Postprandial Plasma Concentrations of Individual Bile Acids and FGF-19 in Patients With Type 2 Diabetes

David P Sonne; F Samuel van Nierop; Willem Kulik; Maarten R Soeters; Tina Vilsbøll Lauritsen; Filip K Knop

doi:10.1210/jc.2016-1607

Postprandial Plasma Concentrations of Individual Bile Acids and FGF-19 in Patients With Type 2 Diabetes

David P Sonne, F Samuel van Nierop, Willem Kulik, Maarten R Soeters, Tina Vilsbøll Lauritsen, Filip K Knop

59 Citations (Scopus)

Abstract

Context: Bile acids regulate lipid and carbohydrate metabolism by interaction with membrane or intracellular proteins including the nuclear farnesoid X receptor (FXR). Postprandial activation of ileal FXR leads to secretion of fibroblast growth factor 19 (FGF-19), a gut hormone that may be implicated in postprandial glucose metabolism. Objective: To describe postprandial plasma concentrations of 12 individual bile acids and FGF-19 in patients with type 2 diabetes (T2D) and healthy controls. Design and Setting: Descriptive study, performed at the Center for Diabetes Research, Gentofte Hospital, Hellerup, Denmark. Participants: Fifteen patients with T2D and 15 healthy matched controls with normal glucose tolerance. Interventions: A 75-g oral glucose tolerance test and three isocaloric and isovolemic liquid meals with low, medium, and high fat content, respectively. Main Outcome Measures: Bile acid and FGF-19 concentrations. Results: Postprandial total bile acid concentrations increased with increasing meal fat content (P < .05), peaked after 1-2 hours, and were higher in T2D patients vs controls (oral glucose tolerance test, low and medium fat meals, P<.05; high fat meal, P=.30). Differences reflected mainly unconjugated and glycine-conjugated forms of deoxycholic acid (DCA) and to a lesser extent cholic acid (CA) and ursodeoxycholic acid (UDCA), whereas chenodeoxycholic acid (CDCA) concentrations were comparable in the two groups. FGF-19 concentrations tended to be lower in T2D patients vs controls, but differences were not statistically significant due to considerable variation. Conclusion: Postprandial plasma patterns of bile acids with FXR agonistic properties (CDCA, DCA, and CA) and FXR antagonistic properties (UDCA) in T2D patients support the notion of a "T2D-bile acid-FGF-19" phenotype with possible pathophysiological implications.

Original language	English
Journal	Endocrinology
Volume	101
Issue number	8
Pages (from-to)	3002-3009
Number of pages	8
ISSN	0013-7227
DOIs	https://doi.org/10.1210/jc.2016-1607
Publication status	Published - Aug 2016

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@article{e860b0775adf49d29b8042beb964c2de,

title = "Postprandial Plasma Concentrations of Individual Bile Acids and FGF-19 in Patients With Type 2 Diabetes",

abstract = "Context: Bile acids regulate lipid and carbohydrate metabolism by interaction with membrane or intracellular proteins including the nuclear farnesoid X receptor (FXR). Postprandial activation of ileal FXR leads to secretion of fibroblast growth factor 19 (FGF-19), a gut hormone that may be implicated in postprandial glucose metabolism. Objective: To describe postprandial plasma concentrations of 12 individual bile acids and FGF-19 in patients with type 2 diabetes (T2D) and healthy controls. Design and Setting: Descriptive study, performed at the Center for Diabetes Research, Gentofte Hospital, Hellerup, Denmark. Participants: Fifteen patients with T2D and 15 healthy matched controls with normal glucose tolerance. Interventions: A 75-g oral glucose tolerance test and three isocaloric and isovolemic liquid meals with low, medium, and high fat content, respectively. Main Outcome Measures: Bile acid and FGF-19 concentrations. Results: Postprandial total bile acid concentrations increased with increasing meal fat content (P < .05), peaked after 1-2 hours, and were higher in T2D patients vs controls (oral glucose tolerance test, low and medium fat meals, P<.05; high fat meal, P=.30). Differences reflected mainly unconjugated and glycine-conjugated forms of deoxycholic acid (DCA) and to a lesser extent cholic acid (CA) and ursodeoxycholic acid (UDCA), whereas chenodeoxycholic acid (CDCA) concentrations were comparable in the two groups. FGF-19 concentrations tended to be lower in T2D patients vs controls, but differences were not statistically significant due to considerable variation. Conclusion: Postprandial plasma patterns of bile acids with FXR agonistic properties (CDCA, DCA, and CA) and FXR antagonistic properties (UDCA) in T2D patients support the notion of a {"}T2D-bile acid-FGF-19{"} phenotype with possible pathophysiological implications.",

author = "Sonne, {David P} and {van Nierop}, {F Samuel} and Willem Kulik and Soeters, {Maarten R} and Lauritsen, {Tina Vilsb{\o}ll} and Knop, {Filip K}",

year = "2016",

month = aug,

doi = "10.1210/jc.2016-1607",

language = "English",

volume = "101",

pages = "3002--3009",

journal = "Journal of Clinical Endocrinology and Metabolism",

issn = "0013-7227",

publisher = "Oxford University Press",

number = "8",

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TY - JOUR

T1 - Postprandial Plasma Concentrations of Individual Bile Acids and FGF-19 in Patients With Type 2 Diabetes

