Pathophysiological Implications of the Incretin Hormones in Patients With Liver Disease With and Without Diabetes

NCT01492283 | Completed DMC

• 2 other identifiers: LINK-1-2011H-1-2011-082
• Study Type: observational
• Target: 48
• Locations: 1 country
• Sites: 1

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.

Conditions

Non Alcoholic Fatty Liver Disease; Type 2 Diabetes; Liver Cirrhosis

Keywords

NAFLD; Incretin hormones

Outcome Measures

Primary Outcomes (1)

• The Incretin effect

  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

  pre dose 0,10, 20, 30, 40, 50, 60, 75, 90, 120, 150, 180, 240 min post dose

Secondary Outcomes (3)

• 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

• 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

• Plasma glucagon response

  pre dose 0,10, 20, 30, 40, 50, 60, 75, 90, 120, 150, 180, 240 min post dose

Study Arms (5)

NAFLD

Non alcoholic fatty liver disease without type 2 diabetes

Other: OGTT; Other: IIGI

NAFLD+T2D

Non alcoholic fatty liver disease with type 2 diabetes

Other: OGTT; Other: IIGI

T2D

Type 2 diabetics without non alcoholic fatty liver disease

Other: OGTT; Other: IIGI

cirrhosis

Patients with liver cirrhosis

Other: OGTT; Other: IIGI

Kontrol groups

Healthy control subjects

Other: OGTT; Other: IIGI

Interventions

OGTT OTHER

50g waterfree glucose dissolved in 300 ml water consumed over 5 min.

Also known as: Waterfree glucose, The Pharmacy of the capital region

Kontrol groups; NAFLD; NAFLD+T2D; T2D; cirrhosis

IIGI OTHER

iso glycemic intravenous (iv) glucose infusion (IIGI) with 20% glucose

Also known as: Glucose infusion, 20%

Kontrol groups; NAFLD; NAFLD+T2D; T2D; cirrhosis

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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

You may qualify if:

• 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
• 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
• NAFLD verified by liver biopsy
• Caucasian \>18 years of age
• Normal 75-g OGTT
• Negative ICA and GAD65-autoantibodies

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Gentofte, Copenhagen: lead

Study Sites (1)

Diabetes Research Division, Gentofte University Hospital, Niels Andersens Vej 65, opgang 4b, 1. sal

Hellerup, 2900, Denmark

Location

Related Publications (2)

• Lauritsen JV, Bergmann N, Junker AE, Gyldenlove M, Skov L, Gluud LL, Hartmann B, Holst JJ, Vilsboll T, Knop FK. Oral glucose has little or no effect on appetite and satiety sensations despite a significant gastrointestinal response. Eur J Endocrinol. 2023 Dec 6;189(6):619-626. doi: 10.1093/ejendo/lvad161.

  PMID: 38035766 DERIVED

• 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.

  PMID: 29506157 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

DNA (whole blood) will be kept for 15 years

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Diabetes Mellitus, Type 2; Liver Cirrhosis

Interventions

Glucose Tolerance Test

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Blood Chemical Analysis; Clinical Chemistry Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Endocrine; Investigative Techniques

Study Officials

• Anders E Junker, MD, phd-student

  Diabetes Research Division, Gentofte Hospital, University of Copenhagen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD PhD-student

Study Record Dates

• First Submitted: December 5, 2011
• First Posted: December 14, 2011
• Study Start: December 1, 2011
• Primary Completion: May 1, 2013
• Study Completion: July 1, 2014
• Last Updated: July 10, 2014

Record last verified: 2014-07

Locations

DK (1)