Publications by authors named "Emmanuel Disse"

63 Publications

Food Preferences and Their Perceived Changes Before and After Bariatric Surgery: a Cross-sectional Study.

Obes Surg 2021 Mar 20. Epub 2021 Mar 20.

Centre Européen Nutrition et Santé (CENS), Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RA), Unité INSERM 1060, Laboratoire CarMeN, Université Claude Bernard Lyon 1, 165, Chemin du Grand Revoyet, 69310, Pierre-Bénite, France.

Purpose: Changes in food preferences, taste, and smell following bariatric surgery have been previously described but with inconsistent results. We aimed to describe current food preferences and their perceived changes before and after the surgery. We further compared food preferences between patients with and without taste or smell alterations, before and above 2 years follow-up, and concerning the success or failure of their surgery.

Materials And Methods: This cross-sectional study was conducted with a self-administered online questionnaire. Two years was the cut-off between short- and long-term follow-up. Success was defined as an excess weight loss (EWL) greater or equal to 50%.

Results: In total, 220 postoperative patients answered the questionnaire. Patients with taste alterations (64%) had significantly lower preferences for red meat, milk, cheese, desserts, fried foods, and water (all p < 0.05) relative to the non-taste alteration group, while those with smell alterations (38%) had significantly lower preference for cheese only (p < 0.05) relative to the non-smell alteration group. Patients with a ≥ 2-year follow-up had a higher liking for desserts, fried foods, fat, bread, hot drinks, and alcohol compared to patients with a < 2-year follow-up (all p < 0.05). Patients having success in surgery had higher liking scores for green vegetables and lower liking scores for starchy foods, milk, and sweet dairy products (all p < 0.05).

Conclusions: Our study suggests that patients who underwent bariatric surgery have different food preference patterns according to their sensory perceptions, the duration of their follow-up, and the success of bariatric surgery.
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http://dx.doi.org/10.1007/s11695-021-05342-9DOI Listing
March 2021

Revision of Mason's procedure (vertical banded gastroplasty) to Roux-en-Y gastric bypass: role of an associated fundectomy in weight loss outcomes.

Surg Obes Relat Dis 2021 Jan 9. Epub 2021 Jan 9.

Department of Digestive Surgery, Center of Bariatric Surgery, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France; Department of Endocrinology Diabetology and Nutrition, Centre Intégré et Spécialisé de l'Obésité de Lyon, Groupement Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre Bénite, France; Université Claude Bernard Lyon 1, Lyon, France; Carmen Lab, INSERM Unit 1060, Groupement Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre Bénite, France.

Background: Vertical banded gastroplasty (VBG) presents a significant rate of long-term complications, and revisions are often necessary. Conversion to Roux-en-Y gastric bypass (RYGB) seems to be preferred, but literature data remain limited.

Objectives: To analyze the indications, safety, results of conversions from VBG to RYGB, and to identify predictive factors of success or failure.

Setting: Two specialized centers of bariatric surgery.

Methods: This bicentric retrospective study included all the patients who benefited from a conversion from VBG to RYGB between 2008 and January 2020. Demographic characteristics, indications, preoperative workups, intraoperative data, complications, and weight loss results were analyzed.

Results: During the study period, 85 patients underwent a conversion to RYGB. The mean body mass index (BMI_ before conversion was 40.6 kg/m. 82.3% of the patients were converted because of weight loss failure and 17.6% because of a complication of their VBG. The global rate of complications was 25%. After an average follow-up of 35 months and a rate of loss to follow-up of 33%, the mean BMI was 33.5 kg/m. The weight loss success rate according to Reinhold's criteria was 64.7%, and resolution of complications was obtained in 89.1%. The association of a fundectomy was a predictive factor of weight loss (odds ratio, .27; P = .04), whereas primary failure of the VBG was a predictive factor of failure.

Conclusion: Conversion from VBG to RYGB remains the procedure of choice to achieve satisfying weight loss and resolution of functional complications. The addition of a fundectomy appeared to have a significant positive impact on weight loss outcomes.
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http://dx.doi.org/10.1016/j.soard.2020.12.014DOI Listing
January 2021

An artificial intelligence-derived tool proposal to ease disordered eating screening in people with obesity.

Eat Weight Disord 2021 Jan 2. Epub 2021 Jan 2.

Centre Intégré de l'Obésité Rhône-Alpes; Fédération Hospitalo-Universitaire DO-iT, Service Endocrinologie Diabète et Nutrition, Groupement Hospitalier Sud, Hospices Civils de Lyon, 165 chemin du Grand Revoyet, 69310, Pierre-Bénite, France.

Purpose: In people with obesity, food addiction (FA) tends to be associated with poorer outcomes. Its diagnosis can be challenging in primary care. Based on the SCOFF example, we aim to determine whether a quicker and simpler screening tool for FA in people with obesity could be developed, using artificial intelligence (machine learning).

Methods: The first step was to look for the most discriminating items, among 152 different ones, to differentiate between FA-positive and FA-negative populations of patients with obesity. Items were ranked using the Fast Correlation-Based Filter (FCBF). Retained items were used to test the performance of nine different predictive algorithms. Then, the construction of a graphic tool was proposed.

Results: Data were available for 176 patients. Only three items had a FCBF score > 0.1: "I eat to forget my problems"; "I eat more when I'm alone"; and "I eat sweets or comfort foods". Naive Bayes classification obtained best predictive performance. Then, we created a 3-item nomogram to predict a positive scoring on the YFAS.

Conclusion: A simple and fast screening tool for detecting high-disordered eating risk is proposed. The next step will be a validation study of the FAST nomogram to ensure its relevance for emotional eating diagnosis.

Level Of Evidence: Level V, cross-sectional descriptive study.

Clinical Trial Registry Number: NCT02857179 at clinicaltrials.gov.
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http://dx.doi.org/10.1007/s40519-020-01076-2DOI Listing
January 2021

Third bariatric procedure for insufficient weight loss or weight regain: how far should we go?

Surg Obes Relat Dis 2021 Jan 1;17(1):96-103. Epub 2020 Sep 1.

Department of Digestive Surgery, Center of Bariatric Surgery, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France; Centre Intégré et Spécialisé de l'Obésité de Lyon, Groupement Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre Bénite, France; Université Claude Bernard Lyon 1, Lyon, France; Carmen lab, INSERM Unit 1060, Université Lyon 1, Lyon, France.

