Background: This study aims to quantify changes in fibroblast growth factor 19 (FGF19) and bile acids (BAs) in patients with uncontrolled type 2 diabetes randomized to Roux-en-Y gastric bypass (RYGB) vs intensive medical management (IMM) and matched for similar reduction in HbA1c after 1 year of treatment. Methods: Blood samples were drawn from patients who underwent a test meal challenge before and 1 year after IMM (n = 15) or RYGB (n = 15). Results: Mean HbA1c decreased from 9.7 to 6.4 % after RYGB and from 9.1 to 6.1 % in the IMM group. At 12 months, the number of diabetes medications used per subject in the RYGB group (2.5 ± 0.5) was less than in the IMM group (4.6 ± 0.3). After RYGB, FGF19 increased in the fasted (93 ± 15 to 152 ± 19 pg/ml; P = 0.008) and postprandial states (area under the curve (AUC), 10.8 ± 1.9 to 23.4 ± 4.1 pg × h/ml × 103; P = 0.006) but remained unchanged following IMM. BAs increased after RYGB (AUC ×103, 6.63 ± 1.3 to 15.16 ± 2.56 μM × h; P = 0.003) and decreased after IMM (AUC ×103, 8.22 ± 1.24 to 5.70 ± 0.70; P = 0.01). No changes were observed in the ratio of 12α-hydroxylated/non-12α-hyroxylated BAs. Following RYGB, FGF19 AUC correlated with BAs (r = 0.54, P = 0.04) and trended negatively with HbA1c (r = −0.44; P = 0.09); these associations were not observed after IMM. Conclusions: BA and FGF19 levels increased after RYGB but not after IMM in subjects who achieved similar improvement in glycemic control. Further studies are necessary to determine whether these hormonal changes facilitate improved glucose homeostasis.
Bibliographical noteFunding Information:
All authors have completed and submitted Disclosure of Potential Conflicts of Interest. Dr Billington reports receiving grant support from Covidien and personal support for consultancy from EnteroMedics Inc. Dr Connett reports receiving grant support from Covidien. Dr Ikramuddin serves as an advisory board member for Novo Nordisk, USGI, and Medica; consults for Metamodix Inc; and receives grant support from Covidien, EnteroMedics, and ReShape Medical. Dr Korner reports receiving institutional grant support from Covidien, travel expenses from American Board of Obesity Medicine, and personal support for serving on the Takeda Speaker Bureau and on the Scientific Advisory Board for Nutrisystem and consulting for the Office of Professional Misconduct and L.E.K Consulting. The study was supported in part by Covidien, Mansfield, MA. The sponsoring agency had no role in the collection, management, analysis, and interpretation of the study data and had no part in the preparation of the manuscript. The sponsor was allowed to review the manuscript prior to submission but had no role in the decision to submit the manuscript for publication. Additional support was received from National Institutes of Health grant DK072011 (J.K.), the National Center for Advancing Translations Sciences Grant UL1 TR000040, and discretionary funds from Columbia University Medical Center (to J.K.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
- Bile acids
- Fibroblast growth factor 19
- Glucagon-like peptide-1
- Roux-en-Y gastric bypass
- Type 2 diabetes mellitus