Effects of Sucralose Supplementation on Glycemic Response, Appetite, and Gut Microbiota in Subjects with Overweight or Obesity: A Randomized Crossover Study Protocol.

Sucralose stands as the most common non-nutritive sweetener; however, its metabolic effects have sparked significant controversy over the years. We aim to examine the effects of sucralose daily intake on glycemia, subjective appetite, and gut microbiota (GM) changes in subjects with overweight or obesity. In this randomized, crossover, and controlled trial, 23 participants with a body mass index between 25 kg/m2 and 39.9 kg/m2 will be assigned to one of two interventions to receive either sucralose (2 mg/kg/day equivalent to 40% of the acceptable daily intake) or glucose (control) for 4 weeks, each phase separated by a 4-week washout period. The glycemic response will be determined during a meal tolerance test, subjective appetite will be evaluated using a visual analog scale, and GM changes will be analyzed by next-generation sequencing of the bacterial rRNA 16S gene from fecal samples. All measures will be performed before and after intervention periods. We hypothesize that sucralose supplementation induces changes in glycemic response, subjective appetite, and gut microbiota in overweight and obese participants. This protocol was approved by the Ethics Committee of the UJAT (No. 0721) and was registered in the Australian New Zealand Clinical Trials Registry (ACTRN12621001531808).

Effects of supplementation of live and heat-treated Bifidobacterium animalis subspecies lactis CECT 8145 on glycemic and insulinemic response, fecal microbiota, systemic biomarkers of inflammation, and white blood cell gene expression of adult dogs.

The popularity of functional ingredients such as probiotics and postbiotics has increased as pet owners seek ways to improve the health quality and longevity of their pets. Limited research has been conducted regarding the use of probiotics and postbiotics and their effects on canine health. The objective of this study was to evaluate the effects of daily supplementation of Bifidobacterium animalis subsp. lactis CECT 8145, in both live probiotic (PRO) and heat-treated postbiotic (POST) forms, on fecal fermentative end-products and microbiome, insulin sensitivity, serum gut hormones, oxidative stress, inflammatory biomarkers, and white blood cell gene expression of adult dogs. Eighteen adult beagles and 18 adult English pointers were used in a double-blinded placebo-controlled parallel group design, with 12 animals per group (6 English pointers and 6 beagles). The study began with a 60 d adaptation period followed by a 90 d period of daily supplementation with either PRO, POST, or placebo (maltodextrin; CON). Longitudinal assessment of body weight, body condition score, and pelvic circumference did not differ among dietary supplements (P > 0.05). Throughout the experimental period, fecal scores did not differ (P > 0.05); however, fecal pH was lower (P = 0.0049) in the dogs fed POST compared with CON. A higher fecal concentration of propionate (P = 0.043) was observed in dogs fed PRO and POST when compared with CON. While PRO and POST supplementation were associated with changes in bacterial composition at the family and genus level, the overall richness and diversity of the microbiome were not significantly affected. Functional analysis of the metagenome also suggests that PRO and POST supplementation induced potentially beneficial changes in the abundance of pathways involved in pathogenicity, amino acid biosynthesis, and DNA repair. No differences in glycemic or insulinemic responses were observed among the groups (P > 0.05). Dogs supplemented with PRO had a higher (P < 0.05) mean white blood cell leptin relative fold gene expression compared with groups POST and CON. Serum metabolites and complete blood cell counts were within normal ranges and all dogs remained healthy throughout the study. Together, these data suggest that the PRO and POST can safely be supplemented for dogs. Moreover, the results of this study support further investigation of the role of PRO and POST in supporting parameters related to gut health and hormonal regulation.

Probiotics, live microorganisms, postbiotics, metabolites of probiotics, or the components that result from probiotic activity, help to maintain a healthy gut environment and are beneficial for general health and well-being. Minimal research has been conducted on the effects of probiotics and postbiotics on canine health. This study evaluated the effects of daily supplementation of Bifidobacterium animalis subsp. lactis CECT 8145 strain, in both live probiotic (PRO) and heat-treated postbiotic (POST) forms. For this study, 36 adult dogs were split into 3 groups: control (CON), PRO, and POST (12 dogs per group). This study examined whether PRO and POST supplements were safe for dogs, improved gut health and energy homeostasis, induced changes in the gut microbiome, or boosted immune health. The results confirm that this strain is safe for dogs, and we also found evidence of positive changes to gut health, such as the increase in fecal propionate concentration after supplementation with both the PRO and POST. Propionate is an important component in overall gut health, with multiple known positive physiological effects. As such these results provide a starting point for future research into the role of Bifidobacterium animalis subsp. lactis CECT 8145 in canine health.

