Clinical trial NCT01492283: Pathophysiological Implications of the Incretin Hormones in Patients With Liver Disease With and Without Diabetes
Official title: Pathophysiological Implications of the Incretin Hormones in Patients With Liver Disease With and Without Diabetes
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Non Alcoholic Fatty Liver Disease
Type 2 Diabetes
Liver Cirrhosis
Keywords: NAFLD
Incretin hormones
Lead sponsor: University Hospital, Gentofte, Copenhagen
Sponsor class: OTHER
First posted: 2011-12-14
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with NAFLD and liver cirrhosis confirmed by liver biopsy, and patients with or without well characterized type 2 diabetes recruited in the the hospitals out patients clinic

Brief summary: The main objective of this study is to analyze the pathophysiological implications of glucagon and the incretin hormones in patients with liver disease (Non alcoholic fatty liver disease (NAFLD) or cirrhosis) with and without diabetes compared with healthy controls. The present study will contribute significantly to the understanding of the pathophysiology of liver disease and glucose metabolism. The final goal is that the results could pave the way for new treatment modalities for patients with liver disease.

Detailed description: Comparison of of insulin secretion (Area Under the Curve (AUC)) during the experimental days. Furthermore a comparison of GIP, GLP1 and glucagon responses as well as plasma glucose levels.

Eligibility criteria: I) Group 1: NAFLD patients with normal glucose tolerance Inclusion criteria

* NAFLD verified by a liver biopsy
* Caucasian \>18 years of age
* Negative islet cell (ICA) and glutamic acid decarboxylase 65 (GAD65) autoantibodies
* Normal 75-g OGTT as specified in the WHO Criteria
* Normal haemoglobin and blood pressure (BP)
* Written informed consent

II) Group 2: NAFLD patients with type 2 diabetes Inclusion criteria

* NAFLD verified by liver biopsy
* T2DM according to the WHO Criteria
* Caucasian \>18 years of age
* Negative ICA and GAD65, normal haemoglobin, normal BP
* Written informed consent

III) Group 3: NAFLD patients without type 2 diabetes Inclusion criteria

* NAFLD verified by liver biopsy
* Caucasian \>18 years of age
* Normal 75-g OGTT
* Negative ICA and GAD65-autoantibodies
* Normal haemoglobin and BP
* Written informed consent

IV) Group 4: Cirrhosis with or without type 2 diabetes Inclusion criteria

* Liver cirrhosis verified by liver biopsy
* Caucasian \> 18 years of age
* Negative ICA and GAD65-autoantibodies
* Normal haemoglobin and BP
* Written informed consent

V) Group 5: Healthy controls Inclusion criteria

* Caucasian \>18 years of age
* Normal 75-g OGTT according to the WHO Criteria
* Negative ICA and GAD65-autoantibodies
* Normal haemoglobin and BP
* Written informed consent

Exclusion criteria (all groups)

* Other known liver disease - viral hepatitis, hereditary haemochromatosis, autoimmune liver disease, alpha-1 trypsin deficiency, Wilson disease, drug induced liver Injury (DILI)
* Treatment with medications that cannot be discontinued for 12 hours
* Unwillingness to participate in protocols
* Pregnancy or lactation

Primary outcomes:
measure: The Incretin effect
timeFrame: pre dose 0,10, 20, 30, 40, 50, 60, 75, 90, 120, 150, 180, 240 min post dose
Secondary outcomes:
measure: Plasma Glucagon like peptide 1 (GLP-1) response
timeFrame: pre dose 0,10, 20, 30, 40, 50, 60, 75, 90, 120, 150, 180, 240 min post dose
measure: Plasma Glucose-dependent insulinotropic peptide (GIP) response
timeFrame: pre dose 0,10, 20, 30, 40, 50, 60, 75, 90, 120, 150, 180, 240 min post dose
measure: Plasma glucagon response
timeFrame: pre dose 0,10, 20, 30, 40, 50, 60, 75, 90, 120, 150, 180, 240 min post dose
Other outcomes:
Locations:
city: Hellerup
country: Denmark
facility: Diabetes Research Division, Gentofte University Hospital, Niels Andersens Vej 65, opgang 4b, 1. sal
Study officials:
affiliation: Diabetes Research Division, Gentofte Hospital, University of Copenhagen
name: Anders E Junker, MD, phd-student
role: PRINCIPAL_INVESTIGATOR
References:
citation: Maagensen H, Junker AE, Jorgensen NR, Gluud LL, Knop FK, Vilsboll T. Bone Turnover Markers in Patients With Nonalcoholic Fatty Liver Disease and/or Type 2 Diabetes During Oral Glucose and Isoglycemic Intravenous Glucose. J Clin Endocrinol Metab. 2018 May 1;103(5):2042-2049. doi: 10.1210/jc.2018-00176.