Fasting Fibroblast Growth Factor 19 Research Articles

Postprandial triglycerides and fibroblast growth factor 19 as potential screening tools for paediatric non-alcoholic fatty liver disease.

Better screening tools for paediatric NAFLD are needed. We tested the hypothesis that the postprandial triglyceride (TG) and fibroblast growth factor 19 (FGF19) response to an abbreviated fat tolerance test (AFTT) could differentiate adolescents with NAFLD from peers with obesity and normal weight. Fifteen controls with normal weight (NW), 13 controls with obesity (OB) and 9 patients with NAFLD completed an AFTT. Following an overnight fast, participants consumed a high-fat meal. TG and FGF19 were measured at baseline and 4h post-meal. Liver steatosis and fibrosis were measured via Fibroscan. Fasting TG and FGF19 did not differ among groups; 4h TG in the NAFLD and OB groups were greater (197 ± 69 mg/dL; 157 ± 72 mg/dL, respectively) than NW (105 ± 45 mg/dL; p < 0.05) and did not differ from one another. Within the entire cohort, 4h TG were stratified by high and low steatosis. Adolescents with high steatosis had 98% greater 4h TG than adolescents with low steatosis. 4h FGF19, but not fasting FGF19, was higher in children with low steatosis compared with high steatosis (p < 0.05). Using area under the receiver operating curve (AUROC), the only biochemical outcome with diagnostic accuracy for NAFLD was 4h TG (0.77 [95% CI: 0.60-0.94; p=0.02]). The postprandial TG response is increased in adolescents with obesity with hepatic steatosis, with or without NAFLD. Our preliminary analysis demonstrates 4h TG differentiate patients with NAFLD from those without, supporting a role for the AFTT as a screening tool for paediatric NAFLD.

Children With Steatosis and Fibrosis Have a Blunted Postprandial FGF19 Response to a High-Fat Meal

ObjectivesThe standard for early screening of NAFLD in children is circulating liver enzymes, but those measures lack clinical specificity and sensitivity for NAFLD. As an alternative candidate, we tested the hypothesis that the postprandial fibroblast growth factor-19 (FGF19) response to an abbreviated fat tolerance test (AFTT) may discriminate pediatric patients with NAFLD from obese and normal weight peers.MethodsIn this cross-sectional study, 15 normal weight controls (6M/9F; age: 17 ± 2y; BMI: 49 ± 24%ile), 13 controls with obesity without NAFLD (5M/8F; age: 17 ± 2y; BMI: 98 ± 1%ile), and 9 patients with NAFLD (7M/2F; age: 15 ± 2y; BMI: 99 ± 0%ile) completed an AFTT. Following an overnight fast, participants consumed a high-fat meal (73% fat; 9 kcal/kg) and FGF19 was measured at baseline and 4h post-meal. Liver steatosis (controlled attenuation parameter (CAP)) and fibrosis (stiffness) were measured via Fibroscan.ResultsTwo-way ANOVA revealed no group × time interaction, time effect, or group effect (p’s > 0.05) for FGF19. Similarly, FGF19 tAUC and ΔFGF19 did not differ across groups (p's > 0.05). There was a medium effect size between the OB control and NAFLD groups (d = 0.57) and the normal weight and NAFLD groups (d = 0.47) and a large effect size between the normal weight and NAFLD groups (d = 0.80) for 4h FGF19, suggesting that a larger sample size may reveal statistically lower values in children with NAFLD. Across all groups, fasting FGF19 was not different between children with high (≥ 220 dB/m) vs. low steatosis (≤ 220 dB/m; p = 0.09), however 4h FGF19 was 256% higher in children with lower steatosis (1406 ± 1371 pg/mL) compared to higher steatosis (394 ± 352 pg/mL; p = 0.007). Likewise, across all groups, fasting FGF19 did not differ between children with no fibrosis (kPa < 6) and children with evidence of fibrosis (kPa > 6; p = 0.11); however, children with no fibrosis had 4-fold higher 4h FGF19 compared to children with evidence of fibrosis (kPa > 6; p = 0.04).ConclusionsThe postprandial rise in FGF19 was blunted in children with higher liver steatosis and fibrosis. A major role of FGF19 is to promote fatty acid oxidation and inhibit triglyceride synthesis in the liver, thus this finding provides insight on how hepatic fat accrues in pediatric NAFLD.Funding SourcesOklahoma Shared Clinical and Translational Resources (OSCTR); Barbara Pass Research Grant, Oklahoma State University.

