Introduction

As sugar consumption contributes to the development of metabolic disease including obesity and type 2 diabetes, a reduction in daily sugar consumption has been proposed as preventive and therapeutic strategy by the World Health Organization [1]. Artificial low-caloric high-intensity sweetener, e.g. acesulfame potassium (ace-K), are often used to replace sugar as they provide sweetness without calories. However, they do not stimulate the secretion of gastrointestinal (GI) satiation hormones and thus lack a satiating effect. Xylitol, a natural low-caloric bulk sweetener, has gained popularity as sugar alternative by offering beneficial properties such as being low-glycemic and low-insulinemic while preserving sweet taste and stimulating the secretion of GI satiation hormones [2]. The effect of orally administered xylitol on subsequent energy intake is not yet known.

Aims & Methods

Therefore, the objective of this study was to investigate the effect of an oral administration of xylitol compared to sucrose, ace-K and tap water on total energy intake during an ad libitum test meal, the secretion of GI satiation hormones and glycemic control.
In this randomized, controlled, double-blind crossover trial, 20 healthy adults with normal weight [age: 27.45 ± 7.86 years, BMI: 23.04 ± 1.41 kg/m² (mean ± SD)] received oral preloads containing either 33.5 g xylitol, 33.5 g sucrose, 0.1675 g ace-K dissolved in 300 mL water or 300 mL pure water in four different study visits. Fifteen minutes later, participants were served an ad libitum test meal where they were allowed to consume as much as they want for 20 minutes. Total energy intake was assessed by calculating the calories of the preloads and weighing food and drinks before and after the test meal. Additionally, blood samples were collected at fixed time points to measure plasma cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), glucose and insulin concentrations.

Results

The results show that total energy intake was significantly lower after xylitol and ace-K compared to sucrose (p_Tukey = 0.03 and p_Tukey < 0.01, respectively), with no differences between xylitol and ace-K or water (p_Tukey= 0.93 and p_Tukey = 1.00, respectively). Plasma CCK concentrations increased significantly after xylitol and sucrose (for both, p_Tukey < 0.01), but not after water (p_Tukey= 0.35), with a significantly higher increase after xylitol compared to sucrose, ace-K or water (for all comparisons, p_Holm < 0.01). Plasma GLP-1 concentrations increased significantly after xylitol and sucrose (p_Tukey = 0.02 and p_Tukey = 0.03, respectively), but not after ace-K or water (p_Tukey = 0.19 and p_Tukey= 0.39, respectively), with no significant differences between xylitol and sucrose, ace-K or water (for all comparisons, p_Holm= 0.66). Plasma glucose concentrations increased significantly after sucrose (p_Tukey< 0.01), but not after xylitol, ace-K or water (for all, p_Tukey= 0.34, p_Tukey = 0.86 and p_Tukey = 0.75, respectively), with no significant differences between xylitol and ace-K or water (for both comparisons, p_Holm = 0.46). Plasma insulin concentrations increased significantly after sucrose (p_Tukey = 0.01), but not after xylitol, ace-K or water (p_Tukey = 0.08, p_Tukey = 0.89 and p_Tukey= 1.00, respectively), with no significant differences between xylitol and sucrose, ace-K or water (for all comparisons, p_Holm = 0.27).

Conclusion

An oral preload with xylitol prior to an ad libitum test meal induces the release of CCK and results in reduced total energy intake compared to an oral preload with sucrose.

References

1. World Health Organization. Guideline: Sugars intake for adults and children. 2015.
2. Wölnerhanssen, B.K., et al., Gut hormone secretion, gastric emptying, and glycemic responses to erythritol and xylitol in lean and obese subjects. Am J Physiol Endocrinol Metab, 2016. 310(11): p. E1053-61.

Introduction

Many prospective studies conducted in healthy volunteers have shown that diet is associated with the risk of developing IBD. By contrast, data are scarce on the role of diet in disease activity in patients with IBD. The aim of the present study was to find dietary factors associated with the risk of IBD relapses.

Aims & Methods

The “Mikinautes” e-cohort is a nationwide French prospective study recruiting IBD patients older than 6 years at inclusion and followed in private practice and public hospitals. French Crohn and Colitis Patients’ association was also involved in the design, funding and recruitment. Patients filled in online questionnaires about their dietary habits and health status. Validated food frequency questionnaires (FFQ) recorded average intakes of 230 food items over the past 12 months. Patients were followed for at least one year and medical records were prospectively collected. Relapse was defined by i) an increased disease activity reported monthly by the patients and/or a clinical report mentioning a relapse, together with ii) a documented consultation with a doctor and iii) a change in IBD therapy, either drug, enteral nutrition and/or surgery).
A posteriori dietary patterns (DPs) were identified using principal component analysis (PCA) performed on 31 food groups. Primary analysis was a Cox model among patients in remission at inclusion to reduce potential reverse causality. Secondary analyses included: i) a Cox model conducted among all patients, which measured the time between the onset of the last relapse before inclusion (or the ongoing relapse at inclusion) and the first relapse during follow-up and ii) a logistic model comparing inactive versus active patients (defined as patients who had at least one relapse at inclusion or over the first year of follow-up). Models were adjusted for age, sex, smoking status and energy intake.

