Abstract

Context: Weight regain (WR) occurs frequently in many individuals after bariatric surgery. Yet, multiple factors contribute to WR and remain poorly understood. Chronic glucocorticoid (GC) exposure is associated with weight gain, accumulation of visceral fat, GC resistance and obesity. However, individuals with obesity display lower mean cortisol levels compared to lean subjects. After a meal tolerance test (MTT), all categories of macronutrient stimulate postprandial rise in circulating cortisol. Randomly selected men exhibiting dysregulated hypothalamic-pituitary-adrenal axis (HPA) based on dexamethasone test had higher cortisol levels after MTT and this was associated with metabolic syndrome. Hormonal changes after bariatric surgery are key contributors to the understanding of WR. Therefore, we hypothesized that meal-stimulated effect on serum cortisol may be higher in post-bariatric surgery patients who experience WR>10% versus those who do not. Objective: To examine the association between meal-stimulated serum cortisol with WR among post- bariatric surgery patients (sleeve or gastric bypass). Design: Cross-sectional study of adults who underwent bariatric surgery (4.8±1.5 years ago) and responded to questionnaire regarding hypoglycemia symptoms and weight status. Methods: Serum cortisol was measured at 0, 60, 90, 120, 240 minutes after MTT; the primary outcome measure WR was calculated as 100 x (current weight-nadir/(preoperative weight-nadir)). Data were analyzed using logistic regression. Results: Participants (n=40) were 80% female, mean age of 49±10 years and 50% underwent gastric bypass. After MTT in both groups (WR or not), serum cortisol increased similarly from 0 to 60 minutes (~7 ug/dL), however afterwards the curve decline rate was different between the groups. After adjustment for preoperative weight and time since surgery, there was not statistical difference in serum cortisol between the groups at 0, 60 or 240 mins. However, at 90 minutes, one unit increase in serum cortisol was associated with 14% lower odds of WR (OR: 0.86, 95% CI: 0.74-0.99; p=0.04) and at 120 minutes 18% lower odds of WR (OR: 0.82, 95% CI: 0.67-0.99; p=0.04). After stratification by type of surgery, at 90 minutes only participants in the sleeve group had lower odds of WR for each unit increase in serum cortisol (OR: 0.77, 95% CI: 0.60-1.00; p=0.048). After, further adjustment for age and sex the association of WR with serum cortisol was no longer statically significant at either 90 or 120 minutes. Conclusion: We observed lower serum cortisol at 90 and 120 minutes after MTT associated with WR after bariatric surgery, which appear to be mediated, at least in part, by age and sex. Further investigation with larger studies is needed to further examine whether an inadequate meal-stimulated cortisol response is associated with WR.

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