Background: Revisional procedures in bariatric surgery are increasing with several debated failure risk factors, such as super obesity and old age. No study has yet evaluated the outcomes and risks of a third bariatric procedure indicated for weight loss failure or weight regain.

Objectives: To assess failure risks of a third bariatric procedure according to Reinhold's criteria (percentage excess weight loss [%EWL] ≤50% and/or body mass index [BMI] ≥35 kg/m).

Setting: A university-affiliated tertiary care center, France.

Methods: From 2009 to 2019, clinical data and weight loss results of patients who benefited from 3 bariatric procedures for weight loss failure or weight regain were collected prospectively and analyzed using a binary logistic regression. Weight loss failure was defined according to Reinhold's criteria.

Results: Among 1401 bariatric procedures performed, 336 patients benefited from 2 or more procedures, and 45 had a third surgery. Eleven patients that were reoperated on because of malnutrition or gastroesophageal reflux disease were excluded from the final analysis. Among 34 patients with 3 procedures because of weight loss failure or regain, mean BMI was 48.3 ± 8.3 kg/m, and mean age was 30 ± 10.7 years. Three out of 34 patients (9%) presented a severe complication (Dindo-Clavien IIIb) and 2 (6%) had a minor one. Achieving Reinhold's weight loss criteria after the second bariatric procedure was a significant predictor of success of the third procedure (β = 2.9 ± 1.3 S.E.).

Conclusion: Not reaching Reinhold's criteria after a second bariatric procedure was identified as a significant risk factor of failure of a third procedure. A third surgery should be carefully discussed especially in case of primary failure of previous procedures.
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http://dx.doi.org/10.1016/j.soard.2020.08.032DOI Listing
January 2021

Anti-PD1 and Anti-PDL1-Induced Hypophysitis: A Cohort Study of 17 Patients with Longitudinal Follow-Up.

J Clin Med 2020 Oct 13;9(10). Epub 2020 Oct 13.

Service d'Endocrinologie, Diabète, Nutrition, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, 69310 Pierre-Bénite, France.

Hypophysitis, secondary to programmed cell death 1 protein (PD1) and programmed cell death 1 ligand 1 (PDL1) inhibitors, were thought to be rare, with only a few studies describing more than one case with long-term follow-up. The aim of the present study was to describe the clinical, laboratory, and morphological characteristics of PD1/PDL1 inhibitor-induced hypophysitis, and its long-term course. This cohort study was conducted at the University Hospital of Lyon, France, with longitudinal follow-up of patients. Seventeen cases of PD1/PDL1 inhibitor-induced hypophysitis were included. The median time to onset of hypophysitis was 28 weeks (range: 10-46). At diagnosis, 16 patients complained of fatigue, 12 of nausea or loss of appetite, while headache was rare. We found no imaging pituitary abnormality. All patients presented adrenocorticotropic hormone (ACTH) deficiency; other pituitary deficiencies were less common ( = 7). At last follow-up (median: 13 months), ACTH deficiency persisted in all but one patient and one patient recovered from gonadotropic deficiency. PD1/PDL1 inhibitor-induced hypophysitis is a clinical entity different from those associated to cytotoxic T-lymphocyte antigen-4 (CTLA4) inhibitors, with less obvious clinical and radiological signs, and probably a different mechanism. The paucity of symptoms demonstrates the need for systematic hormonal follow-up for patients receiving PD1/PDL1 inhibitors.
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http://dx.doi.org/10.3390/jcm9103280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7601962PMC
October 2020

Starch digestibility modulation significantly improves glycemic variability in type 2 diabetic subjects: A pilot study.

Nutr Metab Cardiovasc Dis 2021 01 25;31(1):237-246. Epub 2020 Aug 25.

Centre de Recherche en Nutrition Humaine Rhône-Alpes, Univ-Lyon, CarMeN Laboratory, INSERM, INRA, INSA Lyon, Université Claude Bernard Lyon 1, Hospices Civils de Lyon, F-CRIN/FORCE Network, 69310, Pierre Bénite, France. Electronic address:

Background And Aims: In type 2 diabetes (T2D) patients, the reduction of glycemic variability and postprandial glucose excursions is essential to limit diabetes complications, beyond HbA1c level. This study aimed at determining whether increasing the content of Slowly Digestible Starch (SDS) in T2D patients' diet could reduce postprandial hyperglycemia and glycemic variability compared with a conventional low-SDS diet.

Methods And Results: For this randomized cross-over pilot study, 8 subjects with T2D consumed a controlled diet for one week, containing starchy products high or low in SDS. Glycemic variability parameters were evaluated using a Continuous Glucose Monitoring System. Glycemic variability was significantly lower during High-SDS diet compared to Low-SDS diet for MAGE (Mean Amplitude of Glycemic Excursions, p < 0.01), SD (Standard Deviation, p < 0.05), and CV (Coefficient of Variation, p < 0.01). The TIR (Time In Range) [140-180 mg/dL[ was significantly higher during High-SDS diet (p < 0.0001) whereas TIRs ≥180 mg/dL were significantly lower during High-SDS diet. Post-meals tAUC (total Area Under the Curve) were significantly lower during High-SDS diet.

Conclusion: One week of High-SDS Diet in T2D patients significantly improves glycemic variability and reduces postprandial glycemic excursions. Modulation of starch digestibility in the diet could be used as a simple nutritional tool in T2D patients to improve daily glycemic control. REGISTRATION NUMBER: in clinicaltrials.gov: NCT03289494.
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http://dx.doi.org/10.1016/j.numecd.2020.08.010DOI Listing
January 2021

Efficacy and Safety of the Duodeno-Jejunal Bypass Liner in Patients With Metabolic Syndrome: A Multicenter Randomized Controlled Trial (ENDOMETAB).

Ann Surg 2020 11;272(5):696-702

University Lille, Inserm, CHU Lille, Institut Pasteur Lille U1190 Translational Research for Diabetes, European Genomic Institute for Diabetes, Integrated Center of Obesity, Lille, France.

Objective: The aim of this study was to compare the efficacy and safety of 12-month implantation of a duodeno-jejunal bypass liner (DJBL) with conventional medical care in patients with metabolic syndrome (MS).

Summary Background Data: DJBL is an endoscopic device for treating obesity and related disorders. The persistence of favorable results after 6 months has not been tested in a controlled study.