Anekomochi glutinous rice provides low postprandial glycemic response by enhanced insulin action via GLP-1 release and vagal afferents activation.

Glutinous rice (mochi rice), compared to non-glutinous rice (uruchi rice), exhibits a wide range of glycemic index (GI) values, from low to high. However, the underlying mechanisms behind the variation in GI values remain poorly understood. In this study, we aimed to identify rice cultivars with a low postprandial glycemic response and investigate the mechanisms, focusing on insulin and incretin hormones. We examined seven glutinous rice cultivars and three non-glutinous rice cultivars. We discovered that Anekomochi, a glutinous rice cultivar, has the lowest postprandial glycemic response. Anekomochi significantly enhanced glucagon-like peptide-1 (GLP-1) secretion while suppressing insulin secretion. These effects were completely blunted by inhibiting GLP-1 receptor signaling and denervating the common hepatic branch of vagal afferent nerves that are crucial for sensing intestinal GLP-1. Our findings demonstrate that Anekomochi markedly enhances insulin action via GLP-1 release and vagal afferent neural pathways, thereby leading to a lower postprandial glycemic response.

Manipulation of Post-Prandial Hyperglycaemia in Type 2 Diabetes: An Update for Practitioners.

This review paper explores post-prandial glycemia in type 2 diabetes. Post-prandial glycemia is defined as the period of blood glucose excursion from immediately after the ingestion of food or drink to 4 to 6 hours after the end of the meal. Post-prandial hyperglycemia is an independent risk factor for cardiovascular disease with glucose "excursions" being more strongly associated with markers of oxidative stress than the fasting or pre-prandial glucose level. High blood glucose is a major promoter of enhanced free radical production and is associated with the onset and progression of type 2 diabetes. Oxidative stress impairs insulin action creating a vicious cycle where repeated post-prandial glucose spikes are key drivers in the pathogenesis of the vascular complications of type 2 diabetes, both microvascular and macrovascular. Some authors suggest post-prandial hyperglycemia is the major cause of death in type 2 diabetes. Proper management of post-prandial hyperglycemia could yield up to a 35% cut in overall cardiovascular events, and a 64% cut in myocardial infarction. The benefits of managing post-prandial hyperglycemia are similar in magnitude to those seen in type 2 diabetes patients receiving secondary prevention with statins - prevention which today is regarded as fundamental by all practitioners. Given all the evidence surrounding the impact of post-prandial glycemia on overall outcome, it is imperative that any considered strategy for the management of type 2 diabetes should include optimum dietary, pharma, and lifestyle interventions that address glucose excursion. Achieving a low post-prandial glucose response is key to prevention and progression of type 2 diabetes and cardiometabolic diseases. Further, such therapeutic interventions should be sustainable and must benefit patients in the short and long term with the minimum of intrusion and side effects. This paper reviews the current literature around dietary manipulation of post-prandial hyperglycemia, including novel approaches. A great deal of further work is required to optimize and standardize the dietary management of post-prandial glycemia in type 2 diabetes, including consideration of novel approaches that show great promise.

Slowly hydrolyzable property of microbial dextrans at the small intestinal α-glucosidase levels leads to the modulated glycemic responses in the mouse model.

Dextran-type α-glucans have been known as non-digestible ingredients that can be considered prebiotics to promote colon health. However, recent studies have revealed that various α-linked glucosyl units are hydrolyzed to glucose by small intestinal α-glucosidases. This study analyzed the structural characteristics of exopolysaccharides (EPSs) from Weissella species, and the hydrolysis properties at both in vitro/in vivo levels were investigated. Compared with a previous in vitro digestion model using fungal α-hydrolytic enzymes, dextrans, which mainly consist of α-1,6 linkages with small amounts of α-1,3 linked glucose units, were slowly hydrolyzed to glucose by mammalian mucosal α-glucosidases, resulting in attenuation of the initial glycemic response following administration of EPS samples to mice via oral gavage. The results of this study demonstrate the concept of dextran-type α-glucans as glycemic carbohydrates rather than dietary fibers or prebiotics. Slowly digestible dextrans can be applied as a functional ingredient to regulate postprandial glucose delivery throughout the gastrointestinal tract.

