Impact of exenatide on weight loss and eating behavior in adults with craniopharyngioma-related obesity: the CRANIOEXE randomized placebo-controlled trial.

IMPORTANCE: A major issue in the management of craniopharyngioma-related obesity (CRO) is the ineffectiveness of the current therapeutic approaches. OBJECTIVE: To study the efficacy of glucagon-like peptide-1 analogs compared with placebo in adults with obesity CRO. DESIGN: A double-blind multicenter superiority randomized clinical in trial in two parallel arms. SETTING: Eleven French University Hospital Centers. PARTICIPANTS: Adults with CRO (body mass index > 30 kg/m²) without the sign of recurrence of craniopharyngioma in the past year. INTERVENTIONS: Exenatide or placebo injected subcutaneously twice a day during 26 weeks. MAIN OUTCOMES AND MEASURES: The primary outcome was the mean change in body weight at week 26 in the intention-to-treat population. Secondary outcomes were eating behavior, calories intake, energy expenditure, cardiovascular, metabolic risk factor, quality of life, and the tolerance profile. RESULTS: At week 26, weight decreased from baseline by a mean of -3.8 (SD 4.3) kg for exenatide and -1.6 (3.8) kg for placebo. The adjusted mean treatment difference was -3.1 kg (95% confidence interval [CI] -7.0 to 0.7, P = 0.11). Results were compatible with a higher reduction of hunger score with exenatide compared with placebo (estimated treatment difference in change from baseline to week 26: -2.3, 95% CI -4.5 to -0.2), while all other outcomes did not significantly differ between groups. Adverse events were more common with exenatide versus placebo, and occurred in, respectively, 19 (95%) participants (108 events) and 14 (70%) participants (54 events). CONCLUSIONS AND RELEVANCE: Combined with intensive lifestyle interventions, a 26-week treatment with exenatide was not demonstrated superior to placebo to treat craniopharyngioma-related obesity.

High Risk of Acute Kidney Failure in Kidney Transplant Recipients Early after Bariatric Surgery.

Bariatric surgery is routinely proposed to patients suffering from obesity including kidney transplant recipients. In this specific population, bariatric surgery has a positive impact in long-term outcomes in terms of patient and graft survival. We report here the cases of 4 patients with five post-kidney transplantation bariatric surgeries who experimented acute renal injury early after surgery. Creatinine rising occurred between day 14 and day 20 after surgery. In all cases, it was due to dehydration leading to a pre-renal acute renal failure. The specific care of kidney transplanted patients is discussed: single kidney associated with pre-existing altered kidney function associated with concomitant use of nephrotoxic drugs. Specific education intervention before surgery associated with careful early management of hydration after surgery is mandatory for these patients.

A novel pathogenic variant in MRAP2 in an obese patient with successful outcome of bariatric surgery.

Mutations in genes encoding proteins located in the leptin/melanocortin pathway have been identified in the rare cases of genetic obesities. Heterozygous variants of MRAP2, encoding a G coupled-protein receptor accessory protein implicated in energy control notably via the melanocortin-4 receptor, have been recently identified. A 24-year-old patient with early-onset severe obesity (body mass index [BMI]: 64 kg/m2) associated with hypertension, respiratory complications, nonalcoholic fatty liver disease, and type 2 diabetes was referred to our department. Sleeve gastrectomy was successful. A new heterozygous variant in MRAP2 (NM_138409.4: c.154G>C/p.G52R) variant was identified in the patient DNA. Functional assessment confirmed that this new variant was pathogenic. We report a new pathogenic loss-of-function mutation in MRAP2 in a patient suffering from a severe multicomplicated obesity. This confirms the metabolic phenotype in patients with this monogenic form of obesity. Longer follow-up will be necessary. Our finding will allow a personalized medicine.

Long-Term Results After Bariatric Surgery in Super-Super-Obese Patients.