Methods: We conducted a multicenter randomized controlled trial, stratified by center and diabetes status. The primary endpoint was the remission of MS at 12 months. The secondary endpoints included body mass index (BMI), glucose control, blood pressure, and lipids, assessed at 12 months after implantation, and again, at 12 months after the removal of the DJBL. Up to 174 subjects were planned to be randomized into either the DJBL or the control arm at a 2:1 ratio, respectively. Study enrollment was discontinued by the Scientific Monitoring Committee due to the early termination of the ENDO trial (NCT01728116) by the US Food and Drug Administration. The study was terminated after withdrawal of the device's European Conformity marking by the European Medicines Agency, and an interim analysis was performed.

Results: A total of 82 patients were enrolled (67.5% female, 48.8% with diabetes). At 12 months after randomization, the primary endpoint was met in 6 (12%) DJBL patients and 3 (10%) controls (P = 0.72). Patients in the DJBL group experienced greater BMI loss [mean adjusted difference (95% confidence interval, CI) -3.1 kg/m (-4.4 to -1.9) kg/m, P < 0.001] and HbA1c change [mean adjusted difference -0.5% (95% CI -0.9 to -0.2); P < 0.001] than those in the control group. No difference remained statistically significant at 12 months after the removal of the DJBL. In the DJBL group, 39% of patients experienced at least one device-related serious adverse event, which was classified as Grade III Dindo-Clavien in 22%, and required premature device explantation in 16%.

Conclusions: The present study showed a transient clinical benefit of DJBL, which was only apparent at 1 year, when the device was still in situ, and was obtained at the risk of serious device-related adverse events in 39% of patients. These results do not support the routine use of DJBL for weight loss and glucose control in patients with MS.
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http://dx.doi.org/10.1097/SLA.0000000000004339DOI Listing
November 2020

Prospective multicentre randomised trial comparing the efficacy and safety of single-anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) versus Roux-en-Y gastric bypass (RYGB): SADISLEEVE study protocol.

BMJ Open 2020 09 1;10(9):e037576. Epub 2020 Sep 1.

Department of Endocrinology, Diabetology and Nutrition, Specialized Center for Obesity Management, Hospices Civils de Lyon, Université Lyon 1, Lyon, France.

Introduction: Despite the non-negligible weight loss failure rate at midterm, Roux-en-Y gastric bypass (RYGB) remains the reference procedure in the treatment of morbid obesity with metabolic comorbidities. A recently emerged procedure, the single anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S), could be more effective on weight loss with similar morbidity and lower weight loss failure rate than RYGB. We propose the first randomised, open, multicentre superiority trial comparing the SADI-S to RYGB (SADISLEEVE).

Methods And Analysis: The main objective is to demonstrate the superiority at 2 years after surgery of the SADI-S compared with RYGB in term of excess weight loss percentage. The secondary objectives are the evaluation of nutritional status, metabolic outcomes, overall complication rates and quality of life, within 2 years after surgery. Key inclusion criteria are obese patients with body mass index (BMI) ≥40 kg/m or ≥35 kg/m with at least one comorbid condition and candidate to a first bariatric procedure or after failure of sleeve gastrectomy. Patients randomised by minimisation in two arms, based on centre, surgery as a revisional procedure, presence of type 2 diabetes and BMI >50 kg/m will be included over 2 years.A sample size of 166 patients in each group will have a power of 90% to detect a probability of 0.603 that excess weight loss in the RYGB arm is less than excess weight loss in the SADI-S arm with a 5% two-sided significance level. With a drop-out rate of 10%, it will be necessary to include 183 patients per group.

Ethics And Dissemination: The study was approved by Institutional Review Board of Centre Hospitalier Universitaire Morvan (CPP1089-HPS1). Study was also approved by the French national agency for drug safety (2018061500148). Results will be reported in peer-reviewed scientific journals.

Trial Registration Number: NCT03610256.
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http://dx.doi.org/10.1136/bmjopen-2020-037576DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7467507PMC
September 2020

Design and Validation of a Diet Rich in Slowly Digestible Starch for Type 2 Diabetic Patients for Significant Improvement in Glycemic Profile.

Nutrients 2020 Aug 11;12(8). Epub 2020 Aug 11.

Nutrition Research, Mondelēz International, 91400 Saclay, France.

This study aimed at designing a-diet high in slowly digestible starch (SDS) by carefully selecting high-SDS starchy products and to validate its implementation, acceptance, and impact on the postprandial glycemic response in patients with type 2 diabetes (T2D). Starchy products were screened and classified as being either high (high-SDS) or low (low-SDS) in SDS (in vitro SDS method). A randomized controlled cross-over pilot study was performed: Eight patients with T2D consumed randomly a high-SDS or a low-SDS diet for one week each, while their glycemic profile was monitored for 6 days. Based on 250 food product SDS analyses and dietary recommendations for patients with T2D, the high-SDS and low-SDS diets were designed. The high-SDS diet significantly increased SDS intake and the SDS/carbohydrates proportion compared to the low-SDS diet (61.6 vs. 11.6 g/day and 30% vs. 6%; < 0.0001, respectively). Increasing the SDS/carbohydrate proportion to 50% of the meal was significantly correlated with a 12% decrease in tAUC0-120 min and a 14% decrease in the glycemic peak value ( < 0.001 for both). A high-SDS diet can be easily designed by carefully selecting commercial starchy products and providing relevant recommendations for T2D to improve their glycemic profile.
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http://dx.doi.org/10.3390/nu12082404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468810PMC
August 2020

A series of severe neurologic complications after bariatric surgery in France: the NEUROBAR Study.

Surg Obes Relat Dis 2020 Oct 12;16(10):1429-1435. Epub 2020 Jun 12.

Service d'Endocrinologie, Diabétologie, Nutrition, CHU Grenoble Alpes, Grenoble, France. Electronic address:

Background: Neurologic complications after bariatric surgery are rare, but can have dramatic consequences. Little data are available on this topic.

Objectives: The aim of the Neurologic complications after BARiatric surgery (NEUROBAR) study was to define, which factors (anthropometric, nutritional, surgical, etc.) were frequently associated with neurologic complications after bariatric surgery.

Settings: Data were collected by the French Centers of Obesity Care Management hosted in University Hospitals.

Methods: An online standardized questionnaire was designed and submitted to the 37 French Centers of Obesity Management. This questionnaire included items about patient characteristics, bariatric surgery, neurologic complications, nutritional status, and management. Patients were retrospectively included from January 2010 to November 2018.

