Effect of mulberry fruit extract on glucose fluxes after a wheat porridge meal:a dual isotope study in healthy human subjects

Background: Previous research has shown the efficacy of mulberry extracts for lowering post-prandial glucose (PPG) responses. The postulated mechanism is slowing of glucose absorption, but effects on glucose disposal or endogenous production are also possible. This research assessed the effect of a specified mulberry fruit extract (MFE) on these three glucose flux parameters. Methods: The study used a double-blind, randomized, controlled, full cross-over design. In 3 counter-balanced treatments, 12 healthy adult male subjects, mean (SD) age 24.9 (2.50) years and body mass index 22.5 (1.57) kg/m2, consumed porridge prepared from 13C-labelled wheat, with or without addition of 0.75 g MFE, or a solution of 13C-glucose in water. A co-administered 2H-glucose venous infusion allowed for assessment of glucose disposal. Glucose flux parameters, cumulative absorption (time to 50% absorption, T50%abs), and PPG positive incremental area under the curve from 0 to 120 min (+iAUC0–120) were determined from total and isotopically labelled glucose in plasma. As this exploratory study was not powered for formal inferential statistical tests, results are reported as the mean percent difference (or minutes for T50%abs) between treatments with 95% CI. Results: MFE increased mean T50%abs by 10.2 min, (95% CI 3.9–16.5 min), and reduced mean 2 h post-meal rate of glucose appearance by 8.4% (95% CI −14.9 to −1.4%) and PPG + iAUC0-120 by 11% (95% CI −26.3 to −7.3%), with no significant changes in glucose disposal or endogenous production. Conclusions: The PPG-lowering effect of MFE is primarily mediated by a reduced rate of glucose uptake.</p

Effect of fibre additions to flatbread flour mixes on glucose kinetics:A randomised controlled trial

We previously found that guar gum (GG) and chickpea flour (CPF) added to flatbread wheat flour lowered postprandial blood glucose (PPG) and insulin responses dose dependently. However, rates of glucose influx cannot be determined from PPG, which integrates rates of influx, tissue disposal and hepatic glucose production. The objective was to quantify rates of glucose influx and related fluxes as contributors to changes in PPG with GG and CPF additions to wheat-based flatbreads. In a randomised cross-over design, twelve healthy males consumed each of three different C-13-enriched meals: control flatbreads (C), or C incorporating 15 % CPF with either 2 % (GG2) or 4 % (GG4) GG. A dual isotope technique was used to determine the time to reach 50 % absorption of exogenous glucose (T-50 %abs, primary objective), rate of appearance of exogenous glucose (RaE), rate of appearance of total glucose (RaT), endogenous glucose production (EGP) and rate of disappearance of total glucose (RdT). Additional exploratory outcomes included PPG, insulin, glucose-dependent insulinotropic peptide and glucagon-like peptide 1, which were additionally measured over 4 h. Compared with C, GG2 and GG4 had no significant effect on T-50 %abs. However, GG4 significantly reduced 4-h AUC values for RaE, RaT, RdT and EGP, by 11, 14, 14 and 64 %, respectively, whereas GG2 showed minor effects. Effect sizes over 2 and 4 h were similar except for significantly greater reduction in EGP for GG4 at 2 h. In conclusion, a soluble fibre mix added to flatbreads only slightly reduced rates of glucose influx, but more substantially affected rates of postprandial disposal and hepatic glucose production

Effect of mulberry fruit extract on glucose fluxes after a wheat porridge meal:a dual isotope study in healthy human subjects

Background: Previous research has shown the efficacy of mulberry extracts for lowering post-prandial glucose (PPG) responses. The postulated mechanism is slowing of glucose absorption, but effects on glucose disposal or endogenous production are also possible. This research assessed the effect of a specified mulberry fruit extract (MFE) on these three glucose flux parameters. Methods: The study used a double-blind, randomized, controlled, full cross-over design. In 3 counter-balanced treatments, 12 healthy adult male subjects, mean (SD) age 24.9 (2.50) years and body mass index 22.5 (1.57) kg/m2, consumed porridge prepared from 13C-labelled wheat, with or without addition of 0.75 g MFE, or a solution of 13C-glucose in water. A co-administered 2H-glucose venous infusion allowed for assessment of glucose disposal. Glucose flux parameters, cumulative absorption (time to 50% absorption, T50%abs), and PPG positive incremental area under the curve from 0 to 120 min (+iAUC0–120) were determined from total and isotopically labelled glucose in plasma. As this exploratory study was not powered for formal inferential statistical tests, results are reported as the mean percent difference (or minutes for T50%abs) between treatments with 95% CI. Results: MFE increased mean T50%abs by 10.2 min, (95% CI 3.9–16.5 min), and reduced mean 2 h post-meal rate of glucose appearance by 8.4% (95% CI −14.9 to −1.4%) and PPG + iAUC0-120 by 11% (95% CI −26.3 to −7.3%), with no significant changes in glucose disposal or endogenous production. Conclusions: The PPG-lowering effect of MFE is primarily mediated by a reduced rate of glucose uptake.</p

