Development of an engineered Bacillus subtilis strain for antibiotic-free sucrose isomerase production.

Sucrose isomerase (SIase) catalyzes the hydrolysis and isomerization of sucrose into isomaltulose, a functional sugar extensively used in the food industry. However, the lack of safe and efficient heterologous expression systems for SIase has constrained its production and application. In this study, an engineered Bacillus subtilis strain for antibiotic-free SIase production was developed via a food-grade expression system. First, the B. subtilis strain TEA was modified through the CRISPR/Cas9 system, resulting in a mutant strain TEA4, which exhibited enhanced capabilities for recombinant protein expression. For efficient and safe production of SIase, different constitutive and inducible promoters were evaluated. The maltose-inducible promoter Poglv was found to have an extracellular SIase activity of 21.7 U mL-1 in engineered strain TEA4. Subsequent optimization of the culture medium further increased SIase activity to 26.4 U mL-1 during shake flask cultivation. Eventually, using the crude enzyme solution of the engineered strain in biotransformation reactions resulted in a high yield of isomaltulose under high concentrations sucrose, achieving a maximum yield of 83.1%. These findings demonstrated an engineered B. subtilis strain for antibiotic-free SIase production, paving the way for its scale-up industrial production and application.

Characterization of a unique pH-dependent amylosucrase from Deinococcus cellulosilyticus.

The amylosucrase (ASase, EC 2.4.1.4) utilizes sucrose as the sole substrate to catalyze multifunctional reactions. It can naturally synthesize α-1,4-linked glucans such as amylose as well as sucrose isomers with more favorable properties than sucrose with a lower intestinal digestibility and non-cariogenic properties. The amino acid sequence of the asase gene from Deinococcus cellulosilyticus (DceAS) exhibits low homology with those of other ASases from other Deinococcus species. In this study, we cloned and expressed DceAS and demonstrated its high activity at pH 6 and pH 8 and maintained stability. It showed higher polymerization activity at pH 6 than at pH 8, but similar isomerization activity and produced more turanose and trehalulose at pH 6 than at pH 8 and produced more isomaltulose at pH 8. Furthermore, the molecular weight of DceAS was 226.6 kDa at pH 6 and 145.5 kDa at pH 8, indicating that it existed as a trimer and dimer, respectively under those conditions. Additionally, circular dichroism spectra showed that the DceAS secondary structure was different at pH 6 and pH 8. These differences in reaction products at different pHs can be harnessed to naturally produce sucrose alternatives that are more beneficial to human health.

Isomaltulose Enhances GLP-1 and PYY Secretion to a Mixed Meal in People With or Without Type 2 Diabetes as Compared to Saccharose.

SCOPE: Secretion of the gut hormones glucagon-like peptide (GLP-1) and peptide YY (PYY) are induced by nutrients reaching the lower small intestine which regulate insulin and glucagon release, inhibit appetite, and may improve ß-cell regeneration. The aim is to test the effect of a slowly digested isomaltulose (ISO) compared to the rapidly digested saccharose (SAC) as a snack given 1 h before a standardized mixed meal test (MMT) on GLP-1, PYY, glucose-dependent insulinotropic peptide (GIP), and metabolic responses in participants with or without type 2 diabetes (T2DM). METHODS AND RESULTS: Fifteen healthy volunteers and 15 patients with T2DM consumed either 50 g ISO or SAC 1 h preload of MMT on nonconsecutive days. Clinical parameters and incretin hormones are measured throughout the whole course of MMT. Administration of 50 g ISO as compared to SAC induced a significant increase in GLP-1, GIP, and PYY responses over 2 h after intake of a typical lunch in healthy controls. Patients with T2DM showed reduced overall responses of GLP-1 and delayed insulin release compared to controls while ISO significantly enhanced the GIP and almost tripled the PYY response compared to SAC. CONCLUSION: A snack containing ISO markedly enhances the release of the metabolically advantageous gut hormones PYY and GLP-1 and enhances GIP release in response to a subsequent complex meal.

Effects of ingesting beverages containing glycerol and sodium with isomaltulose or sucrose on fluid retention in young adults: a single-blind, randomized crossover trial.

