AMPK,p-mTOR and LC3II/LC3I were higher in HG+LV-CTRP13 + 3MA group(P＜0.05),while LC3II/LC3I protein expression was lower(P＜0.05).Conclusion CTRP13 overexpression activates AMPK/mTOR-autophagy signaling pathway,which may play a protective role in the function of rLSECs anddelay liver sinusoid capillarization.
LixiLan-L-CN是一项为期 30 周的随机、阳性对照、开放标签、平行分组、多中心研究,在接受基础胰岛素(BI)±口服降糖药(OADs)治疗血糖控制不佳的中国成人(≥18 岁)T2DM患者中,比较甘精胰岛素/利司那肽固定比例复方制剂(iGlarLixi)与甘精胰岛素 100U/ml的疗效和安全性(临床研究注册号:NCT03798080).该研究于 2022 年发表在《Diabetes,Obesity and Metabolism》(Diabetes Obes Metab 2022 Nov;24:2182-2191),现将其主要结果摘译成中文(License Number:5640380204414).
Objective To investigate the correlation between serum renal injury molecule-1(KIM-1)and neutrophil gelatinase-associated lipocalin(NGAL)in the remission of diabetic kidney disease(DKD)after gastric bypass surgery in obese DKD patients.Methods Seventy-nine obese patients with DKD who received gastric bypass surgery in our hospital from January 2021 to January 2022 were selected and divided into DKD remission group(n= 47)and DKD non-remission group(n=32)according to whether UACR decreased to normal level after surgery.Preoperative and postoperative general data were collected and biochemical indices,serum KIM-1 and NGAL levels were detected.Results None of the 79 obese DKD patients had intraoperative complications or switched to laparotomy.BMI,FPG,HbA1c,SBP,DBP,TC,TG,LDL-C,SUA,UACR,KIM-1 and NGAL were decreased after surgery,while HDL-C was increased after surgery(P＜0.05).SBP,DBP,Scr,BUN,UACR,KIM-1 and NGAL in remission group were lower than those in non-remission group(P＜0.05).Spearman correlation analysis showed that the levels of KIM-1 and NGAL were positively correlated with Scr,BUN and UACR(P＜0.05),but negatively correlated with eGFR(P＜0.05).Logistic regression analysis showed that SBP,UACR,KIM-1 and NGAL were influencing factors for DKD remission after gastric bypass surgery.The areas under ROC curve of serum KIM-1,NGAL and combined prediction of DKD remission were 0.801,0.757 and 0.863,respectively.Conclusion Serum KIM-1 and NGAL can predict DKD remission in obese DKD patients after gastric bypass surgery.
Objective To investigate the association of uric acid excretion(UUAE)with obesity and abdominal obesity in newly diagnosed patients with type 2 diabetes mellitus(T2DM).Methods A total of 1175 newly diagnosed T2DM patients hospitalized in the Department of Endocrinology and Metabolism of Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were enrolled in this study from January 2006 to December 2012.According to the quartile of UUAE,they were divided into Q1 group(UUAE＜2383 μmol/24 h,n=295),Q2 group(2383≤UUAE＜2953 μmol/24 h,n=292),Q3 group(2954≤UUAE＜3680 μmol/24 h,n=292)and Q4 group(UUAE＞3680 μmol/24 h,n=293).Clinical data and laboratory examination results were collected,and the prevalence of obesity and abdominal obesity was compared among the four groups.The associations of UUAE with obesity and abdominal obesity were analyzed.Results The prevalence of obesity was 47.9%,while the prevalence of abdominal obesity was 61.9%in the whole study population.After adjusting for age,the prevalence of abdominal obesity was higher in women than in men(P＜0.05).After adjusting for age and gender,the prevalence of obesity and MS was higher in Q4 group than in Q1,Q2,and Q3 groups(P＜0.05),and the prevalence of abdominal obesity was higher in Q4 group than in Q1 and Q2 groups(P＜0.05).Compared with Q1 group,the proportion of men,BMI,WC,DBP,FIns,2 hIns,HOMA-IR,TG,ALT,γ-GT,SUA,UAlb in Q4 group increased(P＜0.05),age,HbA1c,HDL-C decreased(P＜0.05).Logistic regression analysis showed that after adjusting for confounding factors,UUAE was a factor affecting obesity and abdominal obesity.Conclusion UUAE increases the risk of obesity,abdominal obesity and MS in newly diagnosed T2DM patients.UUAE may be used as a simple indicator to assess the risk of metabolic disorders such as obesity and MS in T2DM patients.