Bile Acid Diarrhea in Adults and Adolescents.

Bile acids are central to enterohepatic signaling pathways activated through natural receptors, farnesoid X receptor [FXR mediates synthesis of fibroblast growth factor-19 (FGF-19)], and G protein-coupled bile acid receptor 1 (GPBAR1, also known as TGR5). Although bile acid diarrhea (BAD) is more commonly encountered in ileal resection or disease, there is evidence documenting "idiopathic" BAD in about 20% of adolescents and 30% of adults presenting with chronic, non-bloody diarrhea often attributed to irritable bowel syndrome. Mechanism(s) leading to increased hepatic synthesis and colonic bile acid levels in "idiopathic" BAD include reduced synthesis of FGF-19 by the ileal mucosa, or genetic variation in hepatocyte proteins klotho β and FGF receptor 4 (FGFR4) that mediate negative feedback of bile acid synthesis. The objective of this review is to summarize the diagnosis of BAD in adults and adolescents. In addition to 75 SeHCAT retention for diagnosis of BAD, studies have validated fasting serum 7αC4 and FGF-19, respectively, by-product and inhibitor of hepatic bile acid synthesis, as well as fecal bile acid measurements. These assays are widely available through reference laboratories, and they are being simplified (eg, measurement of primary fecal bile acids in a random stool sample). BAD has also been identified as a co-factor contributing to persistent diarrhea in other diseases in remission including inflammatory bowel disease, microscopic colitis, celiac disease, and neuroendocrine tumors. In summary, advances in diagnosis of BAD provide opportunities for generalists and pediatric and adult gastroenterologists to provide targeted treatment for BAD presenting as chronic non-bloody diarrhea.

Markers of Bile Acid Metabolism in Pediatric Diarrhea Predominant Irritable Bowel Syndrome and Healthy Controls.

Excessive fecal bile acids in adults have been associated with diarrhea-predominant irritable bowel syndrome (IBS-D), but their role in pediatric IBS-D is unknown. Serum markers including 7α-hydroxy-4-cholesten-3-one (C4) and fibroblast growth factor-19 (FGF-19) were validated in adults to detect bile acid diarrhea (BAD) compared to 48-hour fecal bile acid collection (48FBA). Our aims were to assess fasting serum C4 and FGF-19 and 48FBA in a pediatric population, to compare measurements in IBS-D patients and healthy controls (HC), and to determine the prevalence of BAD among children with IBS-D. Using a cross-sectional design, 26 patients with IBS-D and 56 HC were recruited in two pediatric tertiary care centers. Fasting serum C4 and FGF-19 and 48FBA were obtained. Participants completed a 7-day bowel diary coinciding with stool collection. Associations were analyzed using Spearman correlations. Mean age was 14.7 ± 2.5 years (42.3% female) in IBS-D and 12.6 ± 2.4 years (39.3% female) in HC. There was a significant correlation of C4 with 48FBA (r = 0.48, P < 0.05) and an inverse association with FGF-19 (r = -0.43, P < 0.05). No significant differences were noted in C4 (P = 0.32), FGF-19 (P = 0.1), or 48FBA (P = 0.5) between IBS-D and HC groups; however, 20% of IBS-D patients had elevated C4 and 28% had low FGF-19 values.Fecal primary BA was significantly correlated with stool frequency (r = 0.45, P < 0.002). Correlations of C4 with 48FBA and FGF-19 are confirmed in a pediatric population. Twenty percent of pediatric patients with IBS-D had abnormal fasting serum C4. This serum test could be applied to identify BAD in pediatric IBS-D.

Acute Changes of Bile Acids and FGF19 After Sleeve Gastrectomy and Roux-en-Y Gastric Bypass.