We evaluated changes in hyperhydration and beverage hydration index (BHI, a composite measure of fluid balance after consuming a test beverage relative to water) during resting, induced by the consumption of beverages containing glycerol and sodium supplemented with fast-absorbing sucrose or slow-absorbing isomaltulose. In a randomized crossover, single-blinded protocol (clinical trials registry: UMIN000042644), 14 young physically active adults (three women) consumed 1 L of beverage containing either 7% glycerol + 0.5% sodium (Gly + Na), Gly + Na plus 7% sucrose (Gly + Na + Suc), Gly + Na plus 7% isomaltulose (Gly + Na + Iso), or water (CON) over a 40 min period. We assessed the change in plasma volume (ΔPV), BHI (calculated from cumulative urine output following consumption of water relative to that of the beverage), and blood glucose and sodium for 180 min after initiating ingestion. Total urine volume was reduced in all beverages containing glycerol and sodium compared to CON (all P ≤ 0.002). The addition of isomaltulose increased BHI by ∼45% (3.43 ± 1.0 vs. 2.50 ± 0.7 for Gly + Na, P = 0.011) whereas sucrose did not (2.6 ± 0.6, P = 0.826). The PV expansion was earliest for Gly + Na (30 min), slower for Gly + Na + Suc (90 min), and slowest for Gly + Na + Iso (120 min) with a concomitant lag in the increase of blood glucose and sodium concentrations. Supplementation of beverages containing glycerol and sodium with isomaltulose but not sucrose enhances BHI from those of glycerol and sodium only under a resting state, likely due to the slow absorption of isomaltulose-derived monosaccharides (i.e., glucose and fructose).

Habitual isomaltulose intake reduces arterial stiffness associated with postprandial hyperglycemia in middle-aged and elderly people: a randomized controlled trial.

Endothelin-1 (ET-1), produced by vascular endothelial cells, plays a pivotal role in the regulation of vascular tone. Isomaltulose, a naturally occurring sweetener and structural isomer of sucrose, reduces postprandial hyperglycemia, but its effect on arteriosclerosis due to hyperglycemia is unknown. The effects of 12 weeks of isomaltulose administration on ET-1 levels, a peptide that regulates arterial stiffness, blood pressure, and vascular tone, were tested before and after an oral glucose tolerance test. Fifty-four healthy middle-aged and older adults (30 men and 24 women) were divided into two groups: (1) a 25 g isomaltulose jelly drink intake group (Group I, 27 participants, mean age 55 ± 1 years) and (2) a sucrose jelly drink intake group (Group S, 27 participants, mean age 55 ± 1 years), each consuming isomaltulose or sucrose daily for 12 weeks, and a randomized, controlled study was conducted. Participants visited the laboratory before the intervention and 4, 8, and 12 weeks after the intervention to measure carotid-femoral (cf) and brachial-ankle (ba) pulse wave velocity (PWV), systolic blood pressure (BP), plasma glucose (PG), insulin, and ET-1 levels before and 60 and 120 min after a 75-g OGTT. baPWV, and ET-1 levels before intervention were significantly increased after 75-g OGTT compared to before 75-g OGTT in both groups (p < 0.05). The post-intervention baPWV, and ET-1 levels were significantly increased after 75-g OGTT in Group S compared to before 75-g OGTT (p < 0.05), whereas no significant changes were observed in Group I. These results suggest that consumption of isomaltulose, which has a lower GI than sucrose, is more effective in preventing the increases in systemic arterial stiffness associated with postprandial hyperglycemia in healthy middle-aged and older adults.

Robust and recyclable cross-linked enzyme aggregates of sucrose isomerase for isomaltulose production.

A novel cross-linked enzyme aggregates (CLEAs) catalyst was produced by precipitation and cross-linking sucrose isomerase (SIase) for isomaltulose production. The effects of precipitants and cross-linkers on the catalytic performance of the CLEAs were first evaluated. Then, bovine serum albumin (BSA) was used as additive and two immobilized enzymes, cross-linked SIase aggregates (CLSIAs) and CLSIAs-BSA were obtained. All the immobilized preparations exhibited superior thermal stability, pH tolerance, and storage stability compared to the soluble SIase, and showed excellent reusability. These samples still retained more than 61% of their initial activity after ten reuse cycles, with CLSIAs-BSA retaining up to 91.7%. The conversion ratios of sucrose into isomaltulose using CLSIAs-BSA reached 88.4 and 81.2% with sucrose and sugar cane juice as substrate, respectively. Therefore, CLSIAs are a highly effective biocatalyst for the preparation of isomaltulose with great potential for industrial applications.

