Mellody I Cooiman1,2, Suzanne I M Alsters3, Maeva Duquesnoy4, Eric J Hazebroek5, Hanne J Meijers-Heijboer3,6, Harvinder Chahal7, Johanne Le Beyec-Le Bihan8, Karine Clément4,9, Hedi Soula9, Alex I Blakemore10,11, Christine Poitou4,9, Mieke M van Haelst12,13. 1. Department of Bariatric Surgery, Rijnstate Hospital/Vitalys Clinic, Wagnerlaan 55, Arnhem, the Netherlands. mcooimanresearch@gmail.com. 2. Department of Clinical Genetics, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands. mcooimanresearch@gmail.com. 3. Department of Clinical Genetics, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands. 4. Nutrition Department, Reference Center for Rare Diseases, Assistance Publique Hopitaux de Paris, Pitie-Salpetriere Hospital, Paris, France. 5. Department of Bariatric Surgery, Rijnstate Hospital/Vitalys Clinic, Wagnerlaan 55, Arnhem, the Netherlands. 6. Department of Clinical Genetics, Amsterdam UMC, University of Amsterdam, De Boelelaan 1117, Amsterdam, the Netherlands. 7. Department of Diabetes, Endocrinology and Metabolism, Imperial College London, London, UK. 8. Department of Biochemistry for Endocrinology and Oncology, Obesity and Dyslipidemia Genetics Unit, Assistance Publique-Hospitaux de Paris, Sorbonne Université, Pitie-Salpetriere Hospital, Paris, France. 9. INSERM, Nutrition and Obesities, Systemic Approaches (NutriOmics) Research Unit, Sorbonne Université, Paris, France. 10. Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK. 11. Department of Life Sciences, Brunel University London, London, UK. 12. Department of Clinical Genetics, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands. m.vanhaelst@amsterdamumc.nl. 13. Department of Clinical Genetics, Amsterdam UMC, University of Amsterdam, De Boelelaan 1117, Amsterdam, the Netherlands. m.vanhaelst@amsterdamumc.nl.
Abstract
INTRODUCTION: Pathogenic heterozygous MC4R variants are associated with hyperphagia and variable degrees of obesity. Several research groups have reported short-term weight loss outcomes after bariatric surgery in a few patients with MC4R variants, but lack of longer-term data prevents evidence-based clinical decision-making. MATERIALS AND METHODS: Bariatric surgery patients with heterozygous (likely) pathogenic MC4R variants, from three collaborating centers in the Netherlands, France, and the UK, were compared to matched controls (matched 2:1 for age, sex, preoperative BMI, surgical procedure, and diabetes mellitus, but without MC4R mutations). Weight loss and regain outcomes up to 6 years of follow-up were compared. RESULTS: At 60 months of follow-up after RYGB, cases with MC4R variants showed weight regain with a mean of 12.8% (± 10.4 SD) total weight loss (TWL) from nadir, compared to 7.9% (± 10.5 SD) in the controls (p = 0.062). Among patients receiving SG, the cases with MC4R variants experienced inferior weight loss (22.6% TWL) during the first year of follow-up compared to the controls (29.9% TWL) (p = 0.010). CONCLUSIONS: This multicenter study reveals inferior mid-term weight outcomes of cases with MC4R variants after SG, compared to RYGB. Since adequate weight loss outcomes were observed after RYGB, this procedure would appear to be an appropriate surgical approach for this group. However, the pattern of weight regain seen in cases with MC4R variants after both RYGB and SG highlights the need for pro-active lifelong management to prevent relapse, as well as careful expectation management.
INTRODUCTION: Pathogenic heterozygous MC4R variants are associated with hyperphagia and variable degrees of obesity. Several research groups have reported short-term weight loss outcomes after bariatric surgery in a few patients with MC4R variants, but lack of longer-term data prevents evidence-based clinical decision-making. MATERIALS AND METHODS: Bariatric surgery patients with heterozygous (likely) pathogenic MC4R variants, from three collaborating centers in the Netherlands, France, and the UK, were compared to matched controls (matched 2:1 for age, sex, preoperative BMI, surgical procedure, and diabetes mellitus, but without MC4R mutations). Weight loss and regain outcomes up to 6 years of follow-up were compared. RESULTS: At 60 months of follow-up after RYGB, cases with MC4R variants showed weight regain with a mean of 12.8% (± 10.4 SD) total weight loss (TWL) from nadir, compared to 7.9% (± 10.5 SD) in the controls (p = 0.062). Among patients receiving SG, the cases with MC4R variants experienced inferior weight loss (22.6% TWL) during the first year of follow-up compared to the controls (29.9% TWL) (p = 0.010). CONCLUSIONS: This multicenter study reveals inferior mid-term weight outcomes of cases with MC4R variants after SG, compared to RYGB. Since adequate weight loss outcomes were observed after RYGB, this procedure would appear to be an appropriate surgical approach for this group. However, the pattern of weight regain seen in cases with MC4R variants after both RYGB and SG highlights the need for pro-active lifelong management to prevent relapse, as well as careful expectation management.
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