Objective To explore the influence of family history of diabetes and central obesity on prediabetes(Pre-DM)and their interaction.Methods Based on the REACTION studyduring August December 2011 in Dalian,2587 individuals aged≥40 with normal blood glucose(BG)were divided into newly diagnosed Pre-DM(n=522)and BG normal group(NC,n=2065)during follow-up.The influence of family history of DM and central obesity on prediabetes and their interaction were analyzed.Results The age,SBP,DBP,BMI,WC,HDL-C,LDL-C,TG,ALT,GGT,FPG,2 hPG,HbA1c,FIns,HOMA-IR,SUA and the incidence of hypertension,fatty liver disease,dyslipidemia,overweight/obesity and central obesity in Pre-DM group were all higher than those in NC group(P＜0.05).Multivariate logistic regression analysis showed that family history of diabetes and central obesity were risk factors for Pre-DM.After adjustment,no significant multiplicative interaction was shown between diabetes family history and central obesity on the risk of Pre-DM(P=0.764).Quantitative analysis of interaction showed that RERI=0.110,S=1.112 and AP=0.053,suggesting that DM family history and central obesity have no significant additive interaction on the risk of Pre-DM.Conclusion The family history of DM and central obesity are both associated with the occurrence of Pre-DM,but there is no significant interaction.
Studies have shown that m6A modifying enzymes regulated the expression of related factors by m6A methylation modification,and then participated in the regulation of adipogenesis,adipocyte hypertrophy,adipose tissue browning and thermogenesis.This article reviews the research progress of m6A methylation modification on the regulation of adipose tissue metabolism.
Objective To explore the relationship between serum iron(SI)metabolism and glucose and lipid metabolism in patients with type 2 diabetes mellitus(T2DM).Methods A total of 170 T2DM patients hospitalized in the Department of Endocrinology,Lanzhou University First Hospital from 2019 to 2021 were included.During the same period,30 healthy individuals from physical examination center were selected as the normal control(NC)group.Based on HbA1c control,T2DM patients were divided into subgroups with good blood glucose control(H1,HbA1c＜7%,n=39),poor glucose control(H2,7%＜HbA1c＜9%,n=63)and very poor glucose control(H3,HbA1c＞9%,n=68).According to the level of blood lipids,T2DM patients were divided into subgroups with normal blood lipids(L1,n=36)and high blood lipids(L2,n=134).Results Compared with NC group,age,SBP,DBP,BMI,serum ferritin(SF),FPG,FIns,HOMA-IR,TyG,TG,LDL-C and SUA increased inT2DM group(P＜0.05),while SI,TF,total iron binding capacity(TIBC),DI,HDL-C and eGFR decreased(P＜0.05).The levels of TF and TIBC in H3 subgroup were lower than those in H1 subgroup(P＜0.05).LDL-C of L2 subgroup was higher than that of L1 subgroup(P＜0.05),while HDL-C was lower than that of L1 subgroup(P＜0.05).Pearson correlation analysis showed that SF was positively correlated with HbA1c,TyG,TG and SUA(P＜0.05),and negatively correlated with HDL-C and eGFR(P＜0.05).TF was positively correlated with HDL-C and eGFR(P＜0.05),but negatively correlated with age,SBP,DBP,TyG and SUA(P＜0.05).Multiple linear regression analysis showed that SF and FPG were influencing factors for HbA1c in T2DM patients.Conclusion SI metabolism is closely related to glucose and lipid metabolism in T2DM patients.