Gastric bypass (GBP) and sleeve gastrectomy (SG) are both effective bariatric treatments that cause sustained weight loss as well as improvement of type 2 diabetes mellitus (T2DM). The underlying mechanisms are under investigation, including the contribution of alterations in bile acids (BAs) in achieving or maintaining the beneficial metabolic effects after bariatric surgery. The aim of this study is to investigate the acute and short-term effects of GBP and SG on BA compositions and fibroblast growth factor 19 (FGF19) in obese individuals with T2DM and to evaluate any correlations between changes in these measures with glucose metabolic improvements. The levels of both fasting and postprandial plasma BA compositions after oral glucose tolerance test (OGTT), fasting FGF19 and various metabolic indices were measured 1day before and at 3days and 3months after GBP and SG in 19 obese patients (GBP = 8, SG = 11) with T2DM. Body weight loss was observed after both GBP and SG 3months post-operatively, with no significant difference between the two intervention groups (15.0 ± 3.1% vs. 13.9 ± 5.2%, P = 0.761). At 3days post-operation, FGF19 levels increased significantly in both surgery groups (GBP, 118.3 ± 57.3 vs. 363.6 ± 131.0pgmL-1, post-operation P = 0.008; SG, 173.2 ± 127.8 vs. 422.0 ± 243.6pgmL-1, post-operation P = 0.001). Fasting and postprandial increases from pre-operative values in secondary (r = 0.57, P = 0.02; r = 0.58, P = 0.01), conjugated (r = 0.50, P = 0.01; r = 0.48, P = 0.04), glycine-conjugated (r = 0.52, P = 0.05; r = 0.46, P = 0.05) and secondary-conjugated (r = 0.53, P = 0.02; r = 0.60, P = 0.01) BAs correlated with decreases in the postprandial states of glucose (defined by area under the curve (AUC) over 120min (AUC0-120min)). Increases in postprandial primary-conjugated BAs were found to be associated with decreases in HOMA-IR (r = 0.45, P = 0.05). However, increases in fasting and postprandial taurine-conjugated BA correlated with decreases in both basal insulin secretion rate (r = 0.47, P = 0.04; r = 0.48, P = 0.04) and C-peptide level (r = 0.45, P = 0.05; r = 0.47, P = 0.04). After 3months, fasting and postprandial increases in secondary (r = 0.51, P = 0.03; r = 0.48, P = 0.04), secondary-conjugated (r = 0.52, P = 0.02; r = 0.51, P = 0.03) and non-12α-OH (r = 0.51, P = 0.02; r = 0.58, P = 0.01) BAs were found to correlate with increases in Stumvoll Insulin Sensitivity Index. Increases in both fasting and postprandial 12α-OH BAs were correlated with the decreases in glucose AUC (r = 0.46, P = 0.05; r = 0.41, P = 0.04). Both GBP and SG achieve increases in many BA species as early as 3days post-operation, which are sustained at 3months post-operation. Rises in secondary BA and conjugated forms are correlated with early improvements in glucose metabolism at 3days post-operation. These along with 12α-OH BA correlated with improved glucose metabolism at 3months post-operation, suggesting they may contribute to the observed T2DM remission after bariatric surgery.

Bile and fat excretion are biomarkers of clinically significant diarrhoea and constipation in irritable bowel syndrome.

