B0629 - Effects of Heterozygous Variants in the Leptin-Melanocortin Pathway on Transoral Outlet Reduction After Roux-en-Y Gastric Bypass

Monday, October 24, 2022

10:00 AM – 12:00 PM ET

Location: Crown Ballroom

Presenting Author(s)

Khushboo S. Gala, MD

Mayo Clinic
Rochester, MN

Award: Presidential Poster Award

Khushboo S. Gala, MD, Wissam Ghusn, MD, Alan De La Rossa, MD, Lizeth Cifuentes, MD, Fauzi Feris, MD, Alejandro Campos, MD, Daniel Sacoto, MD, Andres Acosta, MD, PhD
Mayo Clinic, Rochester, MN

Introduction: Mutations in the leptin-melanocortin pathway (LMP) are known contributors to severe obesity. Carriers of a heterozygous variants in the LMP have greater weight regain following Roux-en-Y gastric bypass (RYGB) than non-carriers. Transoral outlet reduction (TORe) is a safe endoscopic technique to reduce the size of the gastrojejunal anastomosis aperture, counteracting the weight regain after RYGB. We aim to evaluate weight loss outcome of TORe over one year in patients with obesity and with or without heterozygous variants in the LMP.

Methods: This is a retrospective case-control study from the Mayo Clinic Biobank who were genotyped for an LMP variant and had RYGB surgery followed by TORe procedure. We excluded patients with active malignancy, on an anti-obesity medication, or pregnancy. Patient demographic and medical information were abstracted from the electronic medical records with weight records up to one year after TORe procedure. Total body weight loss percentage (TBWL%) at 1, 3, 6, 9 and 12 months was calculated based on baseline weight at TORe procedure. All continuous data are summarized as the mean and standard deviation (SD). A Wilcoxon 2-sample t-test was conducted to compare TBWL% between groups.

Results: A total of 14 patients were included in the analysis. Four patients (mean age 51.0 [5.2] years, 100% females, body mass index [BMI] 40.5 [8.7] kg/m²) with LMP variant and 10 non-carriers (age 55.4 [15.3] years, 90% females, BMI 37.3 [7.7] kg/m²). There were no baseline differences between carriers and non-carriers at time of TORe procedure (Table 1A). TBWL% was lower in carrier patients after TORe compared to non-carriers at 1, 3, 6, and 9 months. Similarly, TBWL% was lower and achieved significance at one year follow-up (1.6%) in carriers vs. (12.3%) in non-carriers (p=0.03) (Table 1B, graph 1).

Discussion: Patients with a LMP variant and that underwent RYGB showed decreased weight loss after undergoing TORe. Further and larger studies are needed to comprehend the effect of TORe on patients with LMP variants. Patients with a LMP variant and that underwent RYGB showed decreased weight loss after undergoing TORe. Further and larger studies are needed to comprehend the effect of TORe on patients with LMP variants.

Figure: Figure 1: TBWC% of carriers and non-carriers groups at 3, 6, 9, and 12 months.

	Carriers N=4	Non-carriers N=10	Difference (95% CI)	p-value
A) Demographics and Anthropometrics
Females, %	100	90		0.51
Age at TORe, years	51.0 (5.2)	55.4 (15.3)	-4.4 (-16.4 - 7.5)	0.52
Height, m	1.7 (0.1)	1.7 (0.1)	0.05 (-0.1 - 0.2)	0.40
Weight, kg	118 (25.8)	102.4 (22.1)	15.8 (-22.1 - 53.8)	0.18
BMI, kg/m2	40.5 (8.7)	37.3 (7.7)	3.2 (-9.7 - 16.0)	0.55
B) TBWC%
1 month	-8.5 (4.0)	-9.3 (2.8)	-0.8 (-3.3 - 1.7)	0.50
3 months	-9.8 (5.6)	-7.0 (5.6)	2.8 (-5.4- 11.1)	0.40
6 months	-10.0 (6.5)	-6.6 (7.2)	3.4 (-7.3 - 14.1)	0.35
9 months	-9.5 (4.8)	-4.4 (5.4)	5.0 (-5.8 - 15.9)	0.11
12 months	-1.5 (5.9)	-12.3 (3.2)	10.7 (1.8 - 19.6)	0.03
Abbreviations: BMI, Body mass index; TBWC%, Total body weight change percentage; TORe, Transoral outlet reduction

Table: Table 1: Demographics (A) and weight loss outcomes (B) after TORe between patients with LMP gene variants carriers and non-carriers. Values are displayed as means and standard deviation (SD).

Disclosures:

Khushboo Gala indicated no relevant financial relationships.

Wissam Ghusn indicated no relevant financial relationships.

Alan De La Rossa indicated no relevant financial relationships.

Lizeth Cifuentes indicated no relevant financial relationships.

Fauzi Feris indicated no relevant financial relationships.

Alejandro Campos indicated no relevant financial relationships.

Daniel Sacoto indicated no relevant financial relationships.

Andres Acosta: Gila Therapeutics – Consultant, Intellectual Property/Patents, Owner/Ownership Interest. Phenomix Sciences – Intellectual Property/Patents, Owner/Ownership Interest.

Khushboo S. Gala, MD, Wissam Ghusn, MD, Alan De La Rossa, MD, Lizeth Cifuentes, MD, Fauzi Feris, MD, Alejandro Campos, MD, Daniel Sacoto, MD, Andres Acosta, MD, PhD. B0629 - Effects of Heterozygous Variants in the Leptin-Melanocortin Pathway on Transoral Outlet Reduction After Roux-en-Y Gastric Bypass, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.