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,fru...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.AIM 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[AUC_(baseline_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.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[AUC_(baseline_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.CONCLUSION Blood glucose AUC_(baseline_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.展开更多
文摘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.AIM 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[AUC_(baseline_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.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[AUC_(baseline_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.CONCLUSION Blood glucose AUC_(baseline_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.
