RF28 | PSUN301 Sex Differences in the Indolepropionic Acid Alterations in Response to Obesity Surgery

INTRODUCTION: Obesity surgeries improve type 2 diabetes (T2D) in most cases, with effects frequently evident before substantial weight reduction. Therefore, this study hypothesizes that the increase in indolepropionic acid (IPA), a gut-derived tryptophan metabolite considered to be a potential biomarker for the development of T2D, might contribute to the metabolic benefits occurring after obesity surgery. Since sex impacts the pathogenesis of numerous diseases, including T2D, our objective was to investigate sex-specific effects on the changes in IPA in response to obesity surgery. METHODS: One-hundred and twenty-one obese individuals (36 males and 85 females; age 48.4 ± 9.4 years; BMI 42.9 ± 5.3kg/m(2)) participants from the ongoing Kuopio OBesity Surgery (KOBS) Study, who were accepted for Roux-en-Y gastric bypass (RYGB) were included. Serum samples drawn after 12h fasting were available from both baseline and 1-year follow-up visits for measuring IPA by LC-QQQ-MS. Impaired fasting glucose (IFG) was defined as a fasting glucose level ≥5.6nmol/L. RESULTS: Male and female participants had similar ages, BMI and IPA [93.2 (44.3–137.8) vs 67.0 (44.6–113.8) ng/dL, P=0.444, males and females respectively) at baseline. Weight loss after 1 year of RYGB was lower in males in comparison with females (19.8 vs 23.5%, P=0.014). A significant interaction between time and sex on IPA changes was found during the first year of RYGB (P=0.028). We observed an increase in IPA in females but not in males, especially in the youngest female group (median age <48.7 years). Fasting insulin interacted significantly with sex on the changes in IPA (P<0.001), but not fasting glucose (P=0.962). In addition, females had lower prevalence of IFG at 1-year (25 vs 57%, P=0.042, female and male participants respectively), which was associated with changes in IPA independently of weight loss. CONCLUSION: Our results suggest that changes in IPA concentrations may be associated with beneficial changes in glucose metabolism observed after obesity surgery in females. A comprehensive understanding of the sex-specific effects of the IPA could contribute to future non-surgical treatments for T2D. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Monday, June 13, 2022 1:12 p.m. - 1:17 p.m.