Postprandial Blood Glucose and Insulin Response in Healthy Adults When Lentils Replace High-Glycemic Index Food Ingredients in Muffins, Chilies and Soups.

OBJECTIVES: This study aimed to assess postprandial blood glucose response (PBGR), relative glycemic response (RGR) and insulin response when 25 g available carbohydrates (AC) is replaced with cooked lentils in the formulation of muffins, chilies and soups. METHODS: In randomized, crossover studies, healthy adults consumed foods containing 25 g AC from green lentils, red lentils or a control (wheat muffin, n = 24; rice chili, n = 24; potato soup, n = 20). Blood collected at fasting and at 15, 30, 45, 60, 90 and 120 min was analyzed to derive the incremental area under the response curve (iAUC) for glucose, insulin, RGR and maximum concentration (CMAX). Treatment effects were assessed with repeated measures ANOVA. RESULTS: A replacement of 25 g AC with green lentils significantly decreased glucose iAUC compared to chili and soup (p < 0.0001), but not muffin (p = 0.07) controls, while also eliciting a significantly lower insulin iAUC for all three foods (muffin p = 0.03; chili p = 0.0002; soup p < 0.0001). Red lentil foods significantly decreased glucose iAUC (muffin p = 0.02; chili p < 0.0001; soup p < 0.0001) compared to controls, with a significantly lower insulin iAUC for chili and soup (p < 0.0001) but not muffins (p = 0.09). The RGR for muffins, chilies and soups was 88, 58 and 61%, respectively, for green lentils, and 84, 48 and 49%, respectively, for red lentils. CONCLUSIONS: PBGR, insulin and RGR are decreased when lentils are incorporated into food products, providing credible evidence to promote carbohydrate replacement with lentil-based foods.

In Vivo Glycemic Response of Fruit-Based Mango (Mangifera indica) and Pineapple (Ananas comosus) Bars in In Vitro and In Silico Enzyme Inhibitory Effects Studies.

The habitual consumption of snacks has the potential to enrich or harm the diet. They can contribute to excessive caloric intake and hyperglycemia. Thus, there is an increasing interest in snacks with health-promoting properties. This study aimed to demonstrate the beneficial effect of two fruit-based bars on glucose levels through in vitro, in vivo, and in silico assays. Mango (Mangifera indica L.) and pineapple (Ananas comosus L.) bars (MB and PB) were prepared, and chemical composition, postprandial glycemic response, glycemic index (GI), and glycemic load (GL) were evaluated. The inhibitory effect of fruit bar extracts on α-amylase and α-glucosidase activity and their respective molecular docking was assessed. MB and PB showed the lowest postprandial glycemic response vs. the control bar (p < 0.005), a lower GI (CB: 64.20, PB: 53.20, MB: 40.40), and a GL of 10.9 (CB), 7.9 (PB), and 6.1 (MB), (p < 0.05). MB and PB showed the highest inhibition % of α-amylase (61.44 and 59.37%, respectively) and α-glucosidase (64.97 and 64.57%). Naringenin (-1692.5985 and -2757.674 kcal/mol) and ferulic acid (-1692.8904 and -2760.3513 kcal/mol) exhibited more favorable interaction energies against α-amylase and α-glucosidase activity. The presence of polyphenols from the fruit influenced enzymatic inhibition. Likewise, the dietary fiber in the bars evaluated allowed us to observe a positive effect that favors glycemic control, making them a healthy alternative for snacking.

Impaired Carbohydrate Metabolism among Women with Chronic Low Back Pain and the Role of Dietary Carbohydrates: A Randomized Controlled Cross-Over Experiment.

