Dysregulation of Growth Hormone Axis after Roux-en-Y Gastric Bypass
Lei Pei, Cameron Cummings, Hamayle Saeed, Alessandra Amore, Maryam Farahmandsadr, Amanda Sheehan, Rafael Ferraz-Bannitz, Donald C Simonson, Mary-Elizabeth PattiAbstract
Context
Bariatric metabolic surgery has potent effects on glucose metabolism, with increases in insulin sensitivity and insulin secretion contributing to both improved glycemia and/or remission of type 2 diabetes (T2D) and development of hypoglycemia (post-bariatric hypoglycemia, PBH). Previous studies suggest GH secretion and/or action are altered after bariatric surgery and may mediate early post-surgical improvements in glycemic control. Given the importance of GH signaling in glucose metabolism, we hypothesized that reductions in GH signaling and/or action could also contribute to PBH.
Objective
Assessment of GH responses to two distinct stimuli: (1) experimental hypoglycemia induced by hyperinsulinemic hypoglycemic clamp and (2) glucagon stimulation.
Setting
Academic medical center
PARTICIPANTS
Individuals with history of Roux-en-Y gastric bypass (RYGB) with PBH (n=20), without hypoglycemia (n=20), and weight-matched non-surgical controls (n=10).
Main outcomes
GH responses were assessed (1) during experimental hypoglycemia and (2) after glucagon stimulation. Plasma GH receptor (GHR) and insulin-like growth factors and binding proteins were also measured.
Results
Glucagon-stimulated GH levels were 5–6 times higher in both post-RYGB groups vs. controls at 120 minutes: control: 481±137 pg/ml; RYGB non-hypo 2521 ± 678 pg/ml; PBH: 3018 ±137pg/ml (control vs RYGB non-hypo p=0.02; control vs PBH; p=0.005). In contrast, PBH participants showed lower GH responses to experimental hypoglycemia. Additionally, plasma GHR and IGF-1 levels were reduced in PBH vs. controls.
Conclusions
We find that plasma GH response to 2 distinct experimental stimuli differed in participants with a history of bariatric surgery. However, these patterns did not differ in those with and without PBH. Further studies will be required to determine if tissue-level alterations in GH action contribute to improved glycemic control after bariatric surgery.