Objective To explore the relationship between different obesity indicators and carotid intima-media thickness(CIMT)in patients with type 2 diabetes mellitus(T2DM).Methods A total of 1762 T2DM patients who visited the Endocrinology Department of Changzhou Second People's Hospital Affiliated with Nanjing Medical University and the Integrated Traditional Chinese and Western Medicine Hospital Affiliated with Nanjing University of Traditional Chinese Medicine from January 2019 to February 2022 were enrolled in this study.They were divided into youth group(18～44 years old,n=402),middle aged group(45～59 years old,n=1032),and elderly group(≥60 years old,n=328)according to WHO age classification criteria.The influencing factors for CIMT thickening in T2DM patients were analyzed using binary logistic regression,and the evaluation of the predictive effect of different obesity indicators on CIMT thickening was evaluated by receiver operating characteristic(ROC)curves.Results The subcuta-neous fat area,visceral fat area(VFA),neck circumference(NC),BMI,WC,cardiac metabolic index(CMI),Chinese visceral fat index(CAVI),visceral fat index,triglyceride glucose index,body roundness index,lipid aggregation index,HbA1c,DBP,TC,TG,HDL-C,LDL-C were lower in the middle aged and elderly groups than in youth group(P＜0.05).Binary logistic regression showed that VFA,NC,CMI in young T2DM patients,CAVI in middle aged T2DM patients,and NC in elderly T2DM patients were influ-encing factors for CIMT thickening.ROC curve analysis showed that VFA in young T2DM patients,CAVI in middle aged T2DM patients,and NC in elderly T2DM patients had a better predictive effect on CIMT thickening,with areas under the ROC curve of 0.567,0.574,and 0.573 respectively.Conclusion VFA,CAVI,and NC have a certain predictive effect on CIMT thickening in young,middle aged,and elderly T2DM patients.
Objective To investigate the correlation between sex hormone-binding globulin(SHBG)and lipid metabolism and visceral fat area(VFA)in male adults with different glucose tolerance.Methods A total of 473 male subjects were enrolled from the outpatient clinic and ward in PLA NO.903 Hospital from January 2018 to December 2020.All the subjects were divided into three groups according to OGTT results:normal glucose tolerance group(NGT,n=179),impaired glucose regulation group(IGR,n=90)and newly diagnosed type 2 diabetes mellitus group(T2DM,n=204).Serum SHBG level,abdominal visceral fat area(VFA)and biochemical indexes were compared among the three groups.Results Compared with NGT group,WC,WHR,BMI,HbA1c,FPG,2 hPG,2 hIns,TG and VFA were increased(P＜0.05),while SHBG was decreased(P＜0.05)in IGR group.WC,SBP,DBP,HbA1c,FPG,2 hPG,2 hIns,HOMA-IR,TG,FFA,VFA and VFA/SFA were increased,while HOMA-β,SHBG were decreased(P＜0.05)in T2DM group.Compared with IGR group,SBP,HbA1c,FPG,2 hPG,2 hIns and HOMA-IR were increased,HOMA-β was decreased in T2DM group(P＜0.05).Pearson correlation analysis showed that SHBG was positively correlated with HDL-C(P＜0.01),but was negatively correlated with WC,WHR,BMI,2 hIns,SUA,TG,VFA and SFA(P＜0.05 or P＜0.01).Multivariable linear regression analysis showed that HDL-C,TG and VFA were the influencing factors for SHBG.Conclusion Serum SHBG is closely related to abdominal obesity and lipid metabolism.Increasing the level of SHBG can reduce visceral fat accumulation and improve IR.
Objective To investigate the correlation between serum neuregulin 4(Nrg4)level and metabolic associated fatty liver disease(MAFLD)in patients with type 2 diabetes mellitus(T2DM).Methods A total of 240 T2DM patients admitted to the Department of Endocrinology of Second People's Hospital of Yichang from June 2021 to August 2022 were collected and divided into simple T2DM group(n=120)and MAFLD group(MAFLD,n=120).120 healthy individuals were selected as the normal control(NC)group.Results The serum Nrg4 decreased gradually from NC group,T2DM group to MAFLD group(P＜0.05).Pearson correlation analysis showed that serum Nrg4 was negatively correlated with WC,HOMA-IR and hs-CRP(P＜0.05),and positively correlated with HDL-C(P＜0.05).Logistic regression analysis showed that Nrg4,WC,HOMA-IR and hs-CRP were the influencing factors of MAFLD.After adjusting for age,sex,smoking history,BMI,TC,TG,HDL-C,LDL-C,FPG,FIns,HbA1c and other factors,serum Nrg4 was still the influencing factor of MAFLD.Conclusion The decrease of serum Nrg4 is a risk factor for T2DM combined with MAFLD.
