新诊断2型糖尿病患者血清非甲基化胰岛素DNA水平的意义及其影响因素

Significance and influencing factors of serum level of ummethylation INSDNA in patients with newly diagnosed type 2 diabetes mellitus

目的用病例对照研究血非甲基化胰岛素DNA(INSDNA)在新诊断2型糖尿病(NT2DM)中的意义及影响因素。方法选择2018年10月至2020年5月在东莞市厚街医院内分泌科住院的NT2DM患者45例,其中男30例、女15例,年龄(47.0±9.6岁);长病程2型糖尿病(LT2DM)患者23例,其中男15例、女8例,年龄(48.6±8.6岁);糖耐量正常(NGT)20例,其中男13例、女7例,年龄(40.2±5.5岁)。用液滴数字PCR技术(ddPCR)检测血清非甲基化INSDNA及ELSA检测人组织蛋白酶S(Cath-S)和白介素6(IL-6)水平,采用单因素方差分析各组非甲基化INSDNA水平差异及用Spearman相关分析空腹C肽(FC)、Cath-S、IL-6与非甲基化INSDNA水平的相关性。统计学方法采用独立样本t检验、χ^(2)检验。结果NT2DM组患者的血清非甲基化INSDNA水平明显高于NGT组和LT2DM组[3.01(4.64)copies/μl比0.59(0.19)copies/μl、1.77(2.80)copies/μl],差异均有统计学意义(均P<0.01)。NT2DM组的患者Cath-S水平[683.37(283.90)nmol/L比479.70(111.30)nmol/L]、IL-6水平[28.95(9.99)pg/ml比3.42(6.90)pg/ml)]均明显高于NGT组(均P<0.01)。相关分析显示,非甲基化INSDNA水平在NT2DM患者与Cath-S、IL-6和FC呈正相关(r=0.354,P=0.017;r=0.320,P=0.032;r=0.434,P=0.003)。结论血清非甲基化INSDNA水平在NT2DM疾病早期水平较高,随着病程延长而降低,血Cath-S、IL-6和FC可能是影响NT2DM血清非甲基化INSDNA水平的重要因素。

Objective To investigate the significance and influencing factors of serum level of ummethylation insulin DNA(INSDNA)in patients with newly diagnosed type 2 diabetes mellitus(NT2DM)by case control study.Methods Forty-five patients with NT2DM hospitalized at Department of Endocrinology,Dongguan Houjie Hospital from October 2018 to May 2020 were selected,including 30males and 15 females,and theywere(47.0±9.6)years old.Therewere 23 patients with long course T2DM(LT2DM),including 15 males and 8 females,and they were(48.6±8.6)years old.There were 20 patients with normal glucose tolerance(NGT),including 13 males and 7 females,and they were(40.2±5.5)years old.The serum level of unmethylated INSDNA was detected by drop digital polymerase chain reaction(ddPCR),and the levels of human cathepsin S(Cath-S)and interleukin 6(IL-6)by enzyme linked immunosorbent assay(ELISA).One-way ANOVA was used to analyze the difference in the unmethylated INSDNA level between the three groups,and Spearman correlation analysis was used to analyze the correlation of unmethylated INSDNA level with fasting C peptide(FC),Cath-S,and IL-6.Independent-sample t test andχ^(2) test were applied.Results The serum level of unmethylated INSDNA in the patients with NT2DM was significantly higher than those in the patients with NGT and the patients with LT2DM[3.01(4.64)copies/μl vs.0.59(0.19)copies/μl and 1.77(2.80)copies/μl],with statistical differences(both P<0.01).The levels of Cath-S and IL-6 in the patients with NT2DM were significantly higher than those in the patients with NGT[683.37(283.90)nmol/L vs.479.70(111.30)nmol/L and 28.95(9.99)pg/ml vs.3.42(6.90)pg/ml;both P<0.01].The correlation analysis showed that the level of unmethylated INSDNA was positively correlated with the levels of FC,Cath-S,and IL-6 in the patients with NT2DM(r=0.354,P=0.017;r=0.320,P=0.032;r=0.434,P=0.003).Conclusions The serum level of unmethylated INSDNA is higher in patients with T2DM during early stage and decreases as the disease course prolongs.Serum Cath-S,IL-6,and FC may be important factors affecting the level of unmethylated INSDNA.