Effects of a 3-Week Hospital-Controlled Very-Low-Calorie Diet in Severely Obese Patients

Although a very-low-calorie diet (VLCD) is considered safe and has demonstrated benefits among other types of diets, data are scarce concerning its effects on improving health and weight loss in severely obese patients. As part of the personalized weight loss program developed at the Duga Resa Special Hospital for Extended Treatment, Croatia, we evaluated anthropometric, biochemical, and permanent DNA damage parameters (assessed with the cytochalasin B-blocked micronucleus cytome assay—CBMN) in severely obese patients (BMI ≥ 35 kg m−2) after 3-weeks on a 567 kcal, hospital-controlled VLCD. This is the first study on the permanent genomic (in)stability in such VLCD patients. VLCDs caused significant decreases in weight (loss), parameters of the lipid profile, urea, insulin resistance, and reduced glutathione (GSH). Genomic instability parameters were lowered by half, reaching reference values usually found in the healthy population. A correlation was found between GSH decrease and reduced DNA damage. VLCDs revealed susceptible individuals with remaining higher DNA damage for further monitoring. In a highly heterogeneous group (class II and III in obesity, differences in weight, BMI, and other categories) consisting of 26 obese patients, the approach demonstrated its usefulness and benefits in health improvement, enabling an individual approach to further monitoring, diagnosis, treatment, and risk assessment based on changing anthropometric/biochemical VLCD parameters, and CBMN results.

Very low-calorie diet in patients with longstanding type 2 diabetes mellitus: a study of real-world outcomes

Introduction: There is a paucity of evidence regarding the efficacy of a very low-calorie diet (VLCD) in the real-world setting. We evaluated outcomes in patients with type 2 diabetes mellitus (T2DM) who underwent VLCD. Methods: This retrospective observational study included all patients who had undergone VLCD from 2014 to 2017 (n=61). The VLCD consisted of an eight-week 800 kcal/day dietary restriction. Metabolic parameters and medications were recorded at baseline, immediately post-VLCD and at 6 and 12 months. Results: There was a significant reduction in weight of 9.96 kg (p<0.001) immediately post-VLCD, with net weight loss sustained to 12 months (p<0.05). There was a significant reduction in body mass index (BMI) sustained to 12 months (p<0.05). Paired HbA1c data were available for 38 patients. There was a significant reduction in HbA1c of 13.29 mmol/mol immediately post-VLCD (p<0.001), however no significant reduction was observed at 12 months (p>0.05). 78.7% patients had a reduction in T2DM medication burden post-VLCD, sustained in 44.3% of patients at 12 months. Analysis of patients with T2DM diagnosis duration >6 years demonstrated statistically significant weight loss sustained to 12 months (p<0.001). Conclusion: Our results demonstrate sustained reduction in BMI and weight, reduction in medication burden and temporary reduction in HbA1c in patients with T2DM undertaking a VLCD in the real-world setting

The impact of obesity and bariatric surgery on the immune microenvironment of the endometrium

Background The incidence of endometrial cancer is rising in parallel with the obesity epidemic. Obesity increases endometrial cancer risk and weight loss is protective, but the underlying mechanisms are incompletely understood. We hypothesise that the immune microenvironment may influence susceptibility to malignant transformation in the endometrium. The aim of this study was to measure the impact of obesity and weight loss on the immunological landscape of the endometrium. Methods We conducted a prospective cohort study of women with class III obesity (body mass index, BMI ≥ 40 kg/m2) undergoing bariatric surgery or medically-supervised low-calorie diet. We collected blood and endometrial samples at baseline, and two and 12 months after weight loss intervention. Serum was analysed for inflammatory markers CRP, IL-6 and TNF-α. Multiplex immunofluorescence was used to simultaneously identify cells positive for immune markers CD68, CD56, CD3, CD8, FOXP3 and PD-1 in formalin-fixed paraffin-embedded endometrial tissue sections. Kruskal–Wallis tests were used to determine whether changes in inflammatory and immune biomarkers were associated with weight loss. Results Forty-three women with matched serum and tissue samples at all three time points were included in the analysis. Their median age and BMI were 44 years and 52 kg/m2, respectively. Weight loss at 12 months was greater in women who received bariatric surgery (n = 37, median 63.3 kg) than low-calorie diet (n = 6, median 12.8 kg). There were significant reductions in serum CRP (p = 3.62 × 10−6, r = 0.570) and IL-6 (p = 0.0003, r = 0.459), but not TNF-α levels, with weight loss. Tissue immune cell densities were unchanged except for CD8+ cells, which increased significantly with weight loss (p = 0.0097, r = −0.323). Tissue CD3+ cell density correlated negatively with systemic IL-6 levels (p = 0.0376; r = −0.318). Conclusion Weight loss is associated with reduced systemic inflammation and a recruitment of protective immune cell types to the endometrium, supporting the concept that immune surveillance may play a role in endometrial cancer prevention.