Objective To explore the effect of intermittent fasting on blood glucose control in patients with type 2 diabetes mellitus(T2DM)complicated by overweight and obesity.Methods 46 T2DM patients with overweight and obesity were divided into control group(Con,n=22)and intermittent fasting group(IF,n=24)according to their wishes.Con group was given routine diet and drug treatment by specialists in endocrinology.IF group completed the intermittent fasting by using a combination of meal replacement and natural diet,and hypoglycemic drugs were reduced on fasting days.Results Compared with Con group,IF group showed a significant decrease in body weight,BMI,hypoglycemic drug efficacy score,WC,fat index,hip circumference and visceral fat(VF)(P＜0.05).After intervention,the proportion of diabetes in remission or near remission in IF group was higher than that in Con group(P＜0.05).Conclusion Intermittent fasting can reduce the application of hypoglycemic drugs in T2DM patients with overweight and obesity,and can also reduce weight and VF.
Objective To investigate the mechanism by which Liraglutide improves the inflammatory response in metabolic associated fatty liver disease(MAFLD)by regulating the interferon gene stimulating factor(STING)signaling pathway.Methods 20 male C57BL/6J mice were randomly divided into normal diet group(NC),Liraglutide intervention group(NC+Lir group),high fat diet group(HFD group)and Liraglutide intervention high fat diet group(HFD+Lir group),with 5 in each group.Mouse primary hepato-cytes(MPHs)were divided into normal control(Con)group,Liraglutide intervention group(Con+Lir group),palmitic acid group(PA group)and Liraglutide intervention PA group(PA+Lir group).The levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST)in serum and triglyceride(TG)contents in liver were detected.HE and oil red O staining were used to observe the pathological changes in the liver and to calculate the MAFLD activity score(NAS).The mRNA expression levels of STING,IL-1β and TNF-α in tissues and cells were detected by qRT-PCR.The protein expression levels of STING,p-IRF3 and IFN-β were detected by Western blot.Results Body weight,liver tissue weight,serum ALT,AST,liver TG,steatosis,lobular inflammation and balloon-like NAS in HFD group were higher than those in NC group(P＜0.05 or P＜0.01).Body weight,liver tissue weight,serum ALT,AST,liver TG,steatosis,lobular inflammation and balloon-like NAS in HFD+Lir group were lower than those in HFD group(P＜0.05 or P＜0.01).The mRNA expressions of STING,IL-1β,TNF-α and the protein expressions of STING,p-IRF3 and IFN-β in liver of HFD group were higher than those of NC group(P＜0.05).The mRNA expressions of STING,IL-1β,TNF-α and the protein expressions of STING,p-IRF3 and IFN-β in HFD+ Lir group were lower than those in HFD+ Lir group(P＜0.05).The mRNA expressions of STING,IL-1β,TNF-α and the protein expressions of STING,p-IRF3 and IFN-β in PA group were higher than those in Con group(P＜0.01).The mRNA expressions of STING,IL-1β,TNF-α and the protein expressions of STING,p-IRF3 and IFN-β in PA+Lir group were lower than those in PA group(P＜0.05 or P＜0.01).Conclusion Liraglutide ameliorates the high-fat-induced inflammation responses in MAFLD by regulating the STING signaling pathways.
2023 年 4 月 21～23 日,国家代谢性疾病临床医学研究中心、中南大学糖尿病中心及《糖尿病》天地杂志社于湖南长沙共同主办了"第十八届湘雅国际糖尿病免疫学论坛".本届论坛由国家代谢性疾病临床医学研究中心主任、糖尿病免疫学教育部重点实验室主任周智广教授和中南大学代谢综合征研究中心主任刘峰教授共同担任此次大会主席.
当前,肥胖已成为影响我国居民健康的严重公共卫生问题.过去 30 年间,我国居民超重/肥胖快速增长,成年人超重/肥胖率超过 50％,学龄儿童青少年超重/肥胖率接近 20％,约有 5～6 亿成年人和 5000 万儿童青少年超重/肥胖.
目的 评估基于代谢热整合法的无创血糖仪在高海拔地区使用的性能.方法 选取北京地区、西藏拉萨地区居住>5 年的T2DM患者 210 例、395 例,分别于空腹、餐后 2h使用无创血糖仪、实验室全自动生化分析仪(己糖激酶法)检测血糖,采用Parkes误差栅格、平均相对误差(MARD)、Bland-Altman分析检测方法配对血糖值的相关性,比较拉萨(平均海拔 3650 m)与北京(平均海拔＜100 m)多中心试验结果,评估无创血糖仪在高海拔地区的适用性.结果 北京地区 569 个无创血糖仪与静脉血浆检测配对血糖值中 535 个(94.0%)落在一致性界限内,拉萨地区 666 个无创血糖仪与静脉血浆检测配对血糖值中 624 个(93.7%)落在一致性界限内,北京与拉萨地区无创血糖仪和静脉血浆血糖值的MARD为 26.999%、24.817%,差异无统计学意义(P=0.141).结论 与平原地区多中心临床试验结果相比,无创血糖仪在海拔 3650 m的准确性差异无统计意义,基于代谢热整合法的无创血糖仪可用于高海拔地区.
