Lirussi F, Beccarello A, Zanette G, De Monte A, Donadon V, Velussi M, Crepaldi G
Department of Medical and Surgical Sciences, University of Padova, Italy.
Diabetes Nutr Metab. 2002 Aug;15(4):222-31.
In patients with non-insulin dependent diabetes mellitus (T2DM) and associated chronic liver disease, plasma levels of glucose, insulin and triglycerides are high, lipid peroxidation is increased and natural antioxidant reserves are reduced. Thus, we hypothesised that the re-balancing of cell redox levels and amelioration of liver function could result in a better glucose and lipid metabolism. To study this, we assessed the effect of a new oral formulation of an antioxidant agent - silybin-beta-cyclodextrin (named IBI/S) - in patients with chronic alcoholic liver disease and concomitant T2DM.
Sixty outpatients were enrolled in a three-centre, double blind, randomised, IBI/S vs placebo study. Forty-two (21 in the group IBI/S - 135 mg/d silybin per os - and 21 in the placebo group) concluded the 6-month treatment period. The efficacy parameters included fasting and mean daily plasma glucose levels, glycosylated hemoglobin (HbA1c), basal, stimulated C-peptide and insulin levels, total-, HDL-cholesterol and triglycerides levels in addition to conventional liver function tests. Insulin sensitivity was estimated by HOMA-IR. Malondialdehyde (MDA) was also measured before and after treatment as an index of oxidative stress.
Fasting blood glucose levels, which were similar at baseline in IBI/S group and in the placebo group (173.9 mg/dl and 177.1 mg/dl, respectively), decreased to 148.4 mg/dl (-14.7% vs baseline; p = 0.03) in the IBI/S group while they were virtually unchanged in the placebo group. The comparison between the groups at mo 6 (T6) also showed a significant reduction of glucose levels in the IBI/S group (p = 0.03). The same trend was observed in mean daily blood glucose levels, HbA1c and HOMA-IR, although differences were not significant. Basal and stimulated C-peptide values showed that only a few changes had occured in both groups. Such results indicate that insulin secretion was virtually unaffected, as confirmed also by the insulinemia data. Plasma triglycerides concentrations dropped from a baseline value of 186 mg/dl to 111 mg/dl (T6) in the IBI/S group, with significant differences at all instances with respect to baseline values. By contrast, triglycerides increased from 159 mg/dl at entry to 185 mg/dl (T6) in the placebo group. The difference between the groups at T6 was highly significant (p < 0.01). Total and HDL cholesterol as well as liver function tests did not change significantly during the study in both groups. MDA decreased significantly only in the group receiving IBI/S. No clinically relevant side effects were observed in either group.
Oral administration silybin-beta-cyclodextrin in patients with T2DM and compensated chronic alcoholic liver disease causes a significant decrease in both glucose and triglyceride plasma levels. These effects may be due to the recovery of energy substrates, consistent with a reduced lipid peroxidation and an improved insulin activity.
在非胰岛素依赖型糖尿病（T2DM）及相关慢性肝病患者中，血糖、胰岛素和甘油三酯的血浆水平升高，脂质过氧化增加，天然抗氧化储备减少。因此，我们推测细胞氧化还原水平的重新平衡和肝功能的改善可能会导致更好的糖脂代谢。为研究此问题，我们评估了一种新型抗氧化剂口服制剂——水飞蓟宾-β-环糊精（命名为IBI/S）——对慢性酒精性肝病合并T2DM患者的影响。
60名门诊患者参与了一项三中心、双盲、随机、IBI/S与安慰剂对照的研究。42名患者（IBI/S组21名——口服水飞蓟宾135mg/d，安慰剂组21名）完成了6个月的治疗期。疗效参数包括空腹和每日平均血浆葡萄糖水平、糖化血红蛋白（HbA1c）、基础及刺激后的C肽和胰岛素水平、总胆固醇、高密度脂蛋白胆固醇和甘油三酯水平，以及常规肝功能检查。通过稳态模型评估胰岛素抵抗（HOMA-IR）来估计胰岛素敏感性。治疗前后还测定了丙二醛（MDA）作为氧化应激指标。
IBI/S组和安慰剂组的空腹血糖水平在基线时相似（分别为173.9mg/dl和177.1mg/dl），IBI/S组降至148.4mg/dl（较基线降低14.7%；p = 0.03）；而安慰剂组几乎未变。两组在第6个月（T6）时的比较也显示IBI/S组血糖水平显著降低（p = 0.03）。每日平均血糖水平、HbA1c和HOMA-IR也呈现相同趋势，尽管差异不显著。基础及刺激后的C肽值显示两组仅有少量变化。这些结果表明胰岛素分泌几乎未受影响，胰岛素血症数据也证实了这一点。IBI/S组血浆甘油三酯浓度从基线值186mg/dl降至111mg/dl（T6），在所有时间点与基线值相比均有显著差异。相比之下，安慰剂组甘油三酯从入组时的159mg/dl升至185mg/dl（T6）。两组在T6时的差异非常显著（p < 0.01）。两组研究期间总胆固醇、高密度脂蛋白胆固醇以及肝功能检查均无显著变化。仅接受IBI/S的组MDA显著降低。两组均未观察到临床相关副作用。
T2DM和代偿性慢性酒精性肝病患者口服水飞蓟宾-β-环糊精可使血浆葡萄糖和甘油三酯水平显著降低。这些作用可能归因于能量底物的恢复，这与脂质过氧化减少和胰岛素活性改善一致。
