不同剂量的二甲双胍对新诊断2型糖尿病患者直肠异常隐窝灶影响的初步观察

Effect of different doses of Metformin treatment on rectal aberrant crypt foci in patients with newly diagnosed type 2 diabetes

目的探讨持续6个月不同剂量二甲双胍干预对新诊断T2DM患者直肠异常隐窝灶(ACF)数量的影响。方法 120例符合入组标准的新诊断T2DM患者,按1∶1∶1∶1被随机分配至低剂量二甲双胍组(LDG组,500 mg/d),中剂量二甲双胍组(MDG组,1000 mg/d),高剂量二甲双胍组(HDG组,1500mg/d)和对照组(UTG组,未服用二甲双胍),每组均为30例。分别在治疗前、治疗后3个月和6个月,应用放大结肠镜对4组直肠ACF数目进行测量,同时收集并测定临床参数指标。结果与干预前比较,MDG组干预6个月后直肠ACF数目减少[(7.7±6.1)vs(6.1±4.4)个/人,P<0.05];与干预前比较,HDG组干预后3个月、6个月后直肠ACF数目减少[(7.4±5.7)vs(5.1±4.6)vs(4.5±3.4)个/人,P<0.05或P<0.01],其中6个月后直肠ACF数目较3个月时进一步降低(P<0.05)。相关分析发现,6个月后ΔACF与ΔFPG、ΔHbA_1c、ΔHOMA-IR均呈正相关(P<0.05);ΔHOMA-IR、ΔHbA_1c是ΔACF的独立影响因素(P<0.05)。结论二甲双胍对新诊断T2DM患者的直肠ACF形成具有抑制作用,呈现剂量相关性,部分原因可能与其降低血糖、改善肥胖和IR关。

Objective To evaluate the effects of different doses Metformin treatment for 6-month on the number of rectal aberrant crypt foci（ACF）in subjects with newly diagnosed type 2 diabetes（T2DM）.Methods A total of 120 patients with T2DM,who met with inclusion criteria were enrolled in this study and randomly divided into four groups：low-dose Metformin group（LDG,n=30,Metformin 500 mg/day）,middle-dose Metformin group（MDG,n=30,Metformin 1000 mg/day）,high-dose Metformin group（HDG,n=30,Metformin 1500 mg/day）and control group（UTG,without Metformin treatment,n=30）,respectively.All the subjects were followed up for 6 months,and the number of ACF in each subject was examined by magnifying colonoscopy at baseline,3 and 6 months after treatment.Clinical parameters were collected in all the subjects. Results After 6 months of treatment,the mean ACF number was significantly decreased in MDG group compared with the baseline[（7.7±6.1）vs（6.1±4.4）number per patient,P〈0.05].The mean ACF number was significantly decreased after3 and 6 months of treatment in HDG group compared with the baseline[（7.4±5.7）vs（5.1±4.6）vs（4.5±3.4）unmber per patient）,P〈0.05 or P〈0.01],and the mean ACF numbers was significantly lower in 6-month follow up than in3-month follow up（P〈0.05）.Correlation analysis showed that ΔACF correlated positively with ΔFPG,ΔHbA_1c and ΔHOMA-IR.ΔHOMA-IR and ΔHbA_1c were independent factors for ΔACF（P〈0.05）.Conclusion Metformin suppressed ACF formation in newly diagnosed T2DM subjects in a dose-dependent manner.It may be partly through indirect mechanisms such as reducing blood glucose levels and attenuating obesity and insulin resistance.