Results: Thirteen centers included 38 patients (34 females and 4 males) with neurologic complications after bariatric surgery. The 2 main bariatric procedures were gastric bypass and sleeve gastrectomy. More than half of the patients with neurologic complications had a surgical complication after bariatric surgery (53%) and gastrointestinal symptoms, including vomiting (53%). Vitamin B deficiencies were frequent (74%) including at least 47% of cases with deficiency in Vitamin B1.

Conclusion: Early identification of patients with surgical complications and gastrointestinal symptoms after bariatric surgery could help prevent neurologic complications related to nutritional deficiencies.
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http://dx.doi.org/10.1016/j.soard.2020.05.031DOI Listing
October 2020

Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: the CORONADO study.

Diabetologia 2020 08 29;63(8):1500-1515. Epub 2020 May 29.

Département d'Endocrinologie, Diabétologie et Nutrition, CHU Toulouse, Institut des Maladies Métaboliques et Cardiovasculaires, UMR1048 Inserm/UPS, Université de Toulouse, Toulouse, France.

Aims/hypothesis: Coronavirus disease-2019 (COVID-19) is a life-threatening infection caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus. Diabetes has rapidly emerged as a major comorbidity for COVID-19 severity. However, the phenotypic characteristics of diabetes in COVID-19 patients are unknown.

Methods: We conducted a nationwide multicentre observational study in people with diabetes hospitalised for COVID-19 in 53 French centres in the period 10-31 March 2020. The primary outcome combined tracheal intubation for mechanical ventilation and/or death within 7 days of admission. Age- and sex-adjusted multivariable logistic regressions were performed to assess the prognostic value of clinical and biological features with the endpoint. ORs are reported for a 1 SD increase after standardisation.

Results: The current analysis focused on 1317 participants: 64.9% men, mean age 69.8 ± 13.0 years, median BMI 28.4 (25th-75th percentile: 25.0-32.7) kg/m; with a predominance of type 2 diabetes (88.5%). Microvascular and macrovascular diabetic complications were found in 46.8% and 40.8% of cases, respectively. The primary outcome was encountered in 29.0% (95% CI 26.6, 31.5) of participants, while 10.6% (9.0, 12.4) died and 18.0% (16.0, 20.2) were discharged on day 7. In univariate analysis, characteristics prior to admission significantly associated with the primary outcome were sex, BMI and previous treatment with renin-angiotensin-aldosterone system (RAAS) blockers, but not age, type of diabetes, HbA, diabetic complications or glucose-lowering therapies. In multivariable analyses with covariates prior to admission, only BMI remained positively associated with the primary outcome (OR 1.28 [1.10, 1.47]). On admission, dyspnoea (OR 2.10 [1.31, 3.35]), as well as lymphocyte count (OR 0.67 [0.50, 0.88]), C-reactive protein (OR 1.93 [1.43, 2.59]) and AST (OR 2.23 [1.70, 2.93]) levels were independent predictors of the primary outcome. Finally, age (OR 2.48 [1.74, 3.53]), treated obstructive sleep apnoea (OR 2.80 [1.46, 5.38]), and microvascular (OR 2.14 [1.16, 3.94]) and macrovascular complications (OR 2.54 [1.44, 4.50]) were independently associated with the risk of death on day 7.

Conclusions/interpretations: In people with diabetes hospitalised for COVID-19, BMI, but not long-term glucose control, was positively and independently associated with tracheal intubation and/or death within 7 days.

Trial Registration: clinicaltrials.gov NCT04324736.
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http://dx.doi.org/10.1007/s00125-020-05180-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7256180PMC
August 2020

Prevalence of obesity among adult inpatients with COVID-19 in France.

Lancet Diabetes Endocrinol 2020 07 18;8(7):562-564. Epub 2020 May 18.

CarMen Laboratory, INSERM, INRA, INSA Lyon, Université Claude Bernard Lyon 1, Hôpital Lyon Sud, Pierre-Bénite 69495, France; Hospices Civils de Lyon, Département Endocrinologie, Diabète et Nutrition, Hôpital Lyon Sud, Pierre-Bénite 69495, France; COVID-O-HCL Consortium, Hospices Civils de Lyon, Lyon, France.

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http://dx.doi.org/10.1016/S2213-8587(20)30160-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7234780PMC
July 2020

Obesity is Associated with Severe Forms of COVID-19.

Obesity (Silver Spring) 2020 07 21;28(7):1175. Epub 2020 May 21.

CarMen Laboratory, INSERM, INRA, INSA Lyon, Université Claude Bernard Lyon 1, Pierre-Bénite, France.

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http://dx.doi.org/10.1002/oby.22842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7264509PMC
July 2020

[Checkpoint inhibitors-induced hypophysitis].

Bull Cancer 2020 Apr 19;107(4):490-498. Epub 2020 Mar 19.

Hospices civils de Lyon, fédération d'endocrinologie, 28, avenue Doyen-Lépine, 69677 Bron cedex, France; ImmuCare, institut de cancérologie des hospices civils de Lyon (IDCRC-HCL), Lyon, France; Université de Lyon, université Claude-Bernard-Lyon-1, Lyon, France.

Checkpoint inhibitors immunotherapy is more and more prescribed in oncology, causing new immune related endocrine adverse events. Hypophysitis occurs in approximately 10 % of patients treated with anti-CTLA4. It occurs two to three months after initiation of the immunotherapy. The initial presentation is characterized, in typical forms, by the association of headache, asthenia and hyponatremia. Hormonal exploration usually shows ACTH, gonadotropic and thyrotropic deficiencies. ACTH deficiency may be life-threatening and requires urgent supplementation, without awaiting for biological results. MRI is warranted in order to exclude differential diagnoses, such as pituitary metastases. Hypophysitis induced by anti-PD1/PDL1 seems to be a different nosologic entity characterized by a later onset and a less symptomatic presentation. Biologically ACTH deficiency seems to be constant and permanent, and often isolated. Treatment requires high-dose steroids only in case of severe tumor syndrome (resistant headache, visual disturbance) or acute decompensation of ACTH deficiency. Patients always need lifelong hormonal supplementation of pituitary deficits and must be followed and educated specifically. Immunotherapy can be delayed during the acute phase, but can be secondarily continued if there is an oncological benefit. As it is a pauci-symptomatic but potentially life-threatening complication, biological screening must be systematic in patients treated with checkpoint inhibitors.
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http://dx.doi.org/10.1016/j.bulcan.2020.01.012DOI Listing
April 2020

[Thyroid dysfunctions secondary to cancer immunotherapy].

Bull Cancer 2020 Feb 24;107(2):262-271. Epub 2019 Dec 24.

