Leveraging OGTT derived metabolic features to detect Binge-eating disorder in individuals with high weight: a “seek out” machine learning approach

Leveraging OGTT derived metabolic features to detect Binge-eating disorder in individuals with high weight: a “seek out” machine learning approach | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Leveraging OGTT derived metabolic features to detect Binge-eating disorder in individuals with high weight: a “seek out” machine learning approach Cristina Segura-Garcia, Marianna Rania, Anna Procopio, Paolo Zaffino, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4675042/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 18 Feb, 2025 Read the published version in Translational Psychiatry → Version 1 posted 10 You are reading this latest preprint version Abstract Binge eating disorder (BED) carries a 6 times higher risk for obesity and accounts for roughly 30% of type 2 diabetes cases. Timely identification of early glycemic disturbances and comprehensive treatment can impact on the likelihood of associated metabolic complications and the overall outcome. Machine learning (ML) techniques were trained with static and dynamic glucose-derived measures to detect BED among 281 individuals with high weight. The pipeline (training, validation, testing) was conducted twice, on two different datasets (2 hours, and 5 hours-long glucose load). After features selection, multiple ML algorithms were trained to classify the sample. The best classifier was then applied to an independent cohort (N = 21). A sensitivity-based analysis was run to investigate the relevance of each feature in the classification. 14 features were selected as relevant, with the support vector machine showing the best performance in classifying BED in both models. The model on the 5 hours-long OGTT exhibited the best metrics (sensitivity = 0.75, specificity = 0.67, F score = 0.71) diagnosing BED in 7 out of 10 cases. Sex, HOMA-IR, HbA1c and plasma glucose in different times, and hypoglycemia events were the most sensitive features for BED diagnosis. This study is the first to use metabolic hallmarks to train ML algorithms for detecting BED in individuals at high risk for metabolic complications. ML techniques applied to objective and reliable glycemic features might prompt the identification of BED among individuals at high risk for metabolic complications, enabling timely and tailored multidisciplinary treatment. Health sciences/Diseases/Psychiatric disorders/Addiction Health sciences/Biomarkers/Diagnostic markers BED binge-eating ML OGTT hypoglycemia Introduction Binge Eating Disorder (BED) is the most prevalent eating disorder (ED) worldwide ( 1 , 2 ). It is characterized by recurrent episodes of objective binge eating (i.e., consuming large amounts of food in a short period of time) that occur without the physiological sensation of hunger and that are not followed by compensatory behaviors. Core symptoms of the disorder include secrecy, the feeling of losing control overeating, and intense negative emotions such as guilt, shame, and disgust ( 3 ). Far from being solely an “overeating” issue, authors and a plethora of other studies in the last decades have contributed to edge the binge-eating phenomenon towards a broader frame where personality facets, maladaptive schemes, difficulties in understanding, regulating and coping with emotions, impaired decision making, and mood ( 4 – 7 ) remarkably network and account for its considerable complexity ( 8 – 11 ). In contrast to bulimia nervosa, individuals with BED do not engage in behaviors aimed at weight control ( 3 ). Therefore, the untreated illness naturally progress to obesity, the related medical complications ( 12 – 14 ), and other disabling somatic conditions ( 15 , 16 ). Findings suggest that individuals with BED suffer a substantial delay in accessing proper treatment, with the longest duration of untreated illness among all EDs ( 17 ). The secretive nature of binge eating, denial or minimizing of symptoms, the perceived stigma, and the self-blame, guilt and shame that individuals experience within the disorder, surely constitute an inherent barrier to both diagnosis and treatment ( 18 ). On the other hand, many individuals suffering from BED seek care for weight loss or obesity related medical complications rather than for the eating disorder itself ( 19 ). De facto, BED is associated in the long-term with an unfavourable metabolic and inflammatory profile compared to non-BED obesity ( 22 ), and preliminary findings support that disturbances in the glycemic homeostasis may be detectable at an early stage in these patients ( 23 ). Specifically, symptomatic and severe hypoglycemia is more frequently endorsed by this group in the late stages of the extended glucose load. In these settings, individuals rarely are asked about binge-eating ( 20 ), and health practitioners within these services may not have the attitude, the training or expertise in suspecting, diagnosing, or addressing an underlying ED( 21 ). As such, both patients and clinicians related factors, within a plethora of other barriers, prevent early detection and stage-specific intervention, unfavourably affecting the illness trajectory and outstanding the clinical and public healthcare costs ( 24 ). New tools to aid the diagnostic process, shorten the diagnostic delay and the access to treatment, especially for health providers not specialized in the field of mental health and ED, need to be validated and integrated into clinical practice. Artificial intelligence, increasingly prevalent in the mental health care domain, enables the analysis of big data, assess associations between variables, and identifies the most relevant clinical or instrumental features for the diagnostic and treatment process ( 25 ). Machine learning (ML) techniques, a branch of artificial intelligence, have the potential for optimizing prediction of diseases, and have already been suggested for the diagnostic ( 26 – 29 ) and the long-term prediction of outcomes of ED ( 30 , 31 ), although evidence is still in its infancy ( 32 ). Yet, employing algorithms relying solely on psychological variables requires psychometric and/or psychiatric examination, thus confines their use to mental health care settings. Training ML algorithms with metabolic features known to be altered in BED could allow the prompt detection of at-risk individuals or those already affected by the disorder within a larger user base. In the present study ML techniques were used to test the ability of glucose metabolism related features to predict BED among individuals seeking care for the treatment of obesity. Currently, no studies have attempted the use of this technique with a similar purpose. We hypothesized that glucose metabolism related features, embedded in the metabolic screening individuals undergo during the diagnostic pathway for obesity, could likely trace individuals at risk or already experiencing BED. ML could constitute an objective, reliable, and reproducible diagnostic strategy for professionals handling obesity and different expertise. Similarly, it could inform screening, identification, and targeted medical management. Methods and Materials Dataset and pre-processing The dataset for the analysis was gathered from a larger dataset that collects metabolic and psychiatric data from individuals admitted to the diagnostic and therapeutic network of care for obesity (PDTA Obesità) of the University Hospital Renato Dulbecco of Catanzaro (Italy) (eligibility, metabolic and psychiatric examinations in ( 23 )). The PDTA Obesità is a dedicated pathway of care for obesity networked by an interdisciplinary team of specialists (internal medicine, psychiatry, and surgery). The initial dataset included 313 potential cases registered between May 2017 (start of the recruitment) and June 2023 (date of extraction). The dataset was filtered for acquisition of plasma glucose levels at multiple time points over a range between 2 and 5 hours after the oral glucose tolerance test (OGTT), no diabetes, and psychiatric examination for BED diagnosis. The study sample included only subjects negative for type 2 diabetes. A set of independent variables known to be altered in BED were chosen to aid classification of group membership. Demographics (age, sex at birth), BMI, OGTT-derived plasma glucose and insulin values, and dynamic measures of insulin secretion/sensitivity/resistance were included in the analysis for classifying participants in BED/non-BED. Additional derived features, such as curve skewness, first maximum peak, and the number of acquisitions above the detectable value have been computed (Table S1 ). Missing values due to discontinuation of the glucose load (i.e., hypoglycemia) prevented the calculation of OGTT derived measures, resulting in the exclusion of 32 cases. Data transformation for features scaling and standardization was run with the Standard Scaler algorithm from scikit-learn ( 33 ). The final dataset, complete with all the measures for the analysis (Table S1 ), consisted of 281 cases. Experimental Pipeline and data analysis The analysis included three consecutive steps (i.e., training, validation, testing; Fig. 1 ). The whole experimental pipeline was firstly conducted on the complete dataset (N = 281, complete acquisition of glucose plasma during the 2 hours long OGTT; Model 1). It was further run considering only cases who completed the extended 5 hours long OGTT (N = 123; Model 2). Accordingly, two ML models were trained, validated, and tested. To guarantee independent and unbiased datasets, the initial dataset was split in three for the training (218 for Model 1, 88 for Model 2), validation (49 for Model 1, 28 for Model 2), and testing steps (14 for Model 1, 7 for Model 2). For the training step, the dataset was further split in the training and testing dataset (80% and 20%, respectively). Feature selection was performed by running the Recursive Feature Elimination method (RFE) (Fig. 1 -a3) on 150 different folds. RFE algorithm works by iterative removal of irrelevant or redundant features until a desired number of informative features is reached ( 34 ). The set of features that survived the RFE in each fold were recorded to build a global ranking list, from which the 15 most frequent ones were finally selected. This subset of selected features was then used to train five different ML algorithms, both linear and non-linear, to classify the sample in BED/non-BED. ML algorithms included Decision Tree (DT) ( 35 ), Random Forrest Classifier (RFC) ( 36 ), Extra Tree (ET) ( 37 ), Support Vector Machine Classifier (SVC) ( 38 ), Logistic Regression (LR) ( 39 ) (more details in Table S2; Fig. 1 -a4). Also in this case, to ensure a robust selection of the best classifier, this procedure was repeated 150 times, randomly shuffling the cases included into the training/testing datasets (red box in Fig. 1 -A). Results The final dataset included 281 cases (133 BED, 148 non-BED), all White. Respectively, mean age was 40.2 ± 13.1 and 44.4 ± 11.7, and females were overrepresented in both groups (85.7%, 67.6%). Non-BED cases exhibited lower BMI than BED cases (41.4 ± 7.7; 39.1 ± 7.4). RFE dropped several items from the models, providing evidence for 15 significant features for both Model 1 and Model 2 (Table 1 ). Sex, BMI, plasma glucose at the 120’ min, maximum glucose value during the load, hypoglycemia events, Area Under Curve for Insulin and Glucose (AUC Ins-Glu during the 0- to 30-min of the OGTT), skewness of the curve, and three indexes of insulin sensitivity [Gutt’s insulin sensitivity index (Gutt-ISI), Stumvoll index and HOMA-IR] were depicted in both models as significant in discerning BED over non-BED (Table 1 ). Table 1 Performance of the best classifier on the validation set. Results for the Model 1 and 2 . Best Classifier Cases Sensitivity Specificity F 1 score Accuracy Features Model 1 SVCP 49 0.5 0.8 0.58 0.67 AUC Ins−glu 0–30 AUC glu BMI G 30 , G 60 , G 90 , G 120 GUTT Hb1AC HOMA-IR Hypo tot Max Gluc Sex Skewness Stumvoll ISI Model 2 SVCP 28 0.86 0.43 0.71 0.64 AUC Ins−glu 0–30 BMI G 60 , G 120 , G 150 , G 210 , G 270 , G 300 GUTT HOMA-IR Hypo tot Max Gluc Sex Skewness Stumvoll ISI SVCP: support vector machine classifier; BMI: body mass index; HOMA-IR: homeostatic model assessment insulin resistance; ISI: insulin sensitivity index. Table 2 Testing. Results for the two models. Model Cases Sensitivity Specificity F 1 score Accuracy TP TN FP FN Model 1 14 0.35 0.67 0.46 0.5 3 4 2 5 Model 2 7 0.75 0.67 0.67 0.71 2 3 1 1 Model 1 tested on cases with complete 2 hours long OGTT; Model 2 tested on cases with complete 5 hours long OGTT. Across all five ML algorithms, the SVCP outperformed in classifying the groups. For Model 1 (2 hours long OGTT), the classifier correctly identified half of the cases with BED (sensitivity = 0.5), and 80% of non-BED cases (specificity = 0.8) (Table 1 ). On the 5 hours long OGTT dataset (Model 2), the classifier was more sensitive (0.86), but less specific (0.43) (Table 1 ). Accuracy was similar for the two Models (0.67 vs 0.64). Figures S1 -2 show the sensitivity-based analysis conducted on the validation set and for all the classifiers reported in Table S2. Sex, HOMA-IR, Hb1AC, and skewness of the glucose curve scored higher in the Model 1 classification ability. Plasma glucose at the 120’ minute was the most accurate feature of the Model 2. Table 2 reports the performance of the proposed two models tested on the testing cohort. Model 2 exceeded the performance of Model 1 in terms of sensitivity (0.7), specificity (0.67), accuracy (0.71), and the overall ability to predict class membership (0.67). Discussion Present study used a ML approach and data from individuals accessing the care for obesity and no diabetes to identify individual-level metabolic features that could be associated with the diagnosis of BED. It further aimed to investigate the predictive diagnostic accuracy of a pure metabolic based ML approach in screening BED among seekers care for obesity. Results suggest that sex, BMI, and glucose metabolism-related variables such as glucose levels at specific times of the OGTT, skewness of the glucose load, insulin sensitivity indexes, and hypoglycemia events could be crucial when it comes to identifying those individuals suffering from BED among patients with obesity. Cross-sectional studies in population with no diabetes have demonstrated that binge-eating associates with fasting hyperglycemia, insulin resistance, and higher frequency of pre-diabetes phenotypes (e.g., impaired glucose tolerance)( 23 , 42 – 44 ). Hypoglycemia events occurring with neurogenic or neuroglycopenic symptoms and typically reverting with carbohydrates intake (i.e., reactive hypoglycemia)( 45 ) have been recently studied and preliminarily associated to binge-eating during an extended laboratory stimulation, suggesting that individuals suffering from BED, obesity, but no diabetes would suffer from more frequent and more severe hypoglycemia events with respect