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High Prevalence of Positive Genetic Obesity Variants in Postoperative Bariatric Surgery Patients with Weight Regain Presenting for Medical Obesity Intervention

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Abstract

Introduction

Genetic obesity susceptibility in postoperative bariatric surgery weight regain (PBSWR) remains largely unexplored.

Methods

A retrospective case series of adult (N = 27) PBSWR patients who had undergone genetic obesity testing was conducted between Sept. 2020 and March 2022. Primary outcome: frequency of genetic variants in patients experiencing weight regain following bariatric surgery. Secondary outcomes: prevalence of obesity-related comorbidities, nadir BMI achieved post-bariatric surgery, and percent total body weight loss (%TBWL) achieved with obesity pharmacotherapies.

Results

Heterozygous mutations were identified in 22 (81%) patients, with the most prevalent mutations occurring in CEP290, RPGR1P1L, and LEPR genes (3 patients each). Median age was 56 years (interquartile range (IQR) 46.8–65.5), 88% female. Types of surgery were 67% RYGB, 19% SG, 4% gastric band, and 13% revisions. Median nadir BMI postoperatively was 34.0 kg/m2 (IQR 29.0–38.5). A high prevalence of metabolic derangements was noted; patients presented median 80 months (IQR 39–168.5) postoperative for medical weight management with 40% weight regain. BMI at initiation of anti-obesity medication (AOMs) was 41.7 kg/m2 (36.8–44.4). All received AOM and required at least 3 AOMs for weight regain. Semaglutide (N = 21), topiramate (N = 14), and metformin (N = 12) were most prescribed. Median %TBWL for the cohort at the first, second, and third visit was 1.7, 5.0, and 6.5 respectively. Fourteen (52%) achieved 5%TBWL, 10 (37%) achieved 10%TBWL, and 4 (15%) achieved 15%TBWL with combination AOMs and supervised medical intervention.

Conclusion

An unusually high prevalence of genetic obesity variants in PBSWR was found, warranting further research.

Graphical Abstract

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Data Availability

The data that support the findings of this study are available from the corresponding author, GS, upon reasonable request.

Abbreviations

PBSWR:

Post-bariatric surgery weight regain

GLP-1RA:

Glucagon-like peptide 1 receptor agonists

MWL:

Medical weight loss clinic

AOM:

Anti-obesity medications

TBW:

Total body weight

T2DM:

Type 2 diabetes mellitus

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Authors and Affiliations

  1. Department of Surgery, Vanderbilt University School of Medicine, Nashville, TN, 37204, USA

    Jason M. Samuels & Gitanjali Srivastava

  2. Vanderbilt Weight Loss Clinics, Vanderbilt University Medical Center, Nashville, TN, 37204, USA

    Jason M. Samuels, Nina U. Paddu & Gitanjali Srivastava

  3. Department of Medicine, Division of Diabetes, Endocrinology & Metabolism, Vanderbilt University School of Medicine, Nashville, TN, 37204, USA

    Nina U. Paddu, Akhil Rekulapeli, Ayush Madhar & Gitanjali Srivastava

  4. Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN, 37204, USA

    Gitanjali Srivastava

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  1. Jason M. Samuels
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  2. Nina U. Paddu
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  4. Ayush Madhar
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  5. Gitanjali Srivastava
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Correspondence to Gitanjali Srivastava.

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For this type of study, formal consent is not required.

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Conflict of Interest

GS discloses consulting fees from Rhythm, Novo Nordisk, and Eli Lilly outside the submitted work. JMS, NUP, AR, and AM report no financial conflict of interests.

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Key Points

• Heterozygous, Single-allele mutations are common in patients with childhood obesity.

• These mutations appear to impact weight loss after bariatric surgery.

• Early testing for monogenic causes of obesity may be warranted in this cohort.

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Samuels, J.M., Paddu, N.U., Rekulapeli, A. et al. High Prevalence of Positive Genetic Obesity Variants in Postoperative Bariatric Surgery Patients with Weight Regain Presenting for Medical Obesity Intervention. OBES SURG 34, 170–175 (2024). https://doi.org/10.1007/s11695-023-06952-1

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