Isomaltulose alleviates acute colitis via modulating gut microbiota and the Treg/Th17 balance in mice.

Food-grade isomaltulose exhibits significant modulation of gut microbiota and its metabolites in healthy populations. This study further explored the preventive therapeutic effect and anti-colitis potential of isomaltulose on dextran sulfate sodium-induced colitis in mice. Our results suggested that isomaltulose played a significant role in preventing colon shortening, reducing intestinal epithelial destruction and inhibiting inflammatory cell infiltration. Meanwhile, the isomaltulose supplement greatly reduced the production of pro-inflammatory cytokines and restored the balance between T helper type 17 (Th17) cells and regulatory T (Treg) cells. Pathway enrichment analysis for differentially expressed genes (DEGs) also indicated that the anti-inflammatory effect of isomaltulose was closely related to intestinal immunity. Moreover, the disturbed gut microbiota in ulcerative colitis (UC) was partially restored after treatment with isomaltulose. These results suggest that isomaltulose is a promising therapeutic agent for the prevention and adjunctive treatment of UC by maintaining intestinal immune homeostasis and remodeling the gut microbiota.

Blood Glucose Response of a Low-Carbohydrate Oral Nutritional Supplement with Isomaltulose and Soluble Dietary Fiber in Individuals with Prediabetes: A Randomized, Single-Blind Crossover Trial.

A high-energy-type oral dietary supplement (ONS), with a low proportion of available carbohydrate (LC-ONS), which contains a slowly digestible carbohydrate, isomaltulose, and is fortified with soluble dietary fiber, was newly developed for individuals with diabetes or prediabetes. This study aimed to evaluate the impact of LC-ONS on blood glucose levels after ingestion in individuals with prediabetes. A single-blind, randomized crossover clinical trial was performed on 20 individuals with prediabetes. After overnight fasting, all subjects ingested one serving (200 kcal/125 mL) of either LC-ONS (40% energy proportion of available carbohydrates) or standard ONS (ST-ONS, 54% energy proportion of available carbohydrates) on two separate days. The incremental area under the curve of blood glucose levels for 120 min was significantly lower after LC-ONS ingestion compared to ST-ONS (2207 ± 391 mg/dL·min (least mean square value ± standard error) and 3735 ± 391 mg/dL·min, respectively; p < 0.001). The LC-ONS showed significantly lower blood glucose levels than the ST-ONS at all time points, except at baseline. Similarly, the incremental area under the curve of plasma insulin was significantly lower after LC-ONS ingestion. These results suggest that LC-ONS is useful as an ONS for energy supply in individuals with postprandial hyperglycemia.

Effect of Isomaltulose on Glycemic and Insulinemic Responses: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Evidence regarding the effect of isomaltulose on glycemic and insulinemic responses is still conflicting, which limits isomaltulose's application in glycemic management. The purpose of this study was to comprehensively evaluate its effectiveness and evidence quality. We systematically searched PubMed, Embase, and the Cochrane Library for randomized controlled trials (RCTs) prior to October 2021. RCTs were eligible for inclusion if they enrolled adults to oral intake of isomaltulose or other carbohydrates dissolved in water after an overnight fast and compared their 2-h postprandial glucose and insulin concentrations. The DerSimonian-Laird method was used to pool the means of the circulating glucose and insulin concentrations. Both random-effects and fixed-effects models were used to calculate the weighted mean difference in postprandial glucose and insulin concentrations in different groups. Subgroup, sensitivity, and meta-regression analyses were also conducted. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to assess the certainty of evidence. Finally, 11 RCTs (n = 175 participants) were included. The trials were conducted in 4 countries (Japan, Brazil, Germany, and the Netherlands), and all of the enrolled participants were >18 y of age with various health statuses (healthy, type 2 diabetes, impaired glucose tolerance, and hypertension). Moderate evidence suggested that oral isomaltulose caused an attenuated glycemic response compared with sucrose at 30 min. Low evidence suggested that oral isomaltulose caused an attenuated but more prolonged glycemic response than sucrose and an attenuated insulinemic response. Low-to-moderate levels of evidence suggest there may be more benefit of isomaltulose for people with type 2 diabetes, impaired glucose tolerance, or hypertension; older people; overweight or obese people; and Asian people. The study was registered on PROSPERO (International Prospective Register of Systematic Reviews) as CRD42021290396 (available at https://www.crd.york.ac.uk/prospero/).

