Increased Bile Acids and FGF19 After Sleeve Gastrectomy and Roux-en-Y Gastric Bypass Correlate with Improvement in Type 2 Diabetes in a Randomized Trial.

ABSTRACT

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 (FGF19) to such metabolic improvements is unclear. METHODS: We examined associations between changes in BAs, FGF19 (fasting and prandial), with changes in body weight, glycemia, and other metabolic variables in 61 obese patients with T2DM before and 1 year after randomization to SG or RYGB. RESULTS: Weight loss and diabetes remission (defined by HbA1c < 39 mmol/mol [< 5.7%] in the absence of glucose-lowering therapy) after RYGB and SG was similar (mean weight loss - 29 vs - 31 kg, 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 FGF19 were negatively associated with HbA1c (r = - 0.4, p < 0.01) and visceral fat (r = - 0.3, p = 0.04). CONCLUSIONS/INTERPRETATION: The association between increases in secondary, unconjugated BAs and improvements in HBA1c (but not weight) achieved after both RYGB and SG suggest manipulation of BA as a potential strategy for controlling T2DM through weight-independent means.