title: On the role of gallbladder emptying and incretin hormones for nutrient-mediated TSH suppression in patients with type 2 diabetes.
abstract: Bile acids are possible candidate agents in newly identified pathways through which energy expenditure may be regulated. Preclinical studies suggest that bile acids activate the enzyme type 2 iodothyronine deiodinase, which deiodinates thyroxine (T4) to the biologically active triiodothyronine (T3). We aimed to evaluate the influence of bile acid exposure and incretin hormones on thyroid function parameters in patients with type 2 diabetes. Thyroid-stimulating hormone (TSH) and thyroid hormones (total T3 and free T4) were measured in plasma from two human studies: i) 75 g-oral glucose tolerance test (OGTT) and three isocaloric (500 kcal) and isovolaemic (350 ml) liquid meals with increasing fat content with concomitant ultrasonographic evaluation of gallbladder emptying in 15 patients with type 2 diabetes and 15 healthy age, gender and BMI-matched controls (meal-study) and ii) 50 g-OGTT and isoglycaemic intravenous glucose infusions (IIGI) alone or in combination with glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP1) and/or GLP2, in ten patients with type 2 diabetes (IIGI-study). In both studies, TSH levels declined (P<0.01) similarly following all meal and infusion stimuli. T3 and T4 concentrations did not change in response to any of the applied stimuli. TSH levels declined independently of the degree of gallbladder emptying (meal-study), route of nutrient administration and infusion of gut hormones. In conclusion, intestinal bile flow and i.v. infusions of the gut hormones, GIP, GLP1 and/or GLP2, do not seem to affect thyroid function parameters. Thus, the presence of a 'gut-thyroid-pituitary' axis seems questionable.
authors.affiliation: Department of MedicineCenter for Diabetes Research, Gentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, DenmarkDepartment of Biomedical SciencesFaculty of Health and Medical Sciences, The NNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, DenmarkDepartment of EndocrinologyHerlev Hospital, University of Copenhagen, Herlev, Denmark Department of MedicineCenter for Diabetes Research, Gentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, DenmarkDepartment of Biomedical SciencesFaculty of Health and Medical Sciences, The NNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, DenmarkDepartment of EndocrinologyHerlev Hospital, University of Copenhagen, Herlev, Denmark dpsonne@gmail.com.
authors.forename: David P
authors.initials: DP
authors.lastname: Sonne
authors.affiliation: Department of MedicineCenter for Diabetes Research, Gentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, DenmarkDepartment of Biomedical SciencesFaculty of Health and Medical Sciences, The NNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, DenmarkDepartment of EndocrinologyHerlev Hospital, University of Copenhagen, Herlev, Denmark Department of MedicineCenter for Diabetes Research, Gentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, DenmarkDepartment of Biomedical SciencesFaculty of Health and Medical Sciences, The NNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, DenmarkDepartment of EndocrinologyHerlev Hospital, University of Copenhagen, Herlev, Denmark.
authors.forename: Asger
authors.initials: A
authors.lastname: Lund
authors.affiliation: Department of MedicineCenter for Diabetes Research, Gentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, DenmarkDepartment of Biomedical SciencesFaculty of Health and Medical Sciences, The NNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, DenmarkDepartment of EndocrinologyHerlev Hospital, University of Copenhagen, Herlev, Denmark.
authors.forename: Jens
authors.initials: J
authors.lastname: Faber
authors.affiliation: Department of MedicineCenter for Diabetes Research, Gentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, DenmarkDepartment of Biomedical SciencesFaculty of Health and Medical Sciences, The NNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, DenmarkDepartment of EndocrinologyHerlev Hospital, University of Copenhagen, Herlev, Denmark.
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Holst
authors.affiliation: Department of MedicineCenter for Diabetes Research, Gentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, DenmarkDepartment of Biomedical SciencesFaculty of Health and Medical Sciences, The NNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, DenmarkDepartment of EndocrinologyHerlev Hospital, University of Copenhagen, Herlev, Denmark Department of MedicineCenter for Diabetes Research, Gentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, DenmarkDepartment of Biomedical SciencesFaculty of Health and Medical Sciences, The NNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, DenmarkDepartment of EndocrinologyHerlev Hospital, University of Copenhagen, Herlev, Denmark.
authors.forename: Tina
authors.initials: T
authors.lastname: Vilsbøll
authors.affiliation: Department of MedicineCenter for Diabetes Research, Gentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, DenmarkDepartment of Biomedical SciencesFaculty of Health and Medical Sciences, The NNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, DenmarkDepartment of EndocrinologyHerlev Hospital, University of Copenhagen, Herlev, Denmark Department of MedicineCenter for Diabetes Research, Gentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, DenmarkDepartment of Biomedical SciencesFaculty of Health and Medical Sciences, The NNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, DenmarkDepartment of EndocrinologyHerlev Hospital, University of Copenhagen, Herlev, Denmark.
authors.forename: Filip K
authors.initials: FK
authors.lastname: Knop
keywords: GLP1; TGR5; TSH; bile acids; gallbladder; glucagon-like peptide 1; thyroid; thyroid-stimulating hormone; type 2 diabetes