背景:乳果糖被批准用于便秘的对症治疗,糖尿病患者常见的胃肠道(GI)并发症。乳果糖产品含有碳水化合物杂质(例如,乳糖,果糖,半乳糖),这发生在乳果糖制造过程中。这些杂质可能会影响使用乳果糖治疗轻度便秘的2型糖尿病(T2DM)患者的血糖水平。先前对健康受试者的研究显示,口服乳果糖摄入后血糖水平没有增加。然而,目前尚不清楚摄入乳果糖是否会增加糖尿病患者的血糖水平。
目的:评估轻度便秘患者口服乳果糖后的血糖分布,门诊非胰岛素依赖型T2DM患者。
方法:这种前瞻性,双盲,随机化,控制,单中心试验在格拉茨医科大学临床研究中心进行,奥地利,在24名成年白人轻度便秘中,非胰岛素依赖型T2DM患者。符合条件的受试者被随机分配到六个治疗序列之一。每个由4种按性别分层的治疗方法组成,采用不完全区组设计。受试者接受单剂量20g或30g乳果糖(晶体和液体制剂),水作为阴性对照或30g葡萄糖作为阳性对照。在给药后180分钟的时间段内测量毛细管血糖浓度。主要终点是在整个评估期间的血糖浓度曲线下的基线校正面积[AUCbaseline_c(0-180分钟)]。对乳果糖剂量和制剂与水进行定量比较,以相等的乳果糖剂量与葡萄糖。以及液体乳果糖与晶体乳果糖。安全参数包括胃肠道耐受性,在给药后180分钟和24小时评估,和不良事件发生长达24小时后的剂量。
结果:在24名随机和分析的受试者中,摄入20g和30g乳果糖后的血糖浓度-时间曲线与两种乳果糖制剂的水摄入后的血糖浓度-时间曲线几乎相同,尽管碳水化合物杂质的含量不同(晶体和约≤3.0%。30%为液体)。无论乳果糖剂量和制剂如何,乳果糖和水之间的主要终点[AUCbaseline_c(0-180分钟)]没有显著差异。此外,关于所有次要终点,乳果糖制剂显示出与水相当的结果,其中一个例外涉及最大葡萄糖水平。30g剂量后观察到最大血糖略有增加,液体乳果糖,与水相比,平均治疗差异为0.63mmol/L(95%置信区间:0.19,1.07)。与30g液体和结晶乳果糖相比,摄入30g葡萄糖显着增加所有血糖终点,分别(所有P<0.0001)。在不同乳果糖制剂之间没有观察到血糖响应的差异。不出所料,乳果糖可增加排便次数,一般耐受性良好.由于乳果糖的泻药作用,受试者仅经历轻度至中度的GI症状。
结论:轻度便秘患者的血糖AUCbaseline_c(0-180分钟)水平,非胰岛素依赖型T2DM患者不受20g和30g结晶或液体乳果糖制剂中碳水化合物杂质的影响.
BACKGROUND: Lactulose is approved for the symptomatic treatment of constipation, a gastrointestinal (GI) complication common in individuals with diabetes. Lactulose products contain carbohydrate impurities (e.g., lactose, fructose, galactose), which occur during the lactulose manufacturing process. These impurities may affect the blood glucose levels of individuals with type 2 diabetes mellitus (T2DM) using lactulose for the treatment of mild constipation. A previous study in healthy subjects revealed no increase in blood glucose levels after oral lactulose intake. However, it is still unclear whether the intake of lactulose increases blood glucose levels in individuals with diabetes.
OBJECTIVE: To evaluate the blood glucose profile after oral lactulose intake in mildly constipated, non-insulin-dependent subjects with T2DM in an outpatient setting.
METHODS: This prospective, double-blind, randomized, controlled, single-center trial was conducted at the Clinical Research Center at the Medical University of Graz, Austria, in 24 adult Caucasian mildly constipated, non-insulin-dependent subjects with T2DM. Eligible subjects were randomized and assigned to one of six treatment sequences, each consisting of four treatments stratified by sex using an incomplete block design. Subjects received a single dose of 20 g or 30 g lactulose (crystal and liquid formulation), water as negative control or 30 g glucose as positive control. Capillary blood glucose concentrations were measured over a period of 180 min post dose. The primary endpoint was the baseline-corrected area under the curve of blood glucose concentrations over the complete assessment period [AUCbaseline_c (0-180 min)]. Quantitative comparisons were performed for both lactulose doses and formulations vs water for the equal lactulose dose vs glucose, as well as for liquid lactulose vs crystal lactulose. Safety parameters included GI tolerability, which was assessed at 180 min and 24 h post dose, and adverse events occurring up to 24 h post dose.
RESULTS: In 24 randomized and analyzed subjects blood glucose concentration-time curves after intake of 20 g and 30 g lactulose were almost identical to those after water intake for both lactulose formulations despite the different amounts of carbohydrate impurities (≤ 3.0% for crystals and approx. 30% for liquid). The primary endpoint [AUCbaseline_c (0-180 min)] was not significantly different between lactulose and water regardless of lactulose dose and formulation. Also with regard to all secondary endpoints lactulose formulations showed comparable results to water with one exception concerning maximum glucose level. A minor increase in maximum blood glucose was observed after the 30 g dose, liquid lactulose, in comparison to water with a mean treatment difference of 0.63 mmol/L (95% confidence intervals: 0.19, 1.07). Intake of 30 g glucose significantly increased all blood glucose endpoints vs 30 g liquid and crystal lactulose, respectively (all P < 0.0001). No differences in blood glucose response were observed between the different lactulose formulations. As expected, lactulose increased the number of bowel movements and was generally well tolerated. Subjects experienced only mild to moderate GI symptoms due to the laxative action of lactulose.
CONCLUSIONS: Blood glucose AUCbaseline_c (0-180 min) levels in mildly constipated, non-insulin dependent subjects with T2DM are not affected by the carbohydrate impurities contained in 20 g and 30 g crystal or liquid lactulose formulations.