Alejandro Campos1, Lizeth Cifuentes1, Anas Hashem1, Bradley Busebee1, Maria D Hurtado-Andrade1, Maria L Ricardo-Silgado1, Alison McRae1, Alan De la Rosa1, Fauzi Feris1, Joshua T Bublitz2, Donald Hensrud3, Michael Camilleri1, Todd A Kellogg4, Jeanette E Eckel-Passow5, Janet Olson2, Andres Acosta6. 1. Precision Medicine for Obesity Program, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Charlton 8-142, 200 First St. S.W, Rochester, MN, 55902, USA. 2. Division of Epidemiology, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA. 3. Division of General Internal Medicine, Department of Medicine, Mayo Clinic, Rochester, MN, USA. 4. Division of Endocrine & Metabolic Surgery, Department of Surgery, Mayo Clinic, Rochester, MN, USA. 5. Division of Computational Biology, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA. 6. Precision Medicine for Obesity Program, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Charlton 8-142, 200 First St. S.W, Rochester, MN, 55902, USA. acosta.andres@mayo.edu.
Abstract
INTRODUCTION: Heterozygous variants in the leptin-melanocortin pathway are associated with obesity. However, their effect on the long-term outcomes after Roux-en-Y gastric bypass (RYGB) is still unknown. METHODS: In this matched case-control study, 701 participants from the Mayo Clinic Biobank with a history of RYGB were genotyped. Sixty-three patients had a heterozygous variant in the leptin-melanocortin pathway. After excluding patients with potential confounders, carriers were randomly matched (on sex, age, body mass index [BMI], and years since surgery) with two non-carrier controls. The electronic medical record of carriers and matched non-carriers was reviewed for up to 15 years after RYGB. RESULTS: A total of 50 carriers and 100 matched non-carriers with a history of RYGB were included in the study. Seven different genes (LEPR, PCSK1, POMC, SH2B1, SRC1, MC4R, and SIM1) in the leptin-melanocortin pathway were identified. At the time of surgery, the mean age was 50.8 ± 10.6 years, BMI 45.6 ± 7.3 kg/m2, and 79% women. There were no differences in postoperative years of follow-up, Roux limb length, or gastric pouch size between groups. Fifteen years after RYGB, the percentage of total body weight loss (%TBWL) in carriers was - 16.6 ± 10.7 compared with - 28.7 ± 12.9 in non-carriers (diff = 12.1%; 95% CI, 4.8 to 19.3) and the percentage of weight regain after maximum weight loss was 52.7 ± 29.7 in carriers compared with 29.8 ± 20.7 in non-carriers (diff = 22.9%; 95% CI, 5.3 to 40.5). The nadir %TBWL was lower - 32.1 ± 8.1 in carriers compared with - 36.8 ± 10.4 in non-carriers (diff = 4.8%; 95% CI 1.8 to 7.8). CONCLUSIONS: Carriers of a heterozygous variant in the leptin-melanocortin pathway have a progressive and significant weight regain in the mid- and long-term after RYGB. Genotyping patients experiencing significant weight regain after RYGB could help implement multidisciplinary and individualized weight loss interventions to improve weight maintenance after surgery.
INTRODUCTION: Heterozygous variants in the leptin-melanocortin pathway are associated with obesity. However, their effect on the long-term outcomes after Roux-en-Y gastric bypass (RYGB) is still unknown. METHODS: In this matched case-control study, 701 participants from the Mayo Clinic Biobank with a history of RYGB were genotyped. Sixty-three patients had a heterozygous variant in the leptin-melanocortin pathway. After excluding patients with potential confounders, carriers were randomly matched (on sex, age, body mass index [BMI], and years since surgery) with two non-carrier controls. The electronic medical record of carriers and matched non-carriers was reviewed for up to 15 years after RYGB. RESULTS: A total of 50 carriers and 100 matched non-carriers with a history of RYGB were included in the study. Seven different genes (LEPR, PCSK1, POMC, SH2B1, SRC1, MC4R, and SIM1) in the leptin-melanocortin pathway were identified. At the time of surgery, the mean age was 50.8 ± 10.6 years, BMI 45.6 ± 7.3 kg/m2, and 79% women. There were no differences in postoperative years of follow-up, Roux limb length, or gastric pouch size between groups. Fifteen years after RYGB, the percentage of total body weight loss (%TBWL) in carriers was - 16.6 ± 10.7 compared with - 28.7 ± 12.9 in non-carriers (diff = 12.1%; 95% CI, 4.8 to 19.3) and the percentage of weight regain after maximum weight loss was 52.7 ± 29.7 in carriers compared with 29.8 ± 20.7 in non-carriers (diff = 22.9%; 95% CI, 5.3 to 40.5). The nadir %TBWL was lower - 32.1 ± 8.1 in carriers compared with - 36.8 ± 10.4 in non-carriers (diff = 4.8%; 95% CI 1.8 to 7.8). CONCLUSIONS: Carriers of a heterozygous variant in the leptin-melanocortin pathway have a progressive and significant weight regain in the mid- and long-term after RYGB. Genotyping patients experiencing significant weight regain after RYGB could help implement multidisciplinary and individualized weight loss interventions to improve weight maintenance after surgery.
Authors: Lena M S Carlsson; Kajsa Sjöholm; Peter Jacobson; Johanna C Andersson-Assarsson; Per-Arne Svensson; Magdalena Taube; Björn Carlsson; Markku Peltonen Journal: N Engl J Med Date: 2020-10-15 Impact factor: 91.245
Authors: Lars Sjöström; Kristina Narbro; C David Sjöström; Kristjan Karason; Bo Larsson; Hans Wedel; Ted Lystig; Marianne Sullivan; Claude Bouchard; Björn Carlsson; Calle Bengtsson; Sven Dahlgren; Anders Gummesson; Peter Jacobson; Jan Karlsson; Anna-Karin Lindroos; Hans Lönroth; Ingmar Näslund; Torsten Olbers; Kaj Stenlöf; Jarl Torgerson; Göran Agren; Lena M S Carlsson Journal: N Engl J Med Date: 2007-08-23 Impact factor: 91.245