Hospices civils de Lyon, hôpital Lyon Sud, service d'endocrinologie diabète nutrition, 165, chemin du Grand Revoyet, 69310 Pierre-Bénite, France; ImmuCare, Institut de cancérologie des hospices civils de Lyon (IDCRC-HCL), 69003 Lyon, France; Université de Lyon, université Claude Bernard Lyon 1, 69100 Lyon, France.

The immune checkpoint inhibitors (CPI) such as anti-PD(L)1 or anti-CTLA4 had improved long-term patients' outcomes in different malignancies. Thyroid disorders are the most frequent endocrine side effects from CPI reported in clinical trials and in clinical routine practice. The incidence of thyroid dysfunction is variable according to ICP used (more frequent under anti-programmed cell death 1 (PD1) or anti-programmed cell death-ligand 1 (PDL1)). Most thyroid dysfunctions have been reported to occur 2 to 4 courses after CPI initiation. The clinical symptoms are generally nonspecific (asthenia, weight change, rarely cardiac rhythm disorder). These thyroid dysfunctions are commonly painless thyroiditis with a biphasic evolution: thyrotoxicosis followed by a secondary hypothyroidism frequently definitive. Diagnosis is made on a thyroid test (TSH and FT4). In most cases, no further exam is necessary. Beta blockers therapy is recommended in symptomatic thyrotoxicosis with palpitations. Thyroid hormones therapy will be introduced quickly in case of hypothyroidism. Thyroid dysfunctions are not a contra-indication to the continuation of immunotherapy. Due to the high frequency of these complications, close monitoring of the thyroid status is recommended under CPI.
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http://dx.doi.org/10.1016/j.bulcan.2019.10.005DOI Listing
February 2020

The YOMEGA non-inferiority trial - Authors' reply.

Lancet 2019 10;394(10207):1412-1413

Department of Endocrinology, Diabetology and Nutrition, Specialized Center for Obesity Management, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Lyon, France; CarMeN Laboratory, INSERM 1060, Lyon, France; Université Claude Bernard Lyon 1, Lyon, France.

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http://dx.doi.org/10.1016/S0140-6736(19)31914-2DOI Listing
October 2019

Acquired Generalized Lipodystrophy: A New Cause of Anti-PD-1 Immune-Related Diabetes.

Diabetes Care 2019 10 21;42(10):2008-2010. Epub 2019 Aug 21.

French Network of Rare Diseases of Insulin Secretion and Insulin Sensitivity (PRISIS) and FIRENDO Network, Paris and Lyon, France

Objective: Anti-programmed cell death-1 (anti-PD-1) antibodies have revolutionized advanced cancer therapy. Anti-PD-1 therapy is responsible for immune-related adverse events, with frequent endocrine manifestations, including acute-onset type 1 diabetes. Acquired generalized lipodystrophy (AGL) is a rare disease, believed to be immune mediated, characterized by loss of adipose tissue and insulin resistance-associated complications.

Research Design And Methods: We describe the first reported case of AGL induced by immune checkpoint therapy.

Results: A 62-year-old woman with metastatic melanoma treated with nivolumab was referred for major hyperglycemia, hypertriglyceridemia, and nonalcoholic steatohepatitis. She had presented with a rapidly progressive generalized loss of subcutaneous adipose tissue. Diabetes was associated with severe insulin resistance and undetectable plasma leptin. Subcutaneous biopsy revealed atrophic adipose tissue infiltrated with cytotoxic CD8 T lymphocytes and fibrosis.

Conclusions: AGL is an additional immune-related adverse event of anti-PD-1 therapy that leads to severe insulin resistance-associated complications.
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http://dx.doi.org/10.2337/dc18-2535DOI Listing
October 2019

The multifaceted nature of diabetes mellitus induced by checkpoint inhibitors.

Acta Diabetol 2019 Dec 19;56(12):1239-1245. Epub 2019 Aug 19.

Department of Endocrinology and Diabetes, Hospices Civils de Lyon, Lyon-Sud Hospital, Pierre-Bénite, France.

Immune checkpoint inhibitors (CPI) are increasingly being used in oncology, and many autoimmune side effects have been described. Diabetes mellitus (DM) has been reported in approximately 1% of subjects treated with programmed cell death-1 and programmed death ligand 1 (PD-1/PD-L1) inhibitors, alone or in association with CTLA-4 inhibitors. In the present mini-review, we aimed to describe different clinical pictures and pathophysiology associated with these forms of diabetes. Data on CPI-related DM was gathered from the largest case series in the literature and from our centre dedicated to immunotherapy complications (ImmuCare-Hospices Civils de Lyon). Most cases are acute autoimmune insulin-dependent diabetes which are similar to fulminant diabetes (extremely acute onset with concomitant near-normal HbA1c levels). Other cases, however, have a phenotype close to type 2 diabetes or appear as a decompensation of previously known type 2 diabetes. The occurrence of diabetes can also be a complication of autoimmune pancreatitis induced by CPI use. Finally, two cases of diabetes in a context of autoimmune lipoatrophy have recently been described. Regarding the wide variety of CPI-induced diabetes, the discovery of a glucose disorder under CPI should motivate specialised care for aetiological diagnosis and appropriate treatment.
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http://dx.doi.org/10.1007/s00592-019-01402-wDOI Listing
December 2019

Subclinical Hypothyroidism: is it Really Subclinical with Aging?

Aging Dis 2019 Jun 1;10(3):520-529. Epub 2019 Jun 1.

1Service de Gériatrie, Hospices Civils de Lyon, Lyon Sud Hospital, Pierre-Bénite, France.

No recent study has focused on clinical features of subclinical hypothyroidism (SCH), especially in older patients. TSH measurement has remarkably evolved these last 20 years and thus reconsideration is needed. In our prospective multicenter study (2012-2014) including 807 subjects aged <60 years (<60y) and 531 subjects ≥60 years (≥60y), we have monitored 11 hypothyroidism-related clinical signs (hCS) together with TSH, FT4, FT3 and anti-thyroperoxidase antibodies values. hCS expression has been compared in patients with SCH euthyroidism in each age group. The number of hCS above 60y of age were found to be more elevated in the euthyroid population (1.9 1.6, p<0.01) than in the SCH population (2.3 2.6, p=0.41) while increase in hCS is limited to SCH subjects in the <60y group (p<0.01). The percentage of subjects with at least 3 signs increased with SCH in the <60y group (42.6% 25.0%, p<0.01) but not ≥60y (34.4% 33.9%, p=0.96). In older individuals, only three hCS could be related to both SCH and a decreased T3/T4-ratio (0.26 0.27, p<0.01), suggesting either a reduced activity of TSH, or an adaptive response with aging. While hCS are clearly associated with SCH in patients <60y, they are not so informative in older subjects. TSH measurements carried out on the basis of hCS need to be interpreted with caution in aged patients. A reassessment of the TSH reference range in older patients is clearly needed and should be associated to more appropriate monitoring of thyroid dysfunction.
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http://dx.doi.org/10.14336/AD.2018.0817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6538219PMC
June 2019

Attentional bias and response inhibition in severe obesity with food disinhibition: a study of P300 and N200 event-related potential.