目的 探讨神经调节素 1(NRG1)、甲基乙二醛(MG)、高迁移率族蛋白B1(HMGB-1)联合检测在糖尿病周围神经病变(DPN)中的诊断价值.方法 选取 2019 年 1 月至 2020 年 12 月于苏州大学附属第一医院内分泌科住院治疗的T2DM患者 240 例,分为单纯T2DM组(n=108)及合并DPN组(DPN,n=132),比较两组一般资料及生化指标.结果 DPN组血清NRG1、MG及HMGB1高于T2DM组(P＜0.05).Spearman相关分析显示,多伦多临床神经病变评分与血清NRG1、MG及HMGB1 呈正相关(P＜0.05).Logistic回归分析显示,NRG1、MG及HMGB1 是DPN的危险因素.受试者工作特征(ROC)曲线分析显示,NRG1、MG 及 HMGB1 联合检测 DPN 的敏感度、特异度和ROC曲线下面积均高于单独检测(P＜0.05).结论 血清NRG1、MG及HMGB1 与DPN严重程度相关,联合检测对DPN的诊断价值优于单独检测.
目的 探讨T2DM患者血尿酸(SUA)与糖尿病周围神经病变(DPN)的相关性.方法 选取 2021 年 7 月至 2022 年 7 月于空军军医大学第一附属医院内分泌科治疗的T2DM患者 272 例,根据SUA四分位间距分为＜237.10 μmol/L组(n=38)、237.10～289.80 μmol/L组(n=78)、289.80～364.15 μmol/L组(n=110)及≥364.15 μmol/L组(n=46).比较各组一般资料及生化指标.结果 随着SUA水平升高,各组运动/感觉神经潜伏期延长(P<0.05),运动/感觉神经波幅和传导速度降低(P<0.05).Pearson相关分析显示,SUA与运动/感觉神经潜伏期呈正相关(P<0.05),与波幅和传导速度呈负相关(P<0.05).Logistic回归分析显示,DM病程、HbA1c、SUA是T2DM合并DPN的影响因素.受试者工作特征(ROC)曲线分析显示,SUA预测T2DM患者DPN的ROC曲线下面积为 0.626,敏感度为 35.1%,特异度为 89.7%,最佳截断值为 363 μmol/L.结论 高SUA水平是T2DM合并DPN的危险因素,可能对DPN有预测价值.临床应及时检测SUA以评估DPN的发生风险.
DM血管病变早期主要表现为内皮功能改变,内皮功能障碍导致一系列不良血管事件发生,严重DM血管并发症增加死亡风险.DM早期血管内皮功能测定可有效预测DM血管并发症发生发展,评估心血管疾病风险,制订有效治疗方案.本文综述DM早期血管内皮功能测定的研究进展.
目的 探讨尿C-P/肌酐(UCPCR)评估T1DM残存胰岛功能及并发症风险的应用价值.方法 选取 2019 年 1 月至 2020 年 1 月于南京鼓楼医院内分泌科就诊的T1DM患者 75 例,以UCPCR 0.2 pmol/µmol为切点值,将T1DM患者分为有胰岛功能组 19 例(PF,UCPCR≥0.2 pmol/µmol)、微量胰岛功能组 42 例(MF,0＜UCPCR＜0.2 pmol/µmol)及无胰岛功能组 14 例(LF,UCPCR=0 pmol/µmol).结果 Pearson相关分析显示,UCPCR与FC-P、2 hC-P呈正相关(P<0.05),UCPCR＜0.2 pmol/µmol时胰岛功能绝对缺乏.Spearman相关分析显示,UCPCR与DR患病率、心血管病(CVD)风险呈负相关(P<0.05),UCPCR<0.02 pmol/µmol时存在高危或极高危CVD风险.结论 UCPCR是反应T1DM残存胰岛功能的敏感指标,对评估DR及CVD风险有应用价值.
