Response of multiple hormones to glucose and arginine challenge in T2DM after gastric bypass

Abstract

Purpose: In patients with type 2 diabetes mellitus (T2DM), Roux-en-Y gastric bypass (RYGB) leads to beneficial metabolic adaptations, including enhanced incretin secretion, beta-cell function, and systemic insulin sensitivity. We explored the impact of RYGB on pituitary, pancreatic, gut hormones, and cortisol responses to parenteral and enteral nutrient stimulation in patients with obesity and T2DM with repeated sampling up to 2 years after intervention.

Methods: We performed exploratory post hoc analyses in a previously reported randomized trial. Levels of adrenocorticotropic hormone (ACTH), cortisol, growth hormone (GH), glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), peptide YY (PYY), ACTH, insulin, and glucagon were measured in 13 patients with T2DM and obesity at four different visits: before and 4, 24, and 104 weeks after RYGB; and in three sequential conditions on the same day: fasting, intravenous arginine challenge, and OGTT.

Results: RYGB surprisingly induced a rise in ACTH, cortisol, and GH levels upon an oral glucose load, together with enhanced GLP-1 and PYY responses. Fasting and post-arginine GH levels were higher after RYGB, whereas insulin, glucagon, GLP-1, GIP, and cortisol were lower. These endocrine adaptations were seen as early as 4 weeks after surgery and were maintained for up to 2 years.

Conclusion: These findings indicate adaptations of glucose sensing mechanisms and responses in multiple endocrine organs after RYGB, involving the gut, pancreatic islets, the pituitary gland, the adrenals, and the brain.

Keywords: HPA-axis; RYGB; diabetes; gut hormones; nutrient challenge.

Figure 1

Plasma hormonal levels during fasting, 3 min after intravenous arginine administration (AC 3’), and OGTT in patients with obesity and type 2 diabetes before and 4, 24, and 104 weeks after RYGB. (A) ACTH, (B) cortisol, (C) GH, (D) total GLP-1, (E) total GIP, (F) PYY, (G) insulin, and (H) glucagon. Data are presented as mean. Mixed-effects models for differences in hormone levels or AUC_OGTT across visits: *P < 0.05; **P < 0.01; ***P < 0.001. N = 13 (except for glucagon, N = 7). ACTH, adrenocorticotropic hormone; GH, growth hormone; GLP-1, glucagon-like peptide 1; GIP, glucose-dependent insulinotropic polypeptide; PYY, peptide YY; RYGB, Roux-en-Y gastric bypass.

Figure 2

AUC_OGTT of plasma hormone levels in patients with obesity and type 2 diabetes before and 4, 24, and 104 weeks after RYGB. (A) ACTH, (B) cortisol, (C) GH, (D) total GLP-1, (E) total GIP, (F) PYY, (G) insulin, and (H) glucagon. Data presented as mean ± s.e.m. Pairwise comparisons for post-surgery AUC_OGTT with pre-surgery AUC_OGTT with paired t-tests. *P < 0.05; **P < 0.01; ***P < 0.001. N = 13 (except for glucagon, N = 7). ACTH, adrenocorticotropic hormone; GH, growth hormone; GLP-1, glucagon-like peptide 1; GIP, glucose-dependent insulinotropic polypeptide; PYY, peptide YY; RYGB, Roux-en-Y gastric bypass.