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



To describe postprandial plasma concentrations of 12 individual bile acids and FGF-19 in patients with type 2 diabetes (T2D) and healthy controls.



Descriptive study, performed at the Center for Diabetes Research, Gentofte Hospital, Hellerup, Denmark.



Fifteen patients with T2D and 15 healthy matched controls with normal glucose tolerance.



A 75-g oral glucose tolerance test and three isocaloric and isovolemic liquid meals with low, medium, and high fat content, respectively.



Bile acid and FGF-19 concentrations.



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.



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.
Center for Diabetes Research (D.P.S., T.V., F.K.K.), Gentofte Hospital, University of Copenhagen, 2900 Hellerup, Denmark; Department of Endocrinology and Metabolism (F.S.v.N., M.R.S.), Academic Medical Center, University of Amsterdam, 1105AZ Amsterdam, The Netherlands; Department of Clinical Chemistry (W.K.), Laboratory Genetic Metabolic Diseases, Academic Medical Center, University of Amsterdam, 1012WX Amsterdam, The Netherlands; and Novo Nordisk Foundation Center for Basic Metabolic Research and Department of Biomedical Sciences (F.K.K.), Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
David P
DP
Sonne
Center for Diabetes Research (D.P.S., T.V., F.K.K.), Gentofte Hospital, University of Copenhagen, 2900 Hellerup, Denmark; Department of Endocrinology and Metabolism (F.S.v.N., M.R.S.), Academic Medical Center, University of Amsterdam, 1105AZ Amsterdam, The Netherlands; Department of Clinical Chemistry (W.K.), Laboratory Genetic Metabolic Diseases, Academic Medical Center, University of Amsterdam, 1012WX Amsterdam, The Netherlands; and Novo Nordisk Foundation Center for Basic Metabolic Research and Department of Biomedical Sciences (F.K.K.), Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
F Samuel
FS
van Nierop
Center for Diabetes Research (D.P.S., T.V., F.K.K.), Gentofte Hospital, University of Copenhagen, 2900 Hellerup, Denmark; Department of Endocrinology and Metabolism (F.S.v.N., M.R.S.), Academic Medical Center, University of Amsterdam, 1105AZ Amsterdam, The Netherlands; Department of Clinical Chemistry (W.K.), Laboratory Genetic Metabolic Diseases, Academic Medical Center, University of Amsterdam, 1012WX Amsterdam, The Netherlands; and Novo Nordisk Foundation Center for Basic Metabolic Research and Department of Biomedical Sciences (F.K.K.), Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
Willem
W
Kulik
Center for Diabetes Research (D.P.S., T.V., F.K.K.), Gentofte Hospital, University of Copenhagen, 2900 Hellerup, Denmark; Department of Endocrinology and Metabolism (F.S.v.N., M.R.S.), Academic Medical Center, University of Amsterdam, 1105AZ Amsterdam, The Netherlands; Department of Clinical Chemistry (W.K.), Laboratory Genetic Metabolic Diseases, Academic Medical Center, University of Amsterdam, 1012WX Amsterdam, The Netherlands; and Novo Nordisk Foundation Center for Basic Metabolic Research and Department of Biomedical Sciences (F.K.K.), Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
Maarten R
MR
Soeters
Center for Diabetes Research (D.P.S., T.V., F.K.K.), Gentofte Hospital, University of Copenhagen, 2900 Hellerup, Denmark; Department of Endocrinology and Metabolism (F.S.v.N., M.R.S.), Academic Medical Center, University of Amsterdam, 1105AZ Amsterdam, The Netherlands; Department of Clinical Chemistry (W.K.), Laboratory Genetic Metabolic Diseases, Academic Medical Center, University of Amsterdam, 1012WX Amsterdam, The Netherlands; and Novo Nordisk Foundation Center for Basic Metabolic Research and Department of Biomedical Sciences (F.K.K.), Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
Tina
T
Vilsbøll
Center for Diabetes Research (D.P.S., T.V., F.K.K.), Gentofte Hospital, University of Copenhagen, 2900 Hellerup, Denmark; Department of Endocrinology and Metabolism (F.S.v.N., M.R.S.), Academic Medical Center, University of Amsterdam, 1105AZ Amsterdam, The Netherlands; Department of Clinical Chemistry (W.K.), Laboratory Genetic Metabolic Diseases, Academic Medical Center, University of Amsterdam, 1012WX Amsterdam, The Netherlands; and Novo Nordisk Foundation Center for Basic Metabolic Research and Department of Biomedical Sciences (F.K.K.), Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
Filip K
FK
Knop
D000328:Adult; D000368:Aged; D001647:Bile Acids and Salts / Q000097:blood*; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005260:Female; D005346:Fibroblast Growth Factors / Q000097:blood*; D005951:Glucose Tolerance Test; D006801:Humans; D008297:Male; D062407:Meals; D008875:Middle Aged; D019518:Postprandial Period
D001647:Bile Acids and Salts; C117476:FGF19 protein, human; D005346:Fibroblast Growth Factors