Laxative Properties of Microencapsulated Oleic Acid Delivered to the Distal Small Intestine in Patients with Constipation after Bariatric Surgery or Treatment with Glucagon-Like- Peptide 1 Analogues

Background: Constipation is prevalent after bariatric surgery and glucagon-like-peptide 1 (GLP-1) analogues. Increasing fat content in the distal small intestine and colon can enhance colonic peristalsis, potentially alleviating symptoms of constipation. Aim: We investigated whether oleic acid can ameliorate constipation in patients undergoing bariatric surgery or receiving GLP-1 analogues. Methodology: Fourteen adults with chronic constipation according to Rome IV criteria following bariatric surgery or GLP-1 analogues were on stable treatment for constipation for more than 4 weeks. This randomized double-blind crossover trial compared microcapsules containing 21.25 g of oleic acid delivered in the distal small intestine or the stomach. The primary outcome was changed in the number of bowel motions over 24 h. Exploratory endpoints included alterations in straining, diarrhoea, faecal leakage over 24 h and hunger, fullness, nausea and calorie intake for the 3 h after ingesting the microcapsules. Findings: Receiving oleic acid into the distal small intestine increased number of bowel movements per day (2.5 vs 1.1, p = 0.009) and caused softer stool consistency (p = 0.03). 9/14 of the control group passed motions and 13/14 of the intervention group passed motions in 24 h (p = 0.059). No significant differences were observed in straining (p = 0.65), rapid bowel movements (p = 0.08), accidental leakage (p = 0.32), hunger, fullness, nausea or food intake between the groups (all p &gt; 0.05). There were no disparities in safety profile between groups. Conclusion: Microcapsules containing oleic acid delivered to the distal small intestine appear to be a safe and effective relief from chronic constipation in patients undergoing bariatric surgery and/or receiving GLP-1 analogues. Graphical Abstract: (Figure presented.)</p

Changes in food preferences and ingestive behaviors after glucagon-like peptide-1 analog treatment: techniques and opportunities

Glucagon-like peptide-1 (GLP-1) analogs are approved for the treatment of obesity in adults and adolescents. Reports have emerged that the weight loss effect of these medications may be related to changes in food preferences and ingestive behaviors following the treatment. Understanding the mechanisms which impact ingestive behavior could expand opportunities to develop more refined and personalized treatment options for obesity. Recent studies investigating the relationship between GLP-1 analogs and ingestive behaviors were retrieved from PubMed using the search terms: "obesity," "food preference," "taste," "ingestive behavior," "weight loss medication," "anti-obesity medication," "GLP-1 analog," "tirzepatide," "liraglutide," "semaglutide." Measurement tools were studied to compare variables used to assess food intake behavior. The main outcomes from each study were analyzed to evaluate the current standing and future directions of appetitive, ingestive, and consummatory behaviors and their association with GLP-1 analogs. Thus far, studies have primarily explored the weight loss phase and report decreased short-term appetite and food intake upon treatment. However, research during the weight maintenance phase and objective measurements of food intake are notably sparse. Additionally, verbal reports have been primarily used to examine food intake, which can be susceptible to subjectivity. Elucidating the relationship between GLP-1 analogs and ingestive behavior could reveal additional parameters which contribute to their anti-obesity effects. To better understand these mechanisms, it is imperative to consider objective measurements of food intake in future studies. Several measurement tools have been adapted to measure variables of food behavior in humans, and each must be carefully considered with their strengths and limitations to develop optimal investigations. [Abstract copyright: © 2024. The Author(s).