to the counterpart with no ED ( 23 ). More consistently, longitudinal studies have showed that binge-eating contributes to higher odds of metabolic syndrome components in the long-term beyond the risk attributable to obesity alone ( 46 , 47 ). Present results confirm, but more importantly, leverage the relevance of these metabolic correlates in their potentiality to specifically cluster BED vs non-BED in non-psychiatric settings. Overall, this study suggests that modeling OGTT-related metabolic features together with demographics and anthropometrics could assist the diagnostic process, potentially identifying BED in five to seven out of ten of cases, depending on data collection. Specifically, the Models performed similarly in classifying cases not at risk (67%), but the 5 hours long OGTT based Model outperformed in terms of sensitivity (75%), accuracy (71%), and overall ability to predict class membership (0.67 vs 0.47). The relative weight of hypoglycemia in the model, together with the evidence that individuals with BED would experience more hypoglycemia events during the laboratory test at the latest stages of the glucose load (4th -5th hour), could have contributed to the better performance of Model 2 over Model 1. The diagnostic accuracy of the models is surprisingly encouraging considering the diagnostic accuracy the specifically tailored psychometric instruments exhibit. A recent systematic review compared the performances of the most widely used screening questionnaires in detecting BED in overweight or obesity and found high variability across studies ( 48 ). Only moderate accuracy was found for the Eating Disorders Questionnaire (EDE-Q) (sensibility: 0.40–0.87; specificity: 0.62-1), and the Binge Eating Scale (BES) (sensibility: 0.51–0.98; specificity: 0.48–0.76), still considered the most widely used psychometrics tools in the field. Further, the ML algorithms hereby used to detect BED as a psychiatric disorder were exclusively fed with glycemic/insulinemic and other non-psychological features. Authors may, accordingly, speculate that adding psychometric tools specifically designed for BED and tailored to overweight and obesity (e.g., the Eating Behaviors Assessment for Obesity,( 49 )) to the training could potentially booster the diagnostic accuracy of the present model. Other studies have previously tested ML techniques to evaluate the risk, assist the investigation, or predict the outcome of BED ( 26 , 29 , 31 , 50 ). Eric Stice and Christopher D. Desjardins in 2018 used a multiple approach-based classification tree analysis to investigate the interactions of risk factors in the prediction of the onset of EDs in a large dataset of individuals at high risk. The onset of BED was accurately predicted in 64% of cases by a complex four-way interaction between body dissatisfaction, overeating, dieting, and thin-ideal internalization ( 29 ). In the investigation of Linardon and colleagues, a ML-based decision tree classification analysis captured 70% of binge-eaters by examining eating behaviors and cognitions. The two-way interaction of low intuitive eating and high dichotomous thinking resulted largely associated with being classified with recurrent binge eating (84% incidence)( 26 ). Lastly, Forrest L.N. tested two ML approaches to evaluate treatment outcomes in a sample of individuals suffering from BED randomized to six months behavioural or stepped-care treatments. Authors concluded for a slight advantage of the ML over the traditional models, claiming for further empirical confirmation in the EDs literature ( 31 ). Still recognizing the relevance of ML-based investigations based on psychological measures, they require specific training and specialized settings for the analysis. BED goes undiagnosed for many years and suffers from the greatest delay to proper treatments of all EDs ( 17 ). This is partly due to either patient or clinician-related factors ( 18 , 21 ), but surely contributes to the great medical burden and overall disability BED associates with. Further, treatment outcomes often deviate from the expectations ( 51 , 52 ). The highest prevalence of BED is found in clinical samples attending weight loss programs or bariatric surgery ( 53 , 54 ). Training ML algorithms with objective measures embedded within the medical screening individuals suffering from BED could undergo in these settings, could enable a prompt detection in non-specialized settings, would generate more targeted interventions and anticipate clinical progression. To our knowledge, no similar evidence exists so far. The current study is the first that has attempted training ML to diagnose BED basing on objective measures (OGTT-derived features), pioneering the field of metabolic based AI applied to BED. With respect to other studies that used self-report binge episodes to corroborate the diagnosis ( 26 ), BED was diagnosed clinically, thereby enhancing the accuracy of the results. Further analyses on larger datasets and considering other valuable biomarkers could enhance modeling performances and translate to clinical practice its use to inform clinical decisions. Within these strengths, some limitations should be addressed. Embedded within the methodology used, no information can be extracted about the nature of associations between the relevant features and BED class (e.g., higher Hb1Ac in BED vs non-BED). Further, authors acknowledge that the cross-sectional design prevent to infer any causal or temporal association between variables. Although distinct methods were applied to avoid overfitting (i.e., scaling, splitting, features selection with the RFE), an inflation in model accuracy due to the sample size cannot be excluded. The sample was all White, and not gender balanced. Accordingly, results may not be generalizable to samples with other characteristics. Finally, authors selected for the analysis the most informative metabolic features so far associated with BED and known to constitute early markers of late metabolic disruption (e.g., diabetes, metabolic syndrome); still, we recognize that the use of a different set of features or more advanced statistical methodology could produce distinct and perhaps more significant results. Declarations Competing interests The authors declare that they have no competing interests. Ethics approval and consent to participate Eligible patients were fully informed about the aim and the procedures of the study, and that participation was voluntary and free from any compensation. All participants gave written informed consent. The study was approved by the institutional review boards (Local Ethical Committee, n. 53/2013), and all the procedures were performed in accordance with the principles of the Declaration of Helsinki. Funding No fundings were received for this study. 