Biomarkers in irritable bowel syndrome (IBS) may guide targeted therapy in this multifactorial disease. It has been suggested that 75% accuracy and cost <$500 categorise biomarkers as cost-effective. To identify differences in faecal bile acids, faecal fat and fasting serum C4 (7a-hydroxy-4-cholesten-3-one) and fibroblast growth factor 19 (FGF19) among patients with IBS-D, IBS-C and healthy controls and to determine accurate, cost-effective biomarkers for clinically relevant diarrhoea and constipation. We assessed daily stool frequency and consistency (Bristol Stool Form Scale) from validated bowel diaries, 48hours total and individual faecal bile acids, 48hours faecal fat and weight, fasting serum C4 and FGF19, and colonic transit by scintigraphy from healthy volunteers (HV) and patients with IBS-D and IBS-C (Rome III criteria). We utilised multivariate logistic regression to determine biomarkers of clinically significant diarrhoea or constipation based on stool frequency, consistency and weight. Among the 126 HV (44M/82F, 37.5±10.9years [SD]), 64 IBS-D (5M/59F, 41.9±12.2years), and 30 IBS-C (0M/30F, 44.6±10years) patients, there were significant differences between all groups in stool weight, frequency, and consistency; in addition, there were differences in colonic transit at 48hours, faecal fat, and total and individual faecal bile acids between IBS-D and IBS-C. Reduced total and primary faecal bile acids and increased faecal lithocholic acid were significant predictors of decreased faecal weight, frequency and consistency with AUC>0.82 (sensitivity >76%, specificity >72%). Total and primary faecal bile acids and faecal fat were significant predictors of increased stool weight, frequency and consistency with AUC>0.71 (sensitivity >55%, specificity >74%).The faecal parameters had a 11.5 positive likelihood ratio in predicting elevated faecal weight. Faecal bile acids and faecal fat are cost-effective and accurate biomarkers associated with significant bowel dysfunction among IBS-D and IBS-C patients.

Response of fibroblast growth factor 19 and bile acid synthesis after a body weight-adjusted oral fat tolerance test in overweight and obese NAFLD patients: a non-randomized controlled pilot trial

BackgroundNon-alcoholic fatty liver disease (NAFLD) is common both in obese and overweight patients. Fibroblast growth factor 19 (FGF19), an intestinal hormone, could play a role in the complex pathogenesis of NAFLD. The aim of our study was to investigate responses of FGF19 and bile acid (BA) synthesis after a body weight-adjusted oral fat tolerance test (OFTT) in overweight and obese NAFLD patients.MethodsFor this study, we recruited 26 NAFLD patients; 14 overweight (median BMI 28.3 kg/m2), 12 obese (35.3 kg/m2) and 16 healthy controls (24.2 kg/m2). All individuals received 1 g fat (Calogen®) per kg body weight orally. Serum concentrations of FGF19 were determined by ELISA. Concentrations of BAs and BA synthesis marker 7α-hydroxy-4-cholesten-3-one (C4) were measured by gas chromatography-mass spectrometry and high-performance liquid chromatography, respectively; all at 0 (baseline), 2, 4 and 6 h during the OFTT.ResultsBMI correlated negatively with fasting FGF19 concentrations (rho = − 0.439, p = 0.004). FGF19 levels of obese NAFLD patients were significantly (p = 0.01) lower in the fasting state (median 116.0 vs. 178.5 pg/ml), whereas overweight NAFLD patients had significantly (p = 0.004) lower FGF19 concentrations 2 h after the fat load (median 163.0 vs. 244.5 pg/ml), and lowest values at all postprandial time points as compared to controls. Baseline BA concentrations correlated positively with FGF19 values (rho = 0.306, p = 0.048). In all groups, we observed BA increases during the OFTT with a peak at 2 h but no change in C4 levels in overweight/obese NAFLD patients.ConclusionsReduced basal gastrointestinal FGF19 secretion and decreased postprandial response to oral fat together with blunted effect on BA synthesis indicate alterations in intestinal or hepatic FXR signaling in overweight and obese NAFLD subjects. The precise mechanism of FGF19 signaling after oral fat load needs further evaluation.Trial registrationWe have registered the trial retrospectively on 30 Jan 2018 at the German clinical trials register (http://www.drks.de/), and the following number has been assigned DRKS00013942.

Effects of supplemented isoenergetic diets varying in cereal fiber and protein content on the bile acid metabolic signature and relation to insulin resistance