Isomaltulose: From origin to application and its beneficial properties - A bibliometric approach.

Consumers are concerned with the amount of sucrose added to foods and its effects on human health. One way to reduce this concern is through the consumption of sucrose substitutes, such as isomaltulose. Isomaltulose is an alternative sugar that should be regarded by the food industry as much healthier than sucrose, due to its beneficial properties; these include, low glycemic index and slow hydrolysis, prebiotic potential, and low cariogenic potential. In this work, a bibliometric analysis associated with a review of literature was conducted as a rigorous method for exploring and analyzing large volumes of scientific data, to understand the global scenario and identify the trends regarding isomaltulose. Important facts from its history and origin were discussed, as well the main research and countries that have contributed to its growing interest in the food industry. Over the years, from the discovery of new beneficial properties, more studies have been conducted, demonstrating that the interest in isomaltulose has been increasing. Finally, we concluded that isomaltulose is a promising sucrose substitute that could change the scenario of the sugar-rich foods market; and its use for the development of new products is highly encouraged.

Tuning the catalytic performances of a sucrose isomerase for production of isomaltulose with high concentration.

Obtaining a sucrose isomerase (SIase) with high catalytic performance is of great importance in industrial production of isomaltulose (a reducing sugar). In order to obtain such SIase mutant, a high-throughput screening system in microtiter plate format was developed based on a widely used 2,4-dinitrosalicylic acid (DNS) method for determination of reducing sugar. An SIase from Erwinia sp. Ejp617 (ErSIase) was selected to improve its catalytic efficiency. After screening of ~ 8000 mutants from a random mutagenesis library, Q209 and R456 were identified as beneficial positions. Saturation mutagenesis of the two positions resulted in a double-site mutant ErSIase_Q209S-R456H that showed the highest catalytic efficiency, and its specific activity reached 684 U/mg that is 17.5-fold higher than that of the wild-type ErSIase. By employing the lyophilized Escherichia coli (E. coli) cells harboring ErSIase_Q209S-R456H, a high space-time yield (STY = 3.9 kg/(L·d)) was achieved toward 600 g/L sucrose. Furthermore, the in silico analysis suggested that the hydrogen bond network was improved and steric hindrance was reduced due to the beneficial substitutions.Key points• A sucrose isomerase mutant with high catalytic efficiency was obtained.• The highest space-time yield was achieved toward high-concentration sucrose.• The optimized H-bond network contributed to the enhanced catalytic efficiency.

Comparison of hydration efficacy of carbohydrate-electrolytes beverages consisting of isomaltulose and sucrose in healthy young adults: A randomized crossover trial.

Isomaltulose is a low glycemic and insulinaemic carbohydrate now used as an alternative sweetener in beverages. However, it remains unclear if hydration status may be impacted differently with the consumption of beverages containing isomaltulose as compared to sucrose, a common beverage sweetener. Thirteen young adults (7 women) consumed 1 L of a carbohydrate beverage (with low electrolyte content) containing either 6.5%-sucrose, 6.5%-isomaltulose, or water within a 15 min period. For each beverage, beverage hydration index (BHI, a composite measure of fluid balance after consuming a test beverage relative to water) was calculated from urine volume produced over a 3 h period following ingestion of the carbohydrate beverages relative to water. The change in plasma volume (ΔPV), blood glucose, and lactate concentrations were assessed every 30 min post-beverage consumption. Isomaltulose ingestion attenuated urine production as compared to water and sucrose (P ≤ 0.005) over the 3 h post-ingestion period. However, no differences were observed between sucrose and water (P = 0.055). BHI was 1.53 ± 0.44 for isomaltulose (P ≤ 0.022 vs. sucrose and water) and 1.20±0.29 for sucrose (P = 0.210 vs. water). A transient reduction in ΔPV was observed following the ingestion of the isomaltulose beverage (at 30 min, P = 0.007 vs. sucrose). Thereafter, no differences in ΔPV between beverages were measured. Increases in blood glucose and lactate, indices of absorption and utility of glucose, were delayed in the isomaltulose as compared to sucrose beverage. In summary, we demonstrated a greater BHI with a carbohydrate-electrolyte beverage containing isomaltulose as compared to sucrose. This may in part be attributed to a delayed absorption of isomaltulose reducing diuresis.