Introduction: Despite addressing to high risk population, we can propose laparoscopic bariatric surgery to super-super-obese (SSO) patients (body mass index [BMI] ≥60 kg/m2). The aim of this study was to report our experience in terms of weight loss and improvement of medical comorbidities after a follow-up of 5 years in the SSO population who underwent different bariatric procedures. Methods: This retrospective study includes all SSO patients who underwent bariatric surgery (sleeve gastrectomy [SG] and/or gastric bypass) between 2006 and 2017. The population was divided in three groups (SG alone; Roux-en-Y gastric bypass [RYGB] alone and SG+RYGB). The rate of complication and the weight-loss results were analyzed. Results: Among 43 patients who underwent surgery, the mean age was 42[31-54]. There were more women (72%) with the mean preoperative BMI of 64.9 kg/m2 [59.6-70.1]. There were 9 SGs, 26 RYGB, and 8 SG revised to gastric bypass (SG+RYGB) after a median delay of 23.5 months [16.5-32]. The perioperative complication rate was 25%, and there was 1 postoperative death. The median follow-up was 69 months [1-128]. The mean percentage of excess weight loss (%EWL) was 39.2% [18.2-60.3] after 5 years. For the SG group, the %EWL was inferior -27.1 [-3.6 to 57.8], but with no significant difference. An improvement of comorbidities' rate was recorded in all groups of patients. Conclusion: Bariatric surgery in SSO patients leads to an improvement of comorbidities even if the weight-loss results, especially in the SG group, are less favorable. The two steps approach should be re-evaluated by shortening the interval between. Other surgical strategies than RYGB are needed to be evaluated to improve long-term weight loss.

Long-term changes in body image after bariatric surgery: An observational cohort study.

BACKGROUND: While body image improves in the first few months after surgery, data on long-term changes in body image after bariatric surgery are scarce and contradictory. METHODS: We assessed body image through the Stunkard Figure Rating Scale and the Multidimensional Body-Self Relations Questionnaire-Appearance Scale, which measures appearance evaluation and orientation, overweight preoccupation, and self-classified weight. Surveys were conducted before surgery and at regular intervals until 5 years after bariatric surgery. RESULTS: 61 patients were included in the study. No patients were lost to follow-up until 18 months after bariatric surgery. At 5 years, there were 21 patients (34%) lost to follow-up. We detected an overall improvement in body image until 12-18 months post-surgery. Scores declined after 5 years post-surgery but were still higher than preoperative evaluations. Overweight preoccupation did not change throughout the follow-up period. There was a positive correlation between body weight lost and appearance evaluation. There was also a positive correlation between weight loss and the Body Areas Satisfaction Scale. There was a negative correlation between weight loss and overweight preoccupation. Appearance orientation and self-classified weight were not correlated with weight loss. CONCLUSIONS: Body image improved after bariatric surgery but was not maintained for all 5 years after surgery.

The Challenging Management of Craniopharyngiomas in Adults: Time for a Reappraisal?

Craniopharyngiomas (CPs) are rare tumors of the skull base, developing near the pituitary gland and hypothalamus and responsible for severe hormonal deficiencies and an overall increase in mortality rate. While surgery and radiotherapy represent the recommended first-line therapies for CPs, a new paradigm for treatment is currently emerging, as a consequence of accumulated knowledge concerning the molecular mechanisms involved in tumor growth, paving the way for anticipated use of targeted therapies. Significant clinical and basic research conducted in the field of CPs will undoubtedly constitute a real step forward for a better understanding of the behavior of these tumors and prevent associated complications. In this review, our aim is to summarize the multiple steps in the management of CPs in adults and emphasize the most recent studies that will contribute to advancing the diagnostic and therapeutic algorithms.

Five-Year Changes in Weight and Diabetes Status After Bariatric Surgery for Craniopharyngioma-Related Hypothalamic Obesity: a Case-Control Study.