Int J Obes (Lond) 2020 01 9;44(1):204-212. Epub 2019 Apr 9.

Centre Intégré de l'Obésité Rhône-Alpes; Fédération Hospitalo-Universitaire DO-iT, Service Endocrinologie-Diabète-Nutrition, Université de Lyon, Groupement Hospitalier Sud, Hospices Civils de Lyon, Lyon, France.

Background/objective: In obesity there is growing evidence for common mechanism between food intake regulation and substance use disorders, especially more attentional bias and less cognitive control. In the present study we investigated whether severely obese subjects with or without disordered eating exhibit electroencephalographic (EEG) event-related potential (ERP) modifications as observed in substance abusers.

Subjects/methods: A total of 90 women were included; 30 in the normal-weight (NW) group (18.5 < BMI < 24.5 kg/m; no food disinhibition or restriction on the Three-Factor Eating Questionnaire) and 60 participants with BMI ≥ 35 kg/m were separated into two groups (n = 30): without food disinhibition (disinhibition score ≤8; ObFD- group) and with food disinhibition (score >8; ObFD+). Clinical and metabolic parameters as well as compartmental aspects (Eating Disorders Inventory-2, EDI-2) were assessed. Participants underwent an ERP recording with an auditory oddball paradigm.

Results: The mean ± SD P300 amplitudes in Pz were significantly (p < 0.05) lower in ObFD- (12.4 ± 4.6) and ObFD+ (12.5 ± 4.4) groups than in the NW group (15.8 ± 5.9). The mean ± SD N200 amplitude in Cz was significantly lower in the ObFD- group (-2.0 ± 5.4) than in the NW group (-5.2 ± 4.2 vs; p = 0.035). N200 Cz amplitude was correlated with EDI-2 Binge eating risk score (ρ = 0.331; p = 0.01), EDI-2 Body Dissatisfaction score (ρ = 0.351; p = 0.007), and Drive for Thinness score (ρ = 0.26; p = 0.05).

Conclusions: The present study provides evidence for reduction of P300 and N200 amplitude in obese women and that N200 amplitude may be related to more disordered eating and eating disorder risk. This leads to consider attentional bias and response inhibition as core mechanisms in obesity and as possible targets for new therapeutic strategy.
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http://dx.doi.org/10.1038/s41366-019-0360-xDOI Listing
January 2020

Efficacy and safety of one anastomosis gastric bypass versus Roux-en-Y gastric bypass for obesity (YOMEGA): a multicentre, randomised, open-label, non-inferiority trial.

Lancet 2019 Mar 6;393(10178):1299-1309. Epub 2019 Mar 6.

CarMeN Laboratory, Université Claude Bernard Lyon 1, INSERM 1060, Lyon, France; Department of Endocrinology, Diabetology and Nutrition, Specialized Center for Obesity Management, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Benite, France.

Background: One anastomosis gastric bypass (OAGB) is increasingly used in the treatment of morbid obesity. However, the efficacy and safety outcomes of this procedure remain debated. We report the results of a randomised trial (YOMEGA) comparing the outcomes of OAGB versus standard Roux-en-Y gastric bypass (RYGB).

Methods: This prospective, multicentre, randomised non-inferiority trial, was held in nine obesity centres in France. Patients were eligible for inclusion if their body-mass index (BMI) was 40 kg/m or higher, or 35 kg/m or higher with the presence of at least one comorbidity (type 2 diabetes, high blood pressure, obstructive sleep apnoea, dyslipidaemia, or arthritis), and were aged 18-65 years. Key exclusion criteria were a history of oesophagitis, Barrett's oesophagus, severe gastro-oesophageal reflux disease resistant to proton-pump inhibitors, and previous bariatric surgery. Participants were randomly assigned (1:1) to OAGB or RYGB, stratified by centre with blocks of variable size; the study was open-label, with no masking required. RYGB consisted of a 150 cm alimentary limb and a 50 cm biliary limb and OAGB of a single gastrojejunal anastomosis with a 200 cm biliopancreatic limb. The primary endpoint was percentage excess BMI loss at 2 years. The primary endpoint was assessed in the per-protocol population and safety was assessed in all randomised participants. This study is registered with ClinicalTrials.gov, number NCT02139813, and is now completed.

Findings: From May 13, 2014, to March 2, 2016, of 261 patients screened for eligibility, 253 (97%) were randomly assigned to OAGB (n=129) or RYGB (n=124). Five patients did not undergo their assigned surgery, and after undergoing their surgery 14 were excluded from the per-protocol analysis (seven due to pregnancy, two deaths, one withdrawal, and four revisions from OAGB to RYGB) In the per-protocol population (n=117 OAGB, n=117 RYGB), mean age was 43·5 years (SD 10·8), mean BMI was 43·9 kg/m (SD 5·6), 176 (75%) of 234 participants were female, and 58 (27%) of 211 with available data had type 2 diabetes. After 2 years, mean percentage excess BMI loss was -87·9% (SD 23·6) in the OAGB group and -85·8% (SD 23·1) in the RYGB group, confirming non-inferiority of OAGB (mean difference -3·3%, 95% CI -9·1 to 2·6). 66 serious adverse events associated with surgery were reported (24 in the RYGB group vs 42 in the OAGB group; p=0·042), of which nine (21·4%) in the OAGB group were nutritional complications versus none in the RYGB group (p=0·0034).

Interpretation: OAGB is not inferior to RYGB regarding weight loss and metabolic improvement at 2 years. Higher incidences of diarrhoea, steatorrhoea, and nutritional adverse events were observed with a 200 cm biliopancreatic limb OAGB, suggesting a malabsorptive effect.

