Objective:To investigate the function of cytokines,chemokines,and regulatory T cells(Tregs)in the pathogenesis of Type 1 diabeles mellitus(T1DM)in children.Methods:A total of 35 children with T1DM and 30 healthy contr...Objective:To investigate the function of cytokines,chemokines,and regulatory T cells(Tregs)in the pathogenesis of Type 1 diabeles mellitus(T1DM)in children.Methods:A total of 35 children with T1DM and 30 healthy controls were enrolled in this study.Levels of serum cytokines(IL-1α,IL-6,IL-10,IL-12,and TNF-α)and chemokines(MIP-1α,MIP-1βand MCP-1)were detected by enzyme-linked immunosorbent assay.Peripheral blood mononuclear cells(PBMCs)were isolated and culture supernatant of phytohaemagglutinin(PHA)-stimulatcd PBMCs was subjecled to ELISA for levels of cytokines(IL-1α,IL-6,IL-10,IL-12 and TNV-α)in T1DM and control group.Furthermore,flow cytometty was used to determine the percentage of Tregs in PBMCs of two groups.Results:Levels of serum cytokines including IL-1α,IL-6,IL-10 andd TNF-αas well as chemokines,such as MIP-1αand MIP-1βin children with T1DM children were significantly higher than those in healthy controls(P<0.05,respectively).PBMCs with PHA stimulation in T1DM group secreted more IL-1αand TNF-α(P<0.05,respectively),but less IL-10(P<0.05),as compared with control group.Furthermore,the proportion of CD4^+,CD25^+,Foxp3.Tregs in PBMCs isolated from children with T1DM was obviously lower than those in heathy controls(P<0.05).Conclusions:Immune dysfunction.with uprcgulation of inflanunatory factors such as IL-1α.IL-6.TNF-αand MIP-1α.downregulation of IL-10 and Tregs,plays an important role in the pathogenesis of T1DM in children.展开更多
BACKGROUND In addition to insulin resistance,impaired insulin secretion has recently been identified as a crucial factor in the pathogenesis of type 2 diabetes mellitus(T2DM).Scarce clinical data exist for pediatric T...BACKGROUND In addition to insulin resistance,impaired insulin secretion has recently been identified as a crucial factor in the pathogenesis of type 2 diabetes mellitus(T2DM).Scarce clinical data exist for pediatric T2DM.AIM To investigate the association ofβ-cell function and insulin resistance with pediatric T2DM in the first Chinese multicenter study.METHODS This multicenter cross-sectional study included 161 newly diagnosed T2DM children and adolescents between January 2017 and October 2019.Children with normal glycemic levels(n=1935)were included as healthy control subjects.The homeostasis models(HOMAs)were used to assess theβ-cell function(HOMA2-%B)and insulin resistance(HOMA2-IR)levels.The HOMA index was standardized by sex and age.We performed logistic regression analysis to obtain odds ratios(ORs)for T2DM risk using the standardized HOMA index,adjusted for confounding factors including sex,Tanner stage,T2DM family history,body mass index z-score,and lipid profile.RESULTS The male-female ratio of newly diagnosed T2DM patients was 1.37:1(OR=2.20,P=0.011),and the mean ages of onset for boys and girls were 12.5±1.9 years and 12.3±1.7 years,respectively.The prevalence of related comorbidities including obesity,elevated blood pressure,and dyslipidemia was 58.2%,53.2%,and 80.0%,respectively.The T2DM group had lower HOMA2-%B levels(P<0.001)and higher HOMA2-IR levels(P<0.001)than the control group.Both the decrease in HOMA2-%B z-score(OR=8.40,95%CI:6.40-11.02,P<0.001)and the increase in HOMA2-IR z-score(OR=1.79,95%CI:1.60-2.02,P<0.001)were associated with a higher risk of T2DM,and the decrease in HOMA2-%B z-score always had higher ORs than the increase in HOMA2-IR z-score after adjusting for confounding factors.CONCLUSION Besides insulin resistance,β-cell function impairment is also strongly associated with Chinese pediatric T2DM.Gender difference in susceptibility and high comorbidities warrant specific T2DM screening and prevention strategies in Chinese children.展开更多