Bile acids (BA) are potent metabolic regulators influenced by diet. We studied effects of isoenergetic increases in the dietary protein and cereal-fiber contents on circulating BA and insulin resistance (IR) in overweight and obese adults. Randomized controlled nutritional intervention (18 weeks) in 72 non-diabetic participants (overweight/obese: 29/43) with at least one further metabolic risk factor. Participants were group-matched and allocated to four isoenergetic supplemented diets: control; high cereal fiber (HCF); high-protein (HP); or moderately increased cereal fiber and protein (MIX). Whole-body IR and insulin-mediated suppression of hepatic endogenous glucose production were measured using euglycaemic–hyperinsulinemic clamps with [6-62H2] glucose infusion. Circulating BA, metabolic biomarkers, and IR were measured at 0, 6, and 18 weeks. Under isoenergetic conditions, HP-intake worsened IR in obese participants after 6 weeks (M-value: 3.77 ± 0.58 vs. 3.07 ± 0.44 mg/kg/min, p = 0.038), with partial improvement back to baseline levels after 18 weeks (3.25 ± 0.45 mg/kg/min, p = 0.089). No deleterious effects of HP-intake on IR were observed in overweight participants. HCF-diet improved IR in overweight participants after 6 weeks (M-value 4.25 ± 0.35 vs. 4.81 ± 0.31 mg/kg/min, p = 0.016), but did not influence IR in obese participants. Control and MIX diets did not influence IR. HP-induced, but not HCF-induced changes in IR strongly correlated with changes of BA profiles. MIX-diet significantly increased most BA at 18 weeks in obese, but not in overweight participants. BA remained unchanged in controls. Pooled BA concentrations correlated with fasting fibroblast growth factor-19 (FGF-19) plasma levels (r = 0.37; p = 0.003). Higher milk protein intake was the only significant dietary predictor for raised total and primary BA in regression analyses (total BA, p = 0.017; primary BA, p = 0.011). Combined increased intake of dietary protein and cereal fibers markedly increased serum BA concentrations in obese, but not in overweight participants. Possible mechanisms explaining this effect may include compensatory increases of the BA pool in the insulin resistant, obese state; or defective BA transport.

Dynamics of Bile Acid Profiles, GLP-1, and FGF19 After Laparoscopic Gastric Banding.

An increase of bile acids (BAs), fibroblast growth factor 19 (FGF19), and glucagon-like peptide 1 (GLP-1) has been implicated in metabolic improvements after Roux-en-Y gastric bypass and vertical sleeve gastrectomy. However, data are still conflicting regarding their role after laparoscopic adjustable gastric banding (LAGB). To assess the fasting BA, FGF19, and GLP-1 concentrations in plasma before and after LAGB and to test for correlations with immunometabolic parameters. Furthermore, hepatic farnesoid X receptor (FXR) expression and regulation of FXR-dependent genes were analyzed. Observational study at the University Hospital Innsbruck. Twenty obese patients. Fasting plasma samples were taken before, 3, 6, and 12 months after LAGB. Liver biopsies were obtained at surgery and after 6 months postoperatively. BA profiles, GLP-1 and FGF19 levels, hepatic FXR expression and regulation of FXR target genes were determined. Total, conjugated, and secondary BAs transiently increased 3 months after LAGB (P < 0.01). Only one BA, glycolithocholic acid sulfate, remained significantly elevated throughout the whole follow-up period (P < 0.05). GLP-1 had increased transiently 3 months after surgery (P < 0.01), whereas FGF19 levels increased continuously (P < 0.05). Insulin, homeostasis model assessment index, C-reactive protein, FGF19, and GLP-1 correlated positively with different BAs. No differences were seen in hepatic FXR expression and FXR-regulated genes. Our study results, not only identified LAGB-induced changes in BAs and BA-induced hormones, but also revealed associations between changes in BA profile with GLP-1 and FGF19.

Chenodeoxycholic acid stimulated fibroblast growth factor 19 response - a potential biochemical test for bile acid diarrhoea.

