The role of intestinal integrity and inflammation in the pathogenesis of insulin resistance and non-alcoholic steatohepatitis in morbid obesity.

The role of intestinal integrity and inflammation in the pathogenesis of insulin resistance and non-alcoholic steatohepatitis in morbid obesity. - Intestinal permeability in diabetes type 2 and fatty liver disease

Status

Active, not recruiting

Phases

Unknown

Study type

Observational

Source

NL-OMON

Registry ID

NL-OMON33407

Enrollment

190

Registered

2009-08-26

Start date

2010-09-07

Completion date

Unknown

Last updated

2024-05-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

fatty liver disease NAFLD non-alcoholic steatohepatitis

Interventions

None listed

Eligibility

Age

18 Years to 99 Years

Inclusion criteria

Inclusion criteria: Researchpopulation: • BMI >40 or BMI>35 kg/m2 with co-morbidities • planned for bariatric surgery • Age 18-60 years (to prevent inclusion of patients who are unable to give informed consent and to have inclusion criteria adjusted to the criteria for surgical intervention) Control population: • BMI 20-25 • planned for Nissen fundoplication or cholecystectomy • Age 18-60 years old

Exclusion criteria

Exclusion criteria: For all patients: • Age 60 years • Diabetes Mellitus type I • Inflammatory diseases such as auto-immune diseases (due to a higher inflammatory profile) • Degenerative disase • Alcohol or drug abuse • use of corticosteroids and / or prednisolone (confounding effect on inflammatory status)

Design outcomes

Primary

Measure	Time frame
Primary study parameters: •Intestinal permeability, by measurement of excretion of orally administered sugars in urine after intake of ibuprofen (2x400mg) •Plasma endotoxin levels, measured by LAL and ENDOCAB assay •IR/Diabetes type II prevalence, measured by fasted glucose/insulin plasma levels and HbA1c •The extent of NAFLD/ NASH by histopathological stainings of the liver biopsies	—

Secondary

Measure	Time frame
Secundary study parameters: •Intestinal damage -Plasma levels IFABP, ILBP and LFABP -Histology, gene expression and plasma/urine levels of tight-junction proteins (claudin, ZO-1, occludin) •Intestinal microflora -faecal flora content •Inflammatory parameters -Plasma levels CRP, IL-6, TNF-a, MPO, PAI-1, adiponectin, leptin, zinc; intracellular zinc in leukocytes -Fat tissue inflammation: gene expression of IL-6, IL-1β, IL-8, IKKβ, infiltration by macrofages -Muscle inflammation & insulin sensitivity: IL-6 and IRS phosphorylation -Liver inflammation: neutrofil infiltration, MPO content, extent of NASH (by Brunt scoring system) •Metabolic parameters -total cholesterol, LDL-cholesterol, HDL-cholesterol, free fatty acids and triglycerides •Liver damage -ALT, AST, LFABP Other study parameters are general health status, Body Mass Index (BMI), waist/hip ratio, and relevant medical history. Furthermore changes in medication intake will be noted as a matter of course.	—

Measure

Time frame

Secundary study parameters: •Intestinal damage -Plasma levels IFABP, ILBP and LFABP -Histology, gene expression and plasma/urine levels of tight-junction proteins (claudin, ZO-1, occludin) •Intestinal microflora -faecal flora content •Inflammatory parameters -Plasma levels CRP, IL-6, TNF-a, MPO, PAI-1, adiponectin, leptin, zinc; intracellular zinc in leukocytes -Fat tissue inflammation: gene expression of IL-6, IL-1β, IL-8, IKKβ, infiltration by macrofages -Muscle inflammation & insulin sensitivity: IL-6 and IRS phosphorylation -Liver inflammation: neutrofil infiltration, MPO content, extent of NASH (by Brunt scoring system) •Metabolic parameters -total cholesterol, LDL-cholesterol, HDL-cholesterol, free fatty acids and triglycerides •Liver damage -ALT, AST, LFABP Other study parameters are general health status, Body Mass Index (BMI), waist/hip ratio, and relevant medical history. Furthermore changes in medication intake will be noted as a matter of course.

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Countries

Netherlands

Outcome results