Increased Bile Acids and FGF-19 after Sleeve Gastrectomy and Roux-en-Y Gastric Bypass Correlate with Improvement in Type 2 Diabetes in a Randomized Trial

Background: Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB), are both effective bariatric procedures to treat type 2 diabetes (T2DM) and obesity. The contribution of changes in bile acids (BAs) and fibroblast growth factor19 (FGF-19) to such metabolic improvements is unclear.

Methods: We examined associations between changes in BAs, FGF-19 (fasting and prandial), with changes in body weight, glycemia and other metabolic variables in 61 obese patients with T2DM before and one year after randomisation to SG or RYGB.

Results: Weight loss and diabetes remission (defined by HbA1c <39mmol/mol [<5.7%] in absence of glucose lowering therapy) after RYGB and SG was similar (mean weight loss -29kg vs. -31kg, p=0.50; diabetes remission proportion 37.5% vs. 34%, p=1.0). Greater increments in fasting and prandial levels of total, secondary and unconjugated BAs were seen after RYGB than SG. Fasting and prandial increases in total (r=-0.3, p=0.01; r=-0.2, p=0.04), secondary (r=-0.3, p=0.01; r=-0.4, p=0.01) and unconjugated BA (r=-0.3, p=0.01; r=0.4, p<0.01) correlated with decreases in HbA1c, but not weight. Changes in 12α-OH/non 12α-OH were positively associated with prandial glucose increments (r=0.2, p=0.03), HbA1c (r=0.3, p=0.01) and negatively associated with changes in insulinogenc index (r=-0.3, p=0.01). Only changes in prandial FGF-19 were negatively associated with HbA1c (r=-0.4, p<0.01) and visceral fat (r=-0.3, p=0.04).

Conclusions/Interpretation: The modest association between increases in secondary, unconjugated BAs and improvements in HBA1c, (but not weight) achieved after both RYGB and SG suggest augmentation of BA signalling as one potential strategy for controlling T2DM through weight independent means.