Sequential optimization strategy for the immobilization of Erwinia sp. D12 cells and the production of isomaltulose with high stability and prebiotic potential.

Isomaltulose is a potential substitute for sucrose, with a high stability and prebiotic potential, for wide use in candies and soft drinks. This sugar is obtained from sucrose through enzymatic conversion using microbial glucosyltransferases. This work aimed to optimize a matrix to immobilize glucosyltransferase producing Erwinia sp. D12 cells using a sequential experimental strategy. The cell mass of Erwinia sp. D12 obtained in a bioreactor was immobilized in beads formed by ionic gelation. The conversion of sucrose into isomaltulose using the beads was performed in batch and continuous processes, and the isomaltulose was recovered through crystallization. The stability of isomaltulose was assessed in beverages of different pH values, and its prebiotic potential was verified with the growth of probiotic microorganisms. The optimized matrix composed of alginate (2.0% w/v), CaCl2 (2.0% w/v), gelatin (2.0% w/v), and transglutaminase (0.2% w/v) showed the highest mean of produced isomaltulose (199.82 g/L) after four batches. In addition, high stability during the continuous process resulted in an isomaltulose production above of 230 g/L for up to 72 h. The produced isomaltulose was more stable than sucrose in lemon soft drink and orange and grape energy drinks after 30 days of storage; and promoted the growth of Bifidobacterium animalis and Lactobacillus lactis. In conclusion, the production of isomaltulose by Erwinia sp. D12 cells immobilized using optimized conditions is recommended, due to its high conversion capacity, high stability, and prebiotic potential of crystals obtained.

Immobilization of Sucrose Isomerase from Erwinia sp. with Graphene Oxide and Its Application in Synthesizing Isomaltulose.

Sucrose isomerase (SIase) is a key enzyme used for the production of isomaltulose from sucrose. In this study, an SIase gene from Erwinia sp. Ejp617 (ErSIase) was heterologously expressed in Escherichia coli BL21(DE3), and the recombinant ErSIase was served as biocatalyst combined with the graphene oxide (GO) as carrier for ErSIase immobilization. The Fourier transform infrared spectroscopy, transmission electron microscope, and confocal laser microscopy analyses showed that ErSIase was successfully immobilized on the surface of GO to form ErSIase-GO. The loading capacity of ErSIase on GO reached up to 460 mg/g with a specific activity of 727.04 U/mg protein when the optimal immobilization time of 12 h and the ErSIase/GO ratio of 7.4:4 (w/w) were applied. A high conversion rate of 95.3% was reached from sucrose to isomaltulose using ErSIase-GO as biocatalyst with 600 g/L sucrose as substrate, after 180 min at 40 °C and pH 6.0. Moreover, stabilities of the immobilized ErSIase-GO in the aspects of thermal, pH, and storage were improved, and its activity after 10 batches still remained around 80% under the optimal conditions. The Km value of ErSIase-GO was 29.32 mM, and the kcat/Km was increased to 27.34 s-1 mM-1 when 0.1% (w/v) detergent NP40 was added. These results indicated that the ErSIase was well immobilized onto GO, and the ErSIase-GO is a promising biocatalyst with high operational stability and catalytic activity for industrial production of isomaltulose.

A head-to-head comparison review of biological and toxicological studies of isomaltulose, d-tagatose, and trehalose on glycemic control.

Diabetes mellitus is the most common metabolic disorder contributing to significant morbidity and mortality in humans. Different preventive and therapeutic agents, as well as various pharmacological strategies or non-pharmacological tools, improve the glycemic profile of diabetic patients. Isomaltulose, d-tagatose, and trehalose are naturally occurring, low glycemic sugars that are not synthesized by humans but widely used in food industries. Various studies have shown that these carbohydrates can regulate glucose metabolism and provide support in maintaining glucose homeostasis in patients with diabetes, but also can improve insulin response, subsequently leading to better control of hyperglycemia. In this review, we discussed the anti-hyperglycemic effects of isomaltulose, D-tagatose, and trehalose, comparing their properties with other known sweeteners, and highlighting their importance for the development of the pharmaceutical and food industries.

