SUN-LB100 GDF15 May Be Regulated by Cortisol After Sleeve Bariatric Surgery GDF15 May Be Regulated by Cortisol After Sleeve Bariatric Surgery

Abstract

Context: Weight regain (WR) occurs frequently after surgical weight loss. Yet, factors contributing to WR remain poorly understood. Growth/differentiation factor 15 (GDF15), a stress-responsive hormone, has emerged as a potential therapeutic target in obesity treatment. Increase in GDF15 was reported in response to diet-induced weight loss in preclinical and human studies. After a meal tolerance test (MTT), macronutrients stimulate postprandial increases in circulating cortisol. In addition, individuals with obesity display lower cortisol levels with a flat and blunted diurnal cortisol rhythm compared to lean subjects, thereby exhibiting dysregulated hypothalamic-pituitary-adrenal axis (HPA). Hormonal changes after bariatric surgery are key contributors to understanding WR: GDF15 responses to MTT are unknown. Objective: To compare meal-stimulated GDF15 and cortisol response in adults with versus without WR after sleeve gastrectomy (SG). We hypothesized that MTT (stress-stimulus) will decrease cortisol and GFDF15 in SG patients who experience WR≤10% versus without WR≤10%. Design: Cross-sectional study of adults without diabetes, who underwent SG 3.9±0.8 years ago. Methods: Plasma GDF15, insulin, glucose and serum cortisol were measured at 0, 15, 30, 45, 60, 90, 120, 240 minutes after MTT; Outcome: WR≤10% and was calculated as 100x(weight-nadir/(preoperative weight-nadir)). Analysis: t-test, ANOVA, linear mixed model repeated measures by SAS. Results: N=21, 85% female with mean age 43±10 years. The groups (WR and without-WR) were significantly different with respect to BMI (WR:38.6±7.6 vs without-WR:30.3±3.5, p=0.02) and in overall insulin secretion (WR AUC 6289±3432 vs without-WR AUC 3025±2089, p=0.04) despite similar time since surgery. We observed a reduced cortisol and GDF15 response among the WR group after SG versus without WR. The GDF15 response to MTT between the groups differed after 60 mins where a steady increase in secretion was observed in both groups; however more pronounced in the without-WR group p<0.05. The serum cortisol increased differently from 0 to 60 minutes ~7 ug/dL,p=0.05) and ~3 ug/dL in the both groups respectively, afterwards the curve decline rate was also different between the groups with a faster decline in the without-WR group. The WR group displayed a flat cortisol response vs without-WR group. In addition, among the all subjects after adjustment for cortisol, demographics, time, group, insulin, glucose, time*group, one unit increase in serum cortisol was associated with an increase in GDF15 (4.70;95%CI: 0.69-8.71ng/L). Conclusion: We suggest that GDF15 is regulated by cortisol in subjects with weight regain, elevated insulin secretion and blunted meal-induced cortisol response, indicative of HPA dysregulation. Further investigation is needed to examine the role of GDF15 and cortisol in WR after bariatric surgery.