阿卡波糖干预新诊断2型糖尿病患者肠道菌群分布及血清GDF-15水平的研究

Study of the distribution of intestinal flora and serum levels of GDF-15 in patients with newly diagnosed type 2 diabetes by taking acarbose

目的探讨阿卡波糖对新诊断2型糖尿病(T2DM)患者肠道菌群分布及血清生长分化因子-15(GDF-15)水平的干预情况。方法选择我院新诊断的120例T2DM患者为研究对象,随机分为试验组(n=60)和对照组(n=60),对照组予以安慰剂,试验组受试者服用阿卡波糖,连续治疗14 d。比较两组受试者血糖以及血脂相关指标。采用酶联免疫吸附双抗夹心法(ELISA)测定两组血清GDF-15的表达水平。对粪便样本中所有细菌的16SrRNA-V3区进行DNA测序,对肠道菌群中的分布及丰度进行分析,同时做聚类分析。对肠道菌群通过实时定量PCR进行定量检测。结果治疗后,试验组和对照组受试者血糖及血脂相关指标、肠道菌群的分布以及GDF-15的表达水平均存在明显差异(P<0.05)。治疗后,试验组受试者肠道菌群发生明显变化,且菌群改善组与未改善组血糖及血脂相关指标存在明显差异(P<0.05);血清中GDF-15表达水平与拟杆菌属、IV型梭菌属、韦荣球菌属丰度呈正相关(P<0.05),与厚壁菌门、放线菌门、普雷沃菌属、乳杆菌属、Blautia球菌-直肠真杆菌属丰度呈负相关(P<0.05)。结论阿卡波糖可通过影响患者肠道菌群的分布以及GDF-15的表达水平,对新诊断T2DM患者起到有效的治疗作用。

Objective To investigate the distribution of intestinal flora and serum levels of GDF-15 in patients with newly diagnosed type 2 diabetes（T2DM） by taking acarbose. Methods We selected 120 newly diagnosed T2DM patients in our hospital, who were randomly divided into the experimental group（n = 60） and the control group（n = 60）. The patients in the control group were given placebo. The subjects in the experimental group were taken acarbose for 14 d. The blood glucose and lipid indexes of the two groups were compared. Enzyme linked immunosorbent assay（ELISA） was used to determine the level of serum GDF-15 in the control group and the experimental group. The 16 SrRNA-V3 region of all bacteria in fecal samples was sequenced. The distribution and abundance of intestinal flora wereanalyzed, and cluster analysis was carried out at the same time in DNA. The intestinal flora was quantitatively detected by real-time quantitative PCR. Results After treatment, the blood glucose and lipid, intestinal flora and the expression level of GDF-15 were significantly different between the two groups（P〈0.05）. The intestinal flora of the experimental group changed obviously, and there was a significant difference between the improvement group and the no improvement group in blood glucose and blood lipid（P〈0.05）. The expression level of GDF-15 in serum was positively related to the abundance of Bacteroides, Clostridium IV and Veillonella（P〈0.05）. It was negatively correlated with abundance of phylum firmicutes, Actinomyces, Prevotella, Lactobacillus, and Blautia cocci（P〈0.05）. Conclusion Acarbose can be effective in treating patients with newly diagnosed type 2 diabetes by affecting the distribution of intestinal flora and serum levels of GDF-15.