Bile acid diarrhoea is underdiagnosed and better diagnostic tests are needed. Fasting serum fibroblast growth factor-19 (FGF19) has insufficient diagnostic value, but this may be improved by stimulation. To explore if an impaired FGF19 response identifies primary bile acid diarrhoea. Eight patients with primary bile acid diarrhoea and eight healthy volunteers ingested (i) a meal plus 1250mg chenodeoxycholic acid (CDCA), (ii) 1250mg CDCA or (iii) the meal. Blood was sampled at fasting and repeatedly after stimulation. We analysed FGF19 by enzyme-linked immunosorbent assay and bile acids including 7α-hydroxy-4-cholesten-3-one by liquid chromatography-tandem mass spectrometry. Stimulation with the meal plus CDCA increased median FGF19 in healthy volunteers from fasting 62pg/mL [interquartile range (IQR): 41-138] to 99pg/mL (IQR: 67-147; P=0.012) after 90min and peaked after 150min at 313pg/mL (IQR: 54-512). This response was impaired in primary bile acid diarrhoea patients [fasting 56pg/mL (IQR: 42-79); 90min: 48pg/mL [IQR: 37-63); 150min: 57pg/mL (48-198)]. Receiver operating characteristics (ROCAUC ) for fasting FGF19 was 0.55 (P=0.75) and at 90min 0.84 (P=0.02). The difference in FGF19 from fasting to 90min after the meal plus CDCA separated the groups (ROCAUC 1.0; P=0.001). 7α-hydroxy-4-cholesten-3-one was elevated in primary bile acid diarrhoea (P=0.038) and not significantly affected by stimulation. The FGF19 response following chenodeoxycholic acid plus meal is impaired in primary bile acid diarrhoea. This may provide a biochemical diagnostic test.

Factors associated with fibroblast growth factor 19 increment after oral glucose loading in patients who were previously admitted for coronary angiography

BackgroundWe investigated factors associated with fibroblast growth factor 19 (FGF-19) increment after oral glucose loading (OGL) in human subjects. MethodsA total of 240 outpatients without known diabetes who were previously admitted for coronary angiography underwent an oral glucose tolerance test. FGF-19 increment (pg/ml) was calculated as FGF-19 2h after OGL minus fasting FGF-19. ResultsOverall, FGF-19 significantly increased after OGL (from 123 [78–201] to 141 [80–237], p=0.001). By age tertiles (≦54, 55–64, ≧65), FGF-19 significantly increased only in patients aged ≧65 (from 143 [98–209] to 189 [124–332], p<0.001). By glucose regulation status, FGF-19 significantly increased in patients with normal glucose tolerance (from 117 [78–211] to 153 [106–325], p=0.014) and in patients with prediabetes (from 117 [73–179] to 123 [70–204], p=0.043), but not in patients with diabetes (from 181 [102–243] to 178 [111–275], p=0.139). FGF-19 significantly increased in patients on statin treatment (from 120 [78–207] to 145 [86–264], p<0.001), but not in patients not on statin therapy (from 125 [86–196] to 128 [68–230] pg/ml, p=0.676). These findings remained significant after adjustment for confounders. ConclusionsFGF-19 increment after OGL was positively associated with age, and negatively associated with abnormal glucose regulation and statin treatment.

PTH-251 Bile acid diarrhoea is associated with gallstones

Introduction Bile acid diarrhoea (BAD) is a common disorder which in the primary, idiopathic form may result from low serum fibroblast growth factor 19 (FGF19) producing impaired regulation of bile acid synthesis. 75 Selenium Homocholic Acid Taurate (SeHCAT) 7day retention is used in diagnosis, predicting faecal bile acid loss and correlating with fasting serum FGF19. Several groups have shown that overweight and obesity are associated with BAD and low FGF19. Reduced FXR target gene expression, of which FGF19 is one, is associated with gallstones. We hypothesised that the two conditions might share pathophysiologic mechanisms and commonly coexist. Method SeHCAT 7 day retention values were collected between 2003–2014 in patients being investigated for chronic diarrhoea. Other conditions known to be associated with BAD such as cholecystectomy or Crohn’s disease were recorded. A subset of these patients had fasting FGF19 measured. Retrospectively, gallbladder imaging was added to database following cross-referencing with the NHS trust’s PACS system. Where multiple investigations had been performed, the test nearest to the date of the SeHCAT test was recorded. Imaging reporting gallbladder polyps without gallstones were excluded from the final analysis. Results Of 578 SeHCAT values on the database, 303 (52%) were positive with a value Conclusion Bile acid diarrhoea is associated with gallstones, even when adjusted for cholecystectomy which is a known risk factor for BAD. Bile acid diarrhoea and gallstones may share a pathophysiological mechanism. Disclosure of interest None Declared.