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Longitudinal study of the diagnosis of components of the metabolic syndrome in individuals with binge-eating disorder. Am J Clin Nutr (2010) 91:1568–1573. doi: 10.3945/ajcn.2010.29203 Abraham TM, Massaro JM, Hoffmann U, Yanovski JA, Fox CS. Metabolic characterization of adults with binge eating in the general population: the Framingham Heart Study. Obesity (Silver Spring) (2014) 22:2441–9. doi: 10.1002/oby.20867 House ET, Lister NB, Seidler AL, Li H, Ong WY, McMaster CM, Paxton SJ, Jebeile H. Identifying eating disorders in adolescents and adults with overweight or obesity: A systematic review of screening questionnaires. Int J Eat Disord (2022) 55:1171–1193. doi: 10.1002/EAT.23769 Segura-Garcia C, Aloi M, Rania M, de Filippis R, Carbone EA, Taverna S, Papaianni MC, Liuzza MT, De Fazio P. Development, validation and clinical use of the Eating Behaviors Assessment for Obesity (EBA-O). Eat Weight Disord (2022) 27:2143–2154. doi: 10.1007/s40519-022-01363-0 Raab D, Baumgartl H, Buettner R. Machine Learning Based Diagnosis of Binge Eating Disorder Using EEG Recordings.2020. Bardone-Cone AM, Alvarez A, Gorlick J, Koller KA, Thompson KA, Miller AJ. Longitudinal follow-up of a comprehensive operationalization of eating disorder recovery: Concurrent and predictive validity. Int J Eat Disord (2019) 52:1052–1057. doi: 10.1002/EAT.23128 Salvia MG, Ritholz MD, Craigen KLE, Quatromoni PA. Women’s perceptions of weight stigma and experiences of weight-neutral treatment for binge eating disorder: A qualitative study. EClinicalMedicine (2022) 56: doi: 10.1016/J.ECLINM.2022.101811 De Zwaan M. Binge eating disorder and obesity. Int J Obes (2001) 25:S51–S55. doi: 10.1038/sj.ijo.0801699 Mitchell JE, King WC, Pories W, Wolfe B, Flum DR, Spaniolas K, Bessler M, Devlin M, Marcus MD, Kalarchian M, et al. Binge eating disorder and medical comorbidities in bariatric surgery candidates. Int J Eat Disord (2015) 48:471–476. doi: 10.1002/EAT.22389 Additional Declarations The authors have declared there is NO conflict of interest to disclose Supplementary Files Supplementarymaterial.docx Cite Share Download PDF Status: Published Journal Publication published 18 Feb, 2025 Read the published version in Translational Psychiatry → Version 1 posted Editorial decision: revise 04 Dec, 2024 Review # 1 received at journal 30 Sep, 2024 Review # 2 received at journal 27 Sep, 2024 Reviewer # 2 agreed at journal 25 Sep, 2024 Reviewer # 1 agreed at journal 09 Sep, 2024 Reviewers invited by journal 04 Sep, 2024 Submission checks completed at journal 05 Jul, 2024 First submitted to journal 04 Jul, 2024 Unknown event 03 Jul, 2024 Editor assigned by journal 02 Jul, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Segura-Garcia","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAsklEQVRIiWNgGAWjYPACGwYGZhBtQLyWNJgW4vUchjGI0CLf3n5NuqLmfOJ2dubHHxgK/hDWYnDmTJnkmWO3E3c2swFdRYzDDCRy0iQb2G4nbjjMw5BAlBb5+W+AWv6dA2s5QJz3b7Afk2xsOwDSwthAnMPO5DBbNvYlG284zGbMkGBgTITD2o8/vNnwzU52w/nDjz98+CNHhMMYeJDckkCMBgYG9gfEqRsFo2AUjIKRCwAJ9DbW2k6RFQAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0002-5756-3045","institution":"University Magna Græcia, Catanzaro, Italy","correspondingAuthor":true,"prefix":"","firstName":"Cristina","middleName":"","lastName":"Segura-Garcia","suffix":""},{"id":349378815,"identity":"23c59824-35ce-41ae-8d42-bc490bf5a8b7","order_by":1,"name":"Marianna Rania","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Marianna","middleName":"","lastName":"Rania","suffix":""},{"id":349378816,"identity":"53c2d893-805d-426d-bc17-55d654d3cc28","order_by":2,"name":"Anna 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Fiorentino","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Teresa","middleName":"Vanessa","lastName":"Fiorentino","suffix":""},{"id":349378820,"identity":"c1c0cd51-4f68-4399-91d0-f8e4ecc1160f","order_by":6,"name":"Francesco Andreozzi","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Francesco","middleName":"","lastName":"Andreozzi","suffix":""},{"id":349378821,"identity":"eeb47e38-a18a-4e22-b6c1-03c2ad671fc8","order_by":7,"name":"Carlo Cosentino","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Carlo","middleName":"","lastName":"Cosentino","suffix":""},{"id":349378822,"identity":"da6c8f8a-cac3-4e2b-9ab3-c8614ec6520a","order_by":8,"name":"Franco Arturi","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Franco","middleName":"","lastName":"Arturi","suffix":""}],"badges":[],"createdAt":"2024-07-02 14:40:52","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4675042/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4675042/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41398-025-03281-y","type":"published","date":"2025-02-18T05:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":76674882,"identity":"d2576a60-7522-40d0-80bb-24bf9c7f9902","added_by":"auto","created_at":"2025-02-19 14:18:10","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":642022,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4675042/v1/043db7a8-5e34-42b1-8c29-346cc628e15b.pdf"},{"id":67119625,"identity":"6724bff7-9808-435d-89b4-43101f24cd73","added_by":"auto","created_at":"2024-10-21 11:04:27","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":209616,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"Supplementarymaterial.docx","url":"https://assets-eu.researchsquare.com/files/rs-4675042/v1/0c61593260641e72c42663d6.docx"}],"financialInterests":"The authors have declared there is \u003cb\u003eNO\u003c/b\u003e conflict of interest to disclose","formattedTitle":"Leveraging OGTT derived metabolic features to detect Binge-eating disorder in individuals with high weight: a “seek out” machine learning approach","fulltext":[{"header":"Introduction","content":"\u003cp\u003eBinge Eating Disorder (BED) is the most prevalent eating disorder (ED) worldwide (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). It is characterized by recurrent episodes of objective binge eating (i.e., consuming large amounts of food in a short period of time) that occur without the physiological sensation of hunger and that are not followed by compensatory behaviors. Core symptoms of the disorder include secrecy, the feeling of losing control overeating, and intense negative emotions such as guilt, shame, and disgust (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eFar from being solely an “overeating” issue, authors and a plethora of other studies in the last decades have contributed to edge the binge-eating phenomenon towards a broader frame where personality facets, maladaptive schemes, difficulties in understanding, regulating and coping with emotions, impaired decision making, and mood (\u003cspan additionalcitationids=\"CR5 CR6\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e–\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e) remarkably network and account for its considerable complexity (\u003cspan additionalcitationids=\"CR9 CR10\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e–\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn contrast to bulimia nervosa, individuals with BED do not engage in behaviors aimed at weight control (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Therefore, the untreated illness naturally progress to obesity, the related medical complications (\u003cspan additionalcitationids=\"CR13\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e–\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e), and other disabling somatic conditions (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eFindings suggest that individuals with BED suffer a substantial delay in accessing proper treatment, with the longest duration of untreated illness among all EDs (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). The secretive nature of binge eating, denial or minimizing of symptoms, the perceived stigma, and the self-blame, guilt and shame that individuals experience within the disorder, surely constitute an inherent barrier to both diagnosis and treatment (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). On the other hand, many individuals suffering from BED seek care for weight loss or obesity related medical complications rather than for the eating disorder itself (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). De facto, BED is associated in the long-term with an unfavourable metabolic and inflammatory profile compared to non-BED obesity (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e), and preliminary findings support that disturbances in the glycemic homeostasis may be detectable at an early stage in these patients (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). Specifically, symptomatic and severe hypoglycemia is more frequently endorsed by this group in the late stages of the extended glucose load. In these settings, individuals rarely are asked about binge-eating (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e), and health practitioners within these services may not have the attitude, the training or expertise in suspecting, diagnosing, or addressing an underlying ED(\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAs such, both patients and clinicians related factors, within a plethora of other barriers, prevent early detection and stage-specific intervention, unfavourably affecting the illness trajectory and outstanding the clinical and public healthcare costs (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eNew tools to aid the diagnostic process, shorten the diagnostic delay and the access to treatment, especially for health providers not specialized in the field of mental health and ED, need to be validated and integrated into clinical practice.\u003c/p\u003e \u003cp\u003eArtificial intelligence, increasingly prevalent in the mental health care domain, enables the analysis of big data, assess associations between variables, and identifies the most relevant clinical or instrumental features for the diagnostic and treatment process (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). Machine learning (ML) techniques, a branch of artificial intelligence, have the potential for optimizing prediction of diseases, and have already been suggested for the diagnostic (\u003cspan additionalcitationids=\"CR27 CR28\" citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e–\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e) and the long-term prediction of outcomes of ED (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e), although evidence is still in its infancy (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e). Yet, employing algorithms relying solely on psychological variables requires psychometric and/or psychiatric examination, thus confines their use to mental health care settings.\u003c/p\u003e \u003cp\u003eTraining ML algorithms with metabolic features known to be altered in BED could allow the prompt detection of at-risk individuals or those already affected by the disorder within a larger user base.\u003c/p\u003e \u003cp\u003eIn the present study ML techniques were used to test the ability of glucose metabolism related features to predict BED among individuals seeking care for the treatment of obesity. Currently, no studies have attempted the use of this technique with a similar purpose. We hypothesized that glucose metabolism related features, embedded in the metabolic screening individuals undergo during the diagnostic pathway for obesity, could likely trace individuals at risk or already experiencing BED. ML could constitute an objective, reliable, and reproducible diagnostic strategy for professionals handling obesity and different expertise. Similarly, it could inform screening, identification, and targeted medical management.\u003c/p\u003e"},{"header":"Methods and Materials","content":"\u003ch3\u003eDataset and pre-processing\u003c/h3\u003e\u003cp\u003eThe dataset for the analysis was gathered from a larger dataset that collects metabolic and psychiatric data from individuals admitted to the diagnostic and therapeutic network of care for obesity (PDTA Obesità) of the University Hospital Renato Dulbecco of Catanzaro (Italy) (eligibility, metabolic and psychiatric examinations in (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e)). The PDTA Obesità is a dedicated pathway of care for obesity networked by an interdisciplinary team of specialists (internal medicine, psychiatry, and surgery).\u003c/p\u003e\u003cp\u003eThe initial dataset included 313 potential cases registered between May 2017 (start of the recruitment) and June 2023 (date of extraction).\u003c/p\u003e\u003cp\u003eThe dataset was filtered for acquisition of plasma glucose levels at multiple time points over a range between 2 and 5 hours after the oral glucose tolerance test (OGTT), no diabetes, and psychiatric examination for BED diagnosis. The study sample included only subjects negative for type 2 diabetes. A set of independent variables known to be altered in BED were chosen to aid classification of group membership. Demographics (age, sex at birth), BMI, OGTT-derived plasma glucose and insulin values, and dynamic measures of insulin secretion/sensitivity/resistance were included in the analysis for classifying participants in BED/non-BED. Additional derived features, such as curve skewness, first maximum peak, and the number of acquisitions above the detectable value have been computed (Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e). Missing values due to discontinuation of the glucose load (i.e., hypoglycemia) prevented the calculation of OGTT derived measures, resulting in the exclusion of 32 cases.\u003c/p\u003e\u003cp\u003eData transformation for features scaling and standardization was run with the Standard Scaler algorithm from scikit-learn (\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e). The final dataset, complete with all the measures for the analysis (Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e), consisted of 281 cases.\u003c/p\u003e\u003ch2\u003eExperimental Pipeline and data analysis\u003c/h2\u003e\u003cp\u003eThe analysis included three consecutive steps (i.e., training, validation, testing; Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e \u003c/p\u003e\u003cdiv class=\"gridtable\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e\u003cp\u003eThe whole experimental pipeline was firstly conducted on the complete dataset (N = 281, complete acquisition of glucose plasma during the 2 hours long OGTT; Model 1). It was further run considering only cases who completed the extended 5 hours long OGTT (N = 123; Model 2). Accordingly, two ML models were trained, validated, and tested. To guarantee independent and unbiased datasets, the initial dataset was split in three for the training (218 for Model 1, 88 for Model 2), validation (49 for Model 1, 28 for Model 2), and testing steps (14 for Model 1, 7 for Model 2). For the training step, the dataset was further split in the training and testing dataset (80% and 20%, respectively). Feature selection was performed by running the Recursive Feature Elimination method (RFE) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e-a3) on 150 different folds. RFE algorithm works by iterative removal of irrelevant or redundant features until a desired number of informative features is reached (\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e). The set of features that survived the RFE in each fold were recorded to build a global ranking list, from which the 15 most frequent ones were finally selected.