AU - Sonne, David P

AU - van Nierop, F Samuel

AU - Kulik, Willem

AU - Soeters, Maarten R

AU - Lauritsen, Tina Vilsbøll

AU - Knop, Filip K

PY - 2016/8

Y1 - 2016/8

N2 - Context: Bile acids regulate lipid and carbohydrate metabolism by interaction with membrane or intracellular proteins including the nuclear farnesoid X receptor (FXR). Postprandial activation of ileal FXR leads to secretion of fibroblast growth factor 19 (FGF-19), a gut hormone that may be implicated in postprandial glucose metabolism. Objective: To describe postprandial plasma concentrations of 12 individual bile acids and FGF-19 in patients with type 2 diabetes (T2D) and healthy controls. Design and Setting: Descriptive study, performed at the Center for Diabetes Research, Gentofte Hospital, Hellerup, Denmark. Participants: Fifteen patients with T2D and 15 healthy matched controls with normal glucose tolerance. Interventions: A 75-g oral glucose tolerance test and three isocaloric and isovolemic liquid meals with low, medium, and high fat content, respectively. Main Outcome Measures: Bile acid and FGF-19 concentrations. Results: Postprandial total bile acid concentrations increased with increasing meal fat content (P < .05), peaked after 1-2 hours, and were higher in T2D patients vs controls (oral glucose tolerance test, low and medium fat meals, P<.05; high fat meal, P=.30). Differences reflected mainly unconjugated and glycine-conjugated forms of deoxycholic acid (DCA) and to a lesser extent cholic acid (CA) and ursodeoxycholic acid (UDCA), whereas chenodeoxycholic acid (CDCA) concentrations were comparable in the two groups. FGF-19 concentrations tended to be lower in T2D patients vs controls, but differences were not statistically significant due to considerable variation. Conclusion: Postprandial plasma patterns of bile acids with FXR agonistic properties (CDCA, DCA, and CA) and FXR antagonistic properties (UDCA) in T2D patients support the notion of a "T2D-bile acid-FGF-19" phenotype with possible pathophysiological implications.

AB - Context: Bile acids regulate lipid and carbohydrate metabolism by interaction with membrane or intracellular proteins including the nuclear farnesoid X receptor (FXR). Postprandial activation of ileal FXR leads to secretion of fibroblast growth factor 19 (FGF-19), a gut hormone that may be implicated in postprandial glucose metabolism. Objective: To describe postprandial plasma concentrations of 12 individual bile acids and FGF-19 in patients with type 2 diabetes (T2D) and healthy controls. Design and Setting: Descriptive study, performed at the Center for Diabetes Research, Gentofte Hospital, Hellerup, Denmark. Participants: Fifteen patients with T2D and 15 healthy matched controls with normal glucose tolerance. Interventions: A 75-g oral glucose tolerance test and three isocaloric and isovolemic liquid meals with low, medium, and high fat content, respectively. Main Outcome Measures: Bile acid and FGF-19 concentrations. Results: Postprandial total bile acid concentrations increased with increasing meal fat content (P < .05), peaked after 1-2 hours, and were higher in T2D patients vs controls (oral glucose tolerance test, low and medium fat meals, P<.05; high fat meal, P=.30). Differences reflected mainly unconjugated and glycine-conjugated forms of deoxycholic acid (DCA) and to a lesser extent cholic acid (CA) and ursodeoxycholic acid (UDCA), whereas chenodeoxycholic acid (CDCA) concentrations were comparable in the two groups. FGF-19 concentrations tended to be lower in T2D patients vs controls, but differences were not statistically significant due to considerable variation. Conclusion: Postprandial plasma patterns of bile acids with FXR agonistic properties (CDCA, DCA, and CA) and FXR antagonistic properties (UDCA) in T2D patients support the notion of a "T2D-bile acid-FGF-19" phenotype with possible pathophysiological implications.

U2 - 10.1210/jc.2016-1607

DO - 10.1210/jc.2016-1607

M3 - Journal article

C2 - 27270475

SN - 0013-7227

VL - 101

SP - 3002

EP - 3009

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

IS - 8

ER -

Postprandial Plasma Concentrations of Individual Bile Acids and FGF-19 in Patients With Type 2 Diabetes

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