Systemic Lactate Acts as a Metabolic Buffer in Humans and Prevents Nutrient Overflow in the Postprandial Phase

On an organismal level, metabolism needs to react in a well-orchestrated manner to metabolic challenges such as nutrient uptake. Key metabolic hubs in human blood are pyruvate and lactate, both of which are constantly interconverted by very fast exchange fluxes. The quantitative contribution of different food sources to these metabolite pools remains unclear. Here, we applied in vivo stable isotope labeling to determine postprandial metabolic fluxes in response to two carbohydrate sources of different complexity. Depending on the ingested carbohydrate source, glucose or wheat flour, the net direction of the lactate dehydrogenase, and the alanine amino transferase fluxes were adjusted in a way to ensure sufficient availability, while, at the same time, preventing an overflow in the respective metabolite pools. The systemic lactate pool acts as a metabolic buffer which is fueled in the early- and depleted in the late-postprandial phase and thus plays a key role for systemic metabolic homeostasis

The Rate of Glucose Appearance Is Related to Postprandial Glucose and Insulin Responses in Adults:A Systematic Review and Meta-analysis of Stable Isotope Studies

Background: It is often assumed that lower postprandial glucose (PPG) and insulin (PPI) responses are induced by slower glucose influx from the gut (e.g., by delayed carbohydrate digestion). However, changes in the rate of appearance of glucose in the peripheral circulation [rate of appearance of exogenous glucose (RaE)] may be accompanied by changes in endogenous glucose production (EGP) and the rate of disappearance of total glucose into tissues (RdT). The quantitative relationships between reductions in RaE and PPG/PPI levels are unclear. Objectives: The objective was to perform a meta-analysis to quantify the effect of changes in RaE on changes in PPG and PPI levels (primary) and EGP and RdT (secondary). Methods: We systematically searched the Scopus, Medline, and Cochrane library databases through 10 January 2019 for randomized, controlled, carbohydrate-rich interventions that aimed to reduce RaE in humans, measured using dual or triple stable isotope methods. The 2-h net incremental AUCs for all variables were extracted or calculated. Relationships between RaE and outcomes were quantified by weighted regression analyses. Results: There were 12 articles, including 17 comparisons, that satisfied the inclusion criteria. The subjects were mainly men (60%), with age and BMI ranges of 18-40 y and 20.0-27.5 kg/m(2), respectively. A 10% reduction in RaE was associated with reductions in PPG levels, PPI levels, and the RdT of 7% (95% CI: 2%, 12%; P = 0.010), 8% (95% CI: 2%, 13%; P = 0.012), and 11% (95% CI: 4%, 17%; P = 0.005), respectively, but was not significantly associated with a change in EGP (13%; 95% CI: -7%, 33%; P = 0.176). All fluxes together explained 70% and 26% of the variances in PPG and PPI levels, respectively. Conclusions: In adults, reducing glucose RaE by diet is associated with significant reductions in PPG levels, PPI levels, and the rate of glucose disposal

Postprandial Metabolic Effects of Fiber Mixes Revealed by in vivo Stable Isotope Labeling in Humans.

Food supplementation with a fiber mix of guar gum and chickpea flour represents a promising approach to reduce the risk of type 2 diabetes mellitus (T2DM) by attenuating postprandial glycemia. To investigate the effects on postprandial metabolic fluxes of glucose-derived metabolites in response to this fiber mix, a randomized, cross-over study was designed. Twelve healthy, male subjects consumed three different flatbreads either supplemented with 2% guar gum or 4% guar gum and 15% chickpea flour or without supplementation (control). The flatbreads were enriched with ~2% of 13C-labeled wheat flour. Blood was collected at 16 intervals over a period of 360 min after bread intake and plasma samples were analyzed by GC-MS based metabolite profiling combined with stable isotope-assisted metabolomics. Although metabolite levels of the downstream metabolites of glucose, specifically lactate and alanine, were not altered in response to the fiber mix, supplementation of 4% guar gum was shown to significantly delay and reduce the exogenous formation of these metabolites. Metabolic modeling and computation of appearance rates revealed that the effects induced by the fiber mix were strongest for glucose and attenuated downstream of glucose. Further investigations to explore the potential of fiber mix supplementation to counteract the development of metabolic diseases are warranted