Blood glucose response after oral intake of lactulose in healthy volunteers:A randomized,controlled,cross-over study

AIM To investigate possible changes of blood glucose levels after oral intake of lactulose in healthy subjects.METHODS The study was performed as prospective, randomized, two-part study with 4-way cross-over design with n = 12 in each study arm. Capillary blood glucose levels were determined over a time period of 180 min after intake of a single dose of 10 g or 20 g lactulose provided as crystal or liquid formulation. During the manufacturing process of lactulose, impurities with sugars(e.g., lactose, fructose, galactose) occur. Water and 20 g glucose were used as control and reference. Because lactulose is used as a functional food ingredient, it may also be consumed by people with impaired glucose tolerance, including diabetics. Therefore, it is of interest to determine whether the described carbohydrate impurities may increase blood glucose levels after ingestion. RESULTS The blood glucose concentration-time curves after intake of 10 g lactulose, 20 g lactulose, and water were almost identical. None of the three applications showed any changes in blood glucose levels. After intake of 20 g glucose, blood glucose concentration increased by approximately 3 mmol/L(mean Cmax = 8.3 mmol/L), reaching maximum levels after approximately 30 min and returning to baseline within approximately 90 min, which was significantly different to the corresponding 20 g lactulose formulations(P < 0.0001). Comparing the two lactulose formulations, crystals and liquid, in the dosage of 10 g and 20 g, there was no difference in the blood glucose profile and calculated pharmacokinetic parameters despite the different amounts of carbohydrate impurities(1.5% for crystals and 26.45% for liquid). Anyhow, the absolute amount of single sugars was low with 0.3 g in crystals and 5.29 g in liquid formulation in the 20 g dosages. Lactulose was well tolerated by most volunteers, and only some reported mild to moderate mainly gastrointestinal side effects. CONCLUSION The unchanged blood glucose levels after lactulose intake in healthy subjects suggest its safe use in subjects with impaired glucose tolerance.

Blood glucose response after oral lactulose intake in type 2 diabetic individuals

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.