Background: Impaired glucose regulation is suggested to be related to chronic low back pain (CLBP), although it is not clear how they interact with each other. Thus, the primary aim of this study was to investigate differences in postprandial glycemic responses (PPGRs) (the first sign of impaired glucose metabolism) to high- (sucrose) and low-glycemic index (GI) (isomaltulose) beverages in normoglycemic women with CLBP and healthy controls (HCs) and explore whether any group that showed greater PPGRs to high-GI beverage intake would benefit when the high-GI beverage was replaced with a low-GI beverage. Secondly, this study aimed to explore the association between PPGR and pain in patients with CLBP. Methods: This study was registered at clinicaltrials.org (NCT04459104) before the start of the study. In this study, 53 CLBP patients and 53 HCs were recruited. After 11-12 h of fasting, each participant randomly received isomaltulose or sucrose. Blood glucose levels were measured during the fasting state and 15, 30, 45, 60, 90, and 120 min after the beverage intake, and each participant underwent experimental pain measures. Results: Compared to the HCs, the CLBP group showed significantly higher PPGRs to sucrose (p < 0.021). Additionally, the CLBP group showed a significantly higher decrease in PPGR (p = 0.045) when comparing PPGR to sucrose with PPGR to isomaltulose. Correlation analysis revealed a positive association between self-reported pain sensitivity and PPGR to sucrose, while there was no association found between any experimental pain measures and glycemic responses. Conclusions: Overall, these findings suggest that normoglycemic CLBP patients might have a higher risk of developing impaired glucose tolerance than the HCs and might benefit more when high-GI foods are replaced with low-GI ones.

Determining the effects of Candida utilis-fermented pea starch vs. unfermented pea starch, alone or in whole diets, on palatability and glycemic response in dogs and cats.

Current research suggests yeast fermentation has the potential to improve palatability of pea-based diets for both cats and dogs. However, to be useful, fermentation should not compromise other healthy attributes of peas such as a low glycemic response. Fermentation of uncooked pea starch with Candida utilis (ATCC 9950) appeared to increase crude protein, crude fiber content, inorganic compounds (phosphorus and iron) and phenols. Whole diets were designed with fermented and unfermented pea starch to assess palatability, food intake, and glycemic responses in unacclimated, mixed sex Beagle dogs and mixed breed cats (n = 8 and n = 7, respectively). For palatability testing, a control diet was formulated with 30% corn starch as well as test diets with 30% inclusion of fermented or unfermented pea starch (all lab-made), then compared to a commercial diet containing pea starch (Legacy/Horizon). Fermentation had little effect on rapidly digestible starch either in uncooked starch form or when incorporated into whole diets, but did decrease resistant starch by 15% and increase slowly digestible starch by 20%. Palatability tests using either two choices or four choices at a time revealed a significant preference for the fermented pea starch diet (p < 0.01) in both species. For the glycemic responses, a total of four different pea products were included: unfermented pea starch, fermented pea starch, and 30% inclusion of unfermented and fermented pea starch in whole formulated diets. There were no significant changes in glycemic responses with the fermented pea diet compared to the unfermented diet, demonstrating that healthful low glycemic properties of pea starch were retained after C. utilis fermentation. Overall, C. utilis-fermentation technique was successfully adapted to pea starch where it resulted in increased palatability and food intake in dogs and cats, with potential to positively contribute to overall health benefits for both species.

The Synergistic Effect of Compound Sugar with Different Glycemic Indices Combined with Creatine on Exercise-Related Fatigue in Mice.

In this study, a compound sugar (CS) with different glycemic index sugars was formulated via hydrolysis characteristics and postprandial glycemic response, and the impact of CS and creatine emulsion on exercise-related fatigue in mice was investigated. Thirty-five C57BL/6 mice were randomly divided into five groups to supply different emulsions for 4 weeks: initial emulsion (Con), glucose emulsion (62 mg/10 g MW glucose; Glu), CS emulsion (62 mg/10 g MW compound sugar; CS), creatine emulsion (6 mg/10 g MW creatine; Cr), and CS and creatine emulsion (62 mg/10 g MW compound sugar, 6 mg/10 g MW creatine, CS-Cr). Then, the exhaustion time of weight-bearing swimming and forelimb grip strength were measured to evaluate the exercise capacity of mice, and some fatigue-related biochemical indexes of blood were determined. The results demonstrated that the ingestion of CS significantly reduced the peak of postprandial blood glucose levels and prolonged the energy supply of mice compared to ingesting an equal amount of glucose. Mouse exhaustion time was 1.22-fold longer in the CS group than in the glucose group. Additionally, the supplementation of CS increased the liver glycogen content and total antioxidant capacity of mice. Moreover, the combined supplementation of CS and creatine increased relative forelimb grip strength and decreased blood creatine kinase activity. The findings suggested that the intake of CS could enhance exercise capacity, and the combined supplementation of CS and creatine has a synergistic effect in improving performance.

α-Glucan-type exopolysaccharides with varied linkage patterns: Mitigating post-prandial glucose spike and prolonging the glycemic response.