Improvements in Glucose Metabolism Early After Gastric Bypass Surgery Are Not Explained by Increases in Total Bile Acids and Fibroblast Growth Factor 19 Concentrations

Bile acids and fibroblast growth factor 19 (FGF19) have been suggested as key mediators of the improvements in glucose metabolism after Roux-en-Y gastric bypass (RYGB). To describe fasting and postprandial state total bile acid (TBA) and FGF19 concentrations before and after RYGB and relate them to parameters of glucose metabolism, glucagon-like peptide-1, cholecystokinin, and cholesterol fractions. A prospective descriptive study was performed at the Department of Endocrinology, Hvidovre Hospital, Hvidovre, Denmark. Thirteen type 2 diabetic (T2D) patients and 12 normal glucose tolerant (NGT) subjects participated in the study. A 4-hour liquid meal test was performed before and 1 week, 3 months, and 1 year after RYGB. We measured fasting and postprandial TBA and FGF19 concentrations. Fasting TBA concentrations decreased in NGT subjects (P < .001) and were unchanged in T2D patients 1 week after surgery, but then increased gradually in both groups with time from surgery (ANOVA Ptime < .001). Area under the curve (AUC) TBA was decreased in NGT subjects 1 week after RYGB (before surgery, 567 mmol * min/L [interquartile range, 481-826]; 1 wk, 419 [381-508]; P = .009) and was unchanged in T2D patients (894 [573-1002]; 695 [349-1147]; P = .97) but then increased with time from surgery in both groups (Ptime < .001). Fasting FGF19 concentrations were unchanged acutely after RYGB (NGT, 140 pg/mL [100-162], 134 [119-204], P = .42; T2D, 162 [130-196], 154 [104-164], P = .68) and remained unchanged throughout the follow-up period. AUC FGF19 increased gradually with time after surgery (Ptime < .001), resembling the changes seen with AUC TBA. One week after RYGB, glucose metabolism improved, low-density lipoprotein-cholesterol and high-density lipoprotein-cholesterol decreased, and cholecystokinin and glucagon-like peptide-1 secretion increased, whereas FFA concentrations were unchanged. TBA and FGF19 do not explain acute changes in glucose metabolism, cholesterol fractions, and gut hormone secretion after RYGB.

PTU-193 A Novel, Rational Approach to Treating Primary Bile Acid Diarrhoea: a Proof of Concept Study of the FXR Agonist Obeticholic Acid

IntroductionPrimary (idiopathic) bile acid diarrhoea (PBAD) is a common chronic diarrhoeal condition, affecting ~1% of the population, and a large proportion of patients otherwise diagnosed with IBS-D. We showed that...

A decrease in fasting FGF19 levels is associated with the development of non-alcoholic fatty liver disease in obese adolescents

Fibroblast growth factor 19 (FGF19) is a hormone released from the small intestine; recently, it has emerged as an endocrine regulator of glucose and lipid metabolism. The aim of this study was to investigate the role of FGF19 in the development of nonalcoholic fatty liver disease (NAFLD). This study included 23 (17 boys) obese adolescents (mean age of 14.1 years) with NAFLD. The control group consisted of 34 (13 boys) obese peers with normal ultrasonographic imaging and normal liver function tests. The definition of NAFLD was based on clinical criteria: elevated alanine aminotransferase (>35 U/L) and liver steatosis features on ultrasound imaging. Serum FGF19 levels were measured in a fasting blood sample. The definition of insulin resistance was based on the homeostasis model assessment (HOMA) threshold: >2.5. There was a significant difference between mean FGF19 levels in patients with NAFLD and controls (142.2 vs. 206 pg/mL, p=0.04). Mean fasting FGF19 levels were decreased in insulin-resistant patients in comparison with the non-insulin-resistant group (155.0 vs. 221.0 pg/mL, p=0.05). There was an inverse correlation between FGF19 and alanine aminotransferase levels (R=-0.3, p<0.05) and triglycerides (R=-0.27, p<0.05). A decrease in fasting FGF19 is associated with the development of NAFLD in obese adolescents. A decrease in fasting FGF19 levels may be a new important risk factor for NAFLD and the metabolic syndrome in adolescents. Further studies are needed to explain whether exogenous delivery of FGF19 might be therapeutically beneficial.

