Type 2 Diabetes Remission in Patients with Heterozygous Variants in the Leptin-Melanocortin Pathway after Roux-en-Y Gastric Bypass: A Matched Case-Control Study

Background Roux-en-Y gastric bypass (RYGB) is associated with a high rate of type 2 diabetes (T2D) remission. Carriers of heterozygous variants in the leptin-melanocortin pathway (LMP) are more likely to experience weight recurrence after RYGB. Our aim was to investigate if carrier status and associated weight regain affects the rate of T2D remission after RYGB. Methods Carriers of LMP variants with a diagnosis of T2D prior to RYGB (N=16) were matched to non-carriers (N=32) based on sex, age, and BMI. We assessed for post-operative T2D remission status post-surgery on a yearly basis, for up to 15 years. Our primary endpoint was the proportion of patients achieving T2D remission at 1 year. We conducted a survival analysis for all patients that achieved remission at least at one time-point to evaluate for maintenance of T2D remission by using a log-rank test. Results Both carriers and non-carriers had similar baseline and procedural characteristics. The proopiomelanocortin gene in the LMP pathway had the most variants (n=5, 31%). Carriers had a lower total body weight loss percentage at nadir (28.7%+/- 6.9) than non-carriers (33.7%+/- 8.8, p=0.04). The proportion of patients achieving T2D remission at 1 year was 68.8% for carriers and 71.9% for non-carriers (p=1.0). Survival curves for maintenance of first remission were similar for both groups (p=0.73), with a median survival of 8 years for both carriers and non-carriers. Conclusions Despite inferior weight loss outcomes at nadir, carriers had similar T2D remission rates when compared to non-carriers. Weight-independent metabolic benefits of RYGB might contribute to this observation.