Microbial exopolysaccharides (EPSs) are traditionally known as prebiotics that foster colon health by serving as microbiota nutrients, while remaining undigested in the small intestine. However, recent findings suggest that α-glucan structures in EPS, with their varied α-linkage types, can be hydrolyzed by mammalian α-glucosidases at differing rates. This study explores α-glucan-type EPSs, including dextran, alternan, and reuteran, assessing their digestive properties both in vitro and in vivo. Notably, while fungal amyloglucosidase - a common in vitro tool for carbohydrate digestibility analysis - shows limited efficacy in breaking down these structures, mammalian intestinal α-glucosidases can partially degrade them into glucose, albeit slowly. In vivo experiments with mice revealed that various EPSs elicited a significantly lower glycemic response (p < 0.05) than glucose, indicating their nature as carbohydrates that are digested slowly. This leads to the conclusion that different α-glucan-type EPSs may serve as ingredients that attenuate post-prandial glycemic responses. Furthermore, rather than serving as mere dietary fibers, they hold the potential for blood glucose regulation, offering new avenues for managing obesity, Type 2 diabetes, and other related-chronic diseases.

Glucagon-Like Peptide 1 (GLP-1) Receptor Variants and Glycemic Response to Liraglutide: A Pharmacogenetics Study in Iranian People with Type 2 Diabetes Mellitus.

INTRODUCTION: Pharmacogenetics studies suggest that genetic variants have a possible influence on the inter-individual differences in therapeutic response to glucagon-like peptide 1 receptor agonists (GLP-1 RAs). We aimed to examine the potential role of genetic variability of glucagon-like peptide 1 receptor (GLP-1R) on glycemic response to GLP-1 RAs in a population of Iranian people with type 2 diabetes mellitus (T2DM). METHODS: In this study, we analyzed the data from participants in a non-inferiority randomized clinical trial between 2019 and 2020. Patients received liraglutide 1.8 mg/day subcutaneously for 24 weeks. They were stratified by the baseline hemoglobin A1c (HbA1c) into four categories: 7-7.99, 8-8.99, 9-9.99, and ≥ 10%. In each category, subjects with HbA1c reduction greater than the median ΔHbA1c value for that group were defined as optimal responders. The pooled number of optimal/suboptimal responders in the four groups was used for the comparison. We evaluated two genetic variants of GLP-1R, rs6923761 and rs10305420, using Sanger sequencing. Logistic regression analyses were performed to examine the associations of the GLP-1R variants with the glycemic response in different genetic models. RESULTS: Out of 233 participants, 120 individuals were optimal responders. Median HbA1c reduction was - 2.5% in the optimal responder group compared with - 1.0% in the suboptimal responder group (P < 0.001). In genetic models, rs10305420 T allele homozygosity was associated with optimal glycemic response to liraglutide compared with heterozygous and wild-type homozygous states (recessive model: OR 3.28, 95% CI 1.41-7.65, P = 0.006; codominant model: OR 2.52, 95% CI 1.03-6.13, P = 0.04). No significant association was found between rs6923761 variant and HbA1c reduction. CONCLUSION: GLP-1R rs10305420 polymorphism can explain some of the inter-individual differences in glycemic response to liraglutide in a population of Iranian people with T2DM.

Effect of cinnamon spice on continuously monitored glycemic response in adults with prediabetes: a 4-week randomized controlled crossover trial.