Liver fibrosis and liver stiffness in patients with obesity and type 1 diabetes

Aim: To compare hepatic stiffness and fat fraction in patients with obesity and type 1 diabetes (T1D) with type 2 diabetes (T2D) with a similar body mass index (BMI). Methods: In this prospective cross‐sectional study, 90 participants with T1D (BMI 30.5 ± 4.5 kg/m2; diabetes duration 20.5 ± 9.8 years; HbA1c 8.2% ± 1.4%) and 69 with T2D (BMI: 30.8 ± 4.6 kg/m2; diabetes duration: 11.7 ± 7.8 years; HbA1c: 7.3% ± 1.4%) were included. Liver fat fraction and stiffness were examined by magnetic resonance imaging and elastography, respectively. Logistic regressions were used to evaluate associations with biomedical variables. Results: The mean liver stiffness score in patients with obesity and T1D was 2.2 ± 0.5 kPa, while in T2D it was 2.6 ± 0.8 kPa (P &lt; .001). The liver fat fraction in patients with obesity and T1D was 3.7% ± 6.3%, and in T2D it was 10.6% ± 7.9% (P &lt; .001). Metabolic dysfunction‐associated steatotic liver disease (MASLD) was present in 13.3% of patients with T1D and in 69.6% of patients with T2D, whereas fibrosis was suggested in 7.8% of patients with T1D and in 27.5% of patients with T2D. Liver stiffness was four times higher in patients with T2D compared with those with T1D (odds ratio = 5.4, 95% confidence interval: 2.1‐13.6, P &lt; .001). Aspartate transaminase (AST), alanine transaminase, gamma‐glutamyl transferase (GGT), triglycerides and the android‐to‐gynoid ratio were associated with elevated fat fraction in both cohorts. AST and GGT were associated with elevated liver stiffness in both cohorts. Conclusions: Patients with obesity and T1D had lower liver fat and liver stiffness compared with those patients with T2D, despite similar levels of BMI, a longer duration of diabetes and worse glycaemic control

Obesity Treatments to Improve Type 1 Diabetes (OTID): a randomized controlled trial of the combination of glucagon-like peptide 1 analogues and sodium-glucose cotransporter 2 inhibitors—protocol for Obesity Treatments to Improve Type 1 Diabetes (the OTID trial)

Background: The guidelines of the American Diabetes Association and European Association for the Study of Diabetes suggest that patients with obesity type 2 diabetics and chronic kidney disease need either glucagon-like peptide 1 receptor analogues or sodium-glucose cotransporter-2 inhibitors. If neither achieve metabolic control, then the recommendation is to combine both drugs. The evidence base for combining glucagon-like peptide 1 receptor analogues and sodium-glucose cotransporter-2 inhibitors is not well researched, and hence, the impact of the guidelines is limited. The aim of this randomized controlled trial is to test the impact of the combination of glucagon-like peptide 1 receptor analogues/sodium-glucose cotransporter-2 inhibitors on body weight and kidney damage, in patients with type 1 diabetes and chronic kidney disease. In addition, we will explore the associated changes in the metabolic pathways with each of the treatments used in this randomized controlled trial. Methods: In this 6-month randomized control trial, 60 participants aged between 21 and 65 years, with a body mass index above 25 kg/m2, and type 1 diabetics with chronic kidney disease will be randomized to receive 1 of 5 possible treatments: (1) standard care (control), (2) glucagon-like peptide 1 receptor analogues alone, (3) sodium-glucose cotransporter-2 inhibitors alone, (4) combination of glucagon-like peptide 1 receptor analogues and sodium-glucose cotransporter-2 inhibitors and (5) combination of glucagonlike peptide 1 receptor analogues and sodium-glucose cotransporter-2 inhibitors with intensive lifestyle advice. The primary objective will be the percentage change in total body weight from baseline at 6 months. The secondary objectives are to compare the change in glycaemia; blood pressure; dyslipidaemia; albuminuria; proportion of participants reaching weight loss of ≥ 5%, ≥ 10% and ≥ 15%; and change in BMI (kg/m2) from baseline and change in waist circumference (cm). All the experiments will be conducted at the Dasman Diabetes Institute after approval from the local research and ethics committee. Discussion: The present randomized controlled trial aims to investigate the impact of the combination of glucagon-like peptide 1 receptor analogues and sodium-glucose cotransporter-2 inhibitors on body weight and kidney damage in patients with type 1 diabetes mellitus and chronic kidney disease, as well as exploring the associated changes in the metabolic pathways with each of the treatments used. This study addresses the current gap in the evidence base regarding the combination of these two drugs, which is particularly relevant given the American Diabetes Association and European Association for the Study of Diabetes guidelines recommending their combined use for patients with obesity, type 2 diabetes, and chronic kidney disease who do not achieve metabolic control with either drug alone. Trial registration: ClinicalTrials.gov Identifier: NCT05390307 Trial registration date - 25th May 202

A Comparison of Total Food Intake at a Personalised Buffet in People with Obesity, before and 24 Months after Roux-en-Y-Gastric Bypass Surgery