Evaluation of Fibroblast Growth Factor 19 in the Diagnosis of Bile Acid Diarrhea

Introduction The prevalence of bile acid diarrhoea (BAD) is estimated to be 1%, but the condition remains under diagnosed, partly because the selenium homocholic acid taurine (SeHCAT) test is not widely available. Fibroblast Growth Factor 19 (FGF19) produced in the terminal ileum in response to bile acid absorption plays an important role as a negative regulator of bile acid synthesis and low median FGF19 levels were shown in patients with primary BAD. The aim of this study was to evaluate the relationship between fasting FGF19 levels and SeHCAT in a large prospective group of patients defined by SeHCAT results. We also compared FGF19 levels at the time of colonoscopy in order to assess the effect of bowel preparation. Methods Patients recruited with chronic diarrhoea had SeHCAT testing as part of routine workup and provided fasting blood samples. Group 1 (n=74) were diagnosed as having BAD with a SeHCAT value of less than 15% and included patients with any of the possible causes of BAD. Group 2 patients (n=63) had SeHCAT values of greater than 15%. Serum FGF19 was measured in all patients by ELISA. Data were analysed to compare the relationship between FGF19 and SeHCAT in both groups. 17 patients had additional blood samples taken before colonoscopy after a standard bowel prep. Results FGF19 and SeHCAT were positively related (r=-0.49 Spearman rank correlation). The median FGF19 values in Group 1 and Group 2 were 146 pg/ml and 242 pg/ml respectively (p Conclusion The use of SeHCAT to diagnose BAD is currently the gold standard test of choice, but has its limitations. In this large prospective group we have shown a positive correlation between SeHCAT and FGF19. Potentially FGF19, which is a simple blood test, could be utilised as an alternative diagnostic or screening test for this condition. Further development and refinement to account for factors such as obesity, timing of a sample, and the effect of bowel preparation for colonoscopy may improve the sensitivity and specificity of the test.

* Evaluation of fibroblast growth factor 19 in the diagnosis of bile acid diarrhoea

IntroductionThe prevalence of bile acid diarrhoea (BAD) is estimated to be 1%, but the condition remains under diagnosed, partly because the selenium homocholic acid taurine (SeHCAT) test is not widely...

PP-020 A prospective study of fibroblast growth factor 19 in patients with chronic diarrhoea and possible bile acid malabsorption

Introduction Chronic diarrhoea resulting from excess bile acids in the colon (“bile acid malabsorption”, BAM) is usually diagnosed by the selenium homocholic acid taurine (SeHCAT) test and responds to bile acid sequestrants. Other tests for BAM including serum levels of 7α-hydroxy-4-cholesten-3-one are not widely available. Our group suggested that disordered negative feedback inhibition by Fibroblast Growth Factor 19 (FGF19), produced by the ileum, of hepatic bile acid synthesis results in an excess of bile acids entering the colon, causing bile acid diarrhoea. We aim to examine further the role of FGF19 in a larger group of patients with chronic diarrhoea. Methods 62 patients have been prospectively recruited with chronic diarrhoea. All patients had routine investigations for chronic diarrhoea to exclude other causes and all had SeHCAT tests. Three different patient groups were defined according to the diagnosis based on SeHCAT results: SeHCAT 15% (n=28). All patient demographics and symptoms were recorded and fasting blood samples for FGF19 were collected and available in 54 patients. Serum FGF19 was quantified by ELISA using a commercially available kit. Results Fasting FGF19 levels were significantly lower in patients with primary and secondary BAM compared with the chronic diarrhoea group with normal SeHCAT results (medians 160 vs 139 vs 276 pg/ml, p Conclusion This study confirms that serum levels of an easily measurable hormone, FGF19, are significantly reduced in patients with bile acid diarrhoea, and are not affected by chronic diarrhoea per se. These patients also have a higher BMI. Other symptoms such as faecal incontinence, urgency abdominal pain, bloating and steatorrhoea are also common findings in these patients. These results provide further evidence that there is a disruption of a homeostatic mechanism in the control of bile acid synthesis with an overproduction of bile acids leading to chronic watery diarrhoea.