Bile Acid and FGF19 Response to a High Protein, Low-Calorie Meal before and Early after Gastric Bypass

Presentation Number: SUN 579
Date of Presentation: April 2nd, 2017

Elizabeth O Beale*1, Peter Crookes1, WeiAn Lee2 and Viorica Ionut3
1University of Southern California, LA, CA, 2University of Southern CA, Los Angeles, CA, 3Cedars Sinai Medical Center, LA, CA

Abstract

Background: Improvement in glycemic control typically occurs within days of gastric bypass surgery(GB). As bile acids (BAs) are systemically active and promote glucose tolerance it has been proposed that they may mediate this improvement. Early studies reported increased circulating levels of BAs and an effector molecule, FGF19, from three months to several years after GB. More recently however a few studies conducted earlier post-operatively have not shown these changes. Of note all studies evaluating the BA and FGF19 response to a test meal have involved the administration of caloric loads of around 400kcals of a high fat or mixed meal. This is not typical of meals taken shortly after surgery and thus findings may not be representative of those occurring outside the research setting.

Aim: The aim of this pilot study was to assess fasting and post-prandial BA and FGF19 levels in response to a low-calorie, high protein meal before and early after GB.

Methods: Obese adults underwent a 3-hour meal tolerance test before and 1 and 2 months after GB. All subjects had an intact gallbladder. Blood samples were drawn at 8 time points for total BAs, FGF19, insulin, c-peptide and glucose. A standard meal (CarbSolutions 31grams in 85mls water; Richardson Labs, Inc. FL) was ingested over 15minutes under supervision (120kcals: 67% protein 17% fat and 17% carbohydrate). Outcomes were compared among visits using RM-ANOVA, and values at individual time points were compared by 2-tailed paired t-test, with Benjamini-Hochberg adjustment for multiple comparisons.Total BAs were measured by enzymatic assay (Diazyme DZ042A) and human FGF19 by RIA (R&D Systems DF1900).

Results: Eight subjects (3 males) participated. Mean age was 42 years. 3 subjects had type 2 diabetes. The mean pre-operative BMI was 49kg/m2 and at 2 months was 42kg/m2. No statistically significant differences were found for fasting or stimulated BAs or FGF19 across the 3 study visits. One subject had pre-operative fasting and stimulated bile acid levels approximately 5 times higher than seen at any other study visit which contributed to a trend to a lower average fasting and stimulated bile acid levels at the 1 and 2 month study visits. Fasting and stimulated FGF19 tended to rise over the 3 study visits. There was no observable peak in bile acid levels or FGF19 over the 3-hour test. Fasting insulin and c-peptide levels were significantly lower at the 2-month visit compared with the preoperative visit (both: p<0.0001). There was a trend to lower insulin and c-peptide during the meal over the 3 study visits. At each study visit insulin and c-peptide peaked at 30-45 mins following meal ingestion. There was also a trend to lower fasting and stimulated glucose over the 3 visits.

Conclusion: The results suggest that the early improvement seen in glucose tolerance and insulin resistance after GB are not mediated via systemic bile signaling pathways in humans.

 

Nothing to Disclose: EOB, PC, WL, VI