基金supported by a grant from the National Natural Science Foundation of China(no.81200867)
文摘Objective:To investigate the function of cytokines,chemokines,and regulatory T cells(Tregs)in the pathogenesis of Type 1 diabeles mellitus(T1DM)in children.Methods:A total of 35 children with T1DM and 30 healthy controls were enrolled in this study.Levels of serum cytokines(IL-1α,IL-6,IL-10,IL-12,and TNF-α)and chemokines(MIP-1α,MIP-1βand MCP-1)were detected by enzyme-linked immunosorbent assay.Peripheral blood mononuclear cells(PBMCs)were isolated and culture supernatant of phytohaemagglutinin(PHA)-stimulatcd PBMCs was subjecled to ELISA for levels of cytokines(IL-1α,IL-6,IL-10,IL-12 and TNV-α)in T1DM and control group.Furthermore,flow cytometty was used to determine the percentage of Tregs in PBMCs of two groups.Results:Levels of serum cytokines including IL-1α,IL-6,IL-10 andd TNF-αas well as chemokines,such as MIP-1αand MIP-1βin children with T1DM children were significantly higher than those in healthy controls(P<0.05,respectively).PBMCs with PHA stimulation in T1DM group secreted more IL-1αand TNF-α(P<0.05,respectively),but less IL-10(P<0.05),as compared with control group.Furthermore,the proportion of CD4^+,CD25^+,Foxp3.Tregs in PBMCs isolated from children with T1DM was obviously lower than those in heathy controls(P<0.05).Conclusions:Immune dysfunction.with uprcgulation of inflanunatory factors such as IL-1α.IL-6.TNF-αand MIP-1α.downregulation of IL-10 and Tregs,plays an important role in the pathogenesis of T1DM in children.
基金Supported by the National Key Research and Development Program of China,No.2016YFC1305302the National Natural Science Fund of China,No.81600608the Key Research and Development Program of Shandong Province,No.2017GSF18118.
文摘BACKGROUND In addition to insulin resistance,impaired insulin secretion has recently been identified as a crucial factor in the pathogenesis of type 2 diabetes mellitus(T2DM).Scarce clinical data exist for pediatric T2DM.AIM To investigate the association ofβ-cell function and insulin resistance with pediatric T2DM in the first Chinese multicenter study.METHODS This multicenter cross-sectional study included 161 newly diagnosed T2DM children and adolescents between January 2017 and October 2019.Children with normal glycemic levels(n=1935)were included as healthy control subjects.The homeostasis models(HOMAs)were used to assess theβ-cell function(HOMA2-%B)and insulin resistance(HOMA2-IR)levels.The HOMA index was standardized by sex and age.We performed logistic regression analysis to obtain odds ratios(ORs)for T2DM risk using the standardized HOMA index,adjusted for confounding factors including sex,Tanner stage,T2DM family history,body mass index z-score,and lipid profile.RESULTS The male-female ratio of newly diagnosed T2DM patients was 1.37:1(OR=2.20,P=0.011),and the mean ages of onset for boys and girls were 12.5±1.9 years and 12.3±1.7 years,respectively.The prevalence of related comorbidities including obesity,elevated blood pressure,and dyslipidemia was 58.2%,53.2%,and 80.0%,respectively.The T2DM group had lower HOMA2-%B levels(P<0.001)and higher HOMA2-IR levels(P<0.001)than the control group.Both the decrease in HOMA2-%B z-score(OR=8.40,95%CI:6.40-11.02,P<0.001)and the increase in HOMA2-IR z-score(OR=1.79,95%CI:1.60-2.02,P<0.001)were associated with a higher risk of T2DM,and the decrease in HOMA2-%B z-score always had higher ORs than the increase in HOMA2-IR z-score after adjusting for confounding factors.CONCLUSION Besides insulin resistance,β-cell function impairment is also strongly associated with Chinese pediatric T2DM.Gender difference in susceptibility and high comorbidities warrant specific T2DM screening and prevention strategies in Chinese children.