Long-term reductions in the quantity of food consumed, and a shift in intake away from energy dense foods have both been implicated in the potent bariatric effects of Roux-en-Y gastric bypass (RYGB) surgery. We hypothesised that relative to pre-operative assessment, a stereotypical shift to lower intake would be observed at a personalised ad libitum buffet meal 24 months after RYGB, driven in part by decreased selection of high energy density items. At pre-operative baseline, participants (n = 14) rated their preference for 72 individual food items, each of these mapping to one of six categories encompassing high and low-fat choices in combination with sugar, complex carbohydrate or and protein. An 18-item buffet meal was created for each participant based on expressed preferences. Overall energy intake was reduced on average by 60% at the 24-month buffet meal. Reductions in intake were seen across all six food categories. Decreases in the overall intake of all individual macronutrient groups were marked and were generally proportional to reductions in total caloric intake. Patterns of preference and intake, both at baseline and at follow-up appear more idiosyncratic than has been previously suggested by verbal reporting. The data emphasise the consistency with which reductions in ad libitum food intake occur as a sequel of RYGB, this being maintained in the setting of a self-selected ad libitum buffet meal. Exploratory analysis of the data also supports prior reports of a possible relative increase in the proportional intake of protein after RYGB

Complete larval development of the hermit crabs Clibanarius aequabilis and Clibanarius erythropus (Decapoda : Anomura : Diogenidae), under laboratory conditions, with a revision of the larval features of genus Clibanarius

The complete larval development (four zoeae and one megalopa) of Clibanarius aequabilis and C. erythropus, reared under laboratory conditions, is described and illustrated. The larval stages of the two northeastern Atlantic Clibanarius species cannot be easily differentiated. Their morphological characters are compared with those of other known Clibanarius larvae. The genus Clibanarius is very homogeneous with respect to larval characters. All Clibanarius zoeae display a broad and blunt rostrum, smooth abdominal segments and an antennal scale without a terminal spine. Beyond the second zoeal stage, the fourth telson process is present as a fused spine, and the uropods are biramous. In the fourth larval stage all species display a mandibular palp. The Clibanarius megalopa presents weakly developed or no ocular scales, symmetrical chelipeds, apically curved corneous dactylus in the second and third pereiopods, and 5-11 setae on the posterior margin of the telson. Apart from the number of zoeal stages, Clibanarius species may be separated, beyond the second zoeal stage, by the telson formula and the morphology of the fourth telson process.info:eu-repo/semantics/publishedVersio

Desalinated and blended water in Saudi Arabia: human exposure and risk analysis from disinfection byproducts

Saudi Arabia produces the largest amount of desalinated water as a single country. The desalinated water is typically blended with treated groundwater, pH adjusted and chlorinated prior to supply to the communities. The desalinated seawater and/or blended water contains various types of disinfection byproducts (DBPs), some of which may induce cancer risks to human through lifetime exposure. In this study, occurrences of trihalomethanes (THMs) in desalinated and blended water in Saudi Arabia were investigated and their exposure and risks were predicted. The chronic daily intakes of CHCl3, BDCM, DBCM and CHBr3 were estimated to be 8.38×10−5, 7.57×10−5, 2.54×10−5 and 4.32×10−4 mg/kg-day respectively. The overall cancer risk was 1.78×10−5 with the range of 7.40×10−7 – 9.26×10−5 and the average hazard index was 3.49×10−2 with the range of 1.20×10−3 – 2.34×10−1. The loss of disability adjusted life years (DALY) were estimated to be 25.1 per year and the average cancer risk had 8.48×10−7 DALY per person per year. The financial burden was estimated to be US$2.72 million with the range of US$2.52–2.91 million. The findings may assist in better understanding and reducing cancer risks from DBPs in desalinated and blended water

Does Bypass of the Proximal Small Intestine Impact Food Intake, Preference, and Taste Function in Humans? An Experimental Medicine Study Using the Duodenal-Jejunal Bypass Liner

The duodenal-jejunal bypass liner (Endobarrier) is an endoscopic treatment for obesity and type 2 diabetes mellitus (T2DM). It creates exclusion of the proximal small intestine similar to that after Roux-en-Y Gastric Bypass (RYGB) surgery. The objective of this study was to employ a reductionist approach to determine whether bypass of the proximal intestine is the component conferring the effects of RYGB on food intake and sweet taste preference using the Endobarrier as a research tool. A nested mechanistic study within a large randomised controlled trial compared the impact of lifestyle modification with vs. without Endobarrier insertion in patients with obesity and T2DM. Forty-seven participants were randomised and assessed at several timepoints using direct and indirect assessments of food intake, food preference and taste function. Patients within the Endobarrier group lost numerically more weight compared to the control group. Using food diaries, our results demonstrated similar reductions of food intake in both groups. There were no significant differences in food preference and sensory, appetitive reward, or consummatory reward domain of sweet taste function between groups or changes within groups. In conclusion, the superior weight loss seen in patients with obesity and T2DM who underwent the Endobarrier insertion was not due to a reduction in energy intake or change in food preferences