Funding: French Ministry of Health.
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http://dx.doi.org/10.1016/S0140-6736(19)30475-1DOI Listing
March 2019

Fulminant diabetes induced by PD-1 and PD-L1 inhibitors: what about glucose variability?

Acta Diabetol 2019 03 1;56(3):377-378. Epub 2018 Dec 1.

Department of Endocrinology and Diabetes, Hospices Civils de Lyon, Lyon-Sud Hospital, 165 chemin du Grand Revoyet, 69310, Pierre-Bénite, France.

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http://dx.doi.org/10.1007/s00592-018-1262-4DOI Listing
March 2019

3D Chemical Shift-Encoded MRI for Volume and Composition Quantification of Abdominal Adipose Tissue During an Overfeeding Protocol in Healthy Volunteers.

J Magn Reson Imaging 2019 06 16;49(6):1587-1599. Epub 2018 Oct 16.

Univ Lyon, INSA-Lyon, Université Claude Bernard Lyon 1, UJM-Saint Etienne, CNRS, Inserm, CREATIS UMR 5220, U1206, F69621, Lyon, France.

Background: Overweight and obesity are major worldwide health concerns characterized by an abnormal accumulation of fat in adipose tissue (AT) and liver.

Purpose: To evaluate the volume and the fatty acid (FA) composition of the subcutaneous adipose tissue (SAT) and the visceral adipose tissue (VAT) and the fat content in the liver from 3D chemical-shift-encoded (CSE)-MRI acquisition, before and after a 31-day overfeeding protocol.

Study Type: Prospective and longitudinal study.

Subjects: Twenty-one nonobese healthy male volunteers.

Field Strength/sequence: A 3D spoiled-gradient multiple echo sequence and STEAM sequence were performed at 3T.

Assessment: AT volume was automatically segmented on CSE-MRI between L2 to L4 lumbar vertebrae and compared to the dual-energy X-ray absorptiometry (DEXA) measurement. CSE-MRI and MR spectroscopy (MRS) data were analyzed to assess the proton density fat fraction (PDFF) in the liver and the FA composition in SAT and VAT. Gas chromatography-mass spectrometry (GC-MS) analyses were performed on 13 SAT samples as a FA composition countermeasure.

Statistical Tests: Paired t-test, Pearson's correlation coefficient, and Bland-Altman plots were used to compare measurements.

Results: SAT and VAT volumes significantly increased (P < 0.001). CSE-MRI and DEXA measurements were strongly correlated (r = 0.98, P < 0.001). PDFF significantly increased in the liver (+1.35, P = 0.002 for CSE-MRI, + 1.74, P = 0.002 for MRS). FA composition of SAT and VAT appeared to be consistent between localized-MRS and CSE-MRI (on whole segmented volume) measurements. A significant difference between SAT and VAT FA composition was found (P < 0.001 for CSE-MRI, P = 0.001 for MRS). MRS and CSE-MRI measurements of the FA composition were correlated with the GC-MS results (for ndb: r  = 0.83 P < 0.001, r  = 0.84, P = 0.001; for nmidb: r  = 0.74, P = 0.006, r  = 0.66, P = 0.020) DATA CONCLUSION: The follow-up of liver PDFF, volume, and FA composition of AT during an overfeeding diet was demonstrated through different methods. The CSE-MRI sequence associated with a dedicated postprocessing was found reliable for such quantification.

Level Of Evidence: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:1587-1599.
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http://dx.doi.org/10.1002/jmri.26532DOI Listing
June 2019

MFN2-associated lipomatosis: Clinical spectrum and impact on adipose tissue.

J Clin Lipidol 2018 Nov - Dec;12(6):1420-1435. Epub 2018 Jul 25.

Sorbonne Université, Inserm UMR_S 938, Centre de Recherche Saint-Antoine, Institut Hospitalo-Universitaire de Cardio-métabolisme et Nutrition (ICAN), Paris, France; Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Antoine, Laboratoire Commun de Biologie et Génétique Moléculaires, Paris, France.

Background: Multiple symmetric lipomatosis (MSL) is characterized by upper-body lipomatous masses frequently associated with metabolic and neurological signs. MFN2 pathogenic variants were recently implicated in a very rare autosomal recessive form of MSL. MFN2 encodes mitofusin-2, a mitochondrial fusion protein previously involved in Charcot-Marie-Tooth neuropathy.

Objective: To investigate the clinical, metabolic, tissular, and molecular characteristics of MFN2-associated MSL.

Methods: We sequenced MFN2 in 66 patients referred for altered fat distribution with one or several lipomas or lipoma-like regions and performed clinical and metabolic investigations in patients with positive genetic testing. Lipomatous tissues were studied in 3 patients.

Results: Six patients from 5 families carried a homozygous p.Arg707Trp pathogenic variant, representing the largest reported series of MFN2-associated MSL. Patients presented both lipomatous masses and a lipodystrophic syndrome (lipoatrophy, low leptinemia and adiponectinemia, hypertriglyceridemia, insulin resistance and/or diabetes). Charcot-Marie-Tooth neuropathy was of highly variable clinical severity. Lipomatous tissue mainly contained hyperplastic unilocular adipocytes, with few multilocular cells. It displayed numerous mitochondrial alterations (increased number and size, structural defects). As compared to control subcutaneous fat, mRNA and protein expression of leptin and adiponectin was strikingly decreased, whereas the CITED1 and fibroblast growth factor 21 (FGF21) thermogenic markers were strongly overexpressed. Consistently, serum FGF21 was markedly increased, and F-FDG-PET-scan revealed increased fat metabolic activity.

Conclusion: MFN2-related MSL is a novel mitochondrial lipodystrophic syndrome involving both lipomatous masses and lipoatrophy. Its complex neurological and metabolic phenotype justifies careful clinical evaluation and multidisciplinary care. Low leptinemia and adiponectinemia, high serum FGF21, and increased F-FDG body fat uptake may be disease markers.
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http://dx.doi.org/10.1016/j.jacl.2018.07.009DOI Listing
October 2019

A Predictive Model of Weight Loss After Roux-en-Y Gastric Bypass up to 5 Years After Surgery: a Useful Tool to Select and Manage Candidates to Bariatric Surgery.

Obes Surg 2018 11;28(11):3393-3399

Metabolic Center, Hôpital du Valais, Sion, Switzerland.

Introduction: Different factors, such as age, gender, preoperative weight but also the patient's motivation, are known to impact outcomes after Roux-en-Y gastric bypass (RYGBP). Weight loss prediction is helpful to define realistic expectations and maintain motivation during follow-up, but also to select good candidates for surgery and limit failures. Therefore, developing a realistic predictive tool appears interesting.

