FGF 19 and Bile Acids Increase Following Roux-en-Y Gastric Bypass but Not After Medical Management in Patients with Type 2 Diabetes

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. Blood samples were drawn from patients who underwent a test meal challenge before and 1 year after IMM (n = 15) or RYGB (n = 15). 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 x h/ml x 10(3); P = 0.006) but remained unchanged following IMM. BAs increased after RYGB (AUC x10(3), 6.63 +/- 1.3 to 15.16 +/- 2.56 mu M x h; P = 0.003) and decreased after IMM (AUC x10(3), 8.22 +/- 1.24 to 5.70 +/- 0.70; P = 0.01). No changes were observed in the ratio of 12 alpha-hydroxylated/non-12 alpha-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. 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.