\u003c/p\u003e\u003cp\u003eThis subset of selected features was then used to train five different ML algorithms, both linear and non-linear, to classify the sample in BED/non-BED. ML algorithms included Decision Tree (DT) (\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e), Random Forrest Classifier (RFC) (\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e), Extra Tree (ET) (\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e), Support Vector Machine Classifier (SVC) (\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e), Logistic Regression (LR) (\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e) (more details in Table S2; Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e-a4). Also in this case, to ensure a robust selection of the best classifier, this procedure was repeated 150 times, randomly shuffling the cases included into the training/testing datasets (red box in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e-A).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThe final dataset included 281 cases (133 BED, 148 non-BED), all White. Respectively, mean age was 40.2\u0026thinsp;\u0026plusmn;\u0026thinsp;13.1 and 44.4\u0026thinsp;\u0026plusmn;\u0026thinsp;11.7, and females were overrepresented in both groups (85.7%, 67.6%). Non-BED cases exhibited lower BMI than BED cases (41.4\u0026thinsp;\u0026plusmn;\u0026thinsp;7.7; 39.1\u0026thinsp;\u0026plusmn;\u0026thinsp;7.4). RFE dropped several items from the models, providing evidence for 15 significant features for both Model 1 and Model 2 (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Sex, BMI, plasma glucose at the 120\u0026rsquo; min, maximum glucose value during the load, hypoglycemia events, Area Under Curve for Insulin and Glucose (AUC Ins-Glu during the 0- to 30-min of the OGTT), skewness of the curve, and three indexes of insulin sensitivity [Gutt\u0026rsquo;s insulin sensitivity index (Gutt-ISI), Stumvoll index and HOMA-IR] were depicted in both models as significant in discerning BED over non-BED (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePerformance of the best classifier on the validation set. Results for the Model 1 and 2 .\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBest Classifier\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCases\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSensitivity\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSpecificity\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eF\u003csub\u003e1\u003c/sub\u003e score\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eAccuracy\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eFeatures\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModel 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSVCP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eAUC\u003csub\u003eIns\u0026minus;glu\u003c/sub\u003e 0\u0026ndash;30\u003c/p\u003e \u003cp\u003eAUC\u003csub\u003eglu\u003c/sub\u003e\u003c/p\u003e \u003cp\u003eBMI\u003c/p\u003e \u003cp\u003eG\u003csub\u003e30\u003c/sub\u003e, G\u003csub\u003e60\u003c/sub\u003e, G\u003csub\u003e90\u003c/sub\u003e, G\u003csub\u003e120\u003c/sub\u003e\u003c/p\u003e \u003cp\u003eGUTT\u003c/p\u003e \u003cp\u003eHb1AC\u003c/p\u003e \u003cp\u003eHOMA-IR\u003c/p\u003e \u003cp\u003eHypo tot\u003c/p\u003e \u003cp\u003eMax\u003csub\u003eGluc\u003c/sub\u003e\u003c/p\u003e \u003cp\u003eSex\u003c/p\u003e \u003cp\u003eSkewness\u003c/p\u003e \u003cp\u003eStumvoll ISI\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModel 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSVCP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eAUC\u003csub\u003eIns\u0026minus;glu\u003c/sub\u003e 0\u0026ndash;30\u003c/p\u003e \u003cp\u003eBMI\u003c/p\u003e \u003cp\u003eG\u003csub\u003e60\u003c/sub\u003e, G\u003csub\u003e120\u003c/sub\u003e, G\u003csub\u003e150\u003c/sub\u003e, G\u003csub\u003e210\u003c/sub\u003e, G\u003csub\u003e270\u003c/sub\u003e, G\u003csub\u003e300\u003c/sub\u003e\u003c/p\u003e \u003cp\u003eGUTT\u003c/p\u003e \u003cp\u003eHOMA-IR\u003c/p\u003e \u003cp\u003eHypo tot\u003c/p\u003e \u003cp\u003eMax\u003csub\u003eGluc\u003c/sub\u003e\u003c/p\u003e \u003cp\u003eSex\u003c/p\u003e \u003cp\u003eSkewness\u003c/p\u003e \u003cp\u003eStumvoll ISI\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"8\" nameend=\"c8\" namest=\"c1\"\u003e \u003cp\u003eSVCP: support vector machine classifier; BMI: body mass index; HOMA-IR: homeostatic model assessment insulin resistance; ISI: insulin sensitivity index.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eTesting. Results for the two models.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e\u003ccolgroup cols=\"10\"\u003e\u003c/colgroup\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModel\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCases\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSensitivity\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSpecificity\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eF\u003csub\u003e1\u003c/sub\u003e score\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAccuracy\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eTP\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eTN\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eFP\u003c/p\u003e \u003c/th\u003e\u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eFN\u003c/p\u003e \u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModel 1\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.35\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.67\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.46\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.5\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModel 2\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.75\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.67\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.67\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.71\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"10\" nameend=\"c10\" namest=\"c1\"\u003e \u003cp\u003eModel 1 tested on cases with complete 2 hours long OGTT; Model 2 tested on cases with complete 5 hours long OGTT.\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/table\u003e\u003c/div\u003e\u003cbr\u003e \u003cp\u003eAcross all five ML algorithms, the SVCP outperformed in classifying the groups. For Model 1 (2 hours long OGTT), the classifier correctly identified half of the cases with BED (sensitivity\u0026thinsp;=\u0026thinsp;0.5), and 80% of non-BED cases (specificity\u0026thinsp;=\u0026thinsp;0.8) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e1\u003c/span\u003e). On the 5 hours long OGTT dataset (Model 2), the classifier was more sensitive (0.86), but less specific (0.43) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Accuracy was similar for the two Models (0.67 vs 0.64).\u003c/p\u003e \u003cp\u003eFigures \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e-2 show the sensitivity-based analysis conducted on the validation set and for all the classifiers reported in Table S2. Sex, HOMA-IR, Hb1AC, and skewness of the glucose curve scored higher in the Model 1 classification ability. Plasma glucose at the 120\u0026rsquo; minute was the most accurate feature of the Model 2. Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e2\u003c/span\u003e reports the performance of the proposed two models tested on the testing cohort. Model 2 exceeded the performance of Model 1 in terms of sensitivity (0.7), specificity (0.67), accuracy (0.71), and the overall ability to predict class membership (0.67).