PURPOSE: Craniopharyngiomas are tumors located in the hypothalamic region which leads to obesity in about 50% of cases. Long-term efficacy and safety of bariatric surgery are lacking in this peculiar population. The aim of this study is to determine the 5-year weight loss and resolution of type 2 diabetes (T2D) after bariatric surgery in patients operated on craniopharyngioma who had developed hypothalamic obesity. MATERIALS AND METHODS: This is a multicenter french retrospective case-control study. Subjects with craniopharyngioma (n = 23) who underwent sleeve gastrectomy (SG) (n = 9) or Roux-en-Y gastric bypass (RYGB) (n = 14) (median age 35 years [25;43] and BMI 44.2 kg/m2 [40.7; 51.0]; 8/23 with T2D) were individually matched to 2 subjects with common obesity for age, gender, preoperative body mass index, T2D, and type of surgery. RESULTS: TWL% after 1 and 5 years was lower in the craniopharyngioma group than in the control group: 23.1 [15.4; 31.1] (23/23) vs 31.4 [23.9; 35.3] at 1 year (p = 0.008) (46/46) and 17.8 [7.1; 21.9] (23/23) vs 26.2 [18.9; 33.9] at 5 years (p = 0.003) (46/46). After RYGB, TWL% was lower in the craniopharyngioma group compared to the control group (p < 0.001) and comparable after SG both at 1 and 5 years. No difference between the two groups was observed in T2D remission rate and in early and late adverse events. No hormonal deficiency-related acute disease was reported. CONCLUSIONS: Bariatric surgery induced a significant weight loss in the craniopharyngioma group at 1 and 5 years, but less than in common obesity. SG may be more effective than RYGB but this remains to be demonstrated in a larger cohort.

Guideline compliance in bariatric surgery: a French nationwide study.

BACKGROUND: Strict adherence to guidelines with a comprehensive preoperative assessment and rigorous follow-up are essential to improve postoperative and long-term outcomes of bariatric surgery (BS). OBJECTIVES: To investigate the trends in BS in France and to assess the compliance to guidelines in people with obesity before and after BS. SETTING: University Hospital of Bordeaux, France. METHODS: Data on patients who were admitted for a primary BS procedure in France between January 1 and April 1, 2014, were extracted from the French national health insurance system database. Data on patients' characteristics, preoperative assessment, hospitalization, and postoperative follow-up, including medical consultations, laboratory tests, and drug consumption, during the year preceding and the 2 years after BS were collected. RESULTS: Most of the 11,824 patients (60.4%) had sleeve gastrectomy. Rates of reimbursement for preoperative consultations with general practitioners, digestive surgeons, and endocrinologists or internists were 94.5%, 89.2%, and 63%, respectively. Laboratory tests for nutritional and obesity-related co-morbidity evaluations were performed in 94.3% and 91.4%, respectively. Rates of consultation with general practitioners, digestive surgeons, and endocrinologists or internists dropped from 93.1%, 91.2%, and 29.2%, respectively, the first year to 88.4%, 50.3%, and 20%, respectively, the second year after BS (P < .001). Reimbursements for vitamin, iron, and calcium supplementation dropped from 66.6%, 24.9%, and 21%, respectively, the first year to 52.1%, 19.3%, and 11.7%, respectively, the second year after BS (P < .001). CONCLUSION: Overall compliance with guidelines is improving. While preoperative medical assessment is nearly optimal, efforts still should be made in order to improve long-term follow-up in general and patient adherence to micronutrient supplementation in particular.

Exploring eating behavior and psychological mechanisms associated with obesity in patients with craniopharyngioma: a scoping review protocol.