Results

After exclusion of 14 patients with implausible dietary intakes, 693 patients were retained for analyses, comprising 66% of females, 59% Crohn Disease (CD) patients, 34% ulcerative colitis (UC) patients and 7% indeterminate colitis (IC). Median follow-up [Q1-Q3] was 2.1 years [1.6;2.7]. 77% of patients were in remission at inclusion. Their cumulative probability (95% CI) of flare were 18% [15%; 21%] at 1 year and 25% [22%; 29%] at 2 years. In total, 36% of patients had an active disease after one year of follow-up (including active patients at inclusion).
Four DPs were identified through PCA. In CD, primary Cox analysis revealed an association between the second DP and disease activity (HR 95% CI: 0.42 [0.22;0.80] for 3^rdvs 1^st tertile of consumption, p-trend=0.050). This DP was characterized by high intakes of vegetables, fruit, nuts, legumes, cereals, eggs and unsweetened beverages and by a low consumption of dairy products and desserts, bread, sweet/fat or salty/fat products. Secondary analyses confirmed this association (HR: 0.37 [0.18;0.78] for 3^rdvs 1^st tertile, p-trend=0.010; OR: 0.42 [0.22;0.80] for 3^rdvs 1^st tertile, p-trend=0.010). In UC, fruit consumption was protective toward relapse in primary (HR: 0.46 [0.26;0.82] for 3^rdvs 1^st tertile, p-trend=0.009) together with secondary analyses; no dietary pattern was associated with relapse.

Conclusion

A diet characterized by a high consumption of fruit, vegetables, legumes and nuts is associated with a reduction in the risk of relapse by half in patients with CD. High fruit consumption is associated with the same decreased risk of relapse in patients with UC. These results inform dietary counseling in IBD.

References

Acknowledgements: This study was funded by the French association AFA Crohn-RCH France. It was supported by the networks of the Pediatric GETAID, the GETAID, the CREGG, the ANGH and EPIMAD. We thank Nutrinet-Santé, IBD patients and their doctors who contributed to this study.

Disclosure

FC reports receiving research grants from Alpha Wassermann, MaaT pharma, Mayoly Spindler, Medtronic, Nestlé; receiving payment for lectures from AbbVie, AlphaSigma, Ferring, Janssen, Eli Lilly,
Nestlé Health Sciences, Pierre Fabre, Pileje, Takeda, Tillots, Viatris ; receiving consulting fees from AbbVie, Janssen, MaaT pharma, Tillots. HS, SA, CGR, AB, LD and JPH have nothing to declare.

Introduction

Obesity, characterised by excessive body fat accumulation, not only undermines physical health but also poses significant risks to mental well-being. Recent evidence has demonstrated the substantial benefits of Semaglutide in promoting weight loss among individuals with diabetes. Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, not only aids in glycaemic control but has also shown remarkable efficacy in reducing body weight. Therefore, in this study, we investigated the effect of oral Semaglutide on weight loss in individuals with overweight or obesity but without diabetes mellitus.

Aims & Methods

The aim of the study was to evaluate the effectiveness and safety of oral Semaglutide when combined with dietary and lifestyle modifications, compared to dietary and lifestyle modifications alone, for the treatment of overweight or obesity in adults without type 2 diabetes. This randomized controlled trial was conducted in the department of Gastroenterology, Asian Institute of Gastroenterology, Hyderabad from June 2022 to December 2023. Consecutive consenting patients of both genders aged 18 years or older with either a BMI of 30 or greater or a BMI of 27 or greater with one or more treated or untreated weight-related coexisting conditions (i.e., prediabetes, hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease). All the eligible participants after screening were randomized into two groups (Group 1 and 2) by block randomization (block size of 4 and 6) using computer generated random number. Participants in both groups received individual counselling sessions to help them adhere to a reduced-calorie diet (500- kcal deficit per day relative to the energy expenditure estimated at the time) and increased physical activity (with 150 minutes per week of physical activity, such as walking). Participants in group 1 also received oral Semaglutide along with diet and exercise. Treatment was initiated with the 3 mg once-daily dose. The dose was increased to 7 mg and then maximum of 14mg per day in 2-4 weeks interval based on patient tolerance. Participants were assessed for gastrointestinal complaints (nausea, vomiting) during escalation and follow-up. (ClinicalTrials.gov ID: NCT05442450)

Results

A total of 116 (58 per each group) individuals were recruited into the study. Mean percentage(SD) change in body weight from baseline to week 28 was - 10.47% (SD 5.3) with Oral Semaglutide versus 2.4 (SD 4.5) with dietary and lifestyle changes alone (p < 0.001). The mean weightloss noted with Semaglutide was 9.19kg (SD 4.7) compared to 2.3kg (SD 4.5) with dietary and lifestyle measures alone. Subjects who received oral Semaglutide have reported >5%, >10%, >15% and >20% weightloss in 51/58 (87%), 28/58 (48%), 13/58 (22.4%) and 4/58 (6.9%) respectively. Subjects received only dietary and lifestyle changes have lost >5% of baseline weight in 14/58 (24%), >10% in 6/58 (10.34%) and none lost more than 15% of baseline weight. Similarly, body mass index, waist circumference, HbA1C, fasting insulin and CRP were significantly improved with combination of Semaglutide with lifestyle measures. (p<0.001). Body composition analysis revealed a significant change in body fat mass of -7.3 kg (4.8%) with maintained muscle mass in patients who received oral Semaglutide compared to those who underwent diet alone. Adverse events include severe nausea and vomiting noted in the three patients receiving the oral Semaglutide requiring discontinuation of the drug.

Conclusion

In adults with overweight or obesity but without type 2 diabetes, oral Semaglutide combined with dietary and lifestyle modifications resulted in a significant and clinically meaningful reduction in body weight compared to dietary and lifestyle modifications alone.