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003ePresent study used a ML approach and data from individuals accessing the care for obesity and no diabetes to identify individual-level metabolic features that could be associated with the diagnosis of BED. It further aimed to investigate the predictive diagnostic accuracy of a pure metabolic based ML approach in screening BED among seekers care for obesity.\u003c/p\u003e \u003cp\u003eResults suggest that sex, BMI, and glucose metabolism-related variables such as glucose levels at specific times of the OGTT, skewness of the glucose load, insulin sensitivity indexes, and hypoglycemia events could be crucial when it comes to identifying those individuals suffering from BED among patients with obesity.\u003c/p\u003e \u003cp\u003eCross-sectional studies in population with no diabetes have demonstrated that binge-eating associates with fasting hyperglycemia, insulin resistance, and higher frequency of pre-diabetes phenotypes (e.g., impaired glucose tolerance)(\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan additionalcitationids=\"CR43\" citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e). Hypoglycemia events occurring with neurogenic or neuroglycopenic symptoms and typically reverting with carbohydrates intake (i.e., reactive hypoglycemia)(\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e) have been recently studied and preliminarily associated to binge-eating during an extended laboratory stimulation, suggesting that individuals suffering from BED, obesity, but no diabetes would suffer from more frequent and more severe hypoglycemia events with respect to the counterpart with no ED (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). More consistently, longitudinal studies have showed that binge-eating contributes to higher odds of metabolic syndrome components in the long-term beyond the risk attributable to obesity alone (\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e, \u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e).\u003c/p\u003e \u003cp\u003ePresent results confirm, but more importantly, leverage the relevance of these metabolic correlates in their potentiality to specifically cluster BED vs non-BED in non-psychiatric settings. Overall, this study suggests that modeling OGTT-related metabolic features together with demographics and anthropometrics could assist the diagnostic process, potentially identifying BED in five to seven out of ten of cases, depending on data collection. Specifically, the Models performed similarly in classifying cases not at risk (67%), but the 5 hours long OGTT based Model outperformed in terms of sensitivity (75%), accuracy (71%), and overall ability to predict class membership (0.67 vs 0.47). The relative weight of hypoglycemia in the model, together with the evidence that individuals with BED would experience more hypoglycemia events during the laboratory test at the latest stages of the glucose load (4th -5th hour), could have contributed to the better performance of Model 2 over Model 1. The diagnostic accuracy of the models is surprisingly encouraging considering the diagnostic accuracy the specifically tailored psychometric instruments exhibit. A recent systematic review compared the performances of the most widely used screening questionnaires in detecting BED in overweight or obesity and found high variability across studies (\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e). Only moderate accuracy was found for the Eating Disorders Questionnaire (EDE-Q) (sensibility: 0.40\u0026ndash;0.87; specificity: 0.62-1), and the Binge Eating Scale (BES) (sensibility: 0.51\u0026ndash;0.98; specificity: 0.48\u0026ndash;0.76), still considered the most widely used psychometrics tools in the field.\u003c/p\u003e \u003cp\u003eFurther, the ML algorithms hereby used to detect BED as a psychiatric disorder were exclusively fed with glycemic/insulinemic and other non-psychological features. Authors may, accordingly, speculate that adding psychometric tools specifically designed for BED and tailored to overweight and obesity (e.g., the Eating Behaviors Assessment for Obesity,(\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e)) to the training could potentially booster the diagnostic accuracy of the present model.\u003c/p\u003e \u003cp\u003eOther studies have previously tested ML techniques to evaluate the risk, assist the investigation, or predict the outcome of BED (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e). Eric Stice and Christopher D. Desjardins in 2018 used a multiple approach-based classification tree analysis to investigate the interactions of risk factors in the prediction of the onset of EDs in a large dataset of individuals at high risk. The onset of BED was accurately predicted in 64% of cases by a complex four-way interaction between body dissatisfaction, overeating, dieting, and thin-ideal internalization (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e). In the investigation of Linardon and colleagues, a ML-based decision tree classification analysis captured 70% of binge-eaters by examining eating behaviors and cognitions. The two-way interaction of low intuitive eating and high dichotomous thinking resulted largely associated with being classified with recurrent binge eating (84% incidence)(\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). Lastly, Forrest L.N. tested two ML approaches to evaluate treatment outcomes in a sample of individuals suffering from BED randomized to six months behavioural or stepped-care treatments. Authors concluded for a slight advantage of the ML over the traditional models, claiming for further empirical confirmation in the EDs literature (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eStill recognizing the relevance of ML-based investigations based on psychological measures, they require specific training and specialized settings for the analysis.\u003c/p\u003e \u003cp\u003eBED goes undiagnosed for many years and suffers from the greatest delay to proper treatments of all EDs (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). This is partly due to either patient or clinician-related factors (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e), but surely contributes to the great medical burden and overall disability BED associates with. Further, treatment outcomes often deviate from the expectations (\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e, \u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe highest prevalence of BED is found in clinical samples attending weight loss programs or bariatric surgery (\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e, \u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e). Training ML algorithms with objective measures embedded within the medical screening individuals suffering from BED could undergo in these settings, could enable a prompt detection in non-specialized settings, would generate more targeted interventions and anticipate clinical progression.\u003c/p\u003e \u003cp\u003eTo our knowledge, no similar evidence exists so far. The current study is the first that has attempted training ML to diagnose BED basing on objective measures (OGTT-derived features), pioneering the field of metabolic based AI applied to BED. With respect to other studies that used self-report binge episodes to corroborate the diagnosis (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e), BED was diagnosed clinically, thereby enhancing the accuracy of the results. Further analyses on larger datasets and considering other valuable biomarkers could enhance modeling performances and translate to clinical practice its use to inform clinical decisions.