Patients/methods: A Swiss cohort (n = 444), who underwent RYGBP, was used, with multiple linear regression models, to predict weight loss up to 60 months after surgery considering age, height, gender and weight at baseline. We then applied our model on two French cohorts and compared predicted weight to the one finally reached. Accuracy of our model was controlled using root mean square error (RMSE).

Results: Mean weight loss was 43.6 ± 13.0 and 40.8 ± 15.4 kg at 12 and 60 months respectively. The model was reliable to predict weight loss (0.37 < R < 0.48) and RMSE between 5.0 and 12.2 kg. High preoperative weight and young age were positively correlated to weight loss, as well as male gender. Correlations between predicted weight and real weight were highly significant in both validation cohorts (R ≥ 0.7 and P < 0.01) and RMSE increased throughout follow-up between 6.2 and 15.4 kg.

Conclusion: Our statistical model to predict weight loss outcomes after RYGBP seems accurate. It could be a valuable tool to define realistic weight loss expectations and to improve patient selection and outcomes during follow-up. Further research is needed to demonstrate the interest of this model in improving patients' motivation and results and limit the failures.
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http://dx.doi.org/10.1007/s11695-018-3355-0DOI Listing
November 2018

Are we really assessing safety and efficacy of bariatric surgery in patients suffering from bipolar disorder?

Surg Obes Relat Dis 2018 05 3;14(5):723-724. Epub 2018 Feb 3.

Tertiary care center of bariatric surgery Hospices Civils de Lyon, Université Lyon 1 Pierre Bénite, France; Department of Digestive Surgery University Hospital Edouard Herriot Hospices Civils de Lyon Lyon Cedex 03, France.

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http://dx.doi.org/10.1016/j.soard.2018.01.037DOI Listing
May 2018

Deep brain stimulation as a therapeutic option for obesity: A critical review.

Obes Res Clin Pract 2018 May - Jun;12(3):260-269. Epub 2018 Feb 21.

Service d'Endocrinologie-Diabétologie-Maladies de la nutrition, Centre Intégré de l'Obésité, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre Bénite, France; Unité INSERM 1060, Laboratoire CARMEN, CENS-Centre Européen pour la Nutrition et la Santé, Centre de Recherche en Nutrition Humaine Rhône-Alpes., Université Claude Bernard Lyon 1, Pierre Bénite, France.

Despite a better understanding of obesity pathophysiology, treating this disease remains a challenge. New therapeutic options are needed. Targeting the brain is a promising way, considering both the brain abnormalities in obesity and the effects of bariatric surgery on the gut-brain axis. Deep brain stimulation could be an alternative treatment for obesity since this safe and reversible neurosurgical procedure modulates neural circuits for therapeutic purposes. We aimed to provide a critical review of published clinical and preclinical studies in this field. Owing to the physiology of eating and brain alterations in people with obesity, two brain areas, namely the hypothalamus and the nucleus accumbens are putative targets. Preclinical studies with animal models of obesity showed that deep brain stimulation of hypothalamus or nucleus accumbens induces weight loss. The mechanisms of action remain to be fully elucidated. Preclinical data suggest that stimulation of nucleus accumbens reduces food intake, while stimulation of hypothalamus could increase resting energy expenditure. Clinical experience with deep brain stimulation for obesity remains limited to six patients with mixed results, but some clinical trials are ongoing. Thus, drawing clear conclusions about the effectiveness of this treatment is not yet possible, even if the results of preclinical studies are encouraging. Future clinical studies should examine its efficacy and safety, while preclinical studies could help understand its mechanisms of action. We hope that our review will provide ways to design further studies.
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http://dx.doi.org/10.1016/j.orcp.2018.02.004DOI Listing
April 2019

An artificial neural network to predict resting energy expenditure in obesity.

Clin Nutr 2018 10 1;37(5):1661-1669. Epub 2017 Sep 1.

Centre Intégré de l'Obésité Rhône-Alpes, Fédération Hospitalo-Universitaire DO-iT, Department of Endocrinology and Nutrition, Groupement Hospitalier Sud, Hospices Civils de Lyon, Lyon, France; Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RA), Centre Européen Nutrition et Santé (CENS), Lyon, France; Laboratoire CarMeN, Unité INSERM U1060 - INRA 1235 - INSA-Lyon, Université Claude Bernard Lyon 1, Lyon, France.

Background & Aims: The resting energy expenditure (REE) determination is important in nutrition for adequate dietary prescription. The gold standard i.e. indirect calorimetry is not available in clinical settings. Thus, several predictive equations have been developed, but they lack of accuracy in subjects with extreme weight including obese populations. Artificial neural networks (ANN) are useful predictive tools in the area of artificial intelligence, used in numerous clinical fields. The aim of this study was to determine the relevance of ANN in predicting REE in obesity.

Methods: A Multi-Layer Perceptron (MLP) feed-forward neural network with a back propagation algorithm was created and cross-validated in a cohort of 565 obese subjects (BMI within 30-50 kg m) with weight, height, sex and age as clinical inputs and REE measured by indirect calorimetry as output. The predictive performances of ANN were compared to those of 23 predictive REE equations in the training set and in two independent sets of 100 and 237 obese subjects for external validation.

Results: Among the 23 established prediction equations for REE evaluated, the Harris & Benedict equations recalculated by Roza were the most accurate for the obese population, followed by the USA DRI, Müller and the original Harris & Benedict equations. The final 5-fold cross-validated three-layer 4-3-1 feed-forward back propagation ANN model developed in that study improved precision and accuracy of REE prediction over linear equations (precision = 68.1%, MAPE = 8.6% and RMSPE = 210 kcal/d), independently from BMI subgroups within 30-50 kg m. External validation confirmed the better predictive performances of ANN model (precision = 73% and 65%, MAPE = 7.7% and 8.6%, RMSPE = 187 kcal/d and 200 kcal/d in the 2 independent datasets) for the prediction of REE in obese subjects.

Conclusions: We developed and validated an ANN model for the prediction of REE in obese subjects that is more precise and accurate than established REE predictive equations independent from BMI subgroups. For convenient use in clinical settings, we provide a simple ANN-REE calculator available at: https://www.crnh-rhone-alpes.fr/fr/ANN-REE-Calculator.
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http://dx.doi.org/10.1016/j.clnu.2017.07.017DOI Listing
October 2018