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Article

Insulin/IGF-1 Signaling Is Downregulated in Barrett’s Esophagus Patients Undergoing a Moderate Calorie and Protein Restriction Program: A Randomized 2-Year Trial

1
Gastroenterology Unit, Veneto Institute of Oncology IOV-IRCCS, Via Gattamelata 64, 35128 Padua, Italy
2
Department of Surgery, Oncology and Gastroenterology (DiSCOG), University of Padua, Via Giustiniani 2, 35128 Padua, Italy
3
Department of Biomedical Sciences, University of Padua, Viale Colombo 3, 35121 Padua, Italy
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Fondazione Istituto di Ricerca Pediatrica, Città della Speranza, Corso Stati Uniti 4, 35127 Padua, Italy
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Nutritional Support Unit, Veneto Institute of Oncology IOV-IRCCS, Via Gattamelata 64, 35128 Padua, Italy
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Department of Medicine (DIMED), Surgical Pathology Unit, University of Padua, Via Gabelli 61, 35121 Padua, Italy
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Veneto Institute of Oncology IOV-IRCCS, Via Gattamelata 64, 35128 Padua, Italy
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First Surgical Clinic, Department of Surgery, Oncology and Gastroenterology (DiSCOG), University of Padua, Via Giustiniani 2, 35128 Padua, Italy
*
Author to whom correspondence should be addressed.
The authors contributed equally to this work.
Academic Editor: Jaakko Tuomilehto
Nutrients 2021, 13(10), 3638; https://doi.org/10.3390/nu13103638
Received: 20 September 2021 / Revised: 14 October 2021 / Accepted: 15 October 2021 / Published: 17 October 2021
(This article belongs to the Special Issue Human Nutrition and Cancer Prevention)
Obesity and associated insulin resistance (Ins-R) have been identified as important risk factors for esophageal adenocarcinoma development. Elevated calories and protein consumption are also associated with Ins-R and glucose intolerance. We investigated the effect of a 24-month moderate calorie and protein restriction program on overweight or obese patients affected by Barrett’s esophagus (BE), as no similar dietary approach has been attempted to date in this disease context. Anthropometric parameters, levels of serum analytes related to obesity and Ins-R, and the esophageal insulin/IGF-1 signaling pathway were analyzed. This study is registered with ClinicalTrials.gov, number NCT03813381. Insulin, C-peptide, IGF-1, IGF-binding protein 3 (IGFBP3), adipokines, and esophageal expression of the main proteins involved in insulin/IGF-1 signal transduction were quantified using Luminex-XMAP® technology in 46 patients who followed the restriction program (IA) and in 54 controls (CA). Body mass index and waist circumference significantly decreased in 76.1% of IA and 35.2% of CA. IGF-1 levels were reduced in 71.7% of IA and 51.8% of CA. The simultaneous reduction of glycaemia, IGF-1, the IGF-1/IGFBP3 ratio, and the improvement in weight loss-dependent insulin sensitivity, were associated with the downregulation of the insulin/IGF-1 signal on BE tissue. The proposed intervention program was an effective approach to counteract obesity-associated cancer risk factors. The improvement in metabolic condition resulted in a downregulation of the ERK-mediated mitogenic signal in 43.5% of patients, probably affecting the molecular mechanism driving adenocarcinoma development in BE lesions. View Full-Text
Keywords: calorie–protein restriction; Barrett’s esophagus; insulin/IGF-1 signal transduction; esophageal adenocarcinoma prevention; obesity calorie–protein restriction; Barrett’s esophagus; insulin/IGF-1 signal transduction; esophageal adenocarcinoma prevention; obesity
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MDPI and ACS Style

Arcidiacono, D.; Zaramella, A.; Fabris, F.; Sánchez-Rodríguez, R.; Nucci, D.; Fassan, M.; Nardi, M.; Benna, C.; Cristofori, C.; Morbin, T.; Pucciarelli, S.; Fantin, A.; Realdon, S. Insulin/IGF-1 Signaling Is Downregulated in Barrett’s Esophagus Patients Undergoing a Moderate Calorie and Protein Restriction Program: A Randomized 2-Year Trial. Nutrients 2021, 13, 3638. https://doi.org/10.3390/nu13103638

AMA Style

Arcidiacono D, Zaramella A, Fabris F, Sánchez-Rodríguez R, Nucci D, Fassan M, Nardi M, Benna C, Cristofori C, Morbin T, Pucciarelli S, Fantin A, Realdon S. Insulin/IGF-1 Signaling Is Downregulated in Barrett’s Esophagus Patients Undergoing a Moderate Calorie and Protein Restriction Program: A Randomized 2-Year Trial. Nutrients. 2021; 13(10):3638. https://doi.org/10.3390/nu13103638

Chicago/Turabian Style

Arcidiacono, Diletta, Alice Zaramella, Federico Fabris, Ricardo Sánchez-Rodríguez, Daniele Nucci, Matteo Fassan, Mariateresa Nardi, Clara Benna, Chiara Cristofori, Tiziana Morbin, Salvatore Pucciarelli, Alberto Fantin, and Stefano Realdon. 2021. "Insulin/IGF-1 Signaling Is Downregulated in Barrett’s Esophagus Patients Undergoing a Moderate Calorie and Protein Restriction Program: A Randomized 2-Year Trial" Nutrients 13, no. 10: 3638. https://doi.org/10.3390/nu13103638

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