Medical Student University of Ottawa Ottawa, Ontario, Canada
Disclosure(s): National Institutes of Health/NIDDK: Grant/Research Support (Terminated, August 12, 2024)
Disclosure(s):
Bassam Termos: National Institutes of Health/NIDDK: Grant/Research Support (Terminated, August 12, 2024)
Blinded Abstract: Hypothesis: Post-bariatric hypoglycemia (PBH) is an increasingly recognized complication following bariatric surgery, characterized by postprandial hypoglycemia. Previous studies have identified preoperative hypoglycemia symptoms as the strongest predictor of postoperative hypoglycemia, increasing the risk tenfold. We hypothesize that genetic variations may contribute to the risk of PBH. Approach: Whole genome Single Nucleotide Polymorphism (SNP) and exome analyses were conducted on a cohort of 1,959 participants from the Longitudinal Assessment of Bariatric Surgery (LABS) study. Targeted sequencing and quantitative amino acid analysis were performed on a metabolically phenotyped cohort of 75 participants, divided into three groups: (1) post-RYGB (Roux-en-Y Gastric Bypass) with established PBH, (2) post-RYGB without hypoglycemia symptoms, and (3) non-surgical controls.
Results: Exome analysis of the LABS cohort revealed an enrichment of variants in the gene SLC7A10, an amino acid transporter known to regulate adipocyte and systemic metabolism, in participants with hypoglycemia symptoms compared to those without symptoms. Quantitative analysis demonstrated a rise in amino acid levels after a mixed meal and a reduction in the fasting state in PBH but showed no differences between PBH and asymptomatic patients. Polygenic risk score (PRS) analysis and exome sequencing in the cohort are pending.
Conclusions: Our findings suggest a genetic contribution to hypoglycemia risk in post-bariatric surgery patients, specifically implicating the gene SLC7A10. Further studies are needed to explore how specific SLC7A10 variants impact amino acid and glucose metabolism and PBH susceptibility.