BACKGROUND: Previous clinical studies showing that cinnamon spice lowers blood glucose concentrations had inconsistent results. OBJECTIVES: To determine the effect of daily cinnamon spice supplementation in an amount commonly used for seasoning on glucose concentrations in adults with obesity and prediabetes. METHODS: Following a 2-wk run-in period of maintaining a low polyphenol/fiber diet, 18 participants with obesity and prediabetes underwent a 10-wk randomized, controlled, double-blind, crossover trial (mean age 51.1 y; mean fasting plasma glucose 102.9 mg/dL). The participants were randomly assigned to take cinnamon (4 g/d) or placebo for 4-wk, followed by a 2-wk washout period, and then crossed over to the other intervention for an additional 4-wk. Glucose changes were measured with continuous glucose monitoring. Oral glucose tolerance testing immediately following ingestion of cinnamon or placebo was performed at 4-time points to assess their acute effects both at the baseline and end of each intervention phase. Digestive symptom logs were obtained daily. RESULTS: There were 694 follow-up days with 66,624 glucose observations. When compared with placebo, 24-h glucose concentrations were significantly lower when cinnamon was administered [mixed-models; effect size (ES) = 0.96; 95 % confidence interval (CI): -2.9, -1.5; P < 0.001]. Similarly, the mean net-area-under-the-curve (netAUC) for glucose was significantly lower than for placebo when cinnamon was given (over 24 h; ES = -0.66; 95 % CI: 2501.7, 5412.1, P = 0.01). Cinnamon supplementation resulted in lower glucose peaks compared with placebo (Δpeak 9.56 ± 9.1 mg/dL compared with 11.73 ± 8.0 mg/dL; ES = -0.57; 95 % CI: 0.8, 3.7, P = 0.027). Glucose-dependent-insulinotropic-polypeptide concentrations increased during oral glucose tolerance testing + cinnamon testing (mixed-models; ES = 0.51; 95 % CI: 1.56, 100.1, P = 0.04), whereas triglyceride concentrations decreased (mixed-models; ES = 0.55; 95 % CI: -16.0, -1.6, P = 0.02). Treatment adherence was excellent in both groups (cinnamon: 97.6 ± 3.4 % compared with placebo: 97.9 ± 3.7 %; ES = -0.15; 95 % CI: -1.8, 0.2, P = 0.5). No differences were found in digestive symptoms (abdominal pain, borborygmi, bloating, excess flatus, and stools/day) between cinnamon and placebo groups. CONCLUSIONS: Cinnamon, a widely available and low-cost supplement, may contribute to better glucose control when added to the diet in people who have obesity-related prediabetes. This trial was registered at clinicaltrials.gov as NCT04342624.

Effect of 100% Orange Juice and a Volume-Matched Sugar-Sweetened Drink on Subjective Appetite, Food Intake, and Glycemic Response in Adults.

Dietary recommendations to reduce the consumption of free sugars often group 100% fruit juice with other sugar-containing beverages. The objective of this study was to determine the effect of consuming 100% orange juice compared to an orange drink on next-meal food intake (FI), glycemic response, average appetite, emotions, and sensory characteristics in normal-weight adults. Thirty-six normal-weight adults (age: 26.8 ± 0.9 years) consumed, in random order and at least 5 days apart, three 240 mL test beverages as follows: (a) 100% orange juice, (b) orange drink, or (c) water. Subjective sweetness and pleasantness were determined immediately after test beverage consumption. Glycemic response, average appetite, and subjective emotions were measured every 15 min for 60 min. Food intake was determined at a pizza lunch 60 min later. Rest-of-day glycemic response and energy intake (EI) were determined using a continuous glucose monitor and food record, respectively. Lunch FI (p = 0.054) and total EI (p = 0.01) were both lower after 100% orange juice compared with the orange drink. Caloric compensation was 84% after 100% orange juice and -25% after the orange drink (p = 0.047). Average appetite was not significantly different between the test beverages (p > 0.05). Blood glucose iAUC adjusted for available carbohydrate was lower after 100% orange juice compared with the orange drink (p < 0.001). Rest-of-day blood glucose concentrations were lower after 100% orange juice compared with the orange drink (p = 0.03) and water control (p < 0.001). In conclusion, consumption of 100% orange juice as a preload resulted in higher caloric compensation, lower total daily EI, and lower blood glucose concentrations compared to the orange drink.

Gastrointestinal Tolerability and Acute Glycemic Response of Oligosaccharides and Polysaccharides from Cellulose and Xylan in Healthy Adults: Two Double-Blinded, Randomized, Controlled, Cross-over Trials.