Assessment of Glycemic Response to Model Breakfasts Varying in Glycemic Index (GI) in 5-7-Year-Old School Children.

Reduced Glycemic Index (GI) of breakfast has been linked to improved cognitive performance in both children and adult populations across the morning. However, few studies have profiled the post-prandial glycemic response (PPGR) in younger children. The aim of this study was to assess PPGR to breakfast interventions differing in GI in healthy children aged 5-7 years. Eleven subjects completed an open-label, randomized, cross-over trial, receiving three equicaloric test beverages (260 kcal) consisting of 125 mL semi-skimmed milk and 50 g sugar (either glucose, sucrose, or isomaltulose). On a fourth occasion, the sucrose beverage was delivered as intermittent supply. PPGR was measured over 180 min using Continuous Glucose Monitoring (CGM). The incremental area under the curve (3h-iAUC) was highest for the glucose beverage, followed by intermittent sucrose (-21%, p = 0.288), sucrose (-27%, p = 0.139), and isomaltulose (-48%, p = 0.018). The isomaltulose beverage induced the smallest Cmax (7.8 mmol/L vs. >9.2 mmol/L for others) and the longest duration with moderate glucose level, between baseline value and 7.8 mmol/L (150 vs. <115 min for others). These results confirm that substituting mid-high GI sugars (e.g., sucrose and glucose) with low GI sugars (e.g., isomaltulose) during breakfast are a viable strategy for sustained energy release and glycemic response during the morning even in younger children.

Effects of Different Types of Carbohydrates on Arterial Stiffness: A Comparison of Isomaltulose and Sucrose.

Increased arterial stiffness during acute hyperglycemia is a risk factor for cardiovascular disease, but the type of carbohydrate that inhibits it is unknown. The purpose of this study was to determine the efficacy of low-glycemic-index isomaltulose on arterial stiffness during hyperglycemia in middle-aged and older adults. Ten healthy middle-aged and older adult subjects orally ingested a solution containing 25 g of isomaltulose (ISI trial) and sucrose (SSI trial) in a crossover study. In the SSI trial, the brachial-ankle (ba) pulse wave velocity (PWV) increased 30, 60, and 90 min after ingestion compared with that before ingestion (p < 0.01); however, in the ISI trial, the baPWV did not change after ingestion compared with that before ingestion. Blood glucose levels 30 min after intake were lower in the ISI trial than in the SSI trial (p < 0.01). The baPWV and systolic blood pressure were positively correlated 90 min after isomaltulose and sucrose ingestion (r = 0.640, p < 0.05). These results indicate that isomaltulose intake inhibits an acute increase in arterial stiffness. The results of the present study may have significant clinical implications on the implementation of dietary programs for middle-aged and elderly patients.

Improved Glycemic Control and Variability: Application of Healthy Ingredients in Asian Staples.

A reduction in carbohydrate intake and low-carbohydrate diets are often advocated to prevent and manage diabetes. However, limiting or eliminating carbohydrates may not be a long-term sustainable and maintainable approach for everyone. Alternatively, diet strategies to modulate glycemia can focus on the glycemic index (GI) of foods and glycemic load (GL) of meals. To assess the effect of a reduction in glycemic load of a 24 h diet by incorporating innovative functional ingredients (ß-glucan, isomaltulose) and alternative low GI Asian staples (noodles, rice)on glycemic control and variability, twelve Chinese men (Age: 27.0 ± 5.1 years; BMI:21.6 ± 1.8kg/m2) followed two isocaloric, typically Asian, 24h diets with either a reduced glycemic load (LGL) or high glycemic load (HGL) in a randomized, single-blind, controlled, cross-over design. Test meals included breakfast, lunch, snack and dinner and the daily GL was reduced by 37% in the LGL diet. Continuous glucose monitoring provided 24 h glycemic excursion and variability parameters: incremental area under the curve (iAUC), max glucose concentration (Max), max glucose range, glucose standard deviation (SD), and mean amplitude of glycemic excursion (MAGE), time in range (TIR). Over 24h, the LGL diet resulted in a decrease in glucose Max (8.12 vs. 6.90 mmol/L; p = 0.0024), glucose range (3.78 vs. 2.21 mmol/L; p = 0.0005), glucose SD (0.78 vs. 0.43 mmol/L; p = 0.0002), mean amplitude of glycemic excursion (2.109 vs. 1.008; p < 0.0001), and increase in 4.5-6.5mmol/L TIR (82.2 vs. 94.6%; p = 0.009), compared to the HGL diet. The glucose iAUC, MAX, range and SD improved during the 2 h post-prandial window of each LGL meal, and this effect was more pronounced later in the day. The current results validate the dietary strategy of incorporating innovative functional ingredients (ß-glucan, isomaltulose) and replacing Asian staples with alternative low GI carbohydrate sources to reduce daily glycemic load to improve glycemic control and variability as a viable alternative to the reduction in carbohydrate intake alone. These observations provide substantial public health support to encourage the consumption of staples of low GI/GL to reduce glucose levels and glycemic variability. Furthermore, there is growing evidence that the role of chrononutrition, as reported in this paper, requires further examination and should be considered as an important addition to the understanding of glucose homeostasis variation throughout the day.