OBJECTIVE: The objective of the review is to explore the evidence on the behavioral and psychological mechanisms underlying the development of obesity in patients with craniopharyngioma. The review will map the available evidence, identify gaps in the literature, and find avenues of future intervention. INTRODUCTION: Craniopharyngiomas are low-grade intracranial tumors of the supersellar region. Obesity is associated with the tumor or surgery or radiotherapy to treat the tumor; however, the behavioral and psychological processes contributing to that association are not clear. This review will provide a synthesized evidence base of the relevant research. INCLUSION CRITERIA: This review will consider published studies with all types of study designs, including patients with childhood- or adult-onset craniopharyngioma. Articles assessing factors that may impact eating behavior will be included based on the following categories: eating behavior, obesity, neuroimaging, endocrine response, energy expenditure, sleep, and neuropsychology. METHODS: MEDLINE, Embase, and PsycINFO will be searched, in addition to the Cochrane Library, Web of Science, Scopus, ClinicalTrials.gov, NICE evidence search, and International Standard Randomised Controlled Trial Number (ISRCTN). No limits will be placed on the scope of the search. The methodology will follow a three-stage process with two independent reviewers at each stage, including an initial database search, screening of titles and abstracts of retrieved studies, full-text assessment for inclusion criteria, and hand-searching of reference lists. Data will be extracted using a standardized charting form and summarized in tables. The data will be synthesized using a narrative summary and diagrammatic map and will be based on the evidence for each of the proposed research categories.

Gut Microbiota and Mycobiota Evolution Is Linked to Memory Improvement after Bariatric Surgery in Obese Patients: A Pilot Study.

Patients with obesity are known to exhibit gut microbiota dysbiosis and memory deficits. Bariatric surgery (BS) is currently the most efficient anti-obesity treatment and may improve both gut dysbiosis and cognition. However, no study has investigated association between changes of gut microbiota and cognitive function after BS. We prospectively evaluated 13 obese patients on anthropometric data, memory functions, and gut microbiota-mycobiota before and six months after BS. The Rey Auditory Verbal Learning Test (AVLT) and the symbol span (SS) of the Weschler Memory Scale were used to assess verbal and working memory, respectively. Fecal microbiota and mycobiota were longitudinally analyzed by 16S and ITS2 rRNA sequencing respectively. AVLT and SS scores were significantly improved after BS (AVLT scores: 9.7 ± 1.7 vs. 11.2 ± 1.9, p = 0.02, and SS scores: 9.7 ± 23.0 vs. 11.6 ± 2.9, p = 0.05). An increase in bacterial alpha-diversity, and Ruminococcaceae, Prevotella, Agaricus, Rhodotorula, Dipodascus, Malassezia, and Mucor were significantly associated with AVLT score improvement after BS, while an increase in Prevotella and a decrease in Clostridium, Akkermansia, Dipodascus and Candida were linked to SS scores improvement. We identified several changes in the microbial communities that differ according to the improvement of either the verbal or working memories, suggesting a complex gut-brain-axis that evolves after BS.

Hair cortisol and cortisone measurements for the diagnosis of overt and mild Cushing's syndrome.

OBJECTIVE: Hair cortisol (HF) and cortisone (HE) measurements reflect tissular exposure to cortisol over months and are increased in overt Cushing's syndrome (CS). No data is available in mild CS. We compared the diagnostic performance of HF and HE between patients with overt or mild CS. DESIGN: Single centre retrospective study. METHODS: HF&HE were measured by LC-MS/MS in 48 consecutive adult females with Cushing's disease (CD), ectopic ACTH syndrome, secreting adenomas and carcinomas, and adrenal incidentalomas. All had impaired dexamethasone suppression tests. Overt CS (n = 25) was diagnosed in front of specific symptoms, a mean UFC (>1.5 ULN) and increased midnight serum cortisol or salivary cortisol. Mild CS (n = 23) was diagnosed in patients lacking specific symptoms and displaying at least one additional biological abnormality including mildly increased UFC (≤1.5 ULN), increased midnight serum cortisol or salivary cortisol and suppressed plasma ACTH in patients with adrenal tumours. In this study, 84 healthy subjects and obese patients served as controls. RESULTS: HF and HE showed roughly similar performance in overt CS (92 and 100% sensitivity, 91 and 99% specificity, respectively). HF and HE were lower in mild CS but higher than in controls (P < 0.01). HE was correlated with midnight serum cortisol (P < 0.02) and volume of adrenal incidentalomas (P < 0.04) but not with UFC. HF and HE had 59% and 68% sensitivity, and 79 and 94% specificity, respectively, for the diagnosis of mild CS. Contrary to UFC, both HF and HE were in the range of overt CS in 11/23 patients with mild CS. Patients with mild CS and increased HE required more antihypertensive treatments and showed worser lipid profiles than patients with normal HE. CONCLUSIONS: HF and HE measurement performed better in overt than in mild CS but is a useful adjunct to diagnose mild CS and to identify adrenocortical incidentalomas responsible for excessive cortisol exposure.