\u003c/p\u003e \u003cp\u003eWithin these strengths, some limitations should be addressed. Embedded within the methodology used, no information can be extracted about the nature of associations between the relevant features and BED class (e.g., higher Hb1Ac in BED vs non-BED). Further, authors acknowledge that the cross-sectional design prevent to infer any causal or temporal association between variables. Although distinct methods were applied to avoid overfitting (i.e., scaling, splitting, features selection with the RFE), an inflation in model accuracy due to the sample size cannot be excluded. The sample was all White, and not gender balanced. Accordingly, results may not be generalizable to samples with other characteristics.\u003c/p\u003e \u003cp\u003eFinally, authors selected for the analysis the most informative metabolic features so far associated with BED and known to constitute early markers of late metabolic disruption (e.g., diabetes, metabolic syndrome); still, we recognize that the use of a different set of features or more advanced statistical methodology could produce distinct and perhaps more significant results.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eCompeting interests\u003c/h2\u003e \u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e \u003ch2\u003eEthics approval and consent to participate\u003c/h2\u003e \u003cp\u003eEligible patients were fully informed about the aim and the procedures of the study, and that participation was voluntary and free from any compensation. All participants gave written informed consent. The study was approved by the institutional review boards (Local Ethical Committee, n. 53/2013), and all the procedures were performed in accordance with the principles of the Declaration of Helsinki.\u003c/p\u003e \u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eNo fundings were received for this study.\u003c/p\u003e\u003ch2\u003eAuthors' contributions\u003c/h2\u003e \u003cp\u003estatement (CRediT)\u003c/p\u003e\u003ch2\u003eAcknowledgements\u003c/h2\u003e \u003cp\u003eNot applicable.\u003c/p\u003e\u003ch2\u003eAvailability of data and materials\u003c/h2\u003e \u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eQian J, Wu Y, Liu F, Zhu Y, Jin H, Zhang H, Wan Y, Li C, Yu D. An update on the prevalence of eating disorders in the general population: a systematic review and meta-analysis. 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Int J Eat Disord (2015) 48:471\u0026ndash;476. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/EAT.22389\u003c/span\u003e\u003cspan address=\"10.1002/EAT.22389\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"translational-psychiatry","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"tp","sideBox":"Learn more about [Translational Psychiatry](http://www.nature.com/tp/)","snPcode":"41398","submissionUrl":"https://mts-tp.nature.com/cgi-bin/main.plex","title":"Translational Psychiatry","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"BED, binge-eating, ML, OGTT, hypoglycemia","lastPublishedDoi":"10.21203/rs.3.rs-4675042/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4675042/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBinge eating disorder (BED) carries a 6 times higher risk for obesity and accounts for roughly 30% of type 2 diabetes cases. Timely identification of early glycemic disturbances and comprehensive treatment can impact on the likelihood of associated metabolic complications and the overall outcome. Machine learning (ML) techniques were trained with static and dynamic glucose-derived measures to detect BED among 281 individuals with high weight. The pipeline (training, validation, testing) was conducted twice, on two different datasets (2 hours, and 5 hours-long glucose load). After features selection, multiple ML algorithms were trained to classify the sample. The best classifier was then applied to an independent cohort (N\u0026thinsp;=\u0026thinsp;21). A sensitivity-based analysis was run to investigate the relevance of each feature in the classification. 14 features were selected as relevant, with the support vector machine showing the best performance in classifying BED in both models. The model on the 5 hours-long OGTT exhibited the best metrics (sensitivity\u0026thinsp;=\u0026thinsp;0.75, specificity\u0026thinsp;=\u0026thinsp;0.67, F score\u0026thinsp;=\u0026thinsp;0.71) diagnosing BED in 7 out of 10 cases. Sex, HOMA-IR, HbA1c and plasma glucose in different times, and hypoglycemia events were the most sensitive features for BED diagnosis. This study is the first to use metabolic hallmarks to train ML algorithms for detecting BED in individuals at high risk for metabolic complications. ML techniques applied to objective and reliable glycemic features might prompt the identification of BED among individuals at high risk for metabolic complications, enabling timely and tailored multidisciplinary treatment.\u003c/p\u003e","manuscriptTitle":"Leveraging OGTT derived metabolic features to detect Binge-eating disorder in individuals with high weight: a “seek out” machine learning approach","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-10-21 11:04:22","doi":"10.21203/rs.3.rs-4675042/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"revise","date":"2024-12-04T10:02:26+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"This content is not available.","date":"2024-09-30T11:03:12+00:00","index":1,"fulltext":"This content is not available."},{"type":"editorInvitedReview","content":"This content is not available.","date":"2024-09-27T12:40:35+00:00","index":2,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2024-09-25T13:40:59+00:00","index":2,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2024-09-09T07:18:04+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewersInvited","content":"","date":"2024-09-04T08:53:08+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-07-05T09:43:24+00:00","index":"","fulltext":""},{"type":"submitted","content":"Translational Psychiatry","date":"2024-07-04T13:25:50+00:00","index":"","fulltext":""},{"type":"checksFailed","content":"","date":"2024-07-03T10:23:13+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-07-02T14:37:15+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"translational-psychiatry","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"tp","sideBox":"Learn more about [Translational Psychiatry](http://www.nature.com/tp/)","snPcode":"41398","submissionUrl":"https://mts-tp.nature.com/cgi-bin/main.plex","title":"Translational Psychiatry","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"3419725e-a41d-48f4-b61d-8188b1ab93e0","owner":[],"postedDate":"October 21st, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":37079966,"name":"Health sciences/Diseases/Psychiatric disorders/Addiction"},{"id":37079967,"name":"Health sciences/Biomarkers/Diagnostic markers"}],"tags":[],"updatedAt":"2025-02-19T14:17:31+00:00","versionOfRecord":{"articleIdentity":"rs-4675042","link":"https://doi.org/10.1038/s41398-025-03281-y","journal":{"identity":"translational-psychiatry","isVorOnly":false,"title":"Translational Psychiatry"},"publishedOn":"2025-02-18 05:00:00","publishedOnDateReadable":"February 18th, 2025"},"versionCreatedAt":"2024-10-21 11:04:22","video":"","vorDoi":"10.1038/s41398-025-03281-y","vorDoiUrl":"https://doi.org/10.1038/s41398-025-03281-y","workflowStages":[]},"version":"v1","identity":"rs-4675042","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4675042","identity":"rs-4675042","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}