Effects of Isomaltulose Ingestion on Thermoregulatory Responses during Exercise in a Hot Environment.

Isomaltulose is a low glycemic and insulinemic carbohydrate available as a constituent of sports drinks. However, it remains unclear whether thermoregulatory responses (sweating and cutaneous vasodilation) after isomaltulose drink ingestion differ from those of sucrose and water during exercise in a hot environment. Ten young healthy males consumed 10% sucrose, 10% isomaltulose, or water drinks. Thirty-five minutes after ingestion, they cycled for fifteen minutes at 75% peak oxygen uptake in a hot environment (30 °C, 40% relative humidity). Sucrose ingestion induced greater blood glucose concentration and insulin secretion at the pre-exercise state, compared with isomaltulose and/or water trials, with no differences during exercise in blood glucose. Change in plasma volume did not differ between the three trials throughout the experiment, but both sucrose and isomaltulose ingestions similarly increased plasma osmolality, as compared with water (main beverage effect, p = 0.040)-a key response that potentially delays the onset of heat loss responses. However, core temperature thresholds and slopes for heat loss responses were not different between the trials during exercise. These results suggest that ingestion of isomaltulose beverages induces low glycemic and insulinemic states before exercise but does not alter thermoregulatory responses during exercise in a hot environment, compared with sucrose or water.

Comparisons of isomaltulose, sucrose, and mixture of glucose and fructose ingestions on postexercise hydration state in young men.

PURPOSE: Isomaltulose is a low glycemic and insulinaemic carbohydrate available as a constituent in sports drink. However, it remains unclear whether postexercise rehydration achieved by isomaltulose drink ingestion alone differs as compared to other carbohydrates. METHODS: Thirteen young men performed intermittent exercise in the heat (35 °C and relative humidity 40%) to induce a state of hypohydration as defined by a 2% loss in body mass. Thereafter, participants were rehydrated by ingesting drinks equal to the volume of body mass loss with either a mixture of 3.25% glucose and 3.25% fructose, 6.5% sucrose (SUC), or 6.5% isomaltulose (ISO) within the first 30 min of a 3-h recovery. The change in plasma volume (ΔPV) from pre-exercise baseline, blood glucose, and plasma insulin concentration were assessed every 30-min. RESULTS: ΔPV was lower in ISO as compared to SUC until 90 min of the recovery (all P ≤ 0.038) with no difference thereafter (all P ≥ 0.391). The ΔPV were paralleled by concomitant changes in blood glucose levels that were greater in ISO as compared to other drinks after 90 min of the recovery (all P ≤ 0.035). Plasma insulin secretion, which potentially enhances renal sodium reabsorption and fluid retention, did not differ between the trials (interaction, P = 0.653). ISO induced a greater net fluid volume retention as compared to SUC (P = 0.010). CONCLUSION: We showed that rehydration with an isomaltulose drink following exercise-heat stress induces comparable recovery of PV and a greater net fluid retention as compared to other drinks, albeit this response is delayed. The delayed water transport along with glucose absorption may modulate this response. This trial was registered in 25th Sep 2019 at https://www.umin.ac.jp/ as UMIN000038099. (249/250).