Long-Term Effects of Roux-en-Y Gastric Bypass and Sleeve Gastrectomy on Bone Mineral Density: a 4-Year Longitudinal Study.

INTRODUCTION: Bone mineral density (BMD) declines in the initial years after bariatric surgery, but long-term skeletal effects are unclear and comparisons between sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) are rare. DESIGN AND METHODS: An observational longitudinal study of obese patients undergoing SG or RYGB was performed. Whole-body (WB) BMD, along with BMD of the total hip (TH), femoral neck (FN), and lumbar spine (LS), was measured by dual-energy X-ray absorptiometry (DXA) before surgery and yearly thereafter for 4 years. Calciotropic hormones were also measured. RESULTS: Forty-seven patients undergoing RYGB surgery and 28 patients undergoing SG were included. Four years after RYGB, BMD declined by 2.8 ± 5.8% in LS, 8.6 ± 5% in FN, 10.9 ± 6.3% in TH, and 4.2 ± 6.2% in WB, relative to baseline. For SG, BMD declined by 8.1 ± 5.5% in FN, 7.7 ± 6% in TH, 2.0 ± 7.2% in LS, and 2.5 ± 6.4% in WB after 4 years, relative to baseline. Vitamin D levels increased with supplementation in both groups. Whereas parathyroid hormone levels increased slightly in the RYGB group, they decreased modestly in the SG group (P < 0.05 in both groups). CONCLUSIONS: Bone loss after 4 years was comparable between the two procedures, although RYGB was associated with a slightly greater decrease at the TH than SG. Bone health should therefore be monitored after both RYGB and SG.

Effects of a High-Protein/Moderate-Carbohydrate Diet on Appetite, Gut Peptides, and Endocannabinoids-A Preview Study.

Favorable effects of a high-protein/moderate-carbohydrate (HP/MCHO) diet after weight loss on body weight management have been shown. To extend these findings, associations between perception of hunger and satiety with endocannabinoids, and with glucagon-like peptide-1 (GLP-1) and polypeptide YY (PYY) were assessed. At approximately 34 months after weight loss, 22 female and 16 male participants (mean age 64.5 ± 5.9 years; body mass index (BMI) 28.9 ± 3.9 kg/m2) completed a 48 h respiration chamber study. Participants were fed in energy balance with a HP/MCHO diet with 25%:45%:30% or a moderate-protein/high-carbohydrate (MP/HCHO) diet with 15%:55%:30% of energy from protein:carbohydrate:fat. Endocannabinoids and related compounds, relevant postprandial hormones (GLP-1, PYY), hunger, satiety, and ad libitum food intake were assessed. HP/MCHO versus MP/HCHO reduced hunger perception. The lower decremental area under the curve (dAUC) for hunger in the HP/MCHO diet (-56.6% compared to MP, p < 0.05) was associated with the higher AUC for 2-arachidonoylglycerol (2-AG) concentrations (p < 0.05). Hunger was inversely associated with PYY in the HP/MCHO group (r = -0.7, p < 0.01). Ad libitum food intake, homeostatic model assessment for insulin resistance (HOMA-IR) and incremental AUCs for gut peptides were not different between conditions. HP/MCHO versus MP/HCHO diet-induced reduction in hunger was present after 34 months weight maintenance in the post-obese state. HP/MCHO diet-induced decrease of hunger is suggested to interact with increased 2-AG and PYY concentrations.