OBJECTIVE: The aim of this study was to investigate the gastrointestinal tolerability, glycemic and insulinemic responses of Plant Fiber Extract (PFE), a mixture comprising of oligosaccharides and polysaccharides derived from cellulose and xylan. METHODS: Two double-blind, randomized, controlled, cross-over trials were conducted in healthy adults. In the first trial, participants (n = 29) consumed either 25, 35 or 45 g per day of PFE or resistant maltodextrin (Control) for 14 days. The occurrence and severity of gastrointestinal (GI) symptoms, stool parameters, and safety outcomes were evaluated with a combination of surveys and blood analysis respectively. In the second trial (n = 20), the post-prandial glycemic and insulinemic responses after the ingestion of 20 g of PFE diluted in water or incorporated into chocolate chips was measured and then compared to that of glucose and regular chocolate, respectively. RESULTS: For all timepoints (0, 7 and 14 days), within any given dose group, there was no statistically significant difference in the GI symptoms score between PFE and Control. Further, for each test product (PFE or Control), no difference was observed in the same dose group from days 0 and 14. Stool consistency score and number of participants experiencing loose or watery stools was similar between products. No serious adverse events were reported and neither PFE nor Control significantly altered blood or urine safety parameters. The glycemic and insulinemic responses after PFE ingestion in comparison to glucose were 12% and 8% respectively. The glycemic and insulinemic responses after consuming chocolate containing PFE were 20% of that of regular chocolate. CONCLUSION: PFE was well-tolerated by healthy volunteers in doses up to 45 g/day and it elicited comparatively low glycemic and insulinemic responses when consumed alone or when incorporated into a food product.

Complementary Nutritional Improvements of Cereal-Based Products to Reduce Postprandial Glycemic Response.

High glycemic response (GR) is part of cardiometabolic risk factors. Dietary polyphenols, starch digestibility, and dietary fibers could play a role in modulating GR. We formulated cereal products with high dietary fibers, polyphenols, and slowly digestible starch (SDS) contents to test their impact on the glycemic index (GI) and insulin index (II). Twelve healthy subjects were randomized in a crossover-controlled study to measure the GI and II of four biscuits according to ISO-26642(2010). Two types of biscuits were enriched with dietary fibers and polyphenols and high in SDS, and two similar control biscuits with low levels of these compounds were compared. The subjects consumed 50 g of available carbohydrates from the biscuits or from a glucose solution (reference). Glycemic and insulinemic responses were monitored for 2 h after the start of the consumption. The two enriched biscuits led to low GI and II (GI: 46 ± 5 SEM and 43 ± 4 SEM and II: 54 ± 5 SEM and 45 ± 3 SEM) when controls had moderate GI and II (GI: 57 ± 5 SEM and 58 ± 5 SEM and II: 61 ± 4 SEM and 61 ± 4 SEM). A significant difference of 11 and 15 units between the GI of enriched and control products was obtained. These differences may be explained by the polyphenol contents and high SDS levels in enriched products as well as potentially the dietary fiber content. This study provides new proposals of food formulations to induce beneficial health effects which need to be confirmed in a longer-term study in the context of the SINFONI consortium.

Starch-ascorbyl palmitate inclusion complex, a type 5 resistant starch, reduced in vitro digestibility and improved in vivo glycemic response in mice.

The prevalence of type 2 diabetes (T2D) has become a major public health concern worldwide. Slowly digested or indigestible carbohydrates such as resistant starch (RS) are associated with a low glycemic index (GI) and the decreased risk of developing T2D. Recently, starch inclusion complexes (ICs) have raised attention due to their thermally stable structure and high RS content. In this study, starch-ascorbyl palmitate (AP) ICs were produced using two different methods with hydrothermal treatments performed, and their in vitro digestion kinetics and in vivo glycemic response in C57BL/6J mice were investigated to determine their potential as a new type of RS, i.e., RS5. After treatments of annealing followed by acid hydrolysis (ANN-ACH), IC samples produced by both methods retained V-type crystalline structure. Either in their raw or treated conditions, V6h-AP ICs prepared using the "empty" V-type method exhibited a more favorable hydrolysis pattern as compared to its counterpart produced by the DMSO method in terms of a lower hydrolysis rate and equilibrium concentration (C∞) (p < 0.05). From the in vitro results, the ANN-ACH treated V6h-AP IC exhibited an estimated GI (eGI) value of 54.83, falling within the range of low GI foods and was the lowest among all tested samples (p < 0.05). Consistent with the in vitro digestion kinetics, the in vivo results showed that mice fed with ANN-ACH V6h-AP IC exhibited a modest glycemic response as evidenced by the lowest increase in postprandial blood glucose and AUC blood glucose (p < 0.05). In addition, the in vivo GI of the ANN-ACH V6h-AP IC (39.53) was the lowest among all the sample treatments and was even lower than that of the RS2 comparison (56, p < 0.05), indicating its more pronounced effect in modulating the postprandial glycemic response in mice and great potential as a new RS5.

Individual Postprandial Glycemic Responses to Meal Types by Different Carbohydrate Levels and Their Associations with Glycemic Variability Using Continuous Glucose Monitoring.

