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目的验证持续胰岛素皮下输注(CSII)可使1型糖尿病患者肝脏葡萄糖代谢正常化的假说。研究设计和方法血糖控制不良的1型糖尿病患者(T1Dp;糖化血红蛋白8.5%±0.4%),经持续胰岛素皮下输注血糖控制改善的1型糖尿病患者(T1Di;糖化血红蛋白7.0%±0.3%),和正常人(CON;糖化血红蛋白5.2%±0.4%)被纳入研究。通过磁共振频谱来检测体内净生的肝糖元合成和肝糖分解。使用[6,6-2H2]葡萄糖、糖元磷酸化酶(GP)流量及2H2O/扑热息痛糖异生流量来检测内源性葡萄糖产生(EGP)和葡萄糖异生(GNG)。结果与CON组相比,净生糖原合成在T1Dp组降低70%,但与T1Di组没有区别。在空腹时,T1Dp组的EGP比T1Di组和CON组分别高25%和42%,GNG比T1Di组和CON组高74%和67%。T1Dp组的糖原循环(3.5±2.0μmolkg-1min-1)约占GP流量的47%。结论血糖控制不良的1型糖尿病患者不仅空腹葡萄糖异生增加同时糖原循环增加。强化胰岛素治疗可使这些异常得以恢复,表明在长病程的T1D患者中的肝脏葡萄糖代谢异常并不是不可逆转的。
Objective To verify the hypothesis that continuous insulin subcutaneous infusion (CSII) normalizes hepatic glucose metabolism in patients with type 1 diabetes. Study design and methods Patients with type 1 diabetes (T1Dp; HbA1c 8.5% ± 0.4%), patients with type 1 diabetes (T1Di, HbA1c, 7.0% ± 0.3%) with improved glycemic control following sustained subcutaneous insulin infusion, And normal subjects (CON; HbA1c, 5.2% ± 0.4%) were included in the study. Magnetic resonance spectroscopy was used to detect in vivo neoplastic glycogen synthesis and glycogenolysis. Endogenous glucose production (EGP) and gluconeogenesis (GNG) were measured using [6,6-2H2] glucose, glycogen phosphorylase (GP) flux, and 2H2O / paracetamole flow rates. Results Compared with the CON group, neat glycogen synthesis was reduced by 70% in the T1Dp group but not in the T1Di group. At fasting, EGP in T1Dp group was 25% and 42% higher than T1Di group and CON group, respectively, and GNG was 74% and 67% higher than T1Di group and CON group, respectively. Glycogen circulation (3.5 ± 2.0μmolkg-1min-1) in T1Dp group accounted for about 47% of GP flow. Conclusions Patients with type 1 diabetes with poor glycemic control not only have an increased fasting gluconeogenesis but also an increased glycogen cycle. Intensive insulin therapy can restore these abnormalities, indicating that long-term T1D patients with abnormal liver glucose metabolism is not irreversible.