Non Alcoholic Fatty Liver Disease, Type 2 Diabetes, Liver Cirrhosis
Conditions
Keywords
NAFLD, Incretin hormones
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.
Interventions
Sponsors
University Hospital, Gentofte, Copenhagen
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Incretin effect | pre dose 0,10, 20, 30, 40, 50, 60, 75, 90, 120, 150, 180, 240 min post dose | The difference in insulin responses, as assessed by the area under curve (AUC) for plasma insulin and C-peptide concentrations, during the two different glucose stimuli: Oral glucose tolerance test (OGTT) and isoglycemic iv glucose infusion in NAFLD patients with and without diabetes, and cirrhotic patients compared to healthy control subjects |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Glucagon like peptide 1 (GLP-1) response | pre dose 0,10, 20, 30, 40, 50, 60, 75, 90, 120, 150, 180, 240 min post dose | Comparing GLP-1 responses of the different experimental days, compared to healthy control subjects. |
| Plasma Glucose-dependent insulinotropic peptide (GIP) response | pre dose 0,10, 20, 30, 40, 50, 60, 75, 90, 120, 150, 180, 240 min post dose | Comparing GIP responses of the different experimental days, compared to healthy control subjects. |
| Plasma glucagon response | pre dose 0,10, 20, 30, 40, 50, 60, 75, 90, 120, 150, 180, 240 min post dose | Comparing glucagon responses of the different experimental days, compared to healthy control subjects. |
Countries
Denmark
Outcome results
None listed