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Long-Term Weight Outcome After Bariatric Surgery in Patients with Melanocortin-4 Receptor Gene Variants: a Case–Control Study of 105 Patients

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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.

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Acknowledgements

We would like to special thank S.M. Oussaada, MD, for her help in the conceptualization of this manuscript.

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Authors and Affiliations

  1. Department of Bariatric Surgery, Rijnstate Hospital/Vitalys Clinic, Wagnerlaan 55, Arnhem, the Netherlands

    Mellody I. Cooiman & Eric J. Hazebroek

  2. Department of Clinical Genetics, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands

    Mellody I. Cooiman, Suzanne I. M. Alsters, Hanne J. Meijers-Heijboer & Mieke M. van Haelst

  3. Nutrition Department, Reference Center for Rare Diseases, Assistance Publique Hopitaux de Paris, Pitie-Salpetriere Hospital, Paris, France

    Maeva Duquesnoy, Karine Clément & Christine Poitou

  4. Department of Clinical Genetics, Amsterdam UMC, University of Amsterdam, De Boelelaan 1117, Amsterdam, the Netherlands

    Hanne J. Meijers-Heijboer & Mieke M. van Haelst

  5. Department of Diabetes, Endocrinology and Metabolism, Imperial College London, London, UK

    Harvinder Chahal

  6. Department of Biochemistry for Endocrinology and Oncology, Obesity and Dyslipidemia Genetics Unit, Assistance Publique-Hospitaux de Paris, Sorbonne Université, Pitie-Salpetriere Hospital, Paris, France

    Johanne Le Beyec-Le Bihan

  7. INSERM, Nutrition and Obesities, Systemic Approaches (NutriOmics) Research Unit, Sorbonne Université, Paris, France

    Karine Clément, Hedi Soula & Christine Poitou

  8. Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK

    Alex I. Blakemore

  9. Department of Life Sciences, Brunel University London, London, UK

    Alex I. Blakemore

Authors
  1. Mellody I. Cooiman
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Corresponding authors

Correspondence to Mellody I. Cooiman or Mieke M. van Haelst.

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Ethical Approval

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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The authors declare no competing interests.

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Key points

• Inferior weight loss was identified after SG in patients with MC4R variants.

• RYGB appears to be an appropriate surgical approach for patients with MC4R variants.

• Patients with an MC4R variant showed weight regain after both surgical procedures.

• Pro-active lifelong management to prevent relapse is important.

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Cooiman, M.I., Alsters, S.I.M., Duquesnoy, M. et al. Long-Term Weight Outcome After Bariatric Surgery in Patients with Melanocortin-4 Receptor Gene Variants: a Case–Control Study of 105 Patients. OBES SURG 32, 837–844 (2022). https://doi.org/10.1007/s11695-021-05869-x

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