This study aimed to investigate individual postprandial glycemic responses (PPGRs) to meal types with varying carbohydrate levels and examine their associations with 14-day glycemic variability using continuous glucose monitoring (CGM) in young adults. In a two-week intervention study with 34 participants connected to CGM, four meal types and glucose 75 g were tested. PPGRs were recorded for up to 2 h with a 15 min interval after meals. Data-driven cluster analysis was used to group individual PPGRs for each meal type, and correlation analysis was performed of 14-day glycemic variability and control with related factors. Participants had a mean age of 22.5 years, with 22.8% being male. Four meal types were chosen according to carbohydrate levels. The mean glucose excursion for all meal types, except the fruit bowl, exhibited a similar curve with attenuation. Individuals classified as high responders for each meal type exhibited sustained peak glucose levels for a longer duration compared to low responders, especially in meals with carbohydrate contents above 50%. A meal with 45% carbohydrate content showed no correlation with either 14-day glycemic variability or control. Understanding the glycemic response to carbohydrate-rich meals and adopting a meal-based approach when planning diets are crucial to improving glycemic variability and control.

Association of Met420del Variant of Metformin Transporter Gene SLC22A1 with Metformin Treatment Response in Ethiopian Patients with Type 2 Diabetes.

Objective: This study aimed to evaluate whether the M420del variants of SLC22A1 (rs72552763) is associated with metformin treatment response in Ethiopian patients with type 2 diabetes mellitus (T2DM). Patients and Methods: A prospective observational cohort study was conducted on 86 patients with T2DM who had been receiving metformin monotherapy for <1 year. Patients showing ≥0.5% reduction in HbA1c levels from baseline within 3 months and remained low for at least another 3 months were defined as responders while those patients with <0.5% reduction in HbA1c levels and/or those whom started a new class of glucose-lowering drug(s) because of unsatisfactory reduction were defined as non-responders. In addition, good glycemic control was observed when HbA1c ≤7.0%, and the above values were regarded as poor. Genotyping of rs72552763 SNP was performed using TaqMan® Drug Metabolism Enzyme Genotyping Assay and its association with metformin response and glycemic control were assessed by measuring the change in HbA1c and fasting blood glucose levels using Chi-square, logistic regression and Mann-Whitney U-test. Statistical significance was set at p <0.05. Results: The minor allele frequency of the rs72552763 SNP of SLC22A1 was 9.3%. Metformin response was significantly higher in deletion_GAT (del_G) genotypes as compared to the wild-type GAT_GAT (G_G) genotypes. Furthermore, a significantly lower median treatment HbA1 level was found in del_G genotypes as compared to G_G genotypes. However, the association of rs72552763 with metformin response was not replicated at the allele level. In contrast, the minor del_allele was significantly associated with good glycemic control compared to the G_allele, though not replicated at del_G genotypes level. Conclusion: This study demonstrated that metformin response was significantly higher in study participants with a heterozygous carrier of M420del variants of SLC22A1 as compared to the wild-type G_G genotypes after 3 months of treatment.

Structural changes of thermally treated starch during digestion and the impact on postprandial glucose homeostasis.

Intake of foods upon thermal treatment is typically associated with an elevated postprandial glycemic response, which is one of the risk factors for type 2 diabetes development and progression. In this study, rice starch was thermally treated using aqueous phase (boil), air phase (bake), and lipid phase (fry). Peak blood glucose levels in C57 mice increased by 16.94 %, 12.60 %, and 8.1 % after ingestion of thermally treated starch (20.23, 19.48, and 18.70 mmol/L), compared with raw starch (17.30 mmol/L). The insulin response to the intake of thermally treated starch increased (4.73 %-6.83 % higher than the control), whereas the concentration of GLP-1, a hormone used to promote insulin secretion, decreased (1.54 %-8.56 % lower than the control). Furthermore, thermally treated starch accelerated food absorption by enhancing gastrointestinal digestion, exacerbating postprandial glucose fluctuation at the next meal. Structural characterization showed thermal treatment reduced starch branching density and degree of structure order, which were not conducive to preventing the attack of enzymes. During digestion, they were highly hydrolyzed into low-molecular-weight fragments, and the proportion of ultrashort chains substantially increased. These findings provide a better understanding of the fine structure of starch that promotes hypoglycemia and initially explain how diets high in thermally treated starch impair glucose balance.