Oral Hydration, Food Intake, and Nutritional Status Before and After Bariatric Surgery.

BACKGROUND AND AIMS: Bariatric surgery is considered to be the most effective treatment of morbid obesity. Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGBP) are the most popular procedures. We evaluated nutritional status, micro- and macronutrient intake, and oral hydration in patients before and regularly during 1 year after RYGBP and SG. METHODS: All patients that had been through bariatric surgery with at least 1-year post-surgery were retrospectively included in the study. All participants were evaluated once during the 2 months before the surgery and at 1, 3, 6, and 12 months after surgery. Clinical and biological evaluations as well as dietary investigations were performed. RESULTS: Fifty-seven patients were included in this study (28 RYGBP and 29 SG). Patients in the RYGBP group had significantly higher body weight (132.3 ± 22 versus 122.2 ± 22.2 kg, p = 0.039) than patients in the SG group. Before surgery, total energy intake, oral hydration, and vitamin and mineral intakes were not different between the two groups. RYGBP and SG induced significant similar excess weight loss 1 year after surgery, 48.6 29.8% and 57.6 27.6% of body weight respectively. Energy intake significantly decreased 1 month after surgery and slightly increased from 1 to 12 months without reaching baseline intake levels. Macronutrient repartition did not change during follow-up. Oral hydration significantly decreased after RYGBP (- 58%) and showed a trend to be decreased after SG (- 49%). Sixty-five percent of patients still had vitamin D deficiency 1 year after surgery. Whatever the type of surgery, more than 20% had some vitamin deficiency 1 month after surgery. CONCLUSIONS: Calories intake decreases after bariatric surgery, whatever the type of procedure. In addition, the prevalence of vitamin deficiency is high after bariatric surgery. Lastly, oral hydration is importantly decreased after bariatric surgery, especially after RYGBP.

Lifestyle intervention program in deprived obese adult patients and their non-deprived counterparts.

INTRODUCTION: Although it is known that the prevalence of obesity is high in deprived patients, the link between deprivation and obesity, and the impact of deprivation on compliance and efficacy of a lifestyle intervention program are not known. MATERIALS AND METHODS: Deprivation was assessed in 40 patients (23 Females, mean±SD age: 49±17 years) from the diabetology department and 140 patients (101 Females, age: 50±15 years) from the nutrition department of Bordeaux University hospital. Eighty-seven patients suffering from obesity were evaluated before and after a tailored, multidisciplinary lifestyle intervention. Deprivation was assessed using EPICES scores. Deprivation was defined with an EPICES score > 30. RESULTS: Deprived patients suffering from obesity had significantly higher current (43.8 ±8.4 versus 40.9 ± 5.5 kg/m2, p = 0,02) and maximal BMI (46.1± 8.6 versus 42.3± 5.2 kg/m2, p = 0.002) compared to non-deprived obese. Percentage of body weight loss was not different according to deprivation (4.74 ± 0.75 versus 4.65 ± 1.04%, p = 0.9). EPICES scores were not different according to adherence to lifestyle intervention program (20.5 ± 8.5 versus 29.9 ± 3.9 versus 29.0 ±2.5, no follow up versus partial follow up versus total follow up, p = 0,58). CONCLUSION: Deprived patients suffering from obesity have a more serious disease than non-deprived patients. However, neither compliance to the lifestyle intervention program nor body weight loss differed between deprived patients with obesity and non-deprived ones. Deprivation should not be a limitation when enrolling patients with obesity in lifestyle intervention programs.