P-BN03 A systematic review of pre-operative low-calorie diets for laparoscopic cholecystectomy

Background Laparoscopic cholecystectomy is the fourth most common procedure in the UK. Increased liver adiposity, commonly encountered in obesity, anecdotally may increase technical difficulty and surgical risk. Pre-operative low-calorie diets are well-established in bariatric surgery to reduce liver bulk, thereby ameliorating difficulty and risk. Similar diets are often used before laparoscopic cholecystectomy, however, the supporting evidence base is unclear; we performed the first systematic review on their use in this context. Methods PubMed, Embase and Cochrane Central Register of Controlled Trials databases were searched in February 2021. We included English language clinical studies describing pre-operative low-calorie diet for laparoscopic cholecystectomy. Data were extracted for specifics of / adherence to diet, weight change, operative time / difficulty, complications and length of stay. Study quality was qualified using Scottish Intercollegiate Guidelines Network criteria and Jadad score. Results One randomised controlled trial (RCT) and one prospective observational study were identified. Both utilised a pre-operative very low-calorie diet of &lt; 800 kcal/day. Overall weight loss was greater in patients deemed compliant with the intervention. Both demonstrated tendency towards reduced operative difficulty with the intervention. Only the RCT found improvement in operative time. Conclusions Pre-operative very low-calorie diets (&lt; 800 kcal/day for two weeks) may aid weight loss and reduce operative difficulty in laparoscopic cholecystectomy, although evidence supporting their continued use is limited. Further RCTs are warranted to fully evaluate their role in clinical and cost-effectiveness.

A calorie-restricted diet enriched with tree nuts and peanuts reduces the expression of CX3CR1 in peripheral blood mononuclear cells in patients with coronary artery disease

Background: The modification of the gut microbiome has been proposed to alter immune response which is a key driver in low-grade inflammation as well as metabolic markers. This study was conducted to determine the effects of a low-calorie diet with and without nuts on some gut bacterial abundance, metabolic markers, and gene expression in peripheral blood mononuclear cells (PBMCs) in stable coronary artery disease patients with overweight or obesity. Methods: Overweight or obese patients with stable coronary artery disease of both genders were randomly allocated to a nut-free calorie-restricted diet as 25% of energy deficit (CRD) or a CRD enriched with 39–60 gr/d of mixed nuts (CRDEN) for 8 weeks (32 patients in CRD and 35 patients in CRDEN). Mixed nuts consisted of equal amounts of unsalted pistachios, almonds, and peanuts. Microbiota analysis was performed by quantitative real-time polymerase chain reaction method on feces collected before and after the intervention, using primers targeting 16S ribosomal DNA of 4 different bacterial genera, including Bacteroides, Prevotella, Bifidobacterium, and Lactobacillus. We examined the plasma concentrations of glucose, insulin, adiponectin as well as expression of toll-like receptor-4 (TLR4) and fractalkine receptor (CX3CR1) in PBMCs. Results: A significant reduction in expression of CX3CR1 (p=0.04) and a tendency to lower expression of TLR4 in PBMCs (p=0.06) was observed in the CRDEN group at the end of the study compared to the CRD group. The abundance of fecal Prevotella also tended to increase in CRDEN compared to the CRD group (p=0.06). Plasma insulin and adiponectin had no significant changes. There was a positive correlation between fecal Prevotella abundance and plasma adiponectin at baseline (r=0.315, p=0.015) and the end of the study (r=0.380, p=0.003). Conclusion: Our results suggest that the inclusion of mixed tree nuts and peanuts in a low-calorie diet for 8 weeks led to a lower CX3CR expression in PBMCs in a cohort of overweight or obese patients with stable CAD. This finding provides another beneficial effect of diet supplemented with nuts on factors associated with inflammation. Trial registration: this clinical study has been registered at the clinical trial registration center (clinicaltrial.gov): NCT04078919 on September 6, 2019.

Abstract 13393: Liraglutide Improves Myocardial Redox State in Humans by Regulating the Adipose Tissue-Derived Long-Chain Ceramides

Introduction: A notable reduction in major adverse cardiovascular events and cardiovascular mortality was observed in several cardiovascular studies via treatment with liraglutide, which have been suggested to be mediated through several mechanisms including inhibition of oxidative stress. Hypothesis: We hypothesised that treatment with liraglutide reduces oxidative stress via modulating circulating levels of long-chain ceramides. Methods: We measured vascular superoxide production using lucigenin-enhanced chemiluminescence and levels of circulating ceramides using LC-MS/MS in 633 participants of the Oxford Heart Vessels and Fat (OxHVF) cohort. We also measured 33 sphingolipid species (SPL) in plasma from 32 obese individuals (average BMI 33.5±2.5kg/m 2 at inclusion) participating in a randomized clinical trial (RCT) of low calorie diet and liraglutide. Results: We found a significant association between superoxide production by internal mammary arteries (IMA) and circulating levels of long-chain ceramides (C16:0, C17:0, C18:0, C18:1) (A-D) . In the RCT, all participants adhered to an 8-week low-calorie diet (800 kcal/day) (E) , during which they lost 9.9±6.0 kg of body weight exhibiting a significant reduction in BMI ( p <0.0001), which was paralleled by significant effects on the circulating levels of SPL (F) . Following this initial phase, the patients were randomised to liraglutide treatment (1.2 mg daily) or no treatment, for a period of 52 weeks. Liraglutide treatment differentially affected several SPL species compared to the control group despite no significant changes in BMI in any of the two groups (G-J) . Conclusions: In this study, we observed for the first time in human a regulatory effect of liraglutide on the circulating levels of long-chain ceramides that are shown to be associated with vascular oxidative stress suggesting a promising mechanistic link that justifies further exploration.

Elective Surgery in Adult Patients with Excess Weight: Can Preoperative Dietary Interventions Improve Surgical Outcomes? A Systematic Review

This systematic review summarises the literature regarding the impact of preoperative dietary interventions on non-bariatric surgery outcomes for patients with excess weight/obesity, a known risk factor for poor surgical outcomes. Four electronic databases were searched for non-bariatric surgery studies that evaluated the surgical outcomes of a preoperative diet that focused on weight/fat loss or improvement of liver steatosis. Meta-analysis was unfeasible due to the extreme heterogeneity of variables. Fourteen studies, including five randomised controlled trials, were selected. Laparoscopic cholecystectomy, hernia repair, and liver resection were most studied. Diet-induced weight loss ranged from 1.4 kg to 25 kg. Preoperative very low calorie diet (≤800 kcal) or low calorie diet (≤900 kcal) for one to three weeks resulted in: reduction in blood loss for two liver resection and one gastrectomy study (−27 to −411 mL, p < 0.05), and for laparoscopic cholecystectomy, reduction of six minutes in operating time (p < 0.05) and reduced difficulty of aspects of procedure (p < 0.05). There was no difference in length of stay (n = 7 studies). Preoperative ≤ 900 kcal diets for one to three weeks could improve surgical outcomes for laparoscopic cholecystectomy, liver resection, and gastrectomy. Multiple randomised controlled